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Low-Rank Matrix Completion: A Contemporary Survey <s> 3) CONVOLUTIONAL NEURAL NETWORK BASED MATRIX COMPLETION <s> We propose a novel method for constructing wavelet transforms of functions defined on the vertices of an arbitrary finite weighted graph. Our approach is based on defining scaling using the the graph analogue of the Fourier domain, namely the spectral decomposition of the discrete graph Laplacian $\L$. Given a wavelet generating kernel $g$ and a scale parameter $t$, we define the scaled wavelet operator $T_g^t = g(t\L)$. The spectral graph wavelets are then formed by localizing this operator by applying it to an indicator function. Subject to an admissibility condition on $g$, this procedure defines an invertible transform. We explore the localization properties of the wavelets in the limit of fine scales. Additionally, we present a fast Chebyshev polynomial approximation algorithm for computing the transform that avoids the need for diagonalizing $\L$. We highlight potential applications of the transform through examples of wavelets on graphs corresponding to a variety of different problem domains. <s> BIB001 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 3) CONVOLUTIONAL NEURAL NETWORK BASED MATRIX COMPLETION <s> This paper proposes AutoRec, a novel autoencoder framework for collaborative filtering (CF). Empirically, AutoRec's compact and efficiently trainable model outperforms state-of-the-art CF techniques (biased matrix factorization, RBM-CF and LLORMA) on the Movielens and Netflix datasets. <s> BIB002 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 3) CONVOLUTIONAL NEURAL NETWORK BASED MATRIX COMPLETION <s> Deep Learning's recent successes have mostly relied on Convolutional Networks, which exploit fundamental statistical properties of images, sounds and video data: the local stationarity and multi-scale compositional structure, that allows expressing long range interactions in terms of shorter, localized interactions. However, there exist other important examples, such as text documents or bioinformatic data, that may lack some or all of these strong statistical regularities. ::: In this paper we consider the general question of how to construct deep architectures with small learning complexity on general non-Euclidean domains, which are typically unknown and need to be estimated from the data. In particular, we develop an extension of Spectral Networks which incorporates a Graph Estimation procedure, that we test on large-scale classification problems, matching or improving over Dropout Networks with far less parameters to estimate. <s> BIB003 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 3) CONVOLUTIONAL NEURAL NETWORK BASED MATRIX COMPLETION <s> In this work, we are interested in generalizing convolutional neural networks (CNNs) from low-dimensional regular grids, where image, video and speech are represented, to high-dimensional irregular domains, such as social networks, brain connectomes or words' embedding, represented by graphs. We present a formulation of CNNs in the context of spectral graph theory, which provides the necessary mathematical background and efficient numerical schemes to design fast localized convolutional filters on graphs. Importantly, the proposed technique offers the same linear computational complexity and constant learning complexity as classical CNNs, while being universal to any graph structure. Experiments on MNIST and 20NEWS demonstrate the ability of this novel deep learning system to learn local, stationary, and compositional features on graphs. <s> BIB004 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 3) CONVOLUTIONAL NEURAL NETWORK BASED MATRIX COMPLETION <s> We present a scalable approach for semi-supervised learning on graph-structured data that is based on an efficient variant of convolutional neural networks which operate directly on graphs. We motivate the choice of our convolutional architecture via a localized first-order approximation of spectral graph convolutions. Our model scales linearly in the number of graph edges and learns hidden layer representations that encode both local graph structure and features of nodes. In a number of experiments on citation networks and on a knowledge graph dataset we demonstrate that our approach outperforms related methods by a significant margin. <s> BIB005 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 3) CONVOLUTIONAL NEURAL NETWORK BASED MATRIX COMPLETION <s> Matrix completion models are among the most common formulations of recommender systems. Recent works have showed a boost of performance of these techniques when introducing the pairwise relationships between users/items in the form of graphs, and imposing smoothness priors on these graphs. However, such techniques do not fully exploit the local stationarity structures of user/item graphs, and the number of parameters to learn is linear w.r.t. the number of users and items. We propose a novel approach to overcome these limitations by using geometric deep learning on graphs. Our matrix completion architecture combines graph convolutional neural networks and recurrent neural networks to learn meaningful statistical graph-structured patterns and the non-linear diffusion process that generates the known ratings. This neural network system requires a constant number of parameters independent of the matrix size. We apply our method on both synthetic and real datasets, showing that it outperforms state-of-the-art techniques. <s> BIB006 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 3) CONVOLUTIONAL NEURAL NETWORK BASED MATRIX COMPLETION <s> Deep learning has achieved a remarkable performance breakthrough in several fields, most notably in speech recognition, natural language processing, and computer vision. In particular, convolutional neural network (CNN) architectures currently produce state-of-the-art performance on a variety of image analysis tasks such as object detection and recognition. Most of deep learning research has so far focused on dealing with 1D, 2D, or 3D Euclidean-structured data such as acoustic signals, images, or videos. Recently, there has been an increasing interest in geometric deep learning, attempting to generalize deep learning methods to non-Euclidean structured data such as graphs and manifolds, with a variety of applications from the domains of network analysis, computational social science, or computer graphics. In this paper, we propose a unified framework allowing to generalize CNN architectures to non-Euclidean domains (graphs and manifolds) and learn local, stationary, and compositional task-specific features. We show that various non-Euclidean CNN methods previously proposed in the literature can be considered as particular instances of our framework. We test the proposed method on standard tasks from the realms of image-, graph-and 3D shape analysis and show that it consistently outperforms previous approaches. <s> BIB007 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 3) CONVOLUTIONAL NEURAL NETWORK BASED MATRIX COMPLETION <s> We consider the problem of channel estimation for millimeter wave (mmWave) systems, where, to minimize the hardware complexity and power consumption, an analog transmit beamforming and receive combining structure with only one radio frequency (RF) chain at the base station (BS) and mobile station (MS) is employed. Most existing works for mmWave channel estimation exploit sparse scattering characteristics of the channel. In addition to sparsity, mmWave channels may exhibit angular spreads over the angle of arrival (AoA), angle of departure (AoD), and elevation domains. In this paper, we show that angular spreads give rise to a useful low-rank structure that, along with the sparsity, can be simultaneously utilized to reduce the sample complexity, i.e. the number of samples needed to successfully recover the mmWave channel. Specifically, to effectively leverage the joint sparse and low-rank structure, we develop a two-stage compressed sensing method for mmWave channel estimation, where the sparse and low-rank properties are respectively utilized in two consecutive stages, namely, a matrix completion stage and a sparse recovery stage. Our theoretical analysis reveals that the proposed two-stage scheme can achieve a lower sample complexity than a direct compressed sensing method that exploits only the sparse structure of the mmWave channel. Simulation results are provided to corroborate our theoretical results and to show the superiority of the proposed two-stage method. <s> BIB008

In recent years, approaches to use CNN to solve the LRMC problem have been proposed. These approaches are particular useful when a desired low-rank matrix is expressed in a graph structure (e.g., the recommendation matrix with a user graph to express the similarity between users' rating results) BIB002 - BIB004 . The main idea of CNN-based LRMC algorithms is to express the low-rank matrix as a graph structure and then apply CNN to the constructed graph to recover the desired matrix. Graphical Model of a Low-Rank Matrix: Suppose M ∈ R n 1 ×n 2 is the rating matrix in which the columns and rows are indexed by users and products, respectively. The first step of the CNN-based LRMC algorithm is to model the column and row graphs of M using the correlations between its columns and rows. Specifically, in the column graph G c of M, users are represented as vertices, and two vertices i and j are connected by an undirected edge if the correlation ρ ij = | m i ,m j | m i 2 m j 2 between the i and j-th columns of M is larger than the pre-determined threshold . Similarly, we construct the row graph G r of M by denoting each row (product) of M as a vertex and then connecting strongly correlated vertices. To express the connection, we define the adjacency matrix of each graph. The adjacency matrix W c = (w c ij ) ∈ R n 2 ×n 2 of the column graph G c is defined as 1 if the vertices (users) i and j are connected 0 otherwise The adjacency matrix W r ∈ R n 1 ×n 2 of the row graph G r is defined in a similar way. CNN-based LRMC: Let U ∈ R n 1 ×r and V ∈ R n 2 ×r be matrices such that M = UV T . The primary task of the CNN-based approach is to find functions f r and f c mapping the vertex sets of the row and column graphs G r and G c of M to U and V, respectively. Here, each vertex of G r (respective G c ) is mapped to each row of U (respective V) by f r (respective f c ). Since it is difficult to express f r and f c explicitly, we can learn these nonlinear mappings using CNN-based models. In the CNN-based LRMC approach, U and V are initialized at random and updated in each iteration. Specifically, U and V are updated to minimize the following loss function BIB006 : where τ is a regularization parameter. In other words, we find U and V such that the Euclidean distance between the connected vertices is minimized (see u i − u j 2 (w r ij = 1) and v i − v j 2 (w c ij = 1) in (61)). The update procedures of U and V are [67]: 1) Initialize U and V at random and assign each row of U and V to each vertex of the row graph G r and the column graph G c , respectively. 2) Extract the feature matrices U and V by performing a graph-based convolution operation on G r and G c , respectively. 3) Update U and V using the feature matrices U and V, respectively. 4) Compute the loss function in (61) using updated U and V and perform the back propagation to update the filter parameters. 5) Repeat the above procedures until the value of the loss function is smaller than a pre-chosen threshold. One important issue in the CNN-based LRMC approach is to define a graph-based convolution operation to extract the feature matrices U and V (see the second step). Note that the input data G r and G c do not lie on regular lattices like images and thus classical CNN cannot be directly applied to G r and G c . One possible option is to define the convolution operation in the Fourier domain of the graph. In recent years, CNN models based on the Fourier transformation of graph-structure data have been proposed - BIB007 . In , an approach to use the eigendecomposition of the Laplacian has been proposed. To further reduce the model complexity, CNN models using the polynomial filters have been proposed BIB003 - BIB005 . In essence, the Fourier transform of a graph can be computed using the (normalized) graph Laplacian. Let R r be the graph Laplacian of G r (i.e., R r = BIB001 . Then, the graph Fourier transform F r (u) of a vertex assigned with the vector u is defined as where R r = Q r r Q T r is an eigen-decomposition of the graph Laplacian R r BIB001 . Also, the inverse graph Fourier transform Let z be the filter used in the convolution, then the output u of the graph-based convolution on a vertex assigned with the vector u is defined as BIB001 , BIB004 From (62) and (63), BIB002 can be expressed as where G = diag(F r (z)) is the matrix of filter parameters defined in the graph Fourier domain. We next update U and V using the feature matrices U and V. In BIB006 , a cascade of multi-graph CNN followed by long short-term memory (LSTM) recurrent neural network BIB008 One can easily check that F −1 r (F r (u)) = u and F r (F −1 r (u )) = u . has been proposed. The computational cost of this approach is O(r| | + r 2 n 1 + r 2 n 2 ) which is much lower than the SVD-based LRMC techniques (i.e., O(rn 1 n 2 )) as long as r min(n 1 , n 2 ). Finally, we compute the loss function l(U i , V i ) in and then update the filter parameters using the backpropagation. Suppose {U i } i and {V i } i converge to U and V, respectively, then the estimate of M obtained by the CNN-based LRMC is M = U V T .

Low-Rank Matrix Completion: A Contemporary Survey <s> 4) ATOMIC NORM MINIMIZATION <s> The time-frequency and time-scale communities have recently developed a large number of overcomplete waveform dictionaries --- stationary wavelets, wavelet packets, cosine packets, chirplets, and warplets, to name a few. Decomposition into overcomplete systems is not unique, and several methods for decomposition have been proposed, including the method of frames (MOF), Matching pursuit (MP), and, for special dictionaries, the best orthogonal basis (BOB). ::: Basis Pursuit (BP) is a principle for decomposing a signal into an "optimal" superposition of dictionary elements, where optimal means having the smallest l1 norm of coefficients among all such decompositions. We give examples exhibiting several advantages over MOF, MP, and BOB, including better sparsity and superresolution. BP has interesting relations to ideas in areas as diverse as ill-posed problems, in abstract harmonic analysis, total variation denoising, and multiscale edge denoising. ::: BP in highly overcomplete dictionaries leads to large-scale optimization problems. With signals of length 8192 and a wavelet packet dictionary, one gets an equivalent linear program of size 8192 by 212,992. Such problems can be attacked successfully only because of recent advances in linear programming by interior-point methods. We obtain reasonable success with a primal-dual logarithmic barrier method and conjugate-gradient solver. <s> BIB001 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 4) ATOMIC NORM MINIMIZATION <s> In applications throughout science and engineering one is often faced with the challenge of solving an ill-posed inverse problem, where the number of available measurements is smaller than the dimension of the model to be estimated. However in many practical situations of interest, models are constrained structurally so that they only have a few degrees of freedom relative to their ambient dimension. This paper provides a general framework to convert notions of simplicity into convex penalty functions, resulting in convex optimization solutions to linear, underdetermined inverse problems. The class of simple models considered are those formed as the sum of a few atoms from some (possibly infinite) elementary atomic set; examples include well-studied cases such as sparse vectors and low-rank matrices, as well as several others including sums of a few permutations matrices, low-rank tensors, orthogonal matrices, and atomic measures. The convex programming formulation is based on minimizing the norm induced by the convex hull of the atomic set; this norm is referred to as the atomic norm. The facial structure of the atomic norm ball carries a number of favorable properties that are useful for recovering simple models, and an analysis of the underlying convex geometry provides sharp estimates of the number of generic measurements required for exact and robust recovery of models from partial information. These estimates are based on computing the Gaussian widths of tangent cones to the atomic norm ball. When the atomic set has algebraic structure the resulting optimization problems can be solved or approximated via semidefinite programming. The quality of these approximations affects the number of measurements required for recovery. Thus this work extends the catalog of simple models that can be recovered from limited linear information via tractable convex programming. <s> BIB002 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 4) ATOMIC NORM MINIMIZATION <s> The sub-Nyquist estimation of line spectra is a classical problem in signal processing, but currently popular subspace-based techniques have few guarantees in the presence of noise and rely on a priori knowledge about system model order. Motivated by recent work on atomic norms in inverse problems, we propose a new approach to line spectrum estimation that provides theoretical guarantees for the mean-square-error performance in the presence of noise and without advance knowledge of the model order. We propose an abstract theory of denoising with atomic norms which is specialized to provide a convex optimization problem for estimating the frequencies and phases of a mixture of complex exponentials with guaranteed bounds on the mean-squared-error. In general, our proposed optimization problem has no known polynomial time solution, but we provide an efficient algorithm, called DAST, based on the Fast Fourier Transform that achieves nearly the same error rate. We compare DAST with Cadzow's canonical alternating projection algorithm, which performs marginally better under high signal-to-noise ratios when the model order is known exactly, and demonstrate experimentally that DAST outperforms other denoising techniques, including Cadzow's, over a wide range of signal-to-noise ratios. <s> BIB003 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 4) ATOMIC NORM MINIMIZATION <s> In many signal processing applications, the aim is to reconstruct a signal that has a simple representation with respect to a certain basis or frame. Fundamental elements of the basis known as “atoms” allow us to define “atomic norms” that can be used to formulate convex regularizations for the reconstruction problem. Efficient algorithms are available to solve these formulations in certain special cases, but an approach that works well for general atomic norms, both in terms of speed and reconstruction accuracy, remains to be found. This paper describes an optimization algorithm called CoGEnT that produces solutions with succinct atomic representations for reconstruction problems, generally formulated with atomic-norm constraints. CoGEnT combines a greedy selection scheme based on the conditional gradient approach with a backward (or “truncation”) step that exploits the quadratic nature of the objective to reduce the basis size. We establish convergence properties and validate the algorithm via extensive numerical experiments on a suite of signal processing applications. Our algorithm and analysis also allow for inexact forward steps and for occasional enhancements of the current representation to be performed. CoGEnT can outperform the basic conditional gradient method, and indeed many methods that are tailored to specific applications, when the enhancement and truncation steps are defined appropriately. We also introduce several novel applications that are enabled by the atomic-norm framework, including tensor completion, moment problems in signal processing, and graph deconvolution. <s> BIB004 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> 4) ATOMIC NORM MINIMIZATION <s> As a paradigm to recover the sparse signal from a small set of linear measurements, compressed sensing (CS) has stimulated a great deal of interest in recent years. In order to apply the CS techniques to wireless communication systems, there are a number of things to know and also several issues to be considered. However, it is not easy to grasp simple and easy answers to the issues raised while carrying out research on CS. The main purpose of this paper is to provide essential knowledge and useful tips and tricks that wireless communication researchers need to know when designing CS-based wireless systems. First, we present an overview of the CS technique, including basic setup, sparse recovery algorithm, and performance guarantee. Then, we describe three distinct subproblems of CS, viz., sparse estimation, support identification, and sparse detection, with various wireless communication applications. We also address main issues encountered in the design of CS-based wireless communication systems. These include potentials and limitations of CS techniques, useful tips that one should be aware of, subtle points that one should pay attention to, and some prior knowledge to achieve better performance. Our hope is that this paper will be a useful guide for wireless communication researchers and even non-experts to get the gist of CS techniques. <s> BIB005

In ADMiRA, a low-rank matrix can be represented using a small number of rank-one matrices. Atomic norm minimization (ANM) generalizes this idea for arbitrary data in which the data is represented using a small number of basis elements called atom. Example of ANM include sound navigation ranging systems BIB002 and line spectral estimation BIB003 . To be specific, let X = r i=1 α i H i be a signal with k distinct frequency components H i ∈ C n 1 ×n 2 . Then the atom is defined as is the steering vector and b i ∈ C n 2 is the vector of normalized coefficients (i.e., b i 2 = 1). We denote the set of such atoms H i as H. Using H, the atomic norm of X is defined as Note that the atomic norm X H is a generalization of the 1 -norm and also the nuclear norm to the space of sinusoidal signals BIB005 , BIB003 . Let X o be the observation of X, then the problem to reconstruct X can be modeled as the ANM problem: where τ > 0 is a regularization parameter. By using [87, Theorem 1], we have and the equivalent expression of the problem (68) is Note that the problem (70) can be solved via the SDP solver (e.g., SDPT3 ) or greedy algorithms BIB001 , BIB004 .

Low-Rank Matrix Completion: A Contemporary Survey <s> APPENDIX A PROOF OF THE SDP FORM OF NNM <s> The global bandwidth shortage facing wireless carriers has motivated the exploration of the underutilized millimeter wave (mm-wave) frequency spectrum for future broadband cellular communication networks. There is, however, little knowledge about cellular mm-wave propagation in densely populated indoor and outdoor environments. Obtaining this information is vital for the design and operation of future fifth generation cellular networks that use the mm-wave spectrum. In this paper, we present the motivation for new mm-wave cellular systems, methodology, and hardware for measurements and offer a variety of measurement results that show 28 and 38 GHz frequencies can be used when employing steerable directional antennas at base stations and mobile devices. <s> BIB001 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> APPENDIX A PROOF OF THE SDP FORM OF NNM <s> In this paper, we present a flexible low-rank matrix completion (LRMC) approach for topological interference management (TIM) in the partially connected $K$ -user interference channel. No channel state information (CSI) is required at the transmitters except the network topology information. The previous attempt on the TIM problem is mainly based on its equivalence to the index coding problem, but so far only a few index coding problems have been solved. In contrast, in this paper, we present an algorithmic approach to investigate the achievable degrees-of-freedom (DoFs) by recasting the TIM problem as an LRMC problem. Unfortunately, the resulting LRMC problem is known to be NP-hard, and the main contribution of this paper is to propose a Riemannian pursuit (RP) framework to detect the rank of the matrix to be recovered by iteratively increasing the rank. This algorithm solves a sequence of fixed-rank matrix completion problems. To address the convergence issues in the existing fixed-rank optimization methods, the quotient manifold geometry of the search space of fixed-rank matrices is exploited via Riemannian optimization. By further exploiting the structure of the low-rank matrix varieties, i.e., the closure of the set of fixed-rank matrices, we develop an efficient rank increasing strategy to find good initial points in the procedure of rank pursuit. Simulation results demonstrate that the proposed RP algorithm achieves a faster convergence rate and higher achievable DoFs for the TIM problem compared with the state-of-the-art methods. <s> BIB002 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> APPENDIX A PROOF OF THE SDP FORM OF NNM <s> We present a scalable approach for semi-supervised learning on graph-structured data that is based on an efficient variant of convolutional neural networks which operate directly on graphs. We motivate the choice of our convolutional architecture via a localized first-order approximation of spectral graph convolutions. Our model scales linearly in the number of graph edges and learns hidden layer representations that encode both local graph structure and features of nodes. In a number of experiments on citation networks and on a knowledge graph dataset we demonstrate that our approach outperforms related methods by a significant margin. <s> BIB003 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> APPENDIX A PROOF OF THE SDP FORM OF NNM <s> Deep learning has achieved a remarkable performance breakthrough in several fields, most notably in speech recognition, natural language processing, and computer vision. In particular, convolutional neural network (CNN) architectures currently produce state-of-the-art performance on a variety of image analysis tasks such as object detection and recognition. Most of deep learning research has so far focused on dealing with 1D, 2D, or 3D Euclidean-structured data such as acoustic signals, images, or videos. Recently, there has been an increasing interest in geometric deep learning, attempting to generalize deep learning methods to non-Euclidean structured data such as graphs and manifolds, with a variety of applications from the domains of network analysis, computational social science, or computer graphics. In this paper, we propose a unified framework allowing to generalize CNN architectures to non-Euclidean domains (graphs and manifolds) and learn local, stationary, and compositional task-specific features. We show that various non-Euclidean CNN methods previously proposed in the literature can be considered as particular instances of our framework. We test the proposed method on standard tasks from the realms of image-, graph-and 3D shape analysis and show that it consistently outperforms previous approaches. <s> BIB004

Proof: We recall that the standard form of an SDP is expressed as where C is a given matrix, and {A k } l k=1 and {b k } l k=1 are given sequences of matrices and constants, respectively. To convert the NNM problem in (11) into the standard SDP form in (71), we need a few steps. First, we convert the NNM problem in (11) into the epigraph form: 15 min X,t t subject to X * ≤ t, P (X) = P (M). BIB002 Note that min X X * = min X min t: X * ≤t t = min (X,t): X * ≤t t. Next, we transform the constraints in BIB004 to generate the standard form in BIB003 . We first consider the inequality constraint ( X * ≤ t). Note that X * ≤ t if and only if there are symmetric matrices W 1 ∈ R n 1 ×n 1 and W 2 ∈ R n 2 ×n 2 such that [21, Lemma 2] tr(W 1 ) + tr(W 2 ) ≤ 2t and W 1 X X T W 2 0. (73) Then, by denoting Y = W 1 X X T W 2 ∈ R (n 1 +n 2 )×(n 1 +n 2 ) and M = 0 n 1 ×n 1 M M T 0 n 2 ×n 2 where 0 s×t is the (s × t)-dimensional zero matrix, the problem in (72) can be reformulated as min Y,t 2t subject to tr(Y) ≤ 2t, Y 0, where P (Y) = 0 n 1 ×n 1 P (X) (P (X)) T 0 n 2 ×n 2 is the extended sampling operator. We now consider the equality constraint (P (Y) = P ( M)) in . One can easily see that this condition is equivalent to Y, e i e T j+n 1 = M, e i e T j+n 1 , (i, j) ∈ , where {e 1 , · · · , e n 1 +n 2 } be the standard ordered basis of R n 1 +n 2 . Let A k = e i e T j+n 1 and M, e i e T j+n 1 = b k for each of (i, j) ∈ . Then, Y, A k = b k , k = 1, · · · , | |, and thus (74) can be reformulated as min Y,t 2t subject to tr(Y) ≤ 2t Y 0 Y, A k = b k , k = 1, · · · , | |. (77) For example, we consider the case where the desired matrix M is given by M = 1 2 2 4 and the index set of observed entries is = {(2, 1), (2, 2)}. In this case, A 1 = e 2 e T 3 , A 2 = e 2 e T 4 , b 1 = 2, and b 2 = 4. (78) One can express (77) in a concise form as BIB001 , which is the desired result.

Low-Rank Matrix Completion: A Contemporary Survey <s> APPENDIX B PERFORMANCE GUARANTEE OF NNM <s> We consider a problem of considerable practical interest: the recovery of a data matrix from a sampling of its entries. Suppose that we observe m entries selected uniformly at random from a matrix M. Can we complete the matrix and recover the entries that we have not seen? ::: ::: We show that one can perfectly recover most low-rank matrices from what appears to be an incomplete set of entries. We prove that if the number m of sampled entries obeys $$m\ge C\,n^{1.2}r\log n$$ for some positive numerical constant C, then with very high probability, most n×n matrices of rank r can be perfectly recovered by solving a simple convex optimization program. This program finds the matrix with minimum nuclear norm that fits the data. The condition above assumes that the rank is not too large. However, if one replaces the 1.2 exponent with 1.25, then the result holds for all values of the rank. Similar results hold for arbitrary rectangular matrices as well. Our results are connected with the recent literature on compressed sensing, and show that objects other than signals and images can be perfectly reconstructed from very limited information. <s> BIB001 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> APPENDIX B PERFORMANCE GUARANTEE OF NNM <s> This paper provides the best bounds to date on the number of randomly sampled entries required to reconstruct an unknown low rank matrix. These results improve on prior work by Candes and Recht, Candes and Tao, and Keshavan, Montanari, and Oh. The reconstruction is accomplished by minimizing the nuclear norm, or sum of the singular values, of the hidden matrix subject to agreement with the provided entries. If the underlying matrix satisfies a certain incoherence condition, then the number of entries required is equal to a quadratic logarithmic factor times the number of parameters in the singular value decomposition. The proof of this assertion is short, self contained, and uses very elementary analysis. The novel techniques herein are based on recent work in quantum information theory. <s> BIB002 </s> Low-Rank Matrix Completion: A Contemporary Survey <s> APPENDIX B PERFORMANCE GUARANTEE OF NNM <s> This paper is concerned with the problem of recovering an unknown matrix from a small fraction of its entries. This is known as the matrix completion problem, and comes up in a great number of applications, including the famous Netflix Prize and other similar questions in collaborative filtering. In general, accurate recovery of a matrix from a small number of entries is impossible; but the knowledge that the unknown matrix has low rank radically changes this premise, making the search for solutions meaningful. ::: This paper presents optimality results quantifying the minimum number of entries needed to recover a matrix of rank r exactly by any method whatsoever (the information theoretic limit). More importantly, the paper shows that, under certain incoherence assumptions on the singular vectors of the matrix, recovery is possible by solving a convenient convex program as soon as the number of entries is on the order of the information theoretic limit (up to logarithmic factors). This convex program simply finds, among all matrices consistent with the observed entries, that with minimum nuclear norm. As an example, we show that on the order of nr log(n) samples are needed to recover a random n x n matrix of rank r by any method, and to be sure, nuclear norm minimization succeeds as soon as the number of entries is of the form nr polylog(n). <s> BIB003

Sketch of proof: Exact recovery of the desired low-rank matrix M can be guaranteed under the uniqueness condition of the NNM problem BIB001 , BIB003 , BIB002 . To be specific, let M = U V T be the SVD of M where U ∈ R n 1 ×r , ∈ R r×r , and V ∈ R n 2 ×r . Also, let R n 1 ×n 2 = T T ⊥ be the orthogonal decomposition in which T ⊥ is defined as the subspace of matrices whose row and column spaces are orthogonal to the row and column spaces of M, respectively. Here, T is the orthogonal complement of T ⊥ . It has been shown that M is the unique solution of the NNM problem if the following conditions hold true [22, Lemma 3.1]: 1) there exists a matrix Y = UV T + W such that P (Y) = Y, W ∈ T ⊥ , and W < 1, 2) the restriction of the sampling operation P to T is an injective (one-to-one) mapping. The establishment of Y obeying 1) and 2) are in turn conditioned on the observation model of M and its intrinsic coherence property. Under a uniform sampling model of M, suppose the coherence property of M satisfies max(µ(U), µ(V)) ≤ µ 0 , where µ 0 and µ 1 are some constants, e ij is the entry of E = UV T , and µ(U) and µ(V) are the coherences of the column and row spaces of M, respectively. where γ > 2 is some constant and n 1 = n 2 = n, then M is the unique solution of the NNM problem with probability at least 1 − βn −γ . Further, if r ≤ µ −1 0 n 1/5 , (80) can be improved to m ≥ Cµ 0 γ n 1.2 r log n with the same success probability. One direct interpretation of this theorem is that the desired low-rank matrix can be reconstructed exactly using NNM with overwhelming probability even when m is much less than n 1 n 2 .

Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> I. INTRODUCTION <s> This paper describes the concept of sensor networks which has been made viable by the convergence of micro-electro-mechanical systems technology, wireless communications and digital electronics. First, the sensing tasks and the potential sensor networks applications are explored, and a review of factors influencing the design of sensor networks is provided. Then, the communication architecture for sensor networks is outlined, and the algorithms and protocols developed for each layer in the literature are explored. Open research issues for the realization of sensor networks are also discussed. <s> BIB001 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> I. INTRODUCTION <s> Wireless sensors and wireless sensor networks have come to the forefront of the scientific community recently. This is the consequence of engineering increasingly smaller sized devices, which enable many applications. The use of these sensors and the possibility of organizing them into networks have revealed many research issues and have highlighted new ways to cope with certain problems. In this paper, different applications areas where the use of such sensor networks has been proposed are surveyed <s> BIB002 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> I. INTRODUCTION <s> A wireless sensor network (WSN) has important applications such as remote environmental monitoring and target tracking. This has been enabled by the availability, particularly in recent years, of sensors that are smaller, cheaper, and intelligent. These sensors are equipped with wireless interfaces with which they can communicate with one another to form a network. The design of a WSN depends significantly on the application, and it must consider factors such as the environment, the application's design objectives, cost, hardware, and system constraints. The goal of our survey is to present a comprehensive review of the recent literature since the publication of [I.F. Akyildiz, W. Su, Y. Sankarasubramaniam, E. Cayirci, A survey on sensor networks, IEEE Communications Magazine, 2002]. Following a top-down approach, we give an overview of several new applications and then review the literature on various aspects of WSNs. We classify the problems into three different categories: (1) internal platform and underlying operating system, (2) communication protocol stack, and (3) network services, provisioning, and deployment. We review the major development in these three categories and outline new challenges. <s> BIB003 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> I. INTRODUCTION <s> This book presents an in-depth study on recent advances and research in Wireless Sensor Networks (WSNs). Existing WSN applications are described, followed by discussing the ongoing research efforts on some WSNs applications that show the usefulness of sensor networks. Theoretical analysis and factors influencing protocol design are highlighted. The state-of-the-art protocol for WSN protocol stack is explored for transport, routing, data link and physical layers. Moreover, the open research issues are discussed for each of the protocol layers. Furthermore, the synchronization and localization problems in WSNs are investigated along with the existing solutions and open research issues. Finally, the existing evaluation approaches for WSNs including physical testbeds and software simulation environments are overviewed. <s> BIB004 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> I. INTRODUCTION <s> Rapid advances in Wireless Sensor Networks (WSNs) indicate that they are becoming increasingly complex. Consequently users and applications are becoming more demanding. Due to unique characteristics of WSNs, like small dimensions and limited resources and capabilities, Quality of Service (QoS) is imposed as one of the key factors of WSNs. In this paper, we surveyed two main approaches for QoS provisioning in WSNs: layered and cross-layer approach. QoS provisioning with layered approach is surveyed in three WSN layers: MAC, network and transport layer. Current developments show that they can be efficiently used for QoS provisioning. However, they consider QoS only as layer specific isolated set of problems and they are highly dependent on the performance of other layers. Cross-layer approach does not have the restrictions as layered approach and hence can dispose with information from all layers of the communication protocol stack. Although it has huge potential to become the most efficient solution for QoS provisioning in WSNs, current development indicate that there are still many issues and challenges that need to be overcome. Since the concept of the QoS is relatively new in WSNs, there are not a large number of patents currently dealing with this issue, however but in coming years a large increase in the number of such patents is expected. Available patents in this domain are described in the paper. <s> BIB005

The WSNs are defined to be wireless networks composed of a very large number of interconnected nodes which can sense a variety of data, communicate with each other and have computation capabilities. The sensors are usually deployed into the scattered area, known as sensor field. These sensors gather data from an environment and forward it to the Base Station (BS) through multi-hops. The BS, also known as the sink, usually communicates with the users through a satellite or an internet connection BIB001 . Due to diverse and a wide range of applications Wireless Sensor Networks (WSNs) have gained considerable attention in recent years. Advances in miniaturization technologies, especially in Micro-Electro-Mechanical Systems (MEMS), have made it possible to develop Multi-functional Tiny Smart Sensors (MTSE). The MTSE now utilize WSNs and are envisioned to completely replace their conventional networks with WSNs. This will enable WSNs to become an integral part of human lives. The WSNs based on their applications can be divided into two main categories i.e. tracking and monitoring BIB003 , BIB002 . Monitoring application includes inside and outside environmental monitoring such as industrial unit and development monitoring, seismic and structural monitoring, physical condition monitoring and control monitoring. Tracking applications include vehicles, humans, animals and tracking objects. They can also be deployed for a collection of various types of data mentioned above in almost every kind of physical environments such as plain, underground and undersea sensing fields. In every situation, a sensor network gets constrained differently depending on an environment. Some of such networks are described and explained in and the references therein BIB003 . However, WSNs are still facing many challenges such as limited power, bandwidth, mobility and no central controller. The performance of any network including WSNs can be gauged, predicted and improved once the parameters characterizing the network are determined accurately. These parameters of a network include availability, bandwidth, latency, and error rate. Methods and techniques used to determine the parameters are known as Quality of Service (QoS) . At the present stage, WSNs need more attention in QoS provisioning making it a hot issue in current research. However, incorporating QoS is not an easy task usually due to a large number of nodes involved in the network BIB004 , . Some of the important aspects like energy protection, protocol designing, and architecture in WSNs are explored in details but still QoS support issues need more attention BIB005 . In figure 1 , a simple model shows that more users can always be included in the networks given that users are satisfied with the services of the network. Hence, the basic objective of the networks is how to utilize the network resources that provide QoS to users. The rest of this article is planned as follows. In section I-A we present a short summary of the QoS in WSNs while in section II we tabulated QoS-aware protocols designed for WSNs with their advantages, disadvantages and QoS parameters. Comparison and evolution of proposed protocols are made in section III where we have described briefly computational intelligence techniques for QoS managements. Final section IV includes conclusion and some new suggestions.

Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> 2) QoS IN WSNs <s> Practical design and performance solutions for every ad hoc wireless networkAd Hoc Wireless Networks comprise mobile devices that use wireless transmission for communication. They can be set up anywhere and any time because they eliminate the complexities of infrastructure setup and central administration-and they have enormous commercial and military potential. Now, there's a book that addresses every major issue related to their design and performance. Ad Hoc Wireless Networks: Architectures and Protocols presents state-of-the-art techniques and solutions, and supports them with easy-to-understand examples. The book starts off with the fundamentals of wireless networking (wireless PANs, LANs, MANs, WANs, and wireless Internet) and goes on to address such current topics as Wi-Fi networks, optical wireless networks, and hybrid wireless architectures. Coverage includes: Medium access control, routing, multicasting, and transport protocols QoS provisioning, energy management, security, multihop pricing, and much more In-depth discussion of wireless sensor networks and ultra wideband technology More than 200 examples and end-of-chapter problemsAd Hoc Wireless Networks is an invaluable resource for every network engineer, technical manager, and researcher designing or building ad hoc wireless networks. <s> BIB001 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> 2) QoS IN WSNs <s> Sensor networks are distributed networks made up of small sensing devices equipped with processors, memory, and short-range wireless communication. They differ from traditional computer networks in that they have resource constraints, unbalanced mixture traffic, data redundancy, network dynamics, and energy balance. Work within wireless sensor networks (WSNs) Quality of service (QoS) has been isolated and specific either on certain functional layers or application scenarios. However the area of sensor network quality of service (QoS) remains largely open. In this paper we define WSNs QoS requirements within a WSNs application, and then analyzing Issues for QoS Monitoring. <s> BIB002 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> 2) QoS IN WSNs <s> In this paper, we assess the state of the art of Quality of Services (QoS) support in wireless sensor networks (WSNs). Unlike traditional end-to-end multimedia applications, many non-end-to-end mission-critical applications envisioned for WSNs have brought forward new QoS requirements on the network. Further, unique characteristics of WSNs, such as extremely resource-constrained sensors, large-scale random deployment, and novel data-centric communication protocols, pose unprecedented challenges in the area of QoS support in WSNs. Thus, we first review the techniques for QoS support in traditional networks, analyze new QoS requirements in WSNs from a wide variety of applications classified by data delivery models, and propose some non-end-to-end collective QoS parameters. Next, the challenges of QoS support in this new paradigm are presented. Finally, we comment on current research efforts and identify many exciting open issues in order to stimulate more research interest in this largely unexplored area. Keywords— Wireless networks, wireless sensor networks, QoS, collective QoS <s> BIB003 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> 2) QoS IN WSNs <s> Wireless sensor networks (WSNs) are required to provide different levels of Quality of Services (QoS) based on the type of applications. Providing QoS support in wireless sensor networks is an emerging area of research. Due to resource constraints like processing power, memory, bandwidth and power sources in sensor networks, QoS support in WSNs is a challenging task. In this paper, we discuss the QoS requirements in WSNs and present a survey of some of the QoS aware routing techniques in WSNs. We also explore the middleware approaches for QoS support in WSNs and finally, highlight some open issues and future direction of research for providing QoS in WSNs. <s> BIB004 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> 2) QoS IN WSNs <s> Rapid advances in Wireless Sensor Networks (WSNs) indicate that they are becoming increasingly complex. Consequently users and applications are becoming more demanding. Due to unique characteristics of WSNs, like small dimensions and limited resources and capabilities, Quality of Service (QoS) is imposed as one of the key factors of WSNs. In this paper, we surveyed two main approaches for QoS provisioning in WSNs: layered and cross-layer approach. QoS provisioning with layered approach is surveyed in three WSN layers: MAC, network and transport layer. Current developments show that they can be efficiently used for QoS provisioning. However, they consider QoS only as layer specific isolated set of problems and they are highly dependent on the performance of other layers. Cross-layer approach does not have the restrictions as layered approach and hence can dispose with information from all layers of the communication protocol stack. Although it has huge potential to become the most efficient solution for QoS provisioning in WSNs, current development indicate that there are still many issues and challenges that need to be overcome. Since the concept of the QoS is relatively new in WSNs, there are not a large number of patents currently dealing with this issue, however but in coming years a large increase in the number of such patents is expected. Available patents in this domain are described in the paper. <s> BIB005

WSNs are used for a wide range of applications and each application has its own QoS requirements such as delay sensitivity, energy and network lifetime. QoS is an umbrella term for a group of technologies that permit network-sensitive applications to demand and receive expected services levels in terms of QoS requirements . In WSNs, QoS requirements can be specified from two perspectives BIB002 . One is called Network Specific QoS and other as Application Specific QoS. In application specific, each application has different QoS parameters such as data truthfulness, aggregation delay, fault tolerance and exposure BIB003 , . However, in WSNs every class of application also has some common requirements. So the network must fulfil the QoS needs when transmitting the sensed data from sensor field to the sink. Various data delivery models are used such as continuous, query and event driven BIB004 . Each model has its own QoS requirements. The basic QoS issues in WSNs are described below in details BIB005 , BIB004 so the generated data may be redundant. It causes the energy wastage; therefore it should be taken into the description in QoS. There are various QoS parameters and services required for different applications. For multimedia or real-time applications, the QoS metrics are jitter, latency and bandwidth. While the military applications have the security QoS parameters, the emergency and rescue applications have the availability QoS parameters and the applications such as cluster communication in meeting hall have a little energy QoS parameter. Unlike the traditional wired network, the QoS requirements are more unfair by the resources constraints of the nodes. Buffer space, processing power and battery charge are the examples of resource constraints BIB001 . QoS provisioning in individual layers depends on layer capability, so for performance evaluation and QoS assessment each layer has specific parameters that are used. The table below 1 shows the list of parameters in each layer BIB002 .

Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> c: MWTP <s> An important issue of research in wireless sensor networks (WSNs) is to dynamically organize the sensors into a wireless network and route the sensory data from sensors to a sink. Clustering in WSNs is an effective technique for prolonging the network lifetime. In most of the traditional routing in clustered WSNs assumes that there is no obstacle in a field of interest. Although it is not a realistic assumption, it eliminates the effects of obstacles in routing the sensory data. In this paper, we first propose a clustering technique in WSNs named energy-efficient homogeneous clustering that periodically selects the cluster heads according to a hybrid of their residual energy and a secondary parameter, such as the utility of the sensor to its neighbors. In this way, the selected cluster heads have equal number of neighbors and residual energy. We then present a route optimization technique in clustered WSNs among obstacles using Dijkstra's shortest path algorithm. We demonstrate that our work reduces the average hop count, packet delay, and energy-consumption of WSNs. <s> BIB001 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> c: MWTP <s> Energy efficiency is a crucial design issue in energy-constrained wireless networks to ensure uninterrupted information exchange. With the requirement of average end-to-end bit error rate (BER), the problem of joint routing and power allocation optimisation in multihop wireless network is studied here for two network power management policies: one is to minimise overall transmit power and the other is to maximise network lifetime. The proposed minimum total power strategy is optimal for minimising the overall transmit power consumption in the network and is preferable in network with tethered energy resources. To maximise the lifetime of a network with battery-operated nodes, the authors have developed two residual energy-aware joint routing and power allocation strategies: path lifetime maximisation (PLM) strategy and minimum weighted total power (MWTP) strategy. A distributed implementation for these strategies is also presented. Simulation results demonstrate that the proposed strategies achieve significant power saving and prolong network lifetime considerably over traditional routing algorithm with individual link BER constraint. It has also been shown that at reasonably low route refresh interval, the MWTP strategy performs best in terms of network lifetime, whereas at very high route refresh interval, the PLM strategy is optimal for network lifetime maximisation. <s> BIB002

In BIB001 organization of a sensor node in sensor field and the route of the sensor towards the sink which achieves the minimum delay in transmission is developed. Authors have proposed the energy-efficient homogeneous clustering algorithm. It chooses the cluster head periodically. For the routeing, it uses the Dijkstra's shortest path algorithm. It attains the reduced packet delay and minimum energy consumption. Gupta and Bose BIB002 have addressed the energy efficiency issue. To save the power consumption and prolong the network lifetime they have developed two residual energy-aware joint routeing and power allocation strategies.

Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> a: RACOON <s> In this study, Random Contention-based Resource Allocation (RACOON) medium access control (MAC) protocol is proposed to support the quality of service (QoS) for multi-user mobile wireless body area networks (WBANs). Different from existing QoS designs that focus on a single WBAN, a multiuser WBAN QoS should further consider both inter-WBAN interference and inter-WBAN priorities. Similar problems have been studied in both overlapped wireless local area networks (WLANs) and Bluetooth piconets that need QoS supports. However, these solutions are designed for non-medical transmissions that do not consider any priority scheme for medical applications. Most importantly, these studies focus on only static or low mobility networks. Network mobility of WBANs will introduce unnecessary inter-network collisions and energy waste, which are not considered by these solutions. The proposed multiuser-QoS protocol, RACOON, simultaneously satisfies the inter WBAN QoS requirements and overcomes the performance degradation caused by WBAN mobility. Simulation results verify that RACOON provides better latency and energy control, as compared with WBAN QoS protocols without considering the inter-WBAN requirements. <s> BIB001 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> a: RACOON <s> A Sensor Equipped Aquatic (SEA) swarm is a sensor cloud that drifts with water currents and enables 4-D (space and time) monitoring of local underwater events such as contaminants, marine life, and intruders. The swarm is escorted on the surface by drifting sonobuoys that collect data from the underwater sensors via acoustic modems and report it in real time via radio to a monitoring center. The goal of this study is to design an efficient anycast routing algorithm for reliable underwater sensor event reporting to any surface sonobuoy. Major challenges are the ocean current and limited resources (bandwidth and energy). In this paper, these challenges are addressed, and HydroCast, which is a hydraulic-pressure-based anycast routing protocol that exploits the measured pressure levels to route data to the surface sonobuoys, is proposed. This paper makes the following contributions: a novel opportunistic routing mechanism to select the subset of forwarders that maximizes the greedy progress yet limits cochannel interference and an efficient underwater dead end recovery method that outperforms the recently proposed approaches. The proposed routing protocols are validated through extensive simulations. <s> BIB002

In BIB001 , this issue of the mobility of the networks and priority scheme for medical applications are addressed. Network Lee et al. BIB002 have proposed a protocol called HydroCast. It takes the node mobility into consideration which enhances the propagation delay performance and energy consumption. It takes the wireless channel quality into consideration to improve the routeing performance under continuous node movement conditions.

Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> d: LRAGR <s> The mobility and energy scarcity are two main challenges of efficient routing in mobile wireless sensor networks (WSNs). However, messages should be reliably transported to the Sink with low latency in many application scenarios. To accomplish this, a hierarchical routing scheme, Latency and Reliability-aware Geographic Routing (LRGR), is proposed. Firstly, the cluster is formed considering node mobility and residual energy to tackle with the dynamic network topology and constrained energy. To ensure inter-cluster routing, several key ingredients are developed, such as indirect communication amongst adjacent cluster heads using their common gateways, aggregate path metric based on the connectivity, geographical position, residual energy and sojourn time of adjacent cluster heads. Simulation results demonstrate that LRGR can enhance the network lifetime while has lower latency and packet loss ratio when compared to VIBE. <s> BIB001 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> d: LRAGR <s> QoS-aware routing in mobile ad hoc networks (MANETs) is a major challenge due to node mobility and scarcity of resources. QoS-aware routing based on ant colony optimization (ACO) algorithms is a promising approach to overcome these problems. However, as compared to MANETs, vehicular ad hoc networks (VANETs) face additional challenges due to rapid topology change, making the estimation or prediction of QoS parameters difficult or stale. VANETs require time-critical message delivery, as late delivery may result in endangering lives. Currently existing routing protocols usually require the exchange of additional control message between neighbor nodes to compute QoS parameters. This makes the routing protocol too slow to react to fast topology change and also does not consider network congestion when forwarding a data packet. To reduce the overhead introduced to collect information from neighbor nodes and to obtain an accurate estimate of QoS parameters, we use the simple network management protocol to estimate these values locally. This paper describes a new approach for calculating QoS parameter locally and avoiding congestion during data transmission. The simulations are implemented using the network simulator ns-3, and the results show that our approach is scalable and performs well in high mobility. QoS-aware routing in mobile ad hoc networks (MANETs) is a major challenge due to node mobility and scarcity of resources. QoS-aware routing based on ant colony optimization (ACO) algorithms is a promising approach to overcome these problems. However, as compared to MANETs, vehicular ad hoc networks (VANETs) face additional challenges due to rapid topology change, making the estimation or prediction of QoS parameters difficult or stale. VANETs require time-critical message delivery, as late delivery may result in endangering lives. Currently existing routing protocols usually require the exchange of additional control message between neighbor nodes to compute QoS parameters. This makes the routing protocol too slow to react to fast topology change and also does not consider network congestion when forwarding a data packet. To reduce the overhead introduced to collect information from neighbor nodes and to obtain an accurate estimate of QoS parameters, we use the simple network management protocol to estimate these values locally. This paper describes a new approach for calculating QoS parameter locally and avoiding congestion during data transmission. The simulations are implemented using the network simulator ns-3, and the results show that our approach is scalable and performs well in high mobility. <s> BIB002

Rao et al. BIB001 focus on the cluster formation and mobility management. It consists of the two phases, clustering phase and the other is a routeing phase. It uses the energy efficient neighbour discovery protocol (ENDP) at the MAC layer. Low latency and reliability are the achievements of this protocol. e: ACO Y. Dawood Al-Ani and Jochen Seitz discussed the QoS issue in routing in case of the node mobility BIB002 . To address this issue authors have designed a routeing protocol that is based on the ant colony optimization (ACO) algorithms. The NS-2 simulation results show that the proposed protocol achieves the well performances in high mobility.

Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> d: MER <s> This paper considers the problem of power-efficient distributed estimation of vector parameters related to localized phenomena so that both sensor selection and routing structure in a Wireless Sensor Network (WSN) are jointly optimized to obtain the best possible estimation performance at a given querying node, for a given total power budget. First, we formulate our problem as an optimization problem and show that it is an NP-Hard problem. Then, we design two algorithms: a Fixed-Tree Relaxation-Based Algorithm (FTRA) and a very efficient Iterative Distributed Algorithm (IDA) to optimize the sensor selection and routing structure. We also provide a lower bound for our optimization problem and show that our IDA provides a performance that is close to this bound, and it is substantially superior to the previous approaches presented in the literature. An important result from our work is the fact that because of the interplay between communication cost and estimation gain when fusing measurements from different sensors, the traditional Shortest Path Tree (SPT) routing structure, widely used in practice, is no longer optimal. To be specific, our routing structure provides a better trade-off between the overall power efficiency and estimation accuracy. Comparing to more conventional sensor selection and fixed routing algorithms, our proposed algorithms yield a significant amount of energy saving for the same estimation accuracy. <s> BIB001 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> d: MER <s> There is a rich recent literature on information-theoretically secure communication at the physical layer of wireless networks, where secret communication between a single transmitter and receiver has been studied extensively. In this paper, we consider how single-hop physical layer security techniques can be extended to multi-hop wireless networks. We show that guaranteed security can be achieved in multi-hop networks by augmenting physical layer security techniques, such as cooperative jamming, with the higher layer network mechanisms, such as routing. Specifically, we consider the secure minimum energy routing problem, in which the objective is to compute a minimum energy path between two network nodes subject to constraints on the end-to-end communication secrecy and goodput over the path. This problem is formulated as a constrained optimization of transmission power and link selection, which is proved to be NP-hard. Nevertheless, we show that efficient algorithms exist to compute both exact and approximate solutions for the problem. In particular, we develop an exact solution of pseudo-polynomial complexity, as well as an e-optimal approximation of polynomial complexity. Simulation results are also provided to show the utility of our algorithms and quantify their energy savings compared to a combination of (standard) security-agnostic minimum energy routing and physical layer security. In the simulated scenarios, we observe that, by jointly optimizing link selection at the network layer and cooperative jamming at the physical layer, our algorithms reduce the network energy consumption by half. <s> BIB002

In BIB002 another algorithm that considers the issue of energy consumption and physical layer security is designed. For the security, achievement authors have used the cooperative jamming technique. The results show that energy consumption level is very good. e: XLQACF Shah and Lozano BIB001 have designed two algorithms for minimization of the energy consumption namely a Fixed-Tree Relaxation-Based Algorithm (FTRA) and a very efficient Iterative Distributed Algorithm (IDA). They optimize the route selection and achieve the energy saving metric.

Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> a: Indoor-LBS <s> Indoor location-based service (LBS) is generally distinguished from web services that have no physical location and user context. In particular, various resources have dynamic and frequent mobility in indoor environments. In addition, an indoor LBS includes numerous service lookups being requested concurrently and frequently from several locations, even through a network infrastructure requiring high scalability in indoor environments. The traditional centralized LBS approach needs to maintain a geographical map of the entire building or complex in its central server, which can cause low scalability and traffic congestion. This paper presents a self-organizing and fully distributed indoor LBS platform with regional cooperation among devices. A service lookup algorithm based on the proposed distributed architecture searches for the shortest physical path to the nearest service resource. A continuous service binding mechanism guarantees a probabilistic real-time QoS regardless of dynamic and frequent mobility in a soft real-time system such as an indoor LBS. Performance evaluation of the proposed algorithm and platform is compared to the traditional centralized architecture in the experimental evaluation of scalability and real test bed environments. <s> BIB001 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> a: Indoor-LBS <s> MANET routing is critical and routing decision should be made sooner before the node leaves the network. Fast decisions always compensate network performance. In addition, most MANET routing protocols assume a friendly and cooperative environment, and hence are vulnerable to various attacks. Trust and Reputation would serve as a major solution to these problems. Learning the network characteristics and choosing right routing decisions at right times would be a significant solution. In this work, we have done an extensive survey of fault tolerant protocols and ant colony algorithms applied to routing in MANETs. We propose a QoS constrained fault tolerant ant lookahead routing algorithm which attempts to identify valid route and look-ahead route pairs which might help in choosing the alternate path in case of valid route failure. The results prove that the proposed algorithm takes better routing decisions with 20-30 percent improvement compared with existing ant colony algorithms. <s> BIB002

Jeong et al. BIB001 studied the traditional centralized location based services (LBS) which have the problem of traffic congestion and low scalability. They have then developed architecture called a site based self-organizing and completely spread network infrastructure. The proposed indoor LBS platform is adapted to support reliable and efficient services to users or mobile devices in dynamic indoor environments. The proposed SoSP network structural design is comprised of SoSP router. It represents the unit space and it contains four components i.e device proxy, resource manager, SR-Manger and the services agents. A user can easily request any indoor LBS from the physical resources with a mobile device using its wireless communication. Robots can also collaborate with other robots using wireless communication through SoSP router. It uses NSPQ-based services lookup and binding algorithm that searches for the shortest physical path to the nearest services resources. The proposed algorithm is compared to the traditional centralized architecture in the experimental evolution of scalability and real test bed environments. In the first experiment, the scalability is tested. When the number of lookup increases, the proposed lookup engine with NSPQ is highly efficient over time. Data transmission is also tested, the proposed algorithm guaranteeing the soft real-time QoS. It enhances scalability, decentralized fairness and robustness. Indoor LBS platform achieves the following features. It requires no centralized knowledge. The scalability level is good and it requires the zero configurations. Personnel privacy level is also good. The main shortcoming of this approach is that it does not consider throughput, energy consumption, delay parameters. This approach is not good for the small networks. Surendran and Prakash BIB002 have proposed the algorithm for routeing that is based on the ant colony algorithm. The proposed algorithm first learns the characteristics of the network then selects the route. The proposed algorithm is best for secure data transmission. Reliability is the main advantage of this protocol.

Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> e: CNSMR <s> Multicast routing protocols improve the network performance by optimising the parameters such as bandwidth, channel utilisation and throughput rate. In wireless sensor network, the primary multicast routing protocol is geographic multicast routing. This study proposes core network supported multicast routing (CNSMR) protocol, a stateful-based distributed multicast routing protocol for sensor networks. The proposed protocol comprises of heterogeneous nodes such as cluster head (CH) nodes, core nodes (CNs) and sensor nodes (SNs). The distinct set of nodes known as CNs have computing, storage and energy resources more than the SNs. CH nodes and CNs form the core network, and CNs with core network and SNs form the core network supported multicast tree. SNs participate in multicast routing supported by the core network and thus save the node energy. Multicast routing in the proposed core network supported multicast trees balance the load in the network and improve the network performance as compared to the existing WSN multicast routing protocols. The proposed CNSMR protocol is compared with the existing WSN multicast routing protocols such as DCME-MR, Intelligent-MR, H-GMR and OnDemand-MR. Simulation results indicate improvements in delay latency, energy save ratio, throughput rate, end-to-end packet delay, multicast control overhead ratio and packet delivery ratio for the proposed protocol. <s> BIB001 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> e: CNSMR <s> Quality of Service (QoS) in Wireless Sensor Networks (WSNs) is a challenging area of research because of the limited availability of resources in WSNs. The resources in WSNs are processing power, memory, bandwidth, energy, communication capacity, etc. Delay is an important QoS parameter for delivery of delay sensitive data in a time constraint sensor network environment. In this paper, an extended version of a delay aware routing protocol for WSNs is presented along with its performance comparison with different deployment scenarios of sensor nodes, taking IEEE802.15.4 as the underlying MAC protocol. The performance evaluation of the protocol is done by simulation using ns-2 simulator. <s> BIB002 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> e: CNSMR <s> Abstract Opportunistic routing is a new paradigm in routing for wireless sensor network which chooses the node closest to the target node for forwarding the data. It uses the broadcasting nature of wireless sensor networks. Opportunistic routing has increased the efficiency, throughput and reliability of sensor networks. Many energy saving techniques has been introduced using opportunistic routing in wireless sensor networks for increasing the network lifetime. In this article we have elaborated the basic concept of Opportunistic routing, different areas in which it has been claimed to be beneficial, some protocols their metrics and their drawbacks. <s> BIB003 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> e: CNSMR <s> Wireless body area sensor network is a special purpose wireless sensor network that, employing wireless sensor nodes in, on, or around the human body, makes it possible to measure biological parameters of a person for specific applications. One of the most fundamental concerns in wireless body sensor networks is accurate routing in order to send data promptly and properly, and therefore overcome some of the challenges. Routing protocols for such networks are affected by a large number of factors including energy, topology, temperature, posture, the radio range of sensors, and appropriate quality of service in sensor nodes. Since energy is highly important in wireless body area sensor networks, and increasing the network lifetime results in benefiting greatly from sensor capabilities, improving routing performance with reduced energy consumption presents a major challenge. This paper aims to study wireless body area sensor networks and the related routing methods. It also presents a thorough, comprehensive review of routing methods in wireless body area sensor networks from the perspective of energy. Furthermore, different routing methods affecting the parameter of energy will be classified and compared according to their advantages and disadvantages. In this paper, fundamental concepts of wireless body area sensor networks are provided, and then the advantages and disadvantages of these networks are investigated. Since one of the most fundamental issues in wireless body sensor networks is to perform routing so as to transmit data precisely and promptly, we discuss the same issue. As a result, we propose a classification of the available relevant literature with respect to the key challenge of energy in the routing process. With this end in view, all important papers published between 2000 and 2015 are classified under eight categories including `Mobility-Aware', `Thermal-Aware', `Restriction of Location and Number of Relays', `Link-aware', `Cluster- and Tree-Based', `Cross-Layer', `Opportunistic', and `Medium Access Control'. We, then, provide a full description of the statistical analysis of each category in relation to all papers, current hybrid protocols, and the type of simulators used in each paper. Next, we analyze the distribution of papers in each category during various years. Moreover, for each category, the advantages and disadvantages as well as the number of issued papers in different years are given. We also analyze the type of layer and deployment of mathematical models or algorithmic techniques in each category. Finally, after introducing certain important protocols for each category, the goals, advantages, and disadvantages of the protocols are discussed and compared with each other. <s> BIB004

Maddali BIB001 have designed a core network which supports multicast routeing (CNSMR) protocol. It comprises of the heterogeneous nodes. It achieves the high throughput and low latency and good channel utilization for the multicast environment. Sarkar and Murugan surveyed the routeing protocols for wireless sensor networks. In this survey, authors discuss the protocols with respect to QoS parameters. The mean weakness of this survey is that it does not show the pros and cons of each protocol. Bhuyan and Sarma BIB002 surveyed the delay aware QoS routeing protocols for WSNs and checked the performance of these protocols in the grid and random deployment of the nodes. QoS parameters such as DDR and delay are analyzed in the NS-2 simulator. Jadhav and Satao BIB003 have discussed the opportunistic routeing protocol(OPR) for WSNs. When a node wants to transmit the OPR selects the node which is closest to the target node for forwarding. It is most useful for the opportunistic communication. However, this survey does not discuss the pron and cons of each protocol. In BIB004 the routeing protocols for body area sensor networks is studied. Authors have discussed the strengths and weakness of each protocol.

Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> f: HOCA <s> Communication requirements for cognitive radio sensor networks (CRSN) necessitate addressing the problems posed by dynamic spectrum access (DSA) in an inherently resource-constrained sensor networks regime. In this paper, arising challenges for reliability and congestion control due to incorporation of cognitive radio capability into sensor networks are investigated along with the open research issues. Impact of DSA, i.e., activity of licensed users, intermittent spectrum sensing and spectrum handoff functionalities based on spectrum availability, on the performance of the existing transport protocols are inspected. The objective of this paper is to point out the urgent need for a novel reliability and congestion control mechanism for CRSN. To this end, CRSN challenges for transport layer are revealed and simulation experiments are performed to demonstrate the performance of the existing transport protocols in CRSN. <s> BIB001 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> f: HOCA <s> Swarm intelligence is a relatively novel field. It addresses the study of the collective behaviors of systems made by many components that coordinate using decentralized controls and self-organization. A large part of the research in swarm intelligence has focused on the reverse engineering and the adaptation of collective behaviors observed in natural systems with the aim of designing effective algorithms for distributed optimization. These algorithms, like their natural systems of inspiration, show the desirable properties of being adaptive, scalable, and robust. These are key properties in the context of network routing, and in particular of routing in wireless sensor networks. Therefore, in the last decade, a number of routing protocols for wireless sensor networks have been developed according to the principles of swarm intelligence, and, in particular, taking inspiration from the foraging behaviors of ant and bee colonies. In this paper, we provide an extensive survey of these protocols. We discuss the general principles of swarm intelligence and of its application to routing. We also introduce a novel taxonomy for routing protocols in wireless sensor networks and use it to classify the surveyed protocols. We conclude the paper with a critical analysis of the status of the field, pointing out a number of fundamental issues related to the (mis) use of scientific methodology and evaluation procedures, and we identify some future research directions. <s> BIB002 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> f: HOCA <s> Cognitive radio technology has been used to efficiently utilize the spectrum in wireless networks. Although many research studies have been done recently in the area of cognitive radio networks (CRNs), little effort has been made to propose a simulation framework for CRNs. In this paper, a simulation framework based on NS2 (CogNS) for cognitive radio networks is proposed. This framework can be used to investigate and evaluate the impact of lower layers, i.e., MAC and physical layer, on the transport and network layers protocols. Due to the importance of packet drop probability, end-to-end delay and throughput as QoS requirements in real-time reliable applications, these metrics are evaluated over CRNs through CogNS framework. Our simulations demonstrate that the design of new network and transport layer protocols over CRNs should be considered based on CR-related parameters such as activity model of primary users, sensing time and frequency. <s> BIB003 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> f: HOCA <s> This paper presents an optimization framework for a wireless sensor network whereby, in a given route, the optimal relay selection and power allocation are performed subject to signal-to-noise ratio constraints. The proposed approach determines whether a direct transmission is preferred for a given configuration of nodes, or a cooperative transmission. In the latter case, for each node, data transmission to the destination node is performed in two consecutive phases: broadcasting and relaying. The proposed strategy provides the best set of relays, the optimal broadcasting power and the optimal power values for the cooperative transmission phase. Once the minimum-energy transmission policy is obtained, the optimal routes from every node to a sink node are built-up using cooperative transmission blocks. We also present a low-complexity implementation approach of the proposed framework and provide an explicit solution to the optimization problem at hand by invoking the theory of multi-parametric programming. This technique provides the optimal solution as a function of measurable parameters in an off-line manner, and hence the on-line computational tasks are reduced to finding the parameters and evaluating simple functions. The proposed efficient approach has many potential applications in real-world problems and, to the best of the authors' knowledge, it has not been applied to communication problems before. Simulations are presented to demonstrate the efficacy of the approach. <s> BIB004 </s> Quality of Service of Routing Protocols in Wireless Sensor Networks: A Review <s> f: HOCA <s> Wireless sensor networks consist of a large number of small, low-power sensors that communicate through wireless links. Wireless sensor networks for healthcare have emerged in recent years as a result of the need to collect data about patients' physical, physiological, and vital signs in the spaces ranging from personal to hospital and availability of the low cost sensors that enables this data collection. One of the major challenges in these networks is to mitigate congestion. In healthcare applications, such as medical emergencies or monitoring vital signs of patients, because of the importance and criticality of transmitted data, it is essential to avoid congestion as much as possible (and in cases when congestion avoidance is not possible, to control the congestion). In this paper, a data centric congestion management protocol using AQM (Active Queue Managements) is proposed for healthcare applications with respect to the inherent characteristics of these applications. This study deals with end to end delay, energy consumption, lifetime and fairness. The proposed protocol which is called HOCA avoids congestion in the first step (routing phase) using multipath and QoS (Quality of Service) aware routing. And in cases where congestion cannot be avoided, it will be mitigated via an optimized congestion control algorithm. The efficiency of HOCA was evaluated using the OPNET simulator. Simulation results indicated that HOCA was able to achieve its goals. <s> BIB005

Rezaee et al. BIB005 addressed the issue of congestion in medical applications routeing. Authors have proposed the datacentric congestion management protocol using AQM (Active Queue Managements). It uses the multipath routeing to avoid the congestion of traffics. In BIB003 the simulation and the analytical model for the sensor nodes based on discrete time Markov chain (DTMC) is introduced. In BIB001 the existing transport protocols are discussed. In the paper, authors studied the QoS parameters such as reliability. In BIB002 surveys of QoS routeing protocols that are based on the swarm intelligence (SI) is carried out. SI is the intelligent techniques that find a path for transmission that is energy aware. In BIB004 the issue of signal to noise ratio is discussed. Optimal power allocation and route selection are the basic need for optimization. It is argued that cooperative transmission is suitable for Optimal power allocation.

Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> INTRODUCTION <s> Recently, wireless sensor networks (WSNs) have been used in various smart grid applications, including remote power system monitoring and control, power fraud detection, wireless automatic metering, fault diagnostics, demand response, outage detection, overhead transmission line monitoring, load control, and distribution automation. However, harsh smart grid environment propagation characteristics cause great challenges in the reliability of WSN communications in smart grid applications. To this end, the analysis of wireless link reliability and channel characterizations can help network designers to foresee the performance of the deployed WSN for specific smart grid propagation environments, and guide the network engineers to make design decisions for the channel modulation, encoding schemes, output power, and frequency band. This paper presents a detailed analysis of low power wireless link reliability in different smart grid environments, such as 500kV outdoor substation environment, indoor main power control room, and underground network transformer vaults. Specifically, the proposed analysis aims to evaluate the impact of different sensor radio parameters, such as modulation, encoding, transmission power, packet size, as well as the channel propagation characteristics of different smart grid propagation environments on the performance of the deployed sensor network in smart grid. Overall, the main objective of this paper is to help network designers quantifying the impact of the smart grid propagation environment and sensor radio characteristics on low power wireless link reliability in harsh smart grid environments. <s> BIB001 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> INTRODUCTION <s> The concept of the Internet of Things is rapidly becoming a reality, with many applications being deployed within industrial and consumer sectors. At the ‘thing’ level—devices and inter-device network communication—the core technical building blocks are generally the same as those found in wireless sensor network implementations. For the Internet of Things to continue growing, we need more plentiful resources for building intelligent devices and sensor networks. Unfortunately, current commercial devices, e.g., sensor nodes and network gateways, tend to be expensive and proprietary, which presents a barrier to entry and arguably slows down further development. There are, however, an increasing number of open embedded platforms available and also a wide selection of off-the-shelf components that can quickly and easily be built into device and network gateway solutions. The question is whether these solutions measure up to built-for-purpose devices. In the paper, we provide a comparison of existing built-for-purpose devices against open source devices. For comparison, we have also designed and rapidly prototyped a sensor node based on off-the-shelf components. We show that these devices compare favorably to built-for-purpose devices in terms of performance, power and cost. Using open platforms and off-the-shelf components would allow more developers to build intelligent devices and sensor networks, which could result in a better overall development ecosystem, lower barriers to entry and rapid growth in the number of IoT applications. <s> BIB002 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> INTRODUCTION <s> Cyberphysical systems (CPSs) are perceived as the pivotal enabler for a new era of real-time Internetbased communication and collaboration among value-chain participants, e.g., devices, systems, organizations, and humans. The CPS utilization in industrial settings is expected to revolutionize the way enterprises conduct their business from a holistic viewpoint, i.e., from shop-floor to business interactions, from suppliers to customers, and from design to support across the whole product and service lifecycle. Industrial CPS (ICPSs) blur the fabric of cyber (including business) and physical worlds and kickstart an era of systemwide collaboration and information-driven interactions among all stakeholders of the value chain. Therefore, ICPSs are expected to empower the transformation of industry and business at large to a digital, adaptive, networked, and knowledge-based industry with significant long-term impact on the economy, society, environment, and citizens. <s> BIB003 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> INTRODUCTION <s> Abstract For an industry 4.0 environment, the management and offering of services, falls over the construction of a stable and reliable sensor and actuator infrastructure. Industry 4.0 is undergoing increase advancement, infrastructure availability and public acceptance, mainly boosted by the Interconnected Things. The public acceptance drives an increase on investments, carrying an insurgence of companies competing with each other to gain market. Although lessening costs, this insurgence has brought heterogeneous infrastructures and solutions availability, challenging services providers. Among the challenges the security and different technology solutions support are of the most importance. The scattering of solutions and software code have to be conveniently gathered to avoid weak-points, eventually, a menace to be explored by hackers. This paper is a contribution in order to embraces those challenges in a new architecture framework able of supporting the creation of solutions for Smart Grid and Smart Living services providers under the industry 4.0 paradigm. The architecture framework design offers security, simplicity of implementation and maintenance, and is resilient to failures or attacks and technologically independent. Field tests are reported in order to evaluate key aspects of the proposed architecture. <s> BIB004 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> INTRODUCTION <s> Networks of sensors and actuators in automated manufacturing processes are implemented using industrial fieldbuses, where automation units and supervisory systems are also connected to exchange operational information. In the context of the incoming fourth industrial revolution, called Industry 4.0, the management of legacy facilities is a paramount issue to deal with. This paper presents a solution to enhance the connectivity of a legacy Flexible Manufacturing System, which constitutes the first step in the adoption of the Industry 4.0 concept. Such a system includes the fieldbus PROcess FIeld BUS (PROFIBUS) around which sensors, actuators, and controllers are interconnected. In order to establish effective communication between the sensors and actuators network and a supervisory system, a hardware and software approach including Ethernet connectivity is implemented. This work is envisioned to contribute to the migration of legacy systems towards the challenging Industry 4.0 framework. The experimental results prove the proper operation of the FMS and the feasibility of the proposal. <s> BIB005

The digital transformation that is taking place in different technological domains is derived from the penetration and expansion of the Information and Communication Technologies (ICTs) BIB005 . In the industrial environment, the Industry 4.0 is a concept of integration of industry automation, data exchange, and modern manufacturing technologies . It is also commonly referred to as the fourth industrial revolution, as a consequence of an initiative of the German government (Industrie 4.0 homepage), the Industrie 4.0. The Industry 4.0 era is envisioned to be implemented through the so-called Industrial Cyber-Physical Systems (ICPSs), which enable monitoring and control of industrial physical processes and bridge the cyber and virtual worlds BIB003 . The paradigm of Industry 4.0 involves various challenging frameworks like the aforementioned ICPSs, the Industrial Internet-of-Things (IIoT), Big Data, Cloud Computing, Smart Grids, Smart Cities, Hence, open source technology is receiving increasing attention in last years from scientists and practitioners in a multitude of different domains. For instance, the amount of devices within the IoT can be increased thanks to this type of technology BIB002 and open source projects are key accelerators for the industry adoption of IoT . At the hardware level, according to Thames and Schaefer , open source hardware (and its associated open source software) is envisioned to lead to fast and incremental updates to hardware platforms in future manufacturing processes. There are various devices of this type like Raspberry Pi, BeagleBone, Phidget, Intel Edison and Arduino. The latter one is an inexpensive singleboard micro-controller (Arduino online) and is considered as the flagship open source hardware. In fact, it is a powerful tool to develop different applications in the arenas of data acquisition, automation and engineering in general . Concerning the power scenario, renewable energy sources are expected to play a vital role in the mitigation of the greenhouse emissions effects and of the global warming. Even more, their hybridization with hydrogen generation and consumption constitutes an important research field . In particular, Smart Grids (SGs) are the next generation of power grids, emerging as the digital transformation applied to the energy industry, and being an important component of the Industry 4.0 paradigm BIB004 . SGs are defined as a modern electric power grid infrastructure for improved efficiency, reliability, and safety with smooth integration of renewable and distributed energy sources, through automated and distributed controls and modern communication and sensing technologies BIB001 . These power grids are a worthy domain where to apply open source technology . This paper aims at providing a panoramic survey of recent scientific literature reporting the use of open source hardware, namely Arduino, in advanced technological scenarios, proving its validity for control and measurement purposes. Indeed, as a consequence of the benefits associated to open source technology, its inclusion in Research and Development (R&D) projects flows in a natural manner. In this sense, Arduino is being incorporated within a project dealing with the deployment and operation of a Smart Micro-Grid and its digital replica. This will be further commented in section 4. The rest of the paper is organized as follows. The second section provides an overview of the main characteristics of the open source Arduino. Section 3 presents a survey about literature dealing with Arduino in a number of advanced scenarios. The application of Arduino for data sensing and acquisition in the context of research about a Smart Micro-Grid is reported in the fourth section. Finally, the main conclusions of the work are addressed.

Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Humanoid robotics is a field of a great research interest nowadays. This work implements a low-cost teleoperated system to control a humanoid robot, as a first step for further development and study of human motion and walking. A human suit is built, consisting of 8 sensors, 6 resistive linear potentiometers on the lower extremities and 2 digital accelerometers for the arms. The goal is to replicate the suit movements in a small humanoid robot. The data from the sensors is wirelessly transmitted via two ZigBee RF configurable modules installed on each device: the robot and the suit. Replicating the suit movements requires a robot stability control module to prevent falling down while executing different actions involving knees flexion. This is carried out via a feedback control system with an accelerometer placed on the robot's back. The measurement from this sensor is filtered using Kalman. In addition, a two input fuzzy algorithm controlling five servo motors regulates the robot balance. The humanoid robot is controlled by a medium capacity processor and a low computational cost is achieved for executing the different algorithms. Both hardware and software of the system are based on open platforms. The successful experiments carried out validate the implementation of the proposed teleoperated system. <s> BIB001 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract A new data logger using the Arduino open-source electronic platform was developed to solve the current problem of monitoring photovoltaic (PV) systems at low-cost, especially in remote areas or regions in developing countries. The data logger meets all of the relevant requirements in terms of accuracy included in the International Electrotechnical Commission (IEC) standards for PV systems, with a resolution of 18-bits, including 8 analogue inputs for measuring up to 8 PV modules and/or weather sensors, 3 inputs for low-cost analogue temperature sensors and virtually unlimited inputs for digital temperature sensors. The new data logger is completely autonomous, and the prototype has achieved an initial cost of only 60 €. It was tested during a 6-month period under the harsh environmental conditions of the summer and winter in Southern Spain. The results using both the sensors and silicon reference cells indicate that the new system is reliable and exhibits comparable performance to commercial systems. This data logger is of special interest for both solar energy research and applications in developing countries, as it is both open-source and flexible. The data logger can be customised for the specific needs of each project at low-cost. The details of the specific design and its implementation are described. <s> BIB002 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract This paper presents a layered Smart Grid architecture enhancing security and reliability, having the ability to act in order to maintain and correct infrastructure components without affecting the client service. The architecture presented is based in the core of well design software engineering, standing upon standards developed over the years. The layered Smart Grid offers a base tool to ease new standards and energy policies implementation. The ZigBee technology implementation test methodology for the Smart Grid is presented, and provides field tests using ZigBee technology to control the new Smart Grid architecture approach. <s> BIB003 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> This paper develops an energy management system with integration of smart meters for electricity consumers in a smart grid context. The integration of two types of smart meters (SM) are developed: (i) consumer owned SM and (ii) distributor owned SM. The consumer owned SM runs over a wireless platform–ZigBee protocol and the distributor owned SM uses the wired environment–ModBus protocol. The SM are connected to a SCADA system (Supervisory Control And Data Acquisition) that supervises a network of Programmable Logic Controllers (PLC). The SCADA system/PLC network integrates different types of information coming from several technologies present in modern buildings. ::: ::: The developed control strategy implements a hierarchical cascade controller where inner loops are performed by local PLCs, and the outer loop is managed by a centralized SCADA system, which interacts with the entire local PLC network. ::: ::: In order to implement advanced controllers, a communication channel was developed to allow the communication between the SCADA system and the MATLAB software. <s> BIB004 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Low Cost Automation promotes cost effective reference architectures and development approaches to increase flexibility and efficiency of production operations. This has led to the adoption of open networking standards for plant floor communications. OPC-UA may help industrial companies to become Industry 4.0 or Smart Manufacturing as it enables remote access to plant information, achieving thus horizontal and vertical integration. The main goal of this work is to make vertical integration a reality by means of a low-cost CPPS architecture that provide access to process data. The use of this architecture along the whole production automation system may certainly reduce the Total Cost of Ownership (TCO). The paper describes both the hardware platform as well as the software including the proposed configuration file of the OPC-UA server. <s> BIB005 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Recent advancement in the field of electrical technology and cyber system (mainly based on the internet) has brought the key towards accepting and challenging all the issues regarding load management, demand side management, energy management, and efficient allocation of energy, transparency and ease of use of data management and security. This research paper focuses on a Cyber Physical Power System (CPPS), which deals with a Microgrid involving several distributed energy resources that is concerned with controlling the sources and loads by making a proper management between supply and demand, security, robustness and resiliency. A cloud-based centralized control system has also been introduced that provides the infrastructure to offload the heavy computational tasks to be completed by VM, which results in flexibility, predictability and mobility of the system. This research study focuses an ongoing project of Lamar Renewable Energy Microgrid Lab. <s> BIB006 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract The developments on machine-to-machine systems are interesting for control education, not only for the opportunities to apply control and automation solutions to new problems, but also for the availability of new hardware, software and communication platforms. These technologies facilitate a low-cost and easier integration of physical equipment in educational tools such as the remote laboratories. This paper proposes the use of a lightweight protocol for communication with resource-constrained devices, MQTT, as an aid to integrate new devices in educational applications, specifically in those that use web standards such as Javascript to provide interactive user interfaces. To evaluate this approach, an educational application focused on the control of a DC motor position loop, built with EjsS, was developed. This tool uses the MQTT protocol to parametrize and communicate with an Arduino microcontroller that, in turn, controls a physical setup implemented with the Feedback MS150 modular system. The proposed approach enables the easy connection of interactive educational tools to new real equipment, especially those driven by resource-constrained devices. <s> BIB007 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> The protection of Critical Infrastructures represents a fundamental topic of interest for the modern societies. The testing in real scenarios is hard to achieve due to the severe interdependence between these critical systems and the human well-being. The paper is devoted to introduce a low-cost testbed developed to emulate a Critical Infrastructure as complex cyber-physical system. Moreover, it proposes an approach to identify cyber threats exploiting both cyber and physical behavior of the system. Specifically, common tools from model based fault diagnosis and intrusion detection are applied to determine incipient threats and support for the operator in decision making. All the hardware and software developed are implemented in an open-source fashion in order to share investigation resources with the scientific community. <s> BIB008 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> The pervasive presence of interconnected objects enables new communication paradigms where devices can easily reach each other while interacting within their environment. The so-called Internet of Things (IoT) represents the integration of several computing and communications systems aiming at facilitating the interaction between these devices. Arduino is one of the most popular platforms used to prototype new IoT devices due to its open, flexible and easy-to-use architecture. Ardunio Yun is a dual board microcontroller that supports a Linux distribution and it is currently one of the most versatile and powerful Arduino systems. This feature positions Arduino Yun as a popular platform for developers, but it also introduces unique infection vectors from the security viewpoint. In this work, we present a security analysis of Arduino Yun. We show that Arduino Yun is vulnerable to a number of attacks and we implement a proof of concept capable of exploiting some of them. <s> BIB009 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract This paper is a formal overview of standards and patents for Internet of Things (IoT) as a key enabler for the next generation advanced manufacturing, referred as Industry 4.0 (I 4.0). IoT at the fundamental level is a means of connecting physical objects to the Internet as a ubiquitous network that enables objects to collect and exchange information. The manufacturing industry is seeking versatile manufacturing service provisions to overcome shortened product life cycles, increased labor costs, and fluctuating customer needs for competitive marketplaces. This paper depicts a systematic approach to review IoT technology standards and patents. The thorough analysis and overview include the essential standard landscape and the patent landscape based on the governing standards organizations for America, Europe and China where most global manufacturing bases are located. The literature of emerging IoT standards from the International Organization for Standardization (ISO), the International Electrotechnical Commission (IEC) and the Guobiao standards (GB), and global patents issued in US, Europe, China and World Intellectual Property Organization (WIPO) are systematically presented in this study. <s> BIB010 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract Small- and medium-sized manufacturers, as well as large original equipment manufacturers (OEMs), have faced an increasing need for the development of intelligent manufacturing machines with affordable sensing technologies and data-driven intelligence. Existing monitoring systems and prognostics approaches are not capable of collecting the large volumes of real-time data or building large-scale predictive models that are essential to achieving significant advances in cyber-manufacturing. The objective of this paper is to introduce a new computational framework that enables remote real-time sensing, monitoring, and scalable high performance computing for diagnosis and prognosis. This framework utilizes wireless sensor networks, cloud computing, and machine learning. A proof-of-concept prototype is developed to demonstrate how the framework can enable manufacturers to monitor machine health conditions and generate predictive analytics. Experimental results are provided to demonstrate capabilities and utility of the framework such as how vibrations and energy consumption of pumps in a power plant and CNC machines in a factory floor can be monitored using a wireless sensor network. In addition, a machine learning algorithm, implemented on a public cloud, is used to predict tool wear in milling operations. <s> BIB011 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract Recent technological developments have fueled a shift toward the computerization and automation of factories; i.e., Industry 4.0. Unfortunately, many small- and medium-sized factories cannot afford the sensor-embedded machines, cloud system, or high-performance computers required for Industry 4.0. Furthermore, the simple production processes in smaller factories do not require the level of precision found in large factories. In this study, we explored the idea of using inexpensive add-on triaxial sensors for the monitoring of machinery. We developed a dimensionality reduction method with low computational overhead to extract key information from the collected data as well as a neural network to enable automatic analysis of the obtained data. Finally, we performed an experiment at an actual spring factory to demonstrate the validity of the proposed algorithm. The system outlined in this work is meant to bring Industry 4.0 implementations within grasp of small to medium sized factories, by eliminating the need for sensors-embedded machines and high-performance computers. <s> BIB012 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Cyber-physical systems (CPS) are key enabling technologies for the fourth industrial revolution, referred to as Industrie 4.0 or Industry 4.0. The Reference Architecture Model Industrie 4.0 (RAMI4.0) has recently been standardized and OPC Unified Architecture (OPC UA) is listed as the sole recommendation for implementation of a communication layer. Many automation and control systems offer already implementations of OPC UA but no satisfying implementation of OPC UA was found for Arduino, a popular platform for engineering physical computing systems. This paper presents open source integration and application of a customizable OPC UA server on an Arduino Yun board using open62541, an open source and free implementation of OPC UA. The Arduino board discussed in this paper offers hot-end closed-loop temperature control for a 3D printer but the temperature set value and control parameters can be manipulated and requested via OPC UA using OPC UA clients. The application is verified using Prosys OPC UA Client and UaExpert. The results of our research can be used for developing open source cyber-physical systems without specialized knowledge in microcontroller programming, bringing Industry 4.0 applications into classrooms without effort. <s> BIB013 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> The objective of this paper is to develop Arduino-based multi-agent system (MAS) for advanced distributed energy management of a solar-wind micro-grid. High penetration of renewable energy resources needs new coordination and control approaches to meet the stochastic nature of the environment and dynamic loadings. We use multi-agent system for advanced distributed, autonomous energy management of micro-grid to dynamically and flexibly adapt to the changes in the environment as renewable energy resources are intermittent in nature. We consider that a micro-grid which contains two systems each contains solar photo voltaic (PV) system, wind generator system, local consumer, and a battery. We develop a simulation model using Java Agent Development Environment (JADE) in Eclipse IDE for dynamic energy management, which considers the intermittent nature of solar power, randomness of load, dynamic pricing of grid, and variation of critical loads, and choose the best possible action every hour to stabilize and optimize the micro-grid. Furthermore, environment variables are sensed through Arduino Mega micro-controller and given to agents of MAS. The agents take the strategic action, and the resulting actions are reflected in the LED outputs which can be readily deployed in the actual field. MAS increases responsiveness, stability, flexibility, and fault tolerance, thereby increasing operational efficiency and leading to economic and environmental optimization. All the smart grid features are tested using JADE simulations and practically verified through Arduino micro-controller to make micro-grid into smart micro-grid. <s> BIB014 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract The race to achieve smart cities is producing a continuous effort to adapt new developments and knowledge, for administrations and citizens. Information and Communications Technology are called on to be one of the key players to get these cities to use smart devices and sensors (Internet of Things) to know at every moment what is happening within the city, in order to make decisions that will improve the management of resources. The proliferation of these “smart things” is producing significant deployment of networks in the city context. Most of these devices are proprietary solutions, which do not offer free access to the data they provide. Therefore, this prevents the interoperability and compatibility of these solutions in the current smart city developments. This paper presents how to embed an open sensorized platform for both hardware and software in the context of a smart city, more specifically in a university campus. For this integration, GIScience comes into play, where it offers different open standards that allow full control over “smart things” as an agile and interoperable way to achieve this. To test our system, we have deployed a network of different sensorized platforms inside the university campus, in order to monitor environmental phenomena. <s> BIB015 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract This paper focuses on the Fallback Control System (FCS), which is an emergency response method of networked Industrial Control System (ICS) as a countermeasure for cyber-attacks. The FCS is disposed on not networked controllers but controlled objects. After some incidents happen, the FCS isolates the controlled objects from networked controllers and controls the objects safely and locally. This ICS operation switching is one-way from normal one to fallback one and the recovery switching from the fallback one to the normal one still remains open. This is because there is a possibility of cyber-attacks aiming the reconnection of the controlled objects with the network controllers. Motivated by this, this paper proposes a Fallback and Recovery Control System (FRCS) by adding a safety recovery switching to the FCS. Maintaining the fallback control of the controlled object, the virtual operation mode of FRCS connects the networked controller with the virtual controlled object (Plant Simulator). The FRCS evaluates the ICS soundness from the responses between the controller and the virtual object and then reconnects the controller with the actual one. The ICS soundness evaluation is based on the discrete-event system observer. This paper verifies the validity of the proposed recovery switching via a practical experiment. <s> BIB016 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> The cyber-physical system is a core issue of Industrie 4.0. One of the main tasks is to create a digital twin with acquired data from a physical system. In this study, a data acquisition system was constructed for the heterogeneous machines using the sensor-based I/O module. Three different types of heterogeneous machines on the shop floor were considered. The results of the study may be applied to other types of machines. In the end, the application of monitoring machine operation status was conducted. The data were archived into MySQL database for the further application. <s> BIB017 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract This paper describes a novel approach to build a modular and adaptable information platform for Chalmers Smart Industry Hub. The platform utilizes the IoT paradigm i.e. decentralized and event-driven architecture, to interconnect production modules such as an assembly system, ERP, analytics, etc. Real life industrial problems are realized as industrial demonstrators that can utilize one or several production modules to exemplify specific use cases. <s> BIB018 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract The explosion of the interest in the industry 4.0 generated a hype on both academia and business: the former is attracted for the opportunities given by the emergence of such a new field, the latter is pulled by incentives and national investment plans. The Industry 4.0 technological field is not new but it is highly heterogeneous (actually it is the aggregation point of more than 30 different fields of the technology). For this reason, many stakeholders feel uncomfortable since they do not master the whole set of technologies, they manifested a lack of knowledge and problems of communication with other domains. Actually such problem is twofold, on one side a common vocabulary that helps domain experts to have a mutual understanding is missing Riel et al. [1], on the other side, an overall standardization effort would be beneficial to integrate existing terminologies in a reference architecture for the Industry 4.0 paradigm Smit et al. [2]. One of the basics for solving this issue is the creation of shared semantic for industry 4.0. The paper has an intermediate goal and focuses on the development of an enriched dictionary of Industry 4.0 enabling technologies, with definitions and links between them in order to help the user in actively surfing the new domains by starting from known elements to reach the most far away from his/her background and knowledge. <s> BIB019 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract The fourth industrial revolution, also called Industry 4.0, is a new industrial age that have been gaining force and new followers around the world. The Industry 4.0 can be understood as the implementation of the smart factory to provide smart products and services that meet the consumer individual needs. Given its increasing acceptance and repercussion, a reference architecture model for Industry 4.0 (RAMI 4.0) was developed based on vertical integration, horizontal integration and end-to-end engineering. However, RAMI 4.0 initiative requires efforts in different aspects to reach the level of practical implementation. In this sense, this paper aims to present a layered architecture based on RAMI 4.0 to discover equipment to process operations according to the product requirements. The architecture must provide components for a communication between machines and products, and a service that offer a mechanism similar to the domain name system (DNS) to search the equipment to process the operation. In this architecture the equipment are storage in a structure organized hierarchically to assist the search service. The functionalities of the proposed architecture are conceptually modeled using production flow schema (PFS) and their dynamic behaviors are verified and validated by Petri net (PN) models. The architecture is applied in a modular production system to evaluate RAMI 4.0 as a guide for the development of architectures for Industry 4.0. <s> BIB020 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract Photovoltaic system is widely installed to increase the share of renewable energy as well as to reduce the environmental impact of fossil fuel based energy. Photovoltaic (PV) is one of the most potential renewable energy based power generation systems. Monitoring of PV system is very important to send information that allows owners to maintain, operate and control these systems to reduce maintenance costs and to avoid unwanted electric power disruptions. Different monitoring systems have been introduced with the time following different requirements. Circuit complexity, availability of friendly graphical user interface, easy to understand system architecture, maintenance facility and customization ability for end user differ from system to system along with cost issues. This paper provides an overview of architectures and features of various PV monitoring systems based on different methods. There are various technologies for PV monitoring and control, developed as for commercial use or research tasks. It has been seen that a large portion of the work is done on classifications, for example, Internet based Monitoring using Servers, TCP/IP, GPRS and so forth. There are various methodologies for data acquisition, for example, PLC (Power Line Communication), PIC, Reference cell, National Instruments etc. Various requirements are considered while selecting a proper monitoring system for an application. Review of various monitoring technologies with system attributes and working structures have been discussed to get a clear view of merits and demerits of existing PV monitoring systems. All the systems discussed in this paper have pros and cons, and these systems were developed following different requirements. In the end, a particular cost effective monitoring system using Arduino microcontroller has been proposed considering both research and user level requirements from perspectives of cost, availability of parts/modules and features, compatibility with sensors and end-devices etc. <s> BIB021 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> The open-source hardware movement is becoming increasingly popular due to the emergence of successful low-cost technologies, such as Arduino and Raspberry Pi, and thanks to the community of makers that actively share their creations to be freely studied, modified, and re-distributed. Numerous authors have proposed distinct ways to seize this approach for accomplishing a variety of learning goals: enabling scholars to explore scientific concepts, promoting students’ creativity, helping them to be more fluent and expressive with new technologies, and so on. This paper reports a systematic mapping study that overviews the literature on open-source hardware in education by analyzing and classifying 676 publications. The results of our work provide: 1) guidance on the published material (identifying the most relevant papers, publication sources, institutions, and countries); 2) information about the pedagogical uses of open-source hardware (showing its main educational goals, stages, and topics where it is principally applied); and 3) directions for future research. <s> BIB022 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Virtual reality (VR) offers a uniquely experience to interact with imaginary items or features by simulating a user's physical presence in a virtual environment. Recently, VR services that achieve a higher level of realism using advanced VR equipment have been attracting public attention. However, studies for interworking physical devices with digital objects in a virtual environment are still insufficient. In this paper, we propose a virtual twinning system which can provide a user-centered eidetic IoT service in a VR environment by linking physical things to virtual objects. <s> BIB023 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract Digital twins are digital representations of physical products or systems that consist of multiple models from various domains describing them on multiple scales. By means of communication, digital twins change and evolve together with their physical counterparts throughout their lifecycle. Domain-specific partial models that make up the digital twin, such as the CAD model or the degradation model, are usually well known and provide accurate descriptions of certain parts of the physical asset. However, in complex systems, the value of integrating the partial models increases because it facilitates the study of their complex behaviours which only emerge from the interactions between various parts of the system. The paper proposes that the partial models of the digital twin share a common model space that integrates them through a definition of their interrelations and acts as a bridge between the digital twin and the physical asset. The approach is illustrated in a case of a mechatronic product - a differential drive mobile robot developed as a testbed for digital twin research. It is demonstrated how the integrated models add value to different stages of the lifecycle, allowing for evaluation of performance in the design stage and real-time reflection with the physical asset during its operation. <s> BIB024 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> With the increasing availability of affordable open-source embedded hardware platforms, the development of low-cost programmable devices for uncountable tasks has accelerated in recent years. In this sense, the large development community that is being created around popular platforms is also contributing to the construction of Internet of Things applications, which can ultimately support the maturation of the smart-cities era. Popular platforms such as Raspberry Pi, BeagleBoard and Arduino come as single-board open-source platforms that have enough computational power for different types of smart-city applications, while keeping affordable prices and encompassing many programming libraries and useful hardware extensions. As a result, smart-city solutions based on such platforms are becoming common and the surveying of recent research in this area can support a better understanding of this scenario, as presented in this article. Moreover, discussions about the continuous developments in these platforms can also indicate promising perspectives when using these boards as key elements to build smart cities. <s> BIB025 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> LITERATURE SURVEY ABOUT ARDUINO IN ADVANCED SCENARIOS <s> Abstract In this work, a new low-cost and high-performance system for cells voltage monitoring and degradation studies in air-cooled polymer electrolyte fuel cells has been designed, built and validated in the laboratory under experimental conditions. This system allows monitoring in real time the cells’ voltages, the stack current and temperature in fuel cells made of up to 100 cells. The developed system consists of an acquisition system, which complies with all the recommendations and features necessary to perform degradation tests. It is a scalable configuration with a low number of components and great simplicity. Additionally, the cell voltage monitoring (CVM) system offers high rate of accuracy and high reliability and low cost in comparison with other commercial systems. In the same way, looking for an "All-in-One" solution, the acquisition hardware is accompanied by a software tool based on the "plug and play" philosophy. It allows in a simple way obtaining information from the cells and performing a degradation analysis based on the study of the polarisation curve. The different options and tools included in the CVM system permit, in a very intuitive and graphical way, detecting and quantifying the cell degradation without the need of isolating the stack from the system. Experimental tests carried out on the system validate its performance and show the great applicability of the system in cases where cell faults detection and degradation analysis are required. <s> BIB026

In this section, among the ever-increasing literature dealing with Arduino-based developments, recent publications devoted to advanced trends like Industry 4.0, cyber-physical approaches and so forth have been reviewed in order to illustrate the importance and suitability of Arduino. In industrial environments, diverse paradigms are involved, like Industry 4.0, ICPSs, or cybermanufacturing, therefore, Arduino boards have been widely reported as part of these scenarios. To begin with, it must be noted that Arduino has been identified as technology for Industry 4.0 and smart manufacturing by different publications BIB010 BIB018 BIB019 . In BIB020 an architecture for Industry 4.0-enabled factories is developed, where Arduino chips are used in a TCP/IP network. A fog computing framework for process monitoring and prognostics in cyber manufacturing systems is proposed in BIB011 , measuring the vibrations of rotating machinery through Arduino. Another case of usage of Arduino for machine status prediction in the Industry 4.0 era is found in BIB012 . Examples of Arduino utilization for ICPSs have been reported in BIB005 BIB013 . About robotics, interesting works dealing with robotics and Arduino can be found in BIB001 . Concerning facilities integrating Renewable Energy Sources (RES), a number of publications report the successful applications of Arduino. For instance, it has been used for data acquisition and monitoring of hydrogen fuel cells in BIB026 , of photovoltaic systems in BIB002 BIB021 , for weather sensing or as part of simulation frameworks . A special mention is devoted to Smart Grids, where Arduino devices have been used to perform measurement/sensing tasks BIB003 BIB004 BIB006 BIB014 . Scenarios closely related to Smart Grids are Smart Cities and Smart Buildings. In this context, Arduino has been pointed out as an enabling technology for developments in Smart Cities (Costa and DuranFaundez, 2018) , used for the deployment of sensors in BIB015 . Regarding Smart Buildings, Arduino has been reported as means for smart energy metering in (Viciana et al., 2018) . The impact of ICT has enabled the development of systems that are remotely accessed and managed through the network. An important example of this trend is represented by remote laboratories where a user can visualize and/or operate a physically distant facility. A number of publications address the utilization of Arduino boards to implement this type of laboratories with engineering education orientation BIB007 BIB022 or for general purposes . Cyber-security is of the utmost importance in the advanced hyper-connected setups, from modern manufacturing facilities to smart cities passing through critical infrastructures like power plants. In this sense, Arduino chips have been used to study cyber-security issues for industrial control systems in BIB008 BIB009 BIB016 . In the context of the so-called digital replicas (a virtual representation of physical assets), Arduino has been reported as part of the physical counterpart to perform measurement of different magnitudes in BIB017 BIB023 BIB024 . In order to illustrate the existing literature dealing with Arduino utilization in advanced frameworks, Table 1 summarizes the abovementioned publications. BIB001 BIB005 BIB012 BIB013 BIB010 BIB011 BIB018 BIB019 BIB020 RES and Smart Grids BIB003 BIB002 BIB004 BIB006 BIB021 Vivas et al., 2018; Smart Cities BIB015 BIB025 Viciana et al., 2018 Remote laboratories BIB007 BIB022 Cyber-security BIB009 BIB008 BIB016 Digital replica BIB017 BIB023 BIB024 On the view of the surveyed publications, it has been proven that Arduino constitutes a versatile tool very valuable even for challenging scenarios.

Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> APPLICATION OF ARDUINO IN R&D PROJECT ABOUT SMART MICRO-GRID <s> Abstract This work presents a smart microgrid consisting of diesel, photovoltaic (PV), and battery storage plants. One of the key features of smart grid is to provide a redundant high quality power for the consumers. In islanded microgrid, the under frequency and/or voltage collapse, caused by power deficiency, can lead to power outage. The current practice is to shed the load demand until the frequency and voltage are restored. However, the redundancy in supplying power has no meaning as long as the loads are shed. The main objective of this paper is to propose a power management system (PMS) that protects the microgrid against the load shedding. PMS is able to control the microgrid in both centralized and decentralized fashions. To prevent under frequency load shedding (UFLS), this work proposes using battery energy storage system (BESS) to compensate for the power mismatch in the islanded microgrid. A method is presented to estimate the rate of change of frequency and to calculate the power deficiency. The approximated value is exploited as the set-point to dispatch BESS. PV and battery plants are supposed to share the reactive power demand proportionally and thus regulate the voltage at the load bus. This work also suggests two outer control loops, namely, frequency restoration loop (FRL) and difference angle compensator (DAC). These loops ensure microgrid smooth transition from islanded mode to grid-connected mode. The microgrid is configured to investigate the effective utilization of exiting solar PV plant connected to distribution network in Sabah Malaysia. The microgrid is implemented in PSCAD software and tested under different scenarios. The microgrid with PMS shows operational stability and improvements in comparison with the original system. The results indicate that PMS can effectively control the microgrid in all operating modes. <s> BIB001 </s> Survey about the Utilization of Open Source Arduino for Control and Measurement Systems in Advanced Scenarios. Application to Smart Micro-Grid and Its Digital Replica. <s> APPLICATION OF ARDUINO IN R&D PROJECT ABOUT SMART MICRO-GRID <s> Due to the advantage of avoiding upstream disturbance and voltage fluctuation from a power transmission system, Islanded Micro-Grids (IMG) have attracted much attention. In this paper, we first propose a novel self-sufficient Cyber-Physical System (CPS) supported by Internet of Things (IoT) techniques, namely “archipelago micro-grid (MG)”, which integrates the power grid and sensor networks to make the grid operation effective and is comprised of multiple MGs while disconnected with the utility grid. The Electric Vehicles (EVs) are used to replace a portion of Conventional Vehicles (CVs) to reduce CO 2 emission and operation cost. Nonetheless, the intermittent nature and uncertainty of Renewable Energy Sources (RESs) remain a challenging issue in managing energy resources in the system. To address these issues, we formalize the optimal EV penetration problem as a two-stage Stochastic Optimal Penetration (SOP) model, which aims to minimize the emission and operation cost in the system. Uncertainties coming from RESs (e.g., wind, solar, and load demand) are considered in the stochastic model and random parameters to represent those uncertainties are captured by the Monte Carlo-based method. To enable the reasonable deployment of EVs in each MGs, we develop two scheduling schemes, namely Unlimited Coordinated Scheme (UCS) and Limited Coordinated Scheme (LCS), respectively. An extensive simulation study based on a modified 9 bus system with three MGs has been carried out to show the effectiveness of our proposed schemes. The evaluation data indicates that our proposed strategy can reduce both the environmental pollution created by CO 2 emissions and operation costs in UCS and LCS. <s> BIB002

The present work is framed in a research project to implement a Smart Micro-Grid (SMG) integrating renewable energy sources with hydrogen and to develop its digital replica. SMGs can be defined as small scale SG which can be autonomous or grid-tied BIB001 . SMGs integrate physical elements in the power grid and cyber elements (sensor networks, communication networks, and computation core) to make the power grid operation effective BIB002 . The SMG of the aforementioned project combines photovoltaic energy and hydrogen generation/consumption to act as a self-sufficient eco-friendly energy system. A set of monocrystalline photovoltaic modules compose the Photovoltaic Subsystem (PVS). A Polymer Electrolyte Membrane Hydrogen Generator (PEM-HG) and a Polymer Electrolyte Membrane Hydrogen Fuel Cell (PEM-HFC) perform the generation and consumption of hydrogen respectively. The hydrogen is stored in a metal hydride tank whereas an electrochemical battery hosts the electrical flows, playing the role of DC Bus. Finally, DC and AC loads complete the micro-grid. A schematic diagram of the SMG is shown in Figure 3 . An Automation and Monitoring System (AMS) carries out the management and surveillance of the energy flows and interactions between the nodes of the SMG. A Programmable Logic Controller (PLC) and a Supervisory Control and Data Acquisition (SCADA) system compose the AMS together with an Arduino board and a number of sensors (temperature, irradiance, current, voltage, etc.) . The implemented energy control strategy aims to supply the loads and to produce hydrogen when a surplus of solar energy is available. To build the digital replica of the SMG, massive data gathering is required, so Arduino boards are considered a valuable tool to implement costeffective data acquisition equipment. Therefore, Arduino is being used to retrieve data which is considered non-critical for the automation/control tasks, namely environmental magnitudes like temperature and relative humidity. In the initial stage, it is being tested to measure the temperature of one of the photovoltaic modules through low-cost Lm35 sensors. In a previous stage, the retrieved data were validated through the comparison with those provided by a Pt-100 probe placed in the same module. Particularly, an Arduino MEGA 2560 has been chosen. It is based on a micro-controller ATmega2560 and has 54 digital I/O as well as 16 analogue inputs. An Ethernet shield provides Ethernet connectivity in order to share the sensor measurements with the monitoring system. Such a system is based in the package LabVIEW of National Instrument and is responsible of gathering, processing and representing the operational data of the SMG. The structure of the AMS is depicted in Figure 4 .

A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 1.0 INTRODUCTION <s> Discussion boards and online forums are important platforms for people to share information. Users post questions or problems onto discussion boards and rely on others to provide possible solutions and such question-related content sometimes even dominates the whole discussion board. However, to retrieve this kind of information automatically and effectively is still a non-trivial task. In addition, the existence of other types of information (e.g., announcements, plans, elaborations, etc.) makes it difficult to assume that every thread in a discussion board is about a question. We consider the problems of identifying question-related threads and their potential answers as classification tasks. Experimental results across multiple datasets demonstrate that our method can significantly improve the performance in both question detection and answer finding subtasks. We also do a careful comparison of how different types of features contribute to the final result and show that non-content features play a key role in improving overall performance. Finally, we show that a ranking scheme based on our classification approach can yield much better performance than prior published methods. <s> BIB001 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 1.0 INTRODUCTION <s> When people involve with software more in their daily lives, software companies must provide services through handling various operating questions that users request in the forums. However, different from conventional software companies, various types of difficulties, propositions and opinions could be issued by open source software users in addition to the operating questions. These difficulties, propositions and opinions are generally referred as questions in the forums. The questions, as valuable knowledge of the open source project, should be systematically managed. To manage the questions, a common strategy is to construct a FAQ in open source projects. The FAQ can reduce the volume of similar questions in the forums and prevent active forum members from wasting time on answering questions which are already handled before. Most previous literature focuses on existing FAQ retrieval instead of finding and constructing FAQ. This study, as a pioneering work, proposes a configurable and semi-automatic FAQ finding process to assist forum managers in constructing the FAQ. Also, two case studies are conducted to evaluate the effectiveness of the proposed FAQ finding process. <s> BIB002 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 1.0 INTRODUCTION <s> Online discussion forums have become a popular medium for users to discuss with and seek information from other users having similar interests. A typical discussion thread consists of a sequence of posts posted by multiple users. All the posts in a thread are not equally useful and serve a different purpose providing different types of information (some posts contain questions, some answers, etc.). Identifying the purpose and nature of each post in a discussion thread is an interesting research problem as it can help in improving information extraction and intelligent assistance techniques [9]. We study the problem of classifying a given post as per its purpose in the discussion thread. We employ features based on the post’s content, structure of the thread, behavior of the participating users and sentiment analysis of post’s content. We achieve decent classification performance and also analyze the relative importance of different features used for the post classification task. <s> BIB003

Internet forum is a web application that is becoming more and more popular. Its popularity may be attributed to the fact that it provides customer support for business enterprises that use it. Both technical and less technical issues are discussed in forums. Forum brings together experts from all walks of life. Members of a forum can make their contribution at the comfort of their homes without geographical and time zone barriers. Forums have both hierarchical and conversational structures. The hierarchical structure has to do with sub-forums emanating from the main forum, depending on the broadness of the category. For example, a computer technology forum can have hardware and software as sub-forums. The hardware sub-forum may also have motherboards, input devices and output devices as sub-forums. The conversational structure takes place within a sub-forum. A subforum is made up of threads. A thread is the minimal topical unit that addresses a specific topic. A thread is usually initiated by an author's post (usually called initial post), which constitute the topic of discussion. Members who are interested in the topic send reply posts. Figure 1 shows the structure of an Internet forum. Interaction within the forum community is naturally through question and answer scenario. It was empirically confirmed by that 90% of 40 forums investigated contain question-answer the various domains. This is because different business enterprise, which sells on the Internet need to provide customer call-centres to address customers' queries. Mined question-answer pairs can be archived to serve this purpose. This will not only reduce the cost of operating call centres but also enhance response time. Benefits of question-answer pairs are x-rayed in BIB001 BIB003 . Some of the challenges hindering effective Mining of Question-answer pairs are: Lexical chasm, Informal tone and Unfocused Topic mining. In this paper, we carry out an extensive overview of these three challenges that are limiting the potentiality of mining knowledge from Internet forum. Different approaches that researchers consider in overcoming them are explored with actions that have been taken so far to resolve them. We also proffer suggestions that can further assist in addressing the problems. Mining of human generated contents of forums is nontrivial due to its nature. The huge amount of responses and the variations of response context lead to the problems of efficient knowledge accumulation and retrieval BIB002 . Table 1 shows different forums that are serving different purposes with volume of human generated content they contain. The research activities in this domain is focusing on how to use the human generated contents reported in column 3 under the heading "Statistics" for the benefits of mankind. A good number of research activities are going on in the forum domain. Some of these research activities include retrieving relevant forum threads, clustering forum threads, finding similar threads, evaluating threads quality and mining question-answer pairs. Another type of discussion board that is becoming popular is the Community Question Answering (CQA). Some good examples of CQA are Yahoo! Answers, Stackoverflow, and Baidu a popular Chinese CQA. The CQA renders purely question answering services which are similar to that of the Internet forum. The CQA's are highly restrictive. A number of CQA's welcome purely objective contributions that do not call for too much debate from members. Members that wish to seek for subjective opinion may have to turn to Internet forum. A number of commercial question answering services like telephone answering system, chat bot, speaktoit, etc. are systems that benefit directly from automatic mining of QA pairs from CQA and Internet forums. These systems are products of Artificial Intelligence (AI). It should also be noted that the AI researchers are using the mined QA pairs to conduct Machine Learning (ML) training and testing while producing the systems. There are many other uses of QA pairs that can be found in the literature. It is on this premise that we decided to survey some of the issues that hinder effective mining of these QA pairs.

A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 2.0 LEXICAL CHASM IN MINING QA PAIRS <s> In this paper we present the results of a quantitative evaluation of the discrepancies between the Italian ::: and English lexica in terms of lexical gaps. This evaluation has been carried out in the context of ::: MultiWordNet, an ongoing project that aims at building a multilingual lexical database. The quantitative ::: evaluation of the English-to-Italian lexical gaps shows that the English and Italian lexica are highly ::: comparable and gives empirical support to the MultiWordNet model. <s> BIB001 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 2.0 LEXICAL CHASM IN MINING QA PAIRS <s> We describe the architecture of the AskMSR question answering system and systematically evaluate contributions of different system components to accuracy. The system differs from most question answering systems in its dependency on data redundancy rather than sophisticated linguistic analyses of either questions or candidate answers. Because a wrong answer is often worse than no answer, we also explore strategies for predicting when the question answering system is likely to give an incorrect answer. <s> BIB002 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 2.0 LEXICAL CHASM IN MINING QA PAIRS <s> Monolingual translation probabilities have recently been introduced in retrieval models to solve the lexical gap problem. They can be obtained by training statistical translation models on parallel monolingual corpora, such as question-answer pairs, where answers act as the "source" language and questions as the "target" language. In this paper, we propose to use as a parallel training dataset the definitions and glosses provided for the same term by different lexical semantic resources. We compare monolingual translation models built from lexical semantic resources with two other kinds of datasets: manually-tagged question reformulations and question-answer pairs. We also show that the monolingual translation probabilities obtained (i) are comparable to traditional semantic relatedness measures and (ii) significantly improve the results over the query likelihood and the vector-space model for answer finding. <s> BIB003 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 2.0 LEXICAL CHASM IN MINING QA PAIRS <s> Abstract Detecting answers in the threads is an essential task for the online forum oriented question-answer (QA) pair mining. In the forum threads, there normally exist implicit discussion structures with the valuable indicating information for the answer detecting models to locate the best answers. This paper proposes a thread segmentation based answer detecting approach: a forum thread is reorganized into several segments, and a group of features reflecting the discussion structures are extracted based on the segmentation results. Utilizing the segment information, a strategy is put forward to find the best answers. By evaluating the candidate answers in different types of segments with different models, the strategy filters the samples that mislead the decision. The experimental results show that our approach is promising for mining the QA resource in the online forums. <s> BIB004

Lexical chasm, also known as lexical gap, is one of the issues hindering effective mining of knowledge from forums BIB004 BIB002 . A lexical Chasm occurs whenever a language expresses a concept with a lexical unit whereas the other language expresses the same concept with a free combination of words BIB001 . Lexical gap problem can be attributed to different ways of writing that calls for the use of polysemy (same word with different meanings, such as "book" as in the following examples: "The book is on the table" and "I will book my flight tomorrow"), synonym (different words with the same or similar meanings, such as "agree" and "approve" as in "I agree with his going to London" and "I approve his going to London") and the use of paraphrasing. The problem is more severe when retrieving shorter documents such as sentence, question and answer retrieval in QA archives BIB003 . Human generated posts of web forum usually include a very short content, which always have much fewer sentences than that of web pages. The implication of this is that some useful models for similarity computing such as Cosine similarity, Kullback Leibler (KL) divergence and even Query Language that have yielded useful results in information retrieval become less powerful when faced with forum contents. The short contents cannot also provide enough semantic or logical information for deep language processing . In forum's question-answer detection system, it will be difficult to expect a great match between the lexical contents of question and its corresponding answer. In fact, there is often very little similarity between the tokens in a question and the one appearing in its answer. For example, a good answer to the question "Which hotel in Skudai is pet friendly?" might be "No Man's Land at Sri Pulai". The two statements have no tokens in common. Even at times the answers provided may be just a single word. For example the answer to the question "Where can I get a good clipper to buy?" can just be given as "Jusco". The relevance models that are stated above use common tokens to establish similarity. Hence, they failed to yield good results in forums. The established vocabularies for questions and answers are the same, but the probability distributions over those vocabularies are different for questions and their answers. The vocabulary mismatch and non-linkage between query and response vocabularies is often referred to as a lexical chasm. This problem between queries and documents or questions and answers has been identified as a common problem to both information retrieval and question answering BIB003 . It is even more pronounced in question answering because of the prevailing data sparseness in the domain. Bridging the lexical chasm between questions and their answers will require techniques that will move from lexical level toward semantic level. The lexical chasm problem has made it difficult to establish a good similarity between questions and answers posts. As a result of this, researchers have to find alternative approaches to relevance modelling in getting answers in forum threads. Some of these approaches and some relevant suggestions are given in the next section.

A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Query Expansion <s> Language Modeling (LM) has been successfully applied to Information Retrieval (IR). However, most of the existing LM approaches only rely on term occurrences in documents, queries and document collections. In traditional unigram based models, terms (or words) are usually considered to be independent. In some recent studies, dependence models have been proposed to incorporate term relationships into LM, so that links can be created between words in the same sentence, and term relationships (e.g. synonymy) can be used to expand the document model. In this study, we further extend this family of dependence models in the following two ways: (1) Term relationships are used to expand query model instead of document model, so that query expansion process can be naturally implemented; (2) We exploit more sophisticated inferential relationships extracted with Information Flow (IF). Information flow relationships are not simply pairwise term relationships as those used in previous studies, but are between a set of terms and another term. They allow for context-dependent query expansion. Our experiments conducted on TREC collections show that we can obtain large and significant improvements with our approach. This study shows that LM is an appropriate framework to implement effective query expansion. <s> BIB001 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Query Expansion <s> We present an approach to query expansion in answer retrieval that uses Statistical Machine Translation (SMT) techniques to bridge the lexical gap between questions and answers. SMT-based query expansion is done by i) using a full-sentence paraphraser to introduce synonyms in context of the entire query, and ii) by translating query terms into answer terms using a full-sentence SMT model trained on question-answer pairs. We evaluate these global, context-aware query expansion techniques on tfidf retrieval from 10 million question-answer pairs extracted from FAQ pages. Experimental results show that SMTbased expansion improves retrieval performance over local expansion and over retrieval without expansion. <s> BIB002 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Query Expansion <s> Lexical gaps between queries and questions (documents) have been a major issue in question retrieval on large online question and answer (Q&A) collections. Previous studies address the issue by implicitly expanding queries with the help of translation models pre-constructed using statistical techniques. However, since it is possible for unimportant words (e.g., non-topical words, common words) to be included in the translation models, a lack of noise control on the models can cause degradation of retrieval performance. This paper investigates a number of empirical methods for eliminating unimportant words in order to construct compact translation models for retrieval purposes. Experiments conducted on a real world Q&A collection show that substantial improvements in retrieval performance can be achieved by using compact translation models. <s> BIB003 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Query Expansion <s> The relative ineffectiveness of information retrieval systems is largely caused by the inaccuracy with which a query formed by a few keywords models the actual user information need. One well known method to overcome this limitation is automatic query expansion (AQE), whereby the user’s original query is augmented by new features with a similar meaning. AQE has a long history in the information retrieval community but it is only in the last years that it has reached a level of scientific and experimental maturity, especially in laboratory settings such as TREC. This survey presents a unified view of a large number of recent approaches to AQE that leverage various data sources and employ very different principles and techniques. The following questions are addressed. Why is query expansion so important to improve search effectiveness? What are the main steps involved in the design and implementation of an AQE component? What approaches to AQE are available and how do they compare? Which issues must still be resolved before AQE becomes a standard component of large operational information retrieval systems (e.g., search engines)? <s> BIB004

In mining QA pairs from forum, the query question is usually composed from relevant tokens with some of the context dropped. This scenario is a contributory factor to the problem of lexical chasm. For this reason, there has been much interest in query expansion techniques BIB001 BIB002 BIB003 . The basic query expansion technique involves adding words to the query; the words may likely be synonyms or somehow related words in the original query. The techniques used in query expansion can be classified as i) getting synonyms of words by searching for them ii) determining various morphological forms of words by stemming words in the search query iii) correcting spelling errors automatically by searching for the corrected form iv) re-weighting the terms in the original query BIB004 . A more focused expansion can be generated using questionanswer pairs' training set. All it requires is to learn a mapping between words in the query (that is, the question) and their corresponding responses (such as smoking  cigarette, why  because, URL  website and MS  Microsoft). These words are added to the query being used for the mapping to augment the original query to produce a representation that better reflects the underlying information need.

A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Machine Translation <s> Lexical gaps between queries and questions (documents) have been a major issue in question retrieval on large online question and answer (Q&A) collections. Previous studies address the issue by implicitly expanding queries with the help of translation models pre-constructed using statistical techniques. However, since it is possible for unimportant words (e.g., non-topical words, common words) to be included in the translation models, a lack of noise control on the models can cause degradation of retrieval performance. This paper investigates a number of empirical methods for eliminating unimportant words in order to construct compact translation models for retrieval purposes. Experiments conducted on a real world Q&A collection show that substantial improvements in retrieval performance can be achieved by using compact translation models. <s> BIB001 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Machine Translation <s> We propose a new probabilistic approach to information retrieval based upon the ideas and methods of statistical machine translation. The central ingredient in this approach is a statistical model of how a user might distill or "translate" a given document into a query. To assess the relevance of a document to a user's query, we estimate the probability that the query would have been generated as a translation of the document, and factor in the user's general preferences in the form of a prior distribution over documents. We propose a simple, well motivated model of the document-to-query translation process, and describe an algorithm for learning the parameters of this model in an unsupervised manner from a collection of documents. As we show, one can view this approach as a generalization and justification of the "language modeling" strategy recently proposed by Ponte and Croft. In a series of experiments on TREC data, a simple translation-based retrieval system performs well in comparison to conventional retrieval techniques. This prototype system only begins to tap the full potential of translation-based retrieval. <s> BIB002

The basic language modelling structure for retrieval which establishes similarity between a query Q and a document D may be modelled as the probability of the document language model MD built from D generating Q: Query words are often considered to occur independently in a particular document language model, as such, the querylikelihood is calculated as: where q is a query word. The probability is usually calculated using maximum likelihood estimation BIB001 . It should be noted that this basic language model structure does not address lexical gaps issue between queries and question. Information retrieval was viewed by BIB002 as statistical documentquery translation and as such added translation models to map query words to document words. The established translationbased retrieval model obtained by modelling in equation (2) above is: where w represents document word. The translation probability T(q|w) fundamentally represents the level of association between query word q and document word w captured using different machine translation setting BIB001 . The use of translation models judging from traditional information retrieval perspective, produce an implicit query expansion effect, since query words that are not found in a document are mapped to associated words in the document. A positive impact could only be made by this translation-based retrieval models if only the pre-constructed translation models have consistent translation probability distributions.

A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Non-Lexical Features <s> New types of document collections are being developed by various web services. The service providers keep track of non-textual features such as click counts. In this paper, we present a framework to use non-textual features to predict the quality of documents. We also show our quality measure can be successfully incorporated into the language modeling-based retrieval model. We test our approach on a collection of question and answer pairs gathered from a community based question answering service where people ask and answer questions. Experimental results using our quality measure show a significant improvement over our baseline. <s> BIB001 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Non-Lexical Features <s> Discussion boards and online forums are important platforms for people to share information. Users post questions or problems onto discussion boards and rely on others to provide possible solutions and such question-related content sometimes even dominates the whole discussion board. However, to retrieve this kind of information automatically and effectively is still a non-trivial task. In addition, the existence of other types of information (e.g., announcements, plans, elaborations, etc.) makes it difficult to assume that every thread in a discussion board is about a question. We consider the problems of identifying question-related threads and their potential answers as classification tasks. Experimental results across multiple datasets demonstrate that our method can significantly improve the performance in both question detection and answer finding subtasks. We also do a careful comparison of how different types of features contribute to the final result and show that non-content features play a key role in improving overall performance. Finally, we show that a ranking scheme based on our classification approach can yield much better performance than prior published methods. <s> BIB002 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Non-Lexical Features <s> Frequently Asked Questions (FAQ)'s tag is becoming more popular on websites. Research activities have been concentrated on its retrieval rather than construction. FAQ construction can be achieved using a number of sources. Presently, it is mostly done manually by help desk staff and this tends to make it static in nature. In this paper, a comprehensive review of various components that can guarantee effective mining of FAQ from forum threads is presented. The components encompass pre-processing, mining of questions, mining of answers and mining of the FAQ. Besides the general idea and concept, we discuss the strengths and limitations of the various techniques used in these components. In fact, the following questions are addressed in the review. What kind of pre-processing technique is needed for mining FAQ from forum? What are the recent techniques for mining questions from forum threads? What approaches are currently dominating answer retrieval from forum threads? How can we cluster out FAQ from question and answer database?. <s> BIB003

A much more prevalent approach of tackling lexical gaps in web forum question answering is to avoid the use of lexical data. The non-lexical features are at times referred to as structural features. Forum meta data such as authorship, answer length, normalized position of post, etc. are used in determining questions and answers. In BIB002 total number of posts and authorship were used to mine questions with a reasonable performance. A host of these features with detailed descriptions for mining questions and answers are contained in BIB003 . A major problem with nonlexical features is their availability. Some non-lexical features used by some forums may not be found in others. The degree of availability of some non-lexical features across forums can be found in . It is worth noting that combination of both the lexical and non-lexical is desirable for effective mining of question-answer pairs from forum. The lexical features measure the degree of relevance between question and answer while nonlexical can be used to estimate the quality of answers BIB001 .

A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 3.0 CASUAL LANGUAGE <s> Often, in the real world noise is ubiquitous in text communications. Text produced by processing signals intended for human use are often noisy for automated computer processing. Automatic speech recognition, optical character recognition and machine translation all introduce processing noise. Also digital text produced in informal settings such as online chat, SMS, emails, message boards, newsgroups, blogs, wikis and web pages contain considerable noise. In this paper, we present a survey of the existing measures for noise in text. We also cover application areas that ingest this noisy text for various tasks like Information Retrieval and Information Extraction. <s> BIB001 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 3.0 CASUAL LANGUAGE <s> A webforum is a large database of community knowledge, with information of the most recent events and developments. Unfortunately this knowledge is presented in a format easily understood by humans but not automatically by machines. However, from observing several forums for a long time it seems obvious that there are several distinct types of postings and relations between them. ::: ::: One often occurring and very annoying relation between two contributions is the near-duplicate relation. In this paper we propose a work to detect and utilize contribution relations, concentrating on near-duplication. We propose ideas on how to calculate similarity, build groups of similar threads and thus make near-duplicates in forums evident. One of the core theses is, that it is possible to apply information from forum and thread structure to improve existing near-duplicate detection approaches. In addition, the proposed work shows the qualitative and quantitative results of applying such principles, thereby finding out which features are really useful in the near-duplicate detection process. Also proposed are several sample applications, which benefit from forum near-duplicate detection. <s> BIB002 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 3.0 CASUAL LANGUAGE <s> Abstract The rapid expansion in user-generated content on the Web of the 2000s, characterized by social media, has led to Web content featuring somewhat less standardized language than the Web of the 1990s. User creativity and individuality of language creates problems on two levels. The first is that social media text is often unsuitable as data for Natural Language Processing tasks such as Machine Translation, Information Retrieval and Opinion Mining, due to the irregularity of the language featured. The second is that non-native speakers of English, older Internet users and non-members of the “in-group” often find such texts difficult to understand. This paper discusses problems involved in automatically normalizing social media English, various applications for its use, and our progress thus far in a rule-based approach to the issue. Particularly, we evaluate the performance of two leading open source spell checkers on data taken from the microblogging service Twitter, and measure the extent to which their accuracy is improved by pre-processing with our system. We also present our database rules and classification system, results of evaluation experiments, and plans for expansion of the project. <s> BIB003 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 3.0 CASUAL LANGUAGE <s> Automated clustering of threads within and across web forums will greatly benefit both users and forum administrators in efficiently seeking, managing, and integrating the huge volume of content being generated. While clustering has been studied for other types of data, little work has been done on clustering forum threads; the informal nature and special structure of forum data make it interesting to study how to effectively cluster forum threads. In this paper, we apply three state of the art clustering methods (i.e., hierarchical agglomerative clustering, k-Means, and probabilistic latent semantic analysis) to cluster forum threads and study how to leverage the structure of threads to improve clustering accuracy. We propose three different methods for assigning weights to the posts in a forum thread to achieve more accurate representation of a thread. We evaluate all the methods on data collected from three different Linux forums for both within-forum and across-forum clustering. Our results show that the state of the art methods perform reasonably well for this task, but the performance can be further improved by exploiting thread structures. In particular, a parabolic weighting method that assigns higher weights for both beginning posts and end posts of a thread is shown to consistently outperform a standard clustering method. <s> BIB004 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 3.0 CASUAL LANGUAGE <s> Frequently Asked Questions (FAQ)'s tag is becoming more popular on websites. Research activities have been concentrated on its retrieval rather than construction. FAQ construction can be achieved using a number of sources. Presently, it is mostly done manually by help desk staff and this tends to make it static in nature. In this paper, a comprehensive review of various components that can guarantee effective mining of FAQ from forum threads is presented. The components encompass pre-processing, mining of questions, mining of answers and mining of the FAQ. Besides the general idea and concept, we discuss the strengths and limitations of the various techniques used in these components. In fact, the following questions are addressed in the review. What kind of pre-processing technique is needed for mining FAQ from forum? What are the recent techniques for mining questions from forum threads? What approaches are currently dominating answer retrieval from forum threads? How can we cluster out FAQ from question and answer database?. <s> BIB005

Forum content generation is at times done with some laxity. Members initializing or replying a post tends to use an informal tone / language which is more closed to his/her oral habit. The informal tone is often considered in literature as unstructured casual language BIB003 . The useful information is concealed inside majority of trivial, heterogeneous, and sometimes irrelevant, text data of different quality. This attitude usually make forum content to be highly noisy BIB002 BIB004 . The noise content of forum can be said to come from two sources. These sources appear to be in line with sources identified by BIB001 for text generally: 1) noise can occur during the conversion process, when a textual representation of information is produced from some other form. For example, web pages, printed/handwritten documents, camera-captured images, spontaneous speech are all intended for human use. Their conversion into some other forms may results in noisy text. 2) Noise can also be introduced when text is generated in digital form. Most especially in informal settings such as SMS (Short Messaging Service or Texting), online chat, emails, web pages and message boards, the text produced is inherently noisy. This type of text contains spelling errors, special characters, grammar mistakes, non-standard word forms, usage of multilingual words and so on BIB001 . In forum, text normalization activities have been concentrated on the second noise source. Categorization of forum noise as contained in BIB005 is shown in Table 2 .

A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Casual Language Resolution Approaches <s> Research aimed at correcting words in text has focused on three progressively more difficult problems:(1) nonword error detection; (2) isolated-word error correction; and (3) context-dependent work correction. In response to the first problem, efficient pattern-matching and n -gram analysis techniques have been developed for detecting strings that do not appear in a given word list. In response to the second problem, a variety of general and application-specific spelling correction techniques have been developed. Some of them were based on detailed studies of spelling error patterns. In response to the third problem, a few experiments using natural-language-processing tools or statistical-language models have been carried out. This article surveys documented findings on spelling error patterns, provides descriptions of various nonword detection and isolated-word error correction techniques, reviews the state of the art of context-dependent word correction techniques, and discusses research issues related to all three areas of automatic error correction in text. <s> BIB001 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Casual Language Resolution Approaches <s> Web communities are web virtual broadcasting spaces where people can freely discuss anything. While such communities function as discussion boards, they have even greater value as large repositories of archived information. In order to unlock the value of this resource, we need an effective means for searching archived discussion threads. Unfortunately the techniques that have proven successful for searching document collections and the Web are not ideally suited to the task of searching archived community discussions. In this paper, we explore the problem of creating an effective ranking function to predict the most relevant messages to queries in community search. We extract a set of predictive features from the thread trees of newsgroup messages as well as features of message authors and lexical distribution within a message thread. Our final results indicate that when using linear regression with this feature set, our search system achieved a 28.5% performance improvement compared to our baseline system. <s> BIB002 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Casual Language Resolution Approaches <s> We present the first English syllabification system to improve the accuracy of letter-tophoneme conversion. We propose a novel discriminative approach to automatic syllabification based on structured SVMs. In comparison with a state-of-the-art syllabification system, we reduce the syllabification word error rate for English by 33%. Our approach also performs well on other languages, comparing favorably with published results on German and Dutch. <s> BIB003 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Casual Language Resolution Approaches <s> Letter-to-phoneme conversion plays an important role in several applications. It can be a difficult task because the mapping from letters to phonemes can be many-to-many. We present a language independent letter-to-phoneme conversion approach which is based on the popular phrase based Statistical Machine Translation techniques. The results of our experiments clearly demonstrate that such techniques can be used effectively for letter-to-phoneme conversion. Our results show an overall improvement of 5.8% over the baseline and are comparable to the state of the art. We also propose a measure to estimate the difficulty level of L2P task for a language. <s> BIB004 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Casual Language Resolution Approaches <s> Correct stress placement is important in text-to-speech systems, in terms of both the overall accuracy and the naturalness of pronunciation. In this paper, we formulate stress assignment as a sequence prediction problem. We represent words as sequences of substrings, and use the substrings as features in a Support Vector Machine (SVM) ranker, which is trained to rank possible stress patterns. The ranking approach facilitates inclusion of arbitrary features over both the input sequence and output stress pattern. Our system advances the current state-of-the-art, predicting primary stress in English, German, and Dutch with up to 98% word accuracy on phonemes, and 96% on letters. The system is also highly accurate in predicting secondary stress. Finally, when applied in tandem with an L2P system, it substantially reduces the word error rate when predicting both phonemes and stress. <s> BIB005 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Casual Language Resolution Approaches <s> Abstract The rapid expansion in user-generated content on the Web of the 2000s, characterized by social media, has led to Web content featuring somewhat less standardized language than the Web of the 1990s. User creativity and individuality of language creates problems on two levels. The first is that social media text is often unsuitable as data for Natural Language Processing tasks such as Machine Translation, Information Retrieval and Opinion Mining, due to the irregularity of the language featured. The second is that non-native speakers of English, older Internet users and non-members of the “in-group” often find such texts difficult to understand. This paper discusses problems involved in automatically normalizing social media English, various applications for its use, and our progress thus far in a rule-based approach to the issue. Particularly, we evaluate the performance of two leading open source spell checkers on data taken from the microblogging service Twitter, and measure the extent to which their accuracy is improved by pre-processing with our system. We also present our database rules and classification system, results of evaluation experiments, and plans for expansion of the project. <s> BIB006 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Casual Language Resolution Approaches <s> The use of computer mediated communication has resulted in a new form of written text--Microtext--which is very different from well-written text. Tweets and SMS messages, which have limited length and may contain misspellings, slang, or abbreviations, are two typical examples of microtext. Microtext poses new challenges to standard natural language processing tools which are usually designed for well-written text. The objective of this work is to normalize microtext, in order to produce text that could be suitable for further treatment. ::: ::: We propose a normalization approach based on the source channel model, which incorporates four factors, namely an orthographic factor, a phonetic factor, a contextual factor and acronym expansion. Experiments show that our approach can normalize Twitter messages reasonably well, and it outperforms existing algorithms on a public SMS data set. <s> BIB007

A number of methods from different research areas have emerged for identifying and correcting words in text. A good work by BIB001 described in details various methods for correcting spelling mistakes. A common measure for rectifying spelling errors is edit distance or Levenshtein distance. For any two character strings t 1 and t 2 , the edit distance between them is considered as the minimum number of edit operations needed to transform t 1 into t 2 . The expected edit operations are: (i) insertion of a character into a string; (ii) deletion of a character from a string and (iii) replacement of a character of a string by another character. For example, the edit distance between dog and rat is 3. The edit distance model is at times being augmented by a Language Model (LM) from the corpus of Web queries. This is based on the notion of distributional similarity BIB002 between two terms, which is high between a frequently occurring misspelling and its correction, and low between two irrelevant terms only with similar spellings. Open source dictionaries such as Aspell or Hunspell can also be used to fix some of the spelling mistakes found in forum corpora. An empirical result of BIB006 confirms the effectiveness of these open source dictionaries in correcting words in text. However, dictionaries can only correct spelling mistakes with some being able to fix phonetic errors. Noise is often modelled depending on the application. Four different noise channels, namely, Grapheme Channel, Phoneme Channel, Context Channel and Acronym Channel are proposed by BIB007 to fix the four noise classes x-rayed in Table 2 . The noise channels are described in the following four paragraphs. The grapheme channel is responsible for the spelling distortion. A way of modelling this channel is to consider it as being directly proportional to the similarity between a corrupted token and its normalization. The more similar a normalization candidate is to the corrupted token, the more likely it is the correct substitution for it. The phoneme channel is responsible for distortion in pronunciations. It is similar to the grapheme channel; the probability of a correct string being transformed into an incorrect string is proportional to the similarity between the two terms, area of difference being that the similarity in this case is measured on the phonetic representations instead of orthographic forms. A major step in phoneme is Letter-toPhoneme (L2P) conversion, which estimates the pronunciation of a term, represented as a sequence of letters. A lot of research is going on in this area of letter-to-phoneme conversion. Some notable ones are the work of BIB004 BIB005 BIB003 . After the L2P conversion, the similarity measure between two phoneme sequences becomes the same as the similarity measure implemented in the grapheme channel, the only difference is that a uniform weight Levenshtein distance is considered instead of weighted Levenshtein distance. Context channel -a context-based correction procedure would not only handle the problem of real-word errors, i.e., errors that result in another valid word, like form instead of from, but it would also be good in correcting those non-word errors that have more than one possible correction. A good example of such is the string ehre. Without context there is little reasoning one could make, some possible options to considered as the intended correction among others are here, ere, ether, where, there. Developing context-based correction procedures has become a notable challenge for automatic word recognition and error correction in text BIB001 . Correct normalization using context is often determined by considering the n-gram probability. The n-gram language model is normally trained on a large Web corpus to return probability score for a query word or phrase. Acronym Channel -the three channel models considered so far deal with word-to-word normalization. There exist a number of acronyms such as "fyi" (for your information), "asap" (as soon as possible) and "lol" (laugh out loudly) that are commonly used and involve word-to-phrase mappings. The acronym channel can then be considered as a model of one-tomany mapping.

A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 4.0 TOPIC DRIFT <s> Web communities are web virtual broadcasting spaces where people can freely discuss anything. While such communities function as discussion boards, they have even greater value as large repositories of archived information. In order to unlock the value of this resource, we need an effective means for searching archived discussion threads. Unfortunately the techniques that have proven successful for searching document collections and the Web are not ideally suited to the task of searching archived community discussions. In this paper, we explore the problem of creating an effective ranking function to predict the most relevant messages to queries in community search. We extract a set of predictive features from the thread trees of newsgroup messages as well as features of message authors and lexical distribution within a message thread. Our final results indicate that when using linear regression with this feature set, our search system achieved a 28.5% performance improvement compared to our baseline system. <s> BIB001 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 4.0 TOPIC DRIFT <s> Online communities are valuable information sources where knowledge is accumulated by interactions between people. Search services provided by online community sites such as forums are often, however, quite poor. To address this, we investigate retrieval techniques that exploit the hierarchical thread structures in community sites. Since these structures are sometimes not explicit or accurately annotated, we use structure discovery techniques. We then make use of thread structures in retrieval experiments. Our results show that using thread structures that have been accurately annotated can lead to significant improvements in retrieval performance compared to strong baselines. <s> BIB002 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> 4.0 TOPIC DRIFT <s> We propose a method for annotating post-to-post discourse structure in online user forum data, in the hopes of improving troubleshooting-oriented information access. We introduce the tasks of: (1) post classification, based on a novel dialogue act tag set; and (2) link classification. We also introduce three feature sets (structural features, post context features and semantic features) and experiment with three discriminative learners (maximum entropy, SVM-HMM and CRF). We achieve above-baseline results for both dialogue act and link classification, with interesting divergences in which feature sets perform well over the two sub-tasks, and go on to perform preliminary investigation of the interaction between post tagging and linking. <s> BIB003

Threads in Internet forum are composed by many authors. As a result, they are less coherent and more susceptible to sudden jumps in topics. The existence of several topics in a thread is something very common in popular discussions. Even if a unique topic is discussed in a thread, different features and aspects of it may be considered in the discussion. There is a need to uncover the content structure of threads so as to establish post-to-post discourse structure. Specifically, it will be better to establish which earlier post(s) a given post responds to. It has rightly been pointed out by BIB001 BIB002 that post-to-post discourse structure will enhance information retrieval. A good illustration of this problem is contained in BIB003 . Topic drift is mostly found in threads that contain many posts, say 6 and above.

A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Topic Drift Resolution Strategies <s> Message hierarchies in web discussion boards grow with new postings. Threads of messages evolve as new postings focus within or diverge from the original themes of the threads. Thus, just by investigating the subject headings or contents of earlier postings in a message thread, one may not be able to guess the contents of the later postings. The resulting navigation problem is further compounded for blind users who need the help of a screen reader program that can provide only a linear representation of the content. We see that, in order to overcome the navigation obstacle for blind as well as sighted users, it is essential to develop techniques that help identify how the content of a discussion board grows through generalizations and specializations of topics. This knowledge can be used in segmenting the content in coherent units and guiding the users through segments relevant to their navigational goals. Our experimental results showed that the segmentation algorithm described in this paper provides up to 80-85% success rate in labeling messages. The algorithm is being deployed in a software system to reduce the navigational load of blind students in accessing web-based electronic course materials; however, we note that the techniques are equally applicable for developing web indexing and summarization tools for users with sight. <s> BIB001 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Topic Drift Resolution Strategies <s> Text message stream is a newly emerging type of Web data which is produced in enormous quantities with the popularity of Instant Messaging and Internet Relay Chat. It is beneficial for detecting the threads contained in the text stream for various applications, including information retrieval, expert recognition and even crime prevention. Despite its importance, not much research has been conducted so far on this problem due to the characteristics of the data in which the messages are usually very short and incomplete. In this paper, we present a stringent definition of the thread detection task and our preliminary solution to it. We propose three variations of a single-pass clustering algorithm for exploiting the temporal information in the streams. An algorithm based on linguistic features is also put forward to exploit the discourse structure information. We conducted several experiments to compare our approaches with some existing algorithms on a real dataset. The results show that all three variations of the single-pass algorithm outperform the basic single-pass algorithm. Our proposed algorithm based on linguistic features improves the performance relatively by 69.5% and 9.7% when compared with the basic single-pass algorithm and the best variation algorithm in terms of F1 respectively. <s> BIB002 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Topic Drift Resolution Strategies <s> This paper presents a novel approach for extracting high-quality 〈thread-title, reply〉 pairs as chat knowledge from online discussion forums so as to efficiently support the construction of a chatbot for a certain domain. Given a forum, the high-quality 〈thread-title, reply〉 pairs are extracted using a cascaded framework. First, the replies logically relevant to the thread title of the root message are extracted with an SVM classifier from all the replies, based on correlations such as structure and content. Then, the extracted 〈thread-title, reply〉 pairs are ranked with a ranking SVM based on their content qualities. Finally, the Top-N 〈thread-title, reply〉 pairs are selected as chatbot knowledge. Results from experiments conducted within a movie forum show the proposed approach is effective. <s> BIB003 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Topic Drift Resolution Strategies <s> This paper presents a topical text segmentation method based on intended boundaries detection and compares it to a well known default boundaries detection method, c99. We compared the two methods by running them on two different corpora of French texts and results are evaluated by two different methods: one using a modified classic measure, the FScore, the other based on a manual evaluation one the Internet. Our results showed that algorithms that are close when automatically evaluated can be quite far when manually evaluated. <s> BIB004 </s> A Survey Of Challenges And Resolutions Of Mining Question-Answer Pairs From Internet Forum <s> Topic Drift Resolution Strategies <s> We propose a method for annotating post-to-post discourse structure in online user forum data, in the hopes of improving troubleshooting-oriented information access. We introduce the tasks of: (1) post classification, based on a novel dialogue act tag set; and (2) link classification. We also introduce three feature sets (structural features, post context features and semantic features) and experiment with three discriminative learners (maximum entropy, SVM-HMM and CRF). We achieve above-baseline results for both dialogue act and link classification, with interesting divergences in which feature sets perform well over the two sub-tasks, and go on to perform preliminary investigation of the interaction between post tagging and linking. <s> BIB005

The usage of term frequency (TF-IDF) and text similarity methods is a very common approach for extracting topic of discussion BIB002 . Quotation within post is often being used to establish context coherence. It indicates the relevance between a reply and the root message if root message is quoted. Drift resolution is implemented in BIB003 using two quotation features: a reply quoting root message and a reply quoting other replies. A reply quoting root message indicates that the reply is relevant to the message. In contrast, a reply quoting other replies may not be relevant to the root message hence it can be considered as topic drift. A blended quoting technique that utilizes some special features offered from the structure of web forums is proposed by BIB001 to cluster the posts of a discussion with the same topic. In their work, an algorithm that uses temporal information such as time and date of posts, the post authors etc. is implemented to create posting chains that uses topic similarity algorithm augmented with the utilization of the quoting system. An exciting method to track topic drifting in a discussion is proposed by BIB004 . They use lexical similarity and thematic distance to identify topic boundaries in a discussion and fragmented it into topic related clusters. An algorithm proposed by that isolates parts of a discussion in order to extracts the topics using just these parts and not the entire thread is good approach to tackle problem of topic drift in forums. Utilization of term weights and domain technical words will probably enhance performance. Some other popular approaches are the use of dialogue act tagging (DAT) and discourse disentanglement. Dialogue act tagging helps in capturing the purpose of a given utterance in relation to an encompassing discourse. Discourse disentanglement is being implemented to automatically identify coherent sub-discourses in a single thread. The two concepts are implemented in BIB005 to establish post-to-post relationship. Three categories of features, namely, structural features, post context features and semantic features were considered in the work. The use of topic modelling such as Latent Dirichlet Allocation may be necessary for long threads that contain tens of posts.

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Introduction <s> Cognitive radio is being intensively researched as the enabling technology for secondary access to the so-called TV White Spaces (TVWS), large portions of spectrum in theUHF/VHF bands which become available on a geographical basis after digital switchover. Both in the US, and more recently, in the UK the regulators have given conditional endorsement to this new mode of access. This paper reviews the state-of-the-art in technology, regulation and standardization of cognitive access to TVWS. It examines the spectrum opportunity and commercial use cases associated with this form of secondary access. <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Introduction <s> 700MHz band attracted many researchers and stakeholders for mobile communications by providing a rare opportunity to have cost effective wireless solutions due to its excellent propagation characteristics compared to GSM 1800 MHz, 2.1 GHz or 2.5 GHz bands for 3G/BWA. In India, 698–806 MHz more specific 700MHz band mainly used by TV broadcast services. We discuss the scope and nature of opportunities for white space created by Digital Dividend (700 MHz band) in India especially to rural India by providing wireless broadband for the applications like e-education, e-agriculture, e-animal husbandry and e-health which would help in decreasing primary school drop-out rate, in decreasing farmer suicides rate and in decreasing mortality rate. Further use cases for the exploitation of TV White Space suitable for rural India are discussed based on user's and BS geo-location and user's mobility; which is followed by an overview of recent regulatory activities. <s> BIB002 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Introduction <s> TV White Spaces constitutes the major portion of the VHF and UHF TV and which is geographically unused after digital switchover. The most important regulatory trend in the context of Dynamic Spectrum Access (DSA) is the Cognitive access of TV white Spaces. Through spectrum measurement campaign we have estimated the spectrum utilization of TV band in Pune, India. We have designed the measurement set up and methodology for the measurement campaign. Our spectrum occupancy analysis provides the realistic view on the spectrum opportunities in India for (i) spectrum refarming of TV band; (ii) Cognitive Radio operation in TV band. Also we have stressed on the need of quantitative analysis of TVWSs availability and compatibility studies for protection of incumbent services for CR access of TVWSs in India. Also this paper reviews the state-of-the-art in standardization of cognitive access to TVWS. <s> BIB003

With the rapid development of technology, the need for access to wireless Internet has become a daily necessity. This has created severe congestion in the frequency spectrum, especially in urban areas where the number of users is consistently high. This exponential increase in broadband traffic has underscored the need for a more efficient and opportunistic use of the available spectrum. Researchers have highlighted the underutilization of licensed portions of the spectrum as a potential opportunity in addressing the spectrum congestion problem. The use of already licensed portions of the spectrum would be enabled by cognitive radios, which behave as secondary users and use the spectrum whenever the primary users, i.e., the license owners, are not using it. A cognitive radio (CR) is a radio that can change its transmission parameters based on interaction with the environment in which it operates . The use of such radios has been approved both by US and UK regulatory bodies, in 2009 and 2012 respectively BIB001 . The move was motivated by the digital transition in TV broadcasting, which made large swathes of TV spectrum accessible for opportunistic use. This portion of the spectrum is referred to as TV White Space (TVWS) and its capacity is quite high. According to Ofcom research, there is more than 150 MHz of interleaved spectrum in over 50% of locations in UK and 100 MHZ of interleaved spectrum in 90% of locations . However, the availability of TVWS spectrum varies from country to country and depends largely on the channels chosen for TV broadcasting. Most available (unused or vacant) channels can be found in less densely populated areas, such as in developing countries or rural areas BIB002 BIB003 . Frequency bands corresponding to TVWS spectrum are: VHF 30-300 MHz and UHF 300-1000 MHz except for the channels reserved for emergency transmissions. In Europe a challenging aspect of TVWS use is that TV spectrum is not only occupied by fixed TV broadcasting signals but also by licensed Programme Making Special Event (PMSE) devices, e.g., wireless microphones used in small events, concerts or security agencies. PMSE can operate in licensed or unlicensed basis. The detection of such equipment is the subject of research project [6] . Furthermore their protection should be guaranteed based on legislative regulations [7] .

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Wireless Communications and Mobile Computing <s> Wireless indoor positioning systems have become very popular in recent years. These systems have been successfully used in many applications such as asset tracking and inventory management. This paper provides an overview of the existing wireless indoor positioning solutions and attempts to classify different techniques and systems. Three typical location estimation schemes of triangulation, scene analysis, and proximity are analyzed. We also discuss location fingerprinting in detail since it is used in most current system or solutions. We then examine a set of properties by which location systems are evaluated, and apply this evaluation method to survey a number of existing systems. Comprehensive performance comparisons including accuracy, precision, complexity, scalability, robustness, and cost are presented. <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Wireless Communications and Mobile Computing <s> Cognitive radio is being intensively researched as the enabling technology for license-exempt access to the so-called TV White Spaces (TVWS), large portions of spectrum in the UHF/VHF bands which become available on a geographical basis after digital switchover. Both in the US, and more recently, in the UK the regulators have given conditional endorsement to this new mode of access. This paper reviews the state-of-the-art in technology, regulation, and standardisation of cognitive access to TVWS. It examines the spectrum opportunity and commercial use cases associated with this form of secondary access. <s> BIB002 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Wireless Communications and Mobile Computing <s> The spectrum sensing problem has gained new aspects with cognitive radio and opportunistic spectrum access concepts. It is one of the most challenging issues in cognitive radio systems. In this paper, a survey of spectrum sensing methodologies for cognitive radio is presented. Various aspects of spectrum sensing problem are studied from a cognitive radio perspective and multi-dimensional spectrum sensing concept is introduced. Challenges associated with spectrum sensing are given and enabling spectrum sensing methods are reviewed. The paper explains the cooperative sensing concept and its various forms. External sensing algorithms and other alternative sensing methods are discussed. Furthermore, statistical modeling of network traffic and utilization of these models for prediction of primary user behavior is studied. Finally, sensing features of some current wireless standards are given. <s> BIB003 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Wireless Communications and Mobile Computing <s> The FCC recently issued the regulatory rules for cognitive radio use of the TV white space spectrum. These new rules provide an opportunity but they also introduce a number of technical challenges. The challenges require development of cognitive radio technologies like spectrum sensing as well as new wireless PHY and MAC layer designs. These challenges include spectrum sensing of both TV signals and wireless microphone signals, frequency agile operation, geo-location, stringent spectral mask requirements, and of course the ability to provide reliable service in unlicensed and dynamically changing spectrum. After describing these various challenges we will describe some of the possible methods for meeting these challenges. <s> BIB004 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Wireless Communications and Mobile Computing <s> We investigate the efficiency of dynamic frequency selection (DFS) in mitigating interference among neighboring low-power cognitive wireless portable networks operating in the TV white space. We derive an interference model to predict the range and level of interference generated in the TV bands by portable low-height antenna cognitive wireless access points in suburban and urban areas. Based on the aforementioned model, we provide an analysis of the spectral availability for either the scenarios where DFS coexistence is employed or not. The steps of our analysis are introduced in a tutorial fashion, and a coexistence case study of TVWS enabled low-power cognitive wireless portable APs in Japan is presented. Our analysis demonstrates the intrinsic relationship SA holds with the TVWS channel set as well as statistical information (e.g., household density of wards and cities, Internet penetration, and white space radio AP market penetration). <s> BIB005 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Wireless Communications and Mobile Computing <s> Radio spectrum is a necessary barrier for nourishing of economic activities through provision of wireless services. The radio spectrum suitable for the propagation of wireless signals is a limited resource and hence requires optimal allocation as collectively dictated by regulatory, technical and market domains. The current global move to switch from analogue to digital TV has opened up an opportunity for the reallocation of this valuable resource. In one way, spectrum bands once used for analogue TV broadcasting will be completely cleared, leaving a space for deploying new licensed wireless services, and in another way, digital television technology geographically interleaves spectrum bands to avoid interference between neighboring stations-leaving a space for deploying new unlicensed wireless services. The focus of the paper is to assess the availability of geographically interleaved spectrum, also known as television spectrum white spaces (TVWS) and proposing the wireless network scenarios for rural broadband connectivity. <s> BIB006 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Wireless Communications and Mobile Computing <s> TV White Spaces technology is a means of allowing wireless devices to opportunistically use locally-available TV channels (TV White Spaces), enabled by a geolocation database. The geolocation database informs the device of which channels can be used at a given location, and in the UK/EU case, which transmission powers (EIRPs) can be used on each channel based on the technical characteristics of the device, given an assumed interference limit and protection margin at the edge of the primary service coverage area(s). The UK regulator, Ofcom, has initiated a large-scale Pilot of TV White Spaces technology and devices. The ICT-ACROPOLIS Network of Excellence, teaming up with the ICT-SOLDER project and others, is running an extensive series of trials under this effort. The purpose of these trials is to test a number of aspects of white space technology, including the white space device and geolocation database interactions, the validity of the channel availability/powers calculations by the database and associated interference effects on primary services., and the performances of the white spaces devices, among others. An additional key purpose is to undertake a number of research investigations such as into aggregation of TV White Space resources with conventional (licensed/unlicensed) resources, secondary coexistence issues and means to mitigate such issues, and primary coexistence issues under challenging deployment geometries, among others. This paper describes our trials, their intentions and characteristics, objectives, and some early observations. <s> BIB007

While it is not expected that TVWS based broadband access will completely substitute the WiFi technology, such bands may be used to augment spectrum resources when needed BIB005 . The TVWS are convenient for two main reasons: their superior propagation characteristics for wireless communication which enable larger coverage and the minimal infrastructure requirements which makes them ideal for rural and undeveloped areas which are difficult to reach or connect through optical fiber. This is especially convenient for developing countries such as those in Western Balkans, where broadband penetration rates are increasing rapidly as comparing ITU reports on the state of broadband show . In Albania alone, the number of active mobile broadband subscribers has shot up from 8.8 to 52.6 per 100 inhabitants in the last five years. Furthermore, providing fiber optic connection may not be cost-efficient for service providers, due to the high cost, thus access through wireless broadband networks through TVWS could be preferred BIB006 . This being said, the successful implementation of this technology largely depends on the ability to effectively manage and avoid the possible interference caused to the primary users. To enable this, the cognitive radios will have to continuously sense the channel to detect primary user transmissions and ensure that primary users are protected at all times. In case that secondary user is using the spectrum and primary user starts operating, than secondary user has to immediately vacate the channel in order to avoid causing interference to primary user. To ensure this, the UK regulator, Ofcom and Federal Communication Commission (FCC) in the United States, have proposed three methods to be used by secondary users: (i) beacons, (ii) sensing and (iii) geolocation with database. When beacons are used as a controlling method, secondary users will only start transmitting if they have already received a beacon signal implying the vacant channel. The drawback of this method is that it requires the infrastructure of beacons to be implemented and maintained BIB002 . With sensing, the secondary users will sense the spectrum and try to detect the presence of primary users based on the amount of energy received. Secondary users may operate when they do not detect any primary signals. However, in the case of cognitive devices, this is not a straightforward task as it involves detecting other signal characteristics such as modulation and bandwidth, thus increasing device complexity and cost BIB003 . The third technique uses geolocation and databases. Secondary users have to send a query to a database that contains information regarding the spectrum usage in the vicinity during the specific time period. The database will respond with the list of available frequencies including all transmission parameters that need to be followed for secondary transmission to start. This implies that secondary users must have geolocation capability, while the database must be kept updated at all times, which incurs additional overhead. An additional challenge on using geolocation and database access is when secondary users are indoors where GPS connectivity may not be available due to the signal disruption from buildings, walls, etc., BIB004 . Although GPS is one of the most widely used localization techniques, alternative techniques for outdoor and indoor localization using cellular network and wireless local network signals are also possible BIB001 . Techniques involving both spectrum sensing and information coming from geolocation databases have also been proposed and tested . Ofcom, has performed a series of trials, as part of the TVWS pilot project, to test a number of aspects of white space technology, including the white space device and geolocation database interactions, the validity of the channel availability/powers calculations by the database and associated interference aspects on primary services BIB007 . Following the decision by US and UK to allow opportunistic use of TVWS several standards were developed to facilitate its practical implementation. The first international standard to be developed for TVWS cognitive devices was ECMA-392, introduced in 2009. But with the introduction of the idea of WiFi communications in TVWS, a task group to develop a new IEEE 802.11af standard was developed in the same year. The IEEE 802.11af standard was approved in February 2014. In July 2010, the IEEE 802.16h standard was published for WiMAX. Following this, in July 2011, a new standard for cognitive radios that will be used in rural areas and enable spectrum sharing, IEEE 802.22, was introduced . 802.22 wireless access technology is envisioned for rural communications because the coverage is large up to 100 km and there is no need for fixed spectrum which makes it very profitable for operators. Because cognitive radios might be used for different purposes and may operate with different technologies, coexistence and self-coexistence problems arise. We use the term coexistence to describe the situation that arises when primary users and cognitive radio devices (secondary users) exists/operate in the same time and location, whereas self-coexistence describes the cohabitation, in time and space, in the same frequency, of several cognitive radio users or networks which can be of the same or different type. Challenges surface because the different networks tend to selfishly occupy the spectrum to satisfy their own needs without any regards for other network cohabiting in the same spectrum, and the problem is further exacerbated when the various systems using the same spectrum have different operating parameters (transmit power, bandwidth, MAC/PHY layer, etc.).

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> Seventy-five percent of India's population is in rural villages, yet almost 90 percent of the country's phones are in urban sites. The authors propose a fixed cellular radio system, combined with the existing mobile network, as a cost effective way to extend telecommunications services to India's rural areas. > <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> The wireless LAN technology known as WiFi (or wireless fidelity) which is the standard developed by the IEEE 802 Committee is now introduced by internet service providers or by the network operators in the metropolitan hectic areas of developed countries at so-called hotspots such as airports, hotels, cafes, railway stations, etc and facilitates to provide easy and low-cost, high-speed internet connections for the PC, PDA, mobile IP phone users. Implementation of these technologies for various applications including e-health and tele-education, etc, for rural telecommunication development in Japan and by ITU will be described in this paper. The global survey and analysis on the telecommunications environment and the needs of rural communities of the developing countries conducted by ITU will be briefly introduced. The future perspective for the development of rural communications including the applications of e-health care will also be discussed. <s> BIB002 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> DakNet provides extraordinarily low-cost digital communication, letting remote villages leapfrog past the expense of traditional connectivity solutions and begin development of a full-coverage broadband wireless infrastructure. What is the basis for a progressive, market-driven migration from e-governance to universal broadband connectivity that local users will pay for? DakNet, an ad hoc network that uses wireless technology to provide asynchronous digital connectivity, is evidence that the marriage of wireless and asynchronous service may indeed be the beginning of a road to universal broadband connectivity. DakNet has been successfully deployed in remote parts of both India and Cambodia at a cost two orders of magnitude less than that of traditional landline solutions. <s> BIB003 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> Employing wireless technologies to provide connectivity for rural areas is an active topic in the academic and industrial communities. In this article we begin by discussing the challenges of rural communications and reviewing existing wireless technologies that have been proposed or implemented for this market. We then focus on an emerging technology, cognitive radio, that promises to be a viable solution for rural communications. The most notable candidate for rural cognitive radio technology is the IEEE 802.22 standard that is currently being developed and is based on time division duplexing, orthogonal frequency division multiple access, and opportunistic use of the VHF/UHF TV bands. We address two important issues that can affect the success of IEEE 802.22 technology in rural deployments, namely, to: 1) Provide suitable service models 2)Overcome the problem of long TDD turnaround time in large rural cells For the first issue, we introduce a service model that combines TV broadcasting and data services to facilitate service adoption. For the second issue, we propose an adaptive TDD approach that effectively eliminates the requirement for long TDD turn-around time and thus, increases the efficiency of large-coverage rural networks. <s> BIB004 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> Cognitive radio is being intensively researched as the enabling technology for license-exempt access to the so-called TV White Spaces (TVWS), large portions of spectrum in the UHF/VHF bands which become available on a geographical basis after digital switchover. Both in the US, and more recently, in the UK the regulators have given conditional endorsement to this new mode of access. This paper reviews the state-of-the-art in technology, regulation, and standardisation of cognitive access to TVWS. It examines the spectrum opportunity and commercial use cases associated with this form of secondary access. <s> BIB005 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> Cognitive radio is being intensively researched for opportunistic access to the so-called TV White Spaces (TVWS): large portions of the VHF/UHF TV bands which become available on a geographical basis after the digital switchover. Using accurate digital TV (DTV) coverage maps together with a database of DTV transmitters, we develop a methodology for identifying TVWS frequencies at any given location in the United Kingdom. We use our methodology to investigate variations in TVWS as a function of the location and transmit power of cognitive radios, and examine how constraints on adjacent channel interference imposed by regulators may affect the results. Our analysis provides a realistic view on the spectrum opportunity associated with cognitive devices, and presents the first quantitative study of the availability and frequency composition of TWVS outside the United States. <s> BIB006 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> As Digital Television Broadcasting spreads over the world, existing (and more) TV channels can be distributed in less spectrum in the spectrum traditionally allocated to TV broadcasting. This freed spectrum is also referred to as the "Digital Dividend" and its use has been debated around the world. In addition, there is also a debate about the potential use of the "white space" within the TV-bands. This is due to the sparse frequency planning with large interference margins, which is typical in wide area broadcasting. Various technical approaches using Opportunistic Spectrum Access (OSA) have been proposed for unlicensed "white space" access to the TV bands. Most of previous studies have focused on spectrum sensing, i.e. detecting "free channels", where secondary users, utilizing White Space Devices (WSD) could avoid causing harmful interference to the TV receivers. However, interference caused by WSD is not only limited to co-channel interference. In particular, in short-range scenarios, the adjacent channel interference is an equally severe problem. Assessing the feasibility of WSDs in short-range indoor scenarios, taking more interference mechanisms into account is the objective of this paper. An Indoor home scenario with Cable, Rooftop antenna and Set-top antenna reception of DVB-T, has been analyzed. The spectrum reuse opportunities for WSDs have been determined, using the number of channels where it is possible to transmit without causing harmful interference to DVB-T receivers as performance measure. Simulation results show that the number of available channels for indoor unlicensed white space transmission appears to be significant in most of the studied scenarios. <s> BIB007 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> Cognitive radio is being intensively researched as the enabling technology for secondary access to the so-called TV White Spaces (TVWS), large portions of spectrum in theUHF/VHF bands which become available on a geographical basis after digital switchover. Both in the US, and more recently, in the UK the regulators have given conditional endorsement to this new mode of access. This paper reviews the state-of-the-art in technology, regulation and standardization of cognitive access to TVWS. It examines the spectrum opportunity and commercial use cases associated with this form of secondary access. <s> BIB008 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> In order to improve utilization of TV spectrum, regulatory bodies around the world have been developing rules to allow operation by unlicensed users in these bands provided that interference to incumbent broadcasters is avoided. Thus, new services may opportunistically use temporarily unoccupied TV channels, known as television white space. This has motivated several standardization efforts such as IEEE 802.22, 802.11af, 802.19 TG1, and ECMA 392 to further cognitive networking. Specifically, multiple collocated secondary networks are expected to use TVWS, each with distinct requirements (bandwidth, transmission power, different system architectures, and device types) that must all comply with regulatory requirements to protect incumbents. Heterogeneous coexistence in the TVWS is thus expected to be an important research challenge. This article introduces the current regulatory scenario, emerging standards for cognitive wireless networks targeting the TVWS, and discusses possible coexistence scenarios and associated challenges. Furthermore, the article casts an eye on future considerations for these upcoming standards in support of spectrum sharing opportunities as a function of network architecture evolution. <s> BIB009 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> In next generation networks, voice, data, and multimedia services will be converged onto a single network platform with increasing complexity and heterogeneity of underlying wireless and optical networking systems. These services should be delivered in the most cost- and resource-efficient manner with ensured user satisfaction. To this end, service providers are now switching the focus from network Quality of Service (QoS) to user Quality of Experience (QoE), which describes the overall performance of a network from the user perspective. High network QoS can, in many cases, result in high QoE, but it cannot assure high QoE. Optimizing end-to-end QoE must consider other contributing factors of QoE such as the application-level QoS, the capability of terminal equipment and customer premises networks, and subjective user factors. This article discusses challenges and a possible solution for optimizing end-to-end QoE in Next Generation Networks. <s> BIB010 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Cognitive Radio (CR) Network <s> TV white space refers to TV channels that are not used by any licensed services at a particular location and at a particular time. To exploit this unused TVWS spectrum for improved spectrum efficiency, regulatory agencies have begun developing regulations to permit its use this TVWS by unlicensed wireless devices as long as they do not interfere with any licensed services. In the future many heterogeneous, and independently operated, wireless networks may utilize the TVWS. Coexistence between these networks is essential in order to provide a high level of QoS to end users. Consequently, the IEEE 802 LAN/MAN standards committee has approved the P802.19.1 standardization project to specify radio-technology-independent methods for coexistence among dissimilar or independently operated wireless devices and networks. In this article we provide a detailed overview of the regulatory status of TVWS in the United States and Europe, analyze the coexistence problem in TVWS, and summarize existing coexisting mechanisms to improve coexistence in TVWS. The main focus of the article is the IEEE P802.19.1 standardization project, including its requirements and system design, and the major technical challenges ahead. <s> BIB011

The cognitive radio network is composed of secondary devices that communicate among themselves; however the configuration and organization of the network will depend on the technology and standard applied. In general, cognitive devices for use in TVWS are divided into four groups: fixed devices, Mode I personal/portable devices, Mode II personal/portable devices and sensing only devices, as defined by FCC specifications and standards and summarized in Table 1 . Fixed devices can transmit up to 4W EIRP (Effective Isotropic Radiated Power). Due to the high transmission power level these devices are not allowed to operate on adjacent channels of the TV channels that are in use and they must have access to database and geolocation capability. BIB005 . The TVWS database is a central database, managed by reliable authority that contains information on all primary user's operation characteristics, such as: transmission power, allocated channels and usage patterns, location, etc. Secondary networks/users must send a query to this database to ask for available channels in their location. It can be noted that location is usually determined based on GPS connection, which may be available for certain types of secondary devices. Therefore, it is most likely that fixed devices will be used in rural areas where the conditions will change slowly, whereas portable devices will be more appropriate for use in metropolitan areas BIB009 . Sensing only devices are devices that independently sense the radio spectrum in order to detect primary users and avoid harmful interference with them. Their maximum transmit power is 50mW. They are able to sense digital TV, analog TV and wireless microphone transmitted signals at -114dBm. Sensing is performed periodically to determine the availability of a channel, and afterwards, when the channel is allocated, sensing is performed repeatedly over a longer period. Once any kind of signal is detected, within the spectrum they are operating in, these devices stop transmitting within 2s BIB011 . The cognitive radio devices (CRs) are allowed to operate in most of the channels except those that are reserved for public safety or commercial use. Related work shows that the number of available channels in indoor cases is also significant BIB006 BIB007 . It is envisioned that CR networks will be used for the following applications BIB008 : (i) Wide area broadband provision to rural areas (ii) Future home networks and smart grids (iii) Cellular communications (iv) Public Safety As mentioned earlier, CR technology is being viewed as an effective solution for the provision of broadband services in rural areas. Based on a report published by the United Nations, more than 3 billion people live in rural areas . Also in some developing countries such as China and India, around 70 percent of the population live in rural areas. Providing communication services to communities that live in these areas is an important factor towards the betterment of their social and educational development . However, implementation issues present a big challenge considering the high cost versus the low demand. Due to this, different operators are leaning towards low cost solutions. Compared to the cost for wired networks, wireless technologies are more cost-efficient, and several approaches have already been proposed BIB001 BIB002 BIB003 . So far none of these initial proposals has produced feasible solutions to offering services in these areas considering the low demand and high cost. The implementation of CR networks, emerged as an optimal solution which takes advantage of better spectrum usage while coexisting with primary users BIB004 . It is expected that CR will also find an application in future smart grid systems BIB010 .

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Coexistence Challenges for CR Networks in TVWS <s> Today's wireless networks are characterized by a fixed spectrum assignment policy. However, a large portion of the assigned spectrum is used sporadically and geographical variations in the utilization of assigned spectrum ranges from 15% to 85% with a high variance in time. The limited available spectrum and the inefficiency in the spectrum usage necessitate a new communication paradigm to exploit the existing wireless spectrum opportunistically. This new networking paradigm is referred to as NeXt Generation (xG) Networks as well as Dynamic Spectrum Access (DSA) and cognitive radio networks. The term xG networks is used throughout the paper. The novel functionalities and current research challenges of the xG networks are explained in detail. More specifically, a brief overview of the cognitive radio technology is provided and the xG network architecture is introduced. Moreover, the xG network functions such as spectrum management, spectrum mobility and spectrum sharing are explained in detail. The influence of these functions on the performance of the upper layer protocols such as routing and transport are investigated and open research issues in these areas are also outlined. Finally, the cross-layer design challenges in xG networks are discussed. <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Coexistence Challenges for CR Networks in TVWS <s> A Markov chain analysis for spectrum access in licensed bands for cognitive radios is presented and forced termination probability, blocking probability and traffic throughput are derived. In addition, a channel reservation scheme for cognitive radio spectrum handoff is proposed. This scheme allows the tradeoff between forced termination and blocking according to QoS requirements. Numerical results show that the proposed scheme can greatly reduce forced termination probability at a slight increase in blocking probability <s> BIB002 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Coexistence Challenges for CR Networks in TVWS <s> With the explosive growth of wireless multimedia applications over the wireless Internet in recent years, the demand for radio spectral resources has increased significantly. In order to meet the quality of service, delay, and large bandwidth requirements, various techniques such as source and channel coding, distributed streaming, multicast etc. have been considered. In this paper, we propose a technique for distributed multimedia transmission over the secondary user network, which makes use of opportunistic spectrum access with the help of cognitive radios. We use digital fountain codes to distribute the multimedia content over unused spectrum and also to compensate for the loss incurred due to primary user interference. Primary user traffic is modelled as a Poisson process. We develop the techniques to select appropriate channels and study the trade-offs between link reliability, spectral efficiency and coding overhead. Simulation results are presented for the secondary spectrum access model. <s> BIB003 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Coexistence Challenges for CR Networks in TVWS <s> The aim of this thesis is to research in the use of emerging TV white space communications, implementing a geo-location database system. For that, some research and theoretical studies related to cognitive radio and TV white space communications will be done first, focusing on current activities, standarization processes, commercial approaches and related projects. Once the background and the present TV white space communications status is analyzed, a geolocation database system will be designed and developed to prove the potential of this technology. The operation of the database system will be demonstrated through a web interface. In this way, an open and publicly accessible geo-location database system implementation and structure will be created (note that even if several database system creation initiatives are taking place, most of them are private). However, due to the lack of official regulatories, established standards, and actual transmission data (data from TV broadcasters, wireless microphones etc.), only an initial TV white space database system demo will be implemented to model the operation of the same. It will be possible to access and query this database system through a simple web interface for the Oslo area. After analyzing the results of the implementation and looking to other TV white space initiatives, some considerations for future work will be concluded. <s> BIB004 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Coexistence Challenges for CR Networks in TVWS <s> With the rapid deployment of new wireless devices and applications, the last decade has witnessed a growing demand for wireless radio spectrum. However, the fixed spectrum assignment policy becomes a bottleneck for more efficient spectrum utilization, under which a great portion of the licensed spectrum is severely under-utilized. The inefficient usage of the limited spectrum resources urges the spectrum regulatory bodies to review their policy and start to seek for innovative communication technology that can exploit the wireless spectrum in a more intelligent and flexible way. The concept of cognitive radio is proposed to address the issue of spectrum efficiency and has been receiving an increasing attention in recent years, since it equips wireless users the capability to optimally adapt their operating parameters according to the interactions with the surrounding radio environment. There have been many significant developments in the past few years on cognitive radios. This paper surveys recent advances in research related to cognitive radios. The fundamentals of cognitive radio technology, architecture of a cognitive radio network and its applications are first introduced. The existing works in spectrum sensing are reviewed, and important issues in dynamic spectrum allocation and sharing are investigated in detail. <s> BIB005 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Coexistence Challenges for CR Networks in TVWS <s> In order to improve utilization of TV spectrum, regulatory bodies around the world have been developing rules to allow operation by unlicensed users in these bands provided that interference to incumbent broadcasters is avoided. Thus, new services may opportunistically use temporarily unoccupied TV channels, known as television white space. This has motivated several standardization efforts such as IEEE 802.22, 802.11af, 802.19 TG1, and ECMA 392 to further cognitive networking. Specifically, multiple collocated secondary networks are expected to use TVWS, each with distinct requirements (bandwidth, transmission power, different system architectures, and device types) that must all comply with regulatory requirements to protect incumbents. Heterogeneous coexistence in the TVWS is thus expected to be an important research challenge. This article introduces the current regulatory scenario, emerging standards for cognitive wireless networks targeting the TVWS, and discusses possible coexistence scenarios and associated challenges. Furthermore, the article casts an eye on future considerations for these upcoming standards in support of spectrum sharing opportunities as a function of network architecture evolution. <s> BIB006 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Coexistence Challenges for CR Networks in TVWS <s> This paper concerns the analysis of adjacent channel interference of the 3GPP Long Term Evolution (LTE) E-UTRA (Evolved Universal Terrestrial Radio Access) mobile systems into Digital Video Broadcasting - Terrestrial (DVB-T) systems. The simulated performance of both systems allows us to define recommendations for minimizing the interference effects. The subjective quality of the received TV signal has been evaluated experimentally in terms of picture failure (PF). We also investigated the importance of the selection of suitable Spectral Emission Masks (SEMs) of the LTE downlink transmission. Results show that, by using the ECC 148 SEM, both the protection ratio and the minimum distance between LTE towers and DVB-T receivers can be significantly decreased. <s> BIB007 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Coexistence Challenges for CR Networks in TVWS <s> In this paper, we investigate the coexistence problem between the 802.22 and the 802.11af systems in the TV White Spaces (TVWS). We focus on the design of a co-channel coexistence scheme for the 802.22 customer-premises equipments (CPE) and the 802.11af systems. 802.22 and 802.11af are two typical standards envisioned to be widely adopted in the future. However, these two standards are heterogeneous in both power level and PHY/MAC design, making their coexistence challenging. To avoid mutual interference between the two systems, existing solutions have to allocate different channels for the two networks. Due to the city-wide coverage of the 802.22 base station (BS), the spectrum utilization is compromised with existing schemes. In this paper, we first identify the challenges to enable the co-channel coexistence of the 802.22 and the 802.11af systems and then propose a busy-tone based framework. We design a busy-tone for the 802.22 CPEs to exclude the hidden 802.11af terminals. We also show that it is possible for the 802.11af systems to identify the exposed 802.22 CPE transmitters and conduct successful transmissions under interference. We show through extensive simulations that the spectrum utilization can be increased with the proposed co-channel coexistence scheme. <s> BIB008 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Coexistence Challenges for CR Networks in TVWS <s> With the spectrum liberation obtained by the deployment of digital terrestrial television and the analog TV switch-off, new bands are being assigned to IMT LTE. In the first cellular deployments in the digital dividend at the 800 MHz band, problems emerged due to the interference cellular networks can cause to DTT signals. Possible solutions imply either an inefficient use of the spectrum (increasing the guard band and reducing the number of DTT channels) or a high cost (using anti-LTE filters for DTT receivers). The new spectrum allocated to mobile communications is the 700 MHz band, also known as the second digital dividend. In this new IMT band, the LTE uplink is placed in the lower part of the band. Hence, the ITU-R invited several studies to be performed and reported the results to WRC-15. In this article, we analyze the coexistence problem in the 700 MHz band and evaluate the interference of LTE signals to DTT services. Several coexistence scenarios have been considered, and laboratory tests have been performed to measure interference protection ratios. <s> BIB009 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Coexistence Challenges for CR Networks in TVWS <s> With the introduction of digital terrestrial television (DTT) and the analogue television switch-off, terrestrial broadcast spectrum in the UHF band is being released for mobile communications, in particular for fourth generation (4G) long term evolution (LTE) mobile services. This spectrum is known as digital dividend. An impending problem when deploying 4G LTE mobile networks in the digital dividend bands is that interferences may appear in the adjacent radio frequency channels used for DTT. In this paper, we analyze the adjacent coexistence of DTT and 4G LTE networks in the digital dividend bands at 700 MHz and 800 MHz. A generic framework is adopted such that results can be easily extrapolated to different scenarios and bands. Results are presented as a function of the guard band between technologies, for both LTE uplink and downlink adjacent to the DTT signals, and for fixed outdoor and portable indoor DTT reception. Also, the effect of using anti-LTE filters is studied. <s> BIB010

Because existing wireless networks are generally designed to work with fixed frequency allocation, coexistence challenges between wireless networks arise when switching to a cognitive radio environment. In addition, because the available spectrum changes rapidly and there are many different QoS requirements for different applications, CR networks have to handle many additional challenges: interference avoidance with primary users, optimal spectrum band selection for QoS guarantee, seamless communications regardless of the appearance of primary users BIB004 , to name a few. To tackle these challenges, a coexistence decision mechanism (CDM) of a CR network must have these four functionalities: spectrum sensing, spectrum decision, spectrum sharing strategy and spectrum mobility, described in detail in BIB005 BIB001 BIB002 BIB003 . The cycle of cognitive radio functionalities is shown in Figure 1 . To overcome the time delay introduced while performing this complete cycle, solutions such as spectrum prediction for spectrum sensing was proposed . Coexistence issues may arise between different services sharing adjacent portion of the spectrum, such as Digital Terrestrial Television (DTE) and cellular networks operating in the TVWS, as highlighted in BIB010 . In particular the potential interference caused by the LTE network to the DTT signal in the 700 MHz was studied in BIB009 . Both these papers conclude that the interference caused by the LTE network can be significant proposing the use of anti-LTE filters to improve the protection of DTT signals, and a case-by-case study of coexistence issues for DTT network planning. A similar study BIB007 , proposes the application of suitable spectral emission masks on the LTE downlink transmission to mitigate the problem. In particular, coexistence between IEEE 802.22 and 802.11af is challenging due to the differences in operating powers and sensitivity thresholds. The IEEE 802.22 system transmission power is 4W and sensitivity threshold -97 dBm whereas IEEE 802.11af has power transmission of 100 mW and sensitivity threshold -64 dBm . The main differences between the two different IEEE standards are shown in Table 2 . The challenges to enable coexistence arise mainly because of two main reasons: (i) the reception threshold of 802.11af is higher than that of 802.22 receivers resulting on misdetection of 802.22 transmitter from 802.11af transmitter (the hidden terminal problem), and (ii) the transmission power of 802.22 is higher than 802.11af so 802.11af operation can be easily blocked if it is in proximity to the 802.22 transmitter. In the latter case 802.11af will have very little opportunity to transmit BIB008 . Therefore to enable a fair coexistence between heterogeneous wireless networks in TVWS, a coexistence mechanism must be implemented, that addresses these three main challenges: spectrum sharing, interference mitigation and spectrum detection BIB006 , as further detailed in Table 3 .

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Spectrum Availability Detection. <s> There are new system implementation challenges involved in the design of cognitive radios, which have both the ability to sense the spectral environment and the flexibility to adapt transmission parameters to maximize system capacity while coexisting with legacy wireless networks. The critical design problem is the need to process multigigahertz wide bandwidth and reliably detect presence of primary users. This places severe requirements on sensitivity, linearity and dynamic range of the circuitry in the RF front-end. To improve radio sensitivity of the sensing function through processing gain we investigated three digital signal processing techniques: matched filtering, energy detection and cyclostationary feature detection. Our analysis shows that cyclostationary feature detection has advantages due to its ability to differentiate modulated signals, interference and noise in low signal to noise ratios. In addition, to further improve the sensing reliability, the advantage of a MAC protocol that exploits cooperation among many cognitive users is investigated. <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Spectrum Availability Detection. <s> In this paper, we investigate an optimization of threshold level with energy detection to improve the spectrum sensing performance. Determining threshold level to minimize spectrum sensing error both reduces collision probability with primary user and enhances usage level of vacant spectrum, resulting in improving total spectrum efficiency. However, when determining threshold level, spectrum sensing constraint should also be satisfied since it guarantees minimum required protection level of primary user and usage level of vacant spectrum. To minimize spectrum sensing error for given spectrum sensing constraint, we derive an optimal adaptive threshold level by utilizing the spectrum sensing error function and constraint which is given by inequality condition. Simulation results show that the proposed scheme provides better spectrum sensing performance compared to conventional schemes. <s> BIB002 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Spectrum Availability Detection. <s> The cognitive radio literature generally assumes that the functions required for non-cooperative secondary DSA are integrated into a single radio system. It need not be so. In this paper, we model cognitive radio functions as a value chain and explore the implications of different forms of organization of this value chain. We initially explore the consequences of separating the sensing function from other cognitive radio functions. <s> BIB003 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Spectrum Availability Detection. <s> With the increasing spectrum scarcity due to increase in the wireless devices, and limited availability of spectrum for licensed users only, the need for secondary access by unlicensed users is increasing. Cognitive radio turns out to be helping this situation because all that is needed is a technique that could efficiently detect the empty spaces and provide them to the secondary devices without causing any interference to the primary (licensed) users. Spectrum sensing is the foremost function of the cognitive radio which senses the environment for white spaces. Various techniques have been introduced in the spectrum sensing literature and these techniques are still under research. In this paper, we study one of the chiefly used techniques called energy detection spectrum sensing. It is known that when the signals travel in the wireless medium via various channels, they undergo several impairments caused by the different channels like additive white Gaussian noise and Rayleigh fading etc. Here, an attempt is made to assess the energy detection technique over these two wireless channels. <s> BIB004 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Spectrum Availability Detection. <s> The Internet of Things concept has revolutionized the way of using sensors and produced data. The interconnection of sensors to computing systems and to both storage infrastructures and processing facilities in a cloud fashion enables the paradigm of Sensing as a Service (S2aaS). In this paper, we propose a system architecture compliant with the S2aaS model, and detail it for a specific use case, the Spectrum Sensing as a Service (S3aaS). We illustrate the system components, including heterogeneous spectrum sensors, a distributed messaging system, a scheduler, a scalable database with a relevant SQL interface tool, and a user interface tool used to interact with the S3aaS system. Finally, we show the implementation of a proof-of-concept prototype used for assessing its effectiveness in operation. <s> BIB005

Spectrum availability detection or spectrum sensing is the process during which secondary networks while sensing the spectrum must identify available TV channels that can be used without causing harmful interference to primary users. Sensing can be performed in three domains: time, frequency and space. Sensing is used also to identify the types of signals that are occupying the spectrum by determining their: carrier frequency, modulation type, bandwidth etc. Spectrum sensing can be performed using several techniques: energy detection, matched filtering, cyclostationary feature-based sensing, radio-identification based sensing and waveform based sensing. However, due to its simple implementation, the energy detection technique is the one that is most commonly deployed. The signal detection with this technique is based on comparing the sensed signal with a defined SINR threshold BIB004 . The detection threshold is an important parameter that needs to be optimized to minimize the errors in detection, and adaptive techniques on setting this threshold have been investigated in BIB002 . Other techniques require a priori knowledge of regarding primary user transmitted signal, which is not always easy to get, and the implementation at the receiver end is a challenge. For example matched filtering technique is only appropriate to be used in the case that the secondary user knows all the information about the primary user transmitted signal. The computational time is very low but on the other hand the power consumption is high BIB001 . Moreover, the spectrum detection phase does not need to be performed in isolation. Indeed with the increasing number of interconnected sensors in the framework of the Internet of Things paradigm, some authors propose to take advantage of the readily available infrastructure to perform BIB003 . A cloudcomputing platform, which enables precisely this, and allows the Sensing-as-a-Service concept to be used in the context of spectrum availability detection is proposed in BIB005 . While detection of the primary users is crucial to enable self-coexistence, secondary networks must also be able to detect other secondary cognitive networks that operate in the same or neighboring channels. Failing to do so will lead to a decrease in network performance due to increased interference. To overcome this issue, one approach is to enable cooperation among secondary networks in order for them to be able to coordinate and synchronize spectrum usage.

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> In the unlicensed spectrum, any device is free to transmit without a government license that implies exclusive access. Such spectrum has significant benefits, but serious challenges must first be overcome. Foremost is the risk of drastic performance degradation and inefficient spectrum utilization, due to a lack of incentive to conserve shared spectrum. Previous work has shown this problem to be a real possibility. This paper demonstrates that the solution lies in proper regulation of access to unlicensed spectrum and its usage. We present a choice of potential solutions that vary in the degree to which they solve the problem, and in their impact on performance. <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> Under the current system of spectrum allocation, rigid partitioning has resulted in vastly underutilized spectrum bands, even in urban locales. Cognitive radios have been proposed as a way to reuse this underutilized spectrum in an opportunistic manner. To achieve this reuse while guaranteeing non-interference with the primary user, cognitive radios must detect very weak primary signals. However, uncertainties in the noise+interference impose a limit on how low of a primary signal can be robustly detected. ::: In this paper, we show that the presence/absence of possible interference from other opportunistic spectrum users represents a major component of the uncertainty limiting the ability of a cognitive radio network to reclaim a band for its use. Coordination among nearby cognitive radios is required to control this uncertainty. While this coordination can take a form similar to a traditional MAC protocol for data communication, its role is different in that it aims to reduce the uncertainty about interference rather than just reducing the interference itself. ::: We show how the degree of coordination required can vary based on the coherence times and bandwidths involved, as well as the complexity of the detectors themselves. The simplest sensing strategies end up needing the most coordination, while more complex strategies involving adaptive coherent processing and interference prediction can be individually more robust and thereby reduce the need for coordination across different networks. We also show the existence of a coordination radius wall which limits secondary user densities that can be supported irrespective of coordination involved. Furthermore, local cooperation among cognitive radios for collective decision making can reduce the fading margins we need to budget for. This cooperation benefits from increased secondary user densities and hence induces a minima in the power-coordination tradeoff. <s> BIB002 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> One of the reasons for the limitation of bandwidth in current generation wireless networks is the spectrum policy of the Federal Communications Commission (FCC). But, with the spectrum policy reform, open spectrum wireless networks, and spectrum agile radios are set to drive next general wireless networks. In this paper, we investigate continuous-time Markov models for dynamic spectrum access in open spectrum wireless networks. Both queueing and no queueing cases are considered. Analytical results are derived based on the Markov models. A random access protocol is proposed that is shown to achieve airtime fairness. A distributed version of this protocol that uses only local information is also proposed based on homo egualis anthropological model. Inequality aversion by the radio systems to achieve fairness is captured by this model. These protocols are then extended to spectrum agile radios. Extensive simulation results are presented to compare the performances of fixed versus agile radios. <s> BIB003 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> The interference temperature model was proposed by the FCC in 2003 as a way to dynamically manage and allocate spectrum resources. It would allow unlicensed radios to sense their current RF environment and transmit in licensed bands, provided their transmission does not raise the interference temperature for that frequency band over the interference temperature limit. It never received much interest because nobody was sure exactly how to use it or how if it would work. This research focuses on a mathematical analysis of the interference temperature model in an effort to examine the relationships between the capacity achieved by the unlicensed network and the interference caused to the licensed network. We develop a model for the RF environment and determine probability distributions governing interference temperature as a function of various elements in the model. We then determine bounds on the amount of interference caused by implementing such a system. We examine model environments for a wireless WAN and a wireless LAN, each coexisting with a licensed carrier. For each, we quantify both the impact on the licensed signal and also the capacity achieved by our underlay network. By substituting numeric values for RF environments in which the interference temperature model might be applied, we show that achievable capacity is very small, while the impact the licensee can be very large. Based on this, we propose alternate usages for interference temperature and ways to boost capacity. <s> BIB004 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> Cognitive radio has been recently proposed as a promising technology to improve the spectrum utilization efficiency by intelligently sensing and accessing some vacant bands of licensed users. In this paper, we consider the coexistence between a cognitive radio and a licensed user in order to enhance the spectrum efficiency. We develop an approach to allow the cognitive radio to operate in the presence of the licensed user. In order to minimize the interference to the licensed user, the transmit power of the cognitive radio is controlled by using the side information of spectrum sensing. Numerical results will show that the quality of service for the licensed user can be guaranteed in the presence of the cognitive radio by the proposed approach. <s> BIB005 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> In cognitive radio networks, cognitive (unlicensed) users need to continuously monitor spectrum for the presence of primary (licensed) users. In this paper, we illustrate the benefits of cooperation in cognitive radio. We show that by allowing the cognitive users operating in the same band to cooperate we can reduce the detection time and thus increase the overall agility. We first consider a two-user cognitive radio network and show how the inherent asymmetry in the network can be exploited to increase the agility. We show that our cooperation scheme increases the agility of the cognitive users by as much as 35%. We then extend our cooperation scheme to multicarrier networks with two users per carrier and analyze asymptotic agility gain. In Part II of our paper [1], we investigate multiuser single carrier networks. We develop a decentralized cooperation protocol which ensures agility gain for arbitrarily large cognitive network population. <s> BIB006 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> In cognitive radio networks, the secondary users can use the frequency bands when the primary users are not present. Hence secondary users need to constantly sense the presence of the primary users. When the primary users are detected, the secondary users have to vacate that channel. This makes the probability of detection important to the primary users as it indicates their protection level from secondary users. When the secondary users detect the presence of a primary user which is in fact not there, it is referred to as false alarm. The probability of false alarm is important to the secondary users as it determines their usage of an unoccupied channel. Depending on whose interest is of priority, either a targeted probability of detection or false alarm shall be set. After setting one of the probabilities, the other can be optimized through cooperative sensing. In this paper, we show that cooperating all secondary users in the network does not necessary achieve the optimum performance, but instead, it is achieved by cooperating a certain number of users with the highest primary user's signal to noise ratio. Computer simulations have shown that the Pd can increase from 92.03% to 99.88% and Pf can decrease from 6.02% to 0.06% in a network with 200 users. <s> BIB007 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> Cooperative spectrum sensing has been shown to greatly improve the sensing performance in cognitive radio networks. However, if the cognitive users belong to different service providers, they tend to contribute less in sensing in order to achieve a higher throughput. In this paper, we propose an evolutionary game framework to study the interactions between selfish users in cooperative sensing. We derive the behavior dynamics and the stationary strategy of the secondary users, and further propose a distributed learning algorithm that helps the secondary users approach the Nash equilibrium with only local payoff observation. Simulation results show that the average throughput achieved in the cooperative sensing game with more than two secondary users is higher than that when the secondary users sense the primary user individually without cooperation. <s> BIB008 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> A critical problem in open-spectrum communications is fairness with respect to the coexistence of heterogeneous systems with different resource units and traffic models. In addition, the sensing performances of different systems can also lead to unfair resource utilization between systems. To address this problem, we derive a continuous-time Markov chain model to show the effect of sensing performance on system coexistence. The analysis derived from this model is then used as the basis for a sensing threshold control (STC) scheme to achieve fairness. The proposed STC determines the sensing threshold for each system as a way of balancing resource utilization among systems, while guaranteeing target detection probability. Numerical results on the amount of resource utilization by each system demonstrate that the proposed STC achieves a full degree of fairness. <s> BIB009 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> In this paper, a general framework for performance evaluation of cooperative spectrum sensing methods over realistic propagation environments is proposed. In particular, the framework accounts for correlated Log-Normal shadowing in both sensing and reporting channels, and yields simple and easy-to-use formulas for computing the Detection Probability of a distributed network of secondary users using Amplify and Forward (AF) relying for data reporting to the fusion center. Numerical results are also shown to substantiate the accuracy of the proposed framework. <s> BIB010 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> We consider energy detection based spectrum sensing for opportunistic SU (Secondary User) transmissions in cognitive radio networks. Due to the time-varying nature of wireless fading channels and PU (Primary User) activities, the instantaneous SINR (Signal to Interference plus Noise Ratio) at the SU receiver changes from slot to slot in a time-slotted system. Unlike the conventional energy detector which uses a fixed value of energy threshold to detect the PU's occurrence, we let the SU transmitter dynamically adjust the threshold according to the instantaneous SINR. Under the constraint of limiting the average interference to the PU within a target level, the objective is to maximize the SU's average transmission rate and throughput. Our task is to determine a proper policy function for threshold control, which formulates the value of the threshold as a function of the SINR to achieve the above objective. In particular, we consider a linear policy function, which allows a higher threshold and thus more aggressive SU transmissions under a larger SINR. Simulation results show that the SU's average transmission rate can be significantly improved using the optimized policy function. <s> BIB011 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Interference Mitigation and Spectrum Sharing. <s> This work focus on a coexistence study between wireless microphone systems and secondary users of the TV White Spaces, using a Monte-Carlo methodology. Exclusion areas around wireless microphone receivers, for co-channel and adjacent channel interference, are computed, considering indoor and outdoor scenarios. Using this methodology, impact and tendencies of several parameters over the probability of interference are analyzed, like spectral channel spacing, separation distance and propagation scenario. As an example, for outdoor scenarios, the spectral spacing between primary system and secondary users, ranging from 0 MHz (co-channel operation) to 16 MHz (2 DVB-T channels) results in a protection distance of 13.9 km and 2.2 km, respectively. <s> BIB012

Interference mitigation is a very challenging issue especially in areas where availability of channels is limited or where there is overlapping between coverage areas of different networks. This is further accentuated considering the good propagation characteristics of TVWS signals. In environments where heterogeneous networks coexist in TVWS, there are two types of interference that need to be addressed: (i) Interference to and from primary users (ii) Interference among secondary devices or networks To ensure protection of primary users and measure the interference level, FCC Spectrum Policy Task Force has proposed a new metric named interference temperature . Interference temperature is the level of RF power measured in receiving antenna per unit bandwidth . ( , ), is the interference power (in Watts) for frequency f and bandwidth B (in Hz), while k = 1.38 23 Joules per degree Kelvin, is the Boltzmann constant. For a specific location and frequency band, FCC has also established the interference temperature limit, which should not be exceeded by secondary users when allowed to operate simultaneously with the primary user BIB004 . The configuration of the interference temperature limit is further discussed in . Interference from primary users to secondary ones, on the other hand, results from the high transmission power of primary users, e.g., TV stations. In addition to causing interference that will invariably degrade the performance of secondary users, it also may hinder secondary users from detecting the location of primary receivers. To tackle primary/secondary interference there are two types of interference mitigation techniques: interference avoidance and interference control. With interference avoidance, primary and secondary users are not allowed to use the same channel in the same time or the same frequency, and in order to coexist they must detect spectrum gaps and then employ time or frequency separation, i.e., TDMA or FDMA. Using interference control, primary and secondary users can coexist in the same time or frequency if they follow specific coexisting requirements, such as set limits of allowed level of interference, which will guarantee QoS (Quality of Service) for both types of users. While the interference to primary user has been widely investigated, the interference to the secondary user from the primary ones as well as the aggregated interference to secondary users among themselves has not gained as much attention. In most cases the secondary users are assumed to be idle or their degradation of performance is not accounted for. Interference among secondary devices becomes a challenging issue as the number of secondary users/networks that will try to access the spectrum opportunistically increases. Such interference, may also affect primary signal detection as shown in BIB002 . The problem is worsened in areas with limited spectrum availability where many devices might choose the same channel or they will have to work on adjacent or cochannels. It was shown in BIB012 that cochannel interference is avoided by increasing the distance between primary and secondary users whereas adjacent channel interference is mitigated by avoiding the operating frequency between devices by at least three adjacent channels. To enable self-coexistence among secondary networks/devices, several parameters can be adjusted: power control due to the different transmits power levels from different devices, SINR (Signal to Noise Ratio) to estimate PER (Packet error rate), bandwidth and adaptive receiver threshold BIB011 . Self-coexistence is also ensured through spectrum sharing and management among different wireless technologies. Because they are generally expected to have different communications characteristics, this poses an important challenge for cognitive radio networks in TVWS. Based on access priorities, spectrum sharing among wireless heterogeneous systems is classified in two groups: open spectrum sharing and hierarchical spectrum sharing. With open spectrum sharing every system, both primary and secondary have the same priority for accessing the spectrum BIB003 BIB009 . Since in this type of spectrum sharing heterogeneous systems coexist without centralized coordination, spectrum access etiquette is proposed to mitigate the 6 Wireless Communications and Mobile Computing interference and give fairness among users BIB001 . By contrast hierarchical spectrum sharing is when primary users always have priority for spectrum access, while secondary users need to make sure that the interference caused to primary users is not harmful before accessing the spectrum. Based on the impact of interference, hierarchical spectrum sharing is divided into two groups: underlay and overlay spectrum sharing . Underlay spectrum sharing is when the interference caused by a secondary user to a primary receiver is below a predefined threshold. Since the interference in this case is not harmful, the secondary user will be allowed to operate even if the primary user is active. To make this possible, the secondary user must have the channel gain information between its transmitter and the primary receiver . Different interference measurement schemes have been proposed in BIB002 BIB005 . On the other hand, in overlay spectrum sharing, a secondary user may transmit only if the primary user is not active at that time, which is referred to as the idle period . To detect this idle period, the secondary user needs to sense the spectrum. Sensing techniques are discussed later in the paper. Based on their ability and willingness to collaborate or not, there are two possible ways for different networks to access the spectrum. There are schemes for coexistence that are based on cooperative or noncooperative method . Cooperative method means that there has to be cooperation and communication between devices or networks that are sharing the spectrum and are within each other's' interference range. Cooperative methods are normally based on the ability to exchange information between networks of similar or different types. This method overcomes the hidden node problem as all the networks are aware of each other's' geographical positions. Using relays to pass the information among cognitive users that operate in the same band by using amplify and forward protocol was introduced as an idea in BIB006 . For this method there are different mechanisms that can be used, such as: TDMA (Time-Division Multiple Access), FDMA (Frequency-Division Multiple Access) and CDMA (Code-Division Multiple Access). However, considering that spectrum might be shared between heterogeneous networks that have different operational characteristics and requirements, such as: frame rate, guard bands, power allocation, etc., there are many challenges on implementing these techniques. Because of this, adopting a cooperative method for all secondary users may not be very useful as shown in BIB007 . The performance of cooperative spectrum sharing method in a more realistic propagation environment is investigated in BIB010 . Another major drawback in cooperative sensing method is the large amount of information that needs to be exchanged between secondary users inducing high overhead. To deal with the problem of overhead, the GUESS protocol was introduced in . Innoncooperative methods, different networks will make the decisions based on their own observations BIB008 . Different strategies are used for these methods such as: DFS (Dynamic Frequency Selection), DCS (Dynamic Channel Selection), power control, listen before talk, Energy Detection Threshold, etc. Even though this strategy is cheaper and easier to implement, it does not always give the best network performance in terms of throughput and fairness among networks and users.

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Self-Coexistence Decision-Making Mechanisms for CR Networks in TVWS <s> We address the problem of coexistence among wireless networks in TV white space. We present a standard independent framework to enable exchange of information relevant for coexistence based on two mechanisms: centralized and distributed. Both mechanisms introduce the use of multiradio cluster-head equipment (CHE) as a physical entity that acquires relevant information, identifies coexistence opportunities, and implements autonomous coexistence decisions. The major conceptual difference between them lies in the fact that the centralized mechanism utilizes coexistence database(s) as a repository for coexistence related information, where CHEs need to access before making coexistence decisions. On the other hand, the distributed mechanism utilizes a broadcast channel to distribute beacons and directly convey coexistence information between CHEs. Furthermore, we give a concise overview of the current activities in international standardization bodies toward the realization of communications in TVWS along with measures taken to provide coexistence between secondary cognitive networks. <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Self-Coexistence Decision-Making Mechanisms for CR Networks in TVWS <s> With the development of dynamic spectrum access technologies, such as cognitive radio, the secondary use of underutilized TV broadcast spectrum has come a step closer to reality. Recently, a number of wireless standards that incorporate CR technology have been finalized or are being developed to standardize systems that will coexist in the same TV white spaces. In these wireless standards, the widely studied problem of primary-secondary network coexistence has been addressed by the use of incumbent geolocation databases augmented with spectrum sensing techniques. However, the challenging problem of secondary-secondary coexistence?in particular, heterogeneous secondary coexistence- has garnered much less attention in the standards and related literature. The coexistence of heterogeneous secondary networks poses challenging problems due to a number of factors, including the disparity of PHY/MAC strategies of the coexisting systems. In this article, we discuss the mechanisms that have been proposed for heterogeneous coexistence, and propose a taxonomy of those mechanisms targeting TVWSs. Through this taxonomy, our aim is to offer a clear picture of the heterogeneous coexistence issues and related technical challenges, and shed light on the possible solution space. <s> BIB002

Without the use of coexistence mechanisms, the utilization of TVWS spectrum will be significantly reduced. It was shown in BIB001 that without the use of coexistence mechanisms, 92% of available spectrum is overlapped by neighboring networks. Based on the proposed architecture BIB002 , the coexistence mechanisms are classified into three groups: centralized, coordinated and autonomous mechanisms. The difference among these coexistence mechanisms relies on where the coexistence decision is made. (1) Centralized mechanisms -in order to mitigate the interference, these mechanisms use a database in which all coexistence information is collected and stored centrally. Then to pass the information to users, internetwork coordination channels are used BIB001 . However this solution is costly and also ineffective when there are many coexisting devices or even networks that do not want to be part of a centralized control system. (2) Distributed mechanisms -an internetwork coordination channel is proposed so there is no need for central coexistence infrastructure. All the decisions regarding interference mitigation are made individually by each network or device and then the information is passed to others through control channels. This solution also incurs communication overhead, and depends on the willingness of the networks to exchange information. Furthermore, it relies on the existence of a common control channel and assumes that all coexisting networks use the same access technology in order to be able to decode each other's messages (3) Autonomous mechanisms -there is no internetwork coordination channel or central infrastructure available. All the decisions for channel selection and interference mitigation are done only by individual observations. Possible techniques used for this case are: dynamic frequency/channel allocation technique and listen before talk. Even though these type of mechanisms are easy and cheap to implement they do not give a good network performance. Because each system aims at blindly maximizing their own performance, the internetwork interference severely degrades the overall network performance. The different coexistence mechanisms are presented in the Figure 2 . with only a handful of autonomous approaches available. In the following subsections, we start by introducing the IEEE 802.19.1 standards, and then we list and compare some of the CDM solutions proposed in the literature.

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Signal-Based Schemes Tackling the Hidden Terminal Problem. <s> In this paper, we investigate the coexistence problem between the 802.22 and the 802.11af systems in the TV White Spaces (TVWS). We focus on the design of a co-channel coexistence scheme for the 802.22 customer-premises equipments (CPE) and the 802.11af systems. 802.22 and 802.11af are two typical standards envisioned to be widely adopted in the future. However, these two standards are heterogeneous in both power level and PHY/MAC design, making their coexistence challenging. To avoid mutual interference between the two systems, existing solutions have to allocate different channels for the two networks. Due to the city-wide coverage of the 802.22 base station (BS), the spectrum utilization is compromised with existing schemes. In this paper, we first identify the challenges to enable the co-channel coexistence of the 802.22 and the 802.11af systems and then propose a busy-tone based framework. We design a busy-tone for the 802.22 CPEs to exclude the hidden 802.11af terminals. We also show that it is possible for the 802.11af systems to identify the exposed 802.22 CPE transmitters and conduct successful transmissions under interference. We show through extensive simulations that the spectrum utilization can be increased with the proposed co-channel coexistence scheme. <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Signal-Based Schemes Tackling the Hidden Terminal Problem. <s> Cognitive radio (CR) technologies have led to several wireless standards (e.g., IEEE 802.11af and IEEE 802.22) that enable secondary networks to access the TV white-space (TVWS) spectrum. Different unlicensed wireless technologies with different PHY/MAC designs are expected to coexist in the same TVWS spectrum-we refer to such a situation as heterogeneous coexistence. The heterogeneity of the PHY/MAC designs of coexisting CR networks can potentially exacerbate the hidden terminal problem. This problem cannot be addressed by the conventional handshaking/coordination mechanism between two homogeneous networks employing the same radio access technology. In this paper, we present a coexistence protocol, called Spectrum Sharing for Heterogeneous Coexistence (SHARE), that mitigates the hidden terminal problem for the coexistence between two types of networks: one that employs a time-division-multiplexing-based MAC protocol and one that employs a carrier-sense-multiple-access-based MAC protocol. Specifically, SHARE utilizes beacon transmissions and dynamic quiet periods to avoid packet collisions caused by the hidden terminals. Our analytical and simulation results show that SHARE reduces the number of packet collisions and guarantees weighted fairness in partitioning the spectrum among the coexisting secondary networks. <s> BIB002

A partially distributed scheme for spectrum sharing in TVWS, using beacon signals, is proposed in BIB002 . The work focuses specifically at the coexistence problem between TDM and CSMA MAC networks. As the authors underline, the fact that the two networks use different MAC protocols, poses serious challenges for spectrum sharing. The solution proposed, titled SHARE, specifically targets the problem of hidden terminals, which is particularly apparent when heterogeneous networks cohabit the same spectrum space. There are two types of collisions that can occur due to the hidden terminal problem: collisions at TDM receivers caused by hidden CSMA transmitters and vice versa. To mitigate the first group of collisions, the algorithm utilizes beacon signals to prevent CSMA transmitters to access the shared channel. To mitigate the other group of collisions, a dynamic quiet time period is proposed for the TDM transmitters, to reduce the probability of collisions and ensure long-term fairness in spectrum sharing among coexisting networks. The authors assume the presence of a 802.19.1 controller that manages the coexistence for the TDM based secondary networks, which are at all times registered with the 802.19.1 system and are completely synchronized with each other. A similar autonomous scheme is proposed in BIB001 , for enabling coexistence between IEEE 802.11af and 802.22 networks. The basic idea is to use the sensing antenna available at the 802.22 receiver (which normally remains unused during reception period), to send out a busy tone in order to protect its communications from hidden 802.11af terminals. The busy tone, a constant signal transmitted at the same power level as an 802.11af signal, is transmitted by the 802.22 receiver, while it simultaneously receives data from the 802.22 transmitter. The scheme's goal is to protect the communications within 802.22 network, but it does not address the reverse problem or the fairness achieved during channel access. Furthermore, the authors assume that all 802.22 devices, both the base stations and the mobile users, are equipped with two antennas, one of which is used exclusively for sensing. The problem of continuous primary user is largely ignored in both approaches, and the authors in BIB002 explicitly assume that the secondary networks obtain the list of available channels from a TVWS database via 802.19.1 air interface. Therefore, while it is indeed a partially autonomous algorithm, its performance relies heavily on centralized exchange of information. On the other hand, due to the asymmetric transmit powers; neither scheme is able to ensure fairness for the low-power 802.11 networks.

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Distributed and Decentralized Approaches for SelfCoexistence of CR Networks. <s> The depletion of usable radio frequency spectrum has stimulated increasing interest in dynamic spectrum access technologies, such as cognitive radio (CR). In a scenario where multiple co-located CR networks operate in the same swath of white-space (or unlicensed) spectrum with little or no direct coordination, co-channel self-coexistence is a challenging problem. In this paper, we focus on the problem of spectrum sharing among coexisting CR networks that employ orthogonal frequency division multiple access (OFDMA) in their uplink and do not rely on inter-network coordination. An uplink soft frequency reuse (USFR) technique is proposed to enable globally power-efficient and locally fair spectrum sharing. We frame the self-coexistence problem as a non-cooperative game. In each network cell, uplink resource allocation (URA) problem is decoupled into two subproblems: subchannel allocation (SCA) and transmit power control (TPC). We provide a unique optimal solution to the TPC subproblem, while presenting a low-complexity heuristic for the SCA subproblem. After integrating the SCA and TPC games as the URA game, we design a heuristic algorithm that achieves the Nash equilibrium in a distributed manner. In both multi-operator and single-operator coexistence scenarios, our simulation results show that USFR significantly improves self-coexistence in spectrum utilization, power consumption, and intra-cell fairness. <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Distributed and Decentralized Approaches for SelfCoexistence of CR Networks. <s> Very recently, regulatory bodies worldwide have approved dynamic access of unlicensed networks to the TV white space (TVWS) spectrum. Hence, in the near future, multiple heterogeneous and independently operated unlicensed networks will coexist within the same geographical area over shared TVWS. Although heterogeneity and coexistence are not unique to TVWS scenarios, their distinctive characteristics pose new and challenging issues. In this paper, the problem of the coexistence interference among multiple heterogeneous and independently operated secondary networks (SNs) in the absence of secondary cooperation is addressed. Specifically, the optimal coexistence strategy, which adaptively and autonomously selects the channel maximizing the expected throughput in the presence of coexistence interference, is designed. More in detail, at first, an analytical framework is developed to model the channel selection process for an arbitrary SN as a decision process. Then, the problem of the optimal channel selection, i.e., the channel maximizing the expected throughput, is proved to be computationally prohibitive (NP-hard). Finally, under the reasonable assumption of identically distributed interference on the available channels, the optimal channel selection problem is proved not to be NP-hard, and a computationally efficient (polynomial-time) algorithm for finding the optimal strategy is designed. Numerical simulations validate the theoretical analysis. <s> BIB002 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Distributed and Decentralized Approaches for SelfCoexistence of CR Networks. <s> IEEE This paper focuses on coexistence and self- coexistence challenges between secondary heterogeneous wireless networks/users sharing TV Whitespace spectrum. The coexistence problems arise from having several primary and secondary networks of different technologies cohabiting the same licensed spectrum simultaneously. The self- coexistence problems arise from many secondary systems /users coexisting at the same place while using identical or different technologies. In particular, fair distribution of available spectrum becomes a serious issue. In this work we use a game theoretic approach to model the self-coexistence problem as a competitive game between secondary networks. We show that our game belongs to the class of congestion-averse games which are known to posses pure Nash Equilibria. This leads us to a decentralized approach for spectrum sharing among systems with different PHY/MAC characteristics. We show that our proposal outperforms other centralized algorithms in terms of user fairness and per-user theoretical data rates. <s> BIB003

A game theoretic approach for solving the coexistence problem between cognitive radio networks sharing the same spectrum in the uplink is proposed by Gao et. al. in BIB001 . The problem is formulated as an uplink channel allocation problem, which is further subdivided into two subproblems: the subchannel allocation problem and the transmit power allocation problem. The cognitive radio networks, which in the worst case scenario are controlled by different operators, participate in a noncooperative game in which each CR network independently selects the channels it will use in a way that will maximize their own utilities. The game is played in two levels, where players' solve the subchannel allocation game and then in the second level solve the transmission power problem. The authors note, that the second level game has a Nash equilibrium, which can be reached using algorithms such as iterative water filling. The subchannel allocation game, on the other hand, does not possess the properties which guarantee a Nash equilibrium. The authors propose a practical heuristic algorithm, which does not reach the global optimum, but is more efficient as it does not require global knowledge about all the cells operating in the same space. However, the authors address the coexistence problem only in the uplink and on a single channel basis, assuming all other channels have the same characteristics. Furthermore, they do not consider the presence of heterogeneous networks but rather assume that all secondary networks are of the same type, but belonging to different operators. Therefore, issues arising due to differences in MAC/PHY layers are not addressed. An interference avoidance strategy is proposed in BIB002 which aims to adaptively and autonomously enable the CR networks select the channels so as to maximize the throughput in presence of coexistence interference. The coexistence problem is formulated as an optimal sensing sequence and optimal stopping rule optimization problem, with the objective of maximizing the expected reward, i.e., average throughput achievable by the secondary user in a given time-slot. The algorithm is attractive because it features no cooperation overhead among the various networks, i.e., each network independently selects the TVWS channels to use. However, some of the assumptions are too simplistic, such as the hypothesis of identically and independently distributed coexistence interference levels. Furthermore, the authors compare the performance of the algorithm only to a simple sense-before-talk algorithm in terms of expected average throughput, while the complexity of the algorithm is compared to an exhaustive search solution, which is known to have excessive computational times, especially when considering higher number of available channels. In BIB003 the authors propose a decentralized algorithm to address the problem of self-coexistence in TVWS, between secondary networks of three different types, IEEE 802.22, IEEE 802.11af and IEEE.802.15. They consider the usage of independent mechanisms where there is no central manager for decision-making, no database for information queries and storage and no common physical communication channel between the networks for information exchange. The selfcoexistence and interference mitigation are ensured only based on the individual observations of the secondary users, which means that there is no need to synchronize and coordinate between networks to reach a fair solution. The SCDM algorithm is based on congestion-averse games (CAG) for self-coexistence decision-making in TVWS and addresses the challenges of self-coexistence in terms of fairness and efficiency of resource allocation. For comparative purposes to centralized solutions, the same the game is solved also in centralized manner where the authors assume the presence of a controller with global knowledge who applies the CAG algorithm on behalf of networks.

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Centralized Approaches for Self-Coexistence of CR Networks. <s> This paper focuses on the problem of spectrum sharing between secondary networks that access spectrum opportunistically in TV spectrum. Compared to the coexistence problem in the ISM (Industrial, Scientific and Medical) bands, the coexistence situation in TV whitespace (TVWS) is potentially more complex and challenging due to the signal propagation characteristics in TVWS and the disparity of PHY/MAC strategies employed by the systems coexisting in it. In this paper, we propose a novel decision making algorithm for a system of coexistence mechanisms, such as an IEEE 802.19.1-compliant system, that enables coexistence of dissimilar TVWS networks and devices. Our algorithm outperforms existing coexistence decision making algorithms in terms of fairness, and percentage of demand serviced. <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Centralized Approaches for Self-Coexistence of CR Networks. <s> Licensed white space channels can now be used opportunistically by unlicensed users, provided the channels are relinquished when needed by the primary users. In order to maximize their potential, these channels need to be assigned to the secondary users in an efficient manner. The protocols to enable such an assignment need to simultaneously aim for fairness, high throughput, low overhead, and low rate of channel reconfigurations. One way of channel assignment is to allow neighboring access points (APs) to operate on the same channel. However, if not done properly, this may increase the number of collisions resulting in lower throughput. In this paper, we present a new channel assignment algorithm that performs controlled channel sharing among neighboring APs that increases not only the fairness but also the total throughput of the APs. Controlled sharing and assignment of channels leads to a new problem that we call as the Shared Coloring Problem. We design a protocol based on a centralized algorithm, called Share, and its localized version, lShare that work together to meet the objectives. The algorithm has tight bounds on fairness and it provides high system throughput. We also show how the 802.22 MAC layer protocol for wireless regional area networks (WRANs) can be modified considering the typical case of low degree of interference resulting from the operations of Share and lShare. Results from extensive ns-3 simulations based on data traces show that our protocol increases the minimum throughput among all APs by at least 58 percent when compared to the baseline algorithms. <s> BIB002 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> Centralized Approaches for Self-Coexistence of CR Networks. <s> Channel sharing in TV whitespace (TVWS) is challenging because of signal propagation characteristics and diversity in network technologies employed by secondary networks coexisting in TVWS. In this paper, the TVWS sharing problem is modeled as a multiobjective optimization problem, where each objective function tackles an important coexisting requirement, such as interference and disparity in network technologies. We propose an evolutionary algorithm that shares the TVWS among coexisting networks taking care of their channel occupancy requirements. In this paper, the channel occupancy is defined as the time duration; a network desires to radiate on a channel to achieve its desired duty cycle. Simulation results show that the proposed algorithm outperforms existing TVWS sharing algorithms regarding allocation fairness and a fraction of channel occupancy requirements of the coexisting networks. <s> BIB003

In BIB001 the authors propose a centralized algorithm that deals with the problem of spectrum sharing among secondary networks and compare the results to other CDM algorithms that are specified in the IEEE 802.19.1 standard. The algorithm is called Fair Algorithm for Coexistence decision-making in TV whitespace (FACT). Constrains considered in the decision-making process are: contiguous channel allocation, interference, fairness, channel allocation invariability and transmission scheduling constraints. The results showed that FACT algorithm outperforms two other algorithms based on the overall system performance in terms of fairness and percentage of demand serviced. However, being a centralized algorithm, there are evident drawbacks due to the amount of communication overhead and complexity. Indeed the gains in performance compared to the other two algorithms come at the price of higher computational running time. Furthermore, the algorithm cannot guarantee fairness, once the available channels are insufficient to accommodate the users' demands. The authors in BIB003 , on the other hand, formulate the coexistence problem as a multiobjective optimization problem and propose a centralized evolutionary algorithm that shares the TVWS among coexisting networks so that the allocation satisfy the channel occupancy requirements of each network. The objectives modeled include fairness, system throughput maximization and users' demand satisfaction. The authors compare the performance of their algorithm to two other centralized solutions, detailed in BIB001 BIB002 , and show that while their algorithm does not significantly improve system throughput and spectral efficiency, it ranks significantly higher in the fairness indicator, measured using the Jain index. While the authors show that the computation time is significantly shorter than the FACT algorithm, they do not address the overhead incurred, which is significant in both algorithms.

A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Comparative Analysis of Coexistence Algorithms in TV White <s> This paper focuses on the problem of spectrum sharing between secondary networks that access spectrum opportunistically in TV spectrum. Compared to the coexistence problem in the ISM (Industrial, Scientific and Medical) bands, the coexistence situation in TV whitespace (TVWS) is potentially more complex and challenging due to the signal propagation characteristics in TVWS and the disparity of PHY/MAC strategies employed by the systems coexisting in it. In this paper, we propose a novel decision making algorithm for a system of coexistence mechanisms, such as an IEEE 802.19.1-compliant system, that enables coexistence of dissimilar TVWS networks and devices. Our algorithm outperforms existing coexistence decision making algorithms in terms of fairness, and percentage of demand serviced. <s> BIB001 </s> A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces <s> The Comparative Analysis of Coexistence Algorithms in TV White <s> IEEE This paper focuses on coexistence and self- coexistence challenges between secondary heterogeneous wireless networks/users sharing TV Whitespace spectrum. The coexistence problems arise from having several primary and secondary networks of different technologies cohabiting the same licensed spectrum simultaneously. The self- coexistence problems arise from many secondary systems /users coexisting at the same place while using identical or different technologies. In particular, fair distribution of available spectrum becomes a serious issue. In this work we use a game theoretic approach to model the self-coexistence problem as a competitive game between secondary networks. We show that our game belongs to the class of congestion-averse games which are known to posses pure Nash Equilibria. This leads us to a decentralized approach for spectrum sharing among systems with different PHY/MAC characteristics. We show that our proposal outperforms other centralized algorithms in terms of user fairness and per-user theoretical data rates. <s> BIB002

Spaces. In this section we present a comparative analysis between some of the coexistence decision-making algorithms listed above, namely the FACT algorithm presented in BIB001 and the CAG algorithm presented in BIB002 . Algorithms are compared in terms of demand, fairness, and achieved theoretical throughput. Firstly the algorithms are compared in their ability to satisfy bandwidth demand of the networks. We observe in Figure 4 (left) that centralized CAG algorithm significantly outperforms FACT algorithm, while the decentralized CAG algorithm has poorer performance but still performs better than FACT. Secondly we evaluated the fairness of each algorithm. As shown in Figure 4 (right) CAG game solved centrally performs best in terms of fairness and even though FACT performance increases steadily as the number of available channels increases it does not outperform the decentralized CAG. Lastly the algorithms are compared based on the theoretical data rates obtained by each individual user. We observe in Figure 5 that in general the rates obtained with CAG are These results imply that even when networks independently make decisions, the performances are remarkable considering that decentralized implementation does not require overhead or global knowledge. The results are that when the number of channels available is less than demand of the CR networks both cooperative and noncooperative method are able to deliver similar performance in terms of throughput. Things change when the number of channels is increased over the number of channels required. The results shows that the noncooperative method may deliver better results in terms of network throughput, because the centralized/zcooperative methods require more computational time in order to decide which is the best channel allocation. We need to bear in mind that longer computational time limits the time available for users to transmit and receive information. On the other hand, if the number of devices requiring the spectrum is increased, the centralized/cooperative method has better performance compared to noncooperative method in terms of fairness.

A survey on platforms for big data analytics <s> Peer-to-peer networks <s> Parallel computing is now popular and mainstream, but performance and ease of use remain elusive to many end-users. There exists a need for performance improvements that can be easily retrofitted to existing parallel applications. In this paper we present MPI process swapping, a simple performance enhancing add-on to the MPI programming paradigm. MPI process swapping improves performance by dynamically choosing the best available resources throughout application execution, using MPI process over-allocation and real-time performance measurement. Swapping provides fully automated performance monitoring and process management, and a rich set of primitives to control execution behavior manually or through an external tool. Swapping, as defined in this implementation, can be added to iterative MPI applications and requires as few as three lines of source code change. We verify our design for a particle dynamics application on desktop resources within a production commercial environment. <s> BIB001 </s> A survey on platforms for big data analytics <s> Peer-to-peer networks <s> Part I Peer-to-Peer: Notion, Areas, History and Future: What is this Peer-to-Peer about?- Past and Future.- Application Areas.- Part II Unstructured Peer-to-Peer Systems: First and Second Generation of Peer-to-Peer Systems.- Random Graphs, Small-Worlds and Scale-Free Networks.- Part III Structured Peer-to-Peer Systems: Distributed Hash Tables.- Selected DHT Algorithms.- Reliability and Load Balancing in DHTs.- P-Grid: Dynamics of Self-Organizing Processes in Structured P2P Systems.- Part IV Peer-to-Peer-Based Applications: Application-Layer Multicast.- ePost.- Distributed Computing - GRID Computing.- Web Services and Peer-to-Peer.- Part V Self-Organization: Characterization of Self-Organization.- Self-Organization in Peer-to-Peer Systems.- Part VI Search and Retrieval: Peer-to-Peer Search and Scalability.- Algorithmic Aspects of Overlay Networks.- Schema-Based Peer-to-Peer Systems.- Supporting Information Retrieval in Peer-to-Peer Systems.- Hybrid Peer-to-Peer Systems.- Part VII Peer-to-Peer Traffic and Performance Evaluation: ISP Platforms under a Heavy Peer-to-Peer Workload.- Traffic Characteristics and Performance Evaluation of Peer-to-Peer Systems.- Part VIII Peer-to-Peer in Mobile and Ubiquitous Environments: Peer-to-Peer in Mobile Environments.- Spontaneous Collaboration in Mobile P2P Networks.- Epidemic Data Dissemination for Mobile Peer-to-Peer Lookup Services.- Peer-to-Peer and Ubiquitious Computing.- Part IX Business Applications and Markets: Business Applications and Revenue Models.- Peer-to-Peer Market Management.- A Peer-to-Peer Framework for Electronic Markets.- Part X Advanced Issues: Security-Related Issues in Peer-to-Peer Networks.- Accounting in Peer-to-Peer Systems.- The PlanetLab Platform <s> BIB002 </s> A survey on platforms for big data analytics <s> Peer-to-peer networks <s> The term “peer-to-peer” (P2P) refers to a class of systems and applications that employ distributed resources to perform a critical function in a decentralized manner. With the pervasive deployment of computers, P2P is increasingly receiving attention in research, product development, and investment circles. This interest ranges from enthusiasm, through hype, to disbelief in its potential. Some of the benefits of a P2P approach include: improving scalability by avoiding dependency on centralized points; eliminating the need for costly infrastructure by enabling direct communication among clients; and enabling resource aggregation. This survey reviews the field of P2P systems and applications by summarizing the key concepts and giving an overview of the most important systems. Design and implementation issues of P2P systems are analyzed in general, and then revisited for each of the case studies described in Section 6. This survey will help people understand the potential benefits of P2P in the research community and industry. For people unfamiliar with the field it provides a general overview, as well as detailed case studies. It is also intended for users, developers, and information technologies maintaining systems, in particular comparison of P2P solutions with alternative architectures and <s> BIB003

Peer-to-Peer networks BIB003 BIB002 involve millions of machines connected in a network. It is a decentralized and distributed network architecture where the nodes in the networks (known as peers) serve as well as consume resources. It is one of the oldest distributed computing platforms in existence. Typically, Message Passing Interface (MPI) is the communication scheme used in such a setup to communicate and exchange the data between peers. Each node can store the data instances and the scale out is practically unlimited (can be millions of nodes). The major bottleneck in such a setup arises in the communication between different nodes. Broadcasting messages in a peer-to-peer network is cheaper but the aggregation of data/results is much more expensive. In addition, the messages are sent over the network in the form of a spanning tree with an arbitrary node as the root where the broadcasting is initiated. MPI, which is the standard software communication paradigm used in this network, has been in use for several years and is well-established and thoroughly debugged. One of the main features of MPI includes the state preserving process i.e., processes can live as long as the system runs and there is no need to read the same data again and again as in the case of other frameworks such as MapReduce (explained in section "Apache hadoop"). All the parameters can be preserved locally. Hence, unlike MapReduce, MPI is well suited for iterative processing BIB001 . Another feature of MPI is the hierarchical master/slave paradigm. When MPI is deployed in the master-slave model, the slave machine can become the master for other processes. This can be extremely useful for dynamic resource allocation where the slaves have large amounts of data to process. MPI is available for many programming languages. It includes methods to send and receive messages and data. Some other methods available with MPI are 'Broadcast', which is used to broadcast the data or messages over all the nodes and 'Barrier', which is another method that can put a barrier and allows all the processes to synchronize and reach up to a certain point before proceeding further. Although MPI appears to be perfect for developing algorithms for big data analytics, it has some major drawbacks. One of the primary drawbacks is the fault intolerance since MPI has no mechanism to handle faults. When used on top of peer-to-peer networks, which is a completely unreliable hardware, a single node failure can cause the entire system to shut down. Users have to implement some kind of fault tolerance mechanism within the program to avoid such unfortunate situations. With other frameworks such as Hadoop (that are robust to fault tolerance) becoming widely popular, MPI is not being widely used anymore.

A survey on platforms for big data analytics <s> MapReduce <s> MapReduce is a programming model and an associated implementation for processing and generating large data sets. Users specify a map function that processes a key/value pair to generate a set of intermediate key/value pairs, and a reduce function that merges all intermediate values associated with the same intermediate key. Many real world tasks are expressible in this model, as shown in the paper. ::: ::: Programs written in this functional style are automatically parallelized and executed on a large cluster of commodity machines. The run-time system takes care of the details of partitioning the input data, scheduling the program's execution across a set of machines, handling machine failures, and managing the required inter-machine communication. This allows programmers without any experience with parallel and distributed systems to easily utilize the resources of a large distributed system. ::: ::: Our implementation of MapReduce runs on a large cluster of commodity machines and is highly scalable: a typical MapReduce computation processes many terabytes of data on thousands of machines. Programmers find the system easy to use: hundreds of MapReduce programs have been implemented and upwards of one thousand MapReduce jobs are executed on Google's clusters every day. <s> BIB001 </s> A survey on platforms for big data analytics <s> MapReduce <s> A prominent parallel data processing tool MapReduce is gaining significant momentum from both industry and academia as the volume of data to analyze grows rapidly. While MapReduce is used in many areas where massive data analysis is required, there are still debates on its performance, efficiency per node, and simple abstraction. This survey intends to assist the database and open source communities in understanding various technical aspects of the MapReduce framework. In this survey, we characterize the MapReduce framework and discuss its inherent pros and cons. We then introduce its optimization strategies reported in the recent literature. We also discuss the open issues and challenges raised on parallel data analysis with MapReduce. <s> BIB002

The programming model used in Hadoop is MapReduce BIB001 which was proposed by Dean and Ghemawat at Google. MapReduce is the basic data processing scheme used in Hadoop which includes breaking the entire task into two parts, known as mappers and reducers. At a high-level, mappers read the data from HDFS, process it and generate some intermediate results to the reducers. Reducers are used to aggregate the intermediate results to generate the final output which is again written to HDFS. A typical Hadoop job involves running several mappers and reducers across different nodes in the cluster. A good survey about MapReduce for parallel data processing is available in BIB002 .

A survey on platforms for big data analytics <s> MapReduce wrappers <s> There is a growing need for ad-hoc analysis of extremely large data sets, especially at internet companies where innovation critically depends on being able to analyze terabytes of data collected every day. Parallel database products, e.g., Teradata, offer a solution, but are usually prohibitively expensive at this scale. Besides, many of the people who analyze this data are entrenched procedural programmers, who find the declarative, SQL style to be unnatural. The success of the more procedural map-reduce programming model, and its associated scalable implementations on commodity hardware, is evidence of the above. However, the map-reduce paradigm is too low-level and rigid, and leads to a great deal of custom user code that is hard to maintain, and reuse. We describe a new language called Pig Latin that we have designed to fit in a sweet spot between the declarative style of SQL, and the low-level, procedural style of map-reduce. The accompanying system, Pig, is fully implemented, and compiles Pig Latin into physical plans that are executed over Hadoop, an open-source, map-reduce implementation. We give a few examples of how engineers at Yahoo! are using Pig to dramatically reduce the time required for the development and execution of their data analysis tasks, compared to using Hadoop directly. We also report on a novel debugging environment that comes integrated with Pig, that can lead to even higher productivity gains. Pig is an open-source, Apache-incubator project, and available for general use. <s> BIB001 </s> A survey on platforms for big data analytics <s> MapReduce wrappers <s> DryadLINQ is a system and a set of language extensions that enable a new programming model for large scale distributed computing. It generalizes previous execution environments such as SQL, MapReduce, and Dryad in two ways: by adopting an expressive data model of strongly typed .NET objects; and by supporting general-purpose imperative and declarative operations on datasets within a traditional high-level programming language. ::: ::: A DryadLINQ program is a sequential program composed of LINQ expressions performing arbitrary side-effect-free transformations on datasets, and can be written and debugged using standard .NET development tools. The DryadLINQ system automatically and transparently translates the data-parallel portions of the program into a distributed execution plan which is passed to the Dryad execution platform. Dryad, which has been in continuous operation for several years on production clusters made up of thousands of computers, ensures efficient, reliable execution of this plan. ::: ::: We describe the implementation of the DryadLINQ compiler and runtime. We evaluate DryadLINQ on a varied set of programs drawn from domains such as web-graph analysis, large-scale log mining, and machine learning. We show that excellent absolute performance can be attained--a general-purpose sort of 1012 Bytes of data executes in 319 seconds on a 240-computer, 960- disk cluster--as well as demonstrating near-linear scaling of execution time on representative applications as we vary the number of computers used for a job. <s> BIB002 </s> A survey on platforms for big data analytics <s> MapReduce wrappers <s> The size of data sets being collected and analyzed in the industry for business intelligence is growing rapidly, making traditional warehousing solutions prohibitively expensive. Hadoop [3] is a popular open-source map-reduce implementation which is being used as an alternative to store and process extremely large data sets on commodity hardware. However, the map-reduce programming model is very low level and requires developers to write custom programs which are hard to maintain and reuse. <s> BIB003

A certain set of wrappers are currently being developed for MapReduce. These wrappers can provide a better control over the MapReduce code and aid in the source code development. The following wrappers are being widely used in combination with MapReduce. Apache Pig is a SQL-like environment developed at Yahoo BIB001 is being used by many organizations like Yahoo, Twitter, AOL, LinkedIn etc. Hive is another MapReduce wrapper developed by Facebook BIB003 . These two wrappers provide a better environment and make the code development simpler since the programmers do not have to deal with the complexities of MapReduce coding. Programming environments such as DryadLINQ, on the other hand, provide the end users with more flexibility over the MapReduce by allowing the users to have more control over the coding. It is a C# like environment developed at Microsoft Research BIB002 . It uses LINQ (a parallel language) and a cluster execution environment called Dryad. The advantages include better debugging and development using Visual Studio as the tool and interoperation with other languages such as standard .NET. In addition to these wrappers, some researchers have also developed scalable machine learning libraries such as Mahout [14] using MapReduce paradigm.

A survey on platforms for big data analytics <s> Limitations of MapReduce <s> Most scientific data analyses comprise analyzing voluminous data collected from various instruments. Efficient parallel/concurrent algorithms and frameworks are the key to meeting the scalability and performance requirements entailed in such scientific data analyses. The recently introduced MapReduce technique has gained a lot of attention from the scientific community for its applicability in large parallel data analyses. Although there are many evaluations of the MapReduce technique using large textual data collections, there have been only a few evaluations for scientific data analyses. The goals of this paper are twofold. First, we present our experience in applying the MapReduce technique for two scientific data analyses: (i) high energy physics data analyses; (ii) K-means clustering. Second, we present CGL-MapReduce, a streaming-based MapReduce implementation and compare its performance with Hadoop. <s> BIB001 </s> A survey on platforms for big data analytics <s> Limitations of MapReduce <s> The growing demand for large-scale data mining and data analysis applications has led both industry and academia to design new types of highly scalable data-intensive computing platforms. MapReduce and Dryad are two popular platforms in which the dataflow takes the form of a directed acyclic graph of operators. These platforms lack built-in support for iterative programs, which arise naturally in many applications including data mining, web ranking, graph analysis, model fitting, and so on. This paper presents HaLoop, a modified version of the Hadoop MapReduce framework that is designed to serve these applications. HaLoop not only extends MapReduce with programming support for iterative applications, it also dramatically improves their efficiency by making the task scheduler loop-aware and by adding various caching mechanisms. We evaluated HaLoop on real queries and real datasets. Compared with Hadoop, on average, HaLoop reduces query runtimes by 1.85, and shuffles only 4% of the data between mappers and reducers. <s> BIB002 </s> A survey on platforms for big data analytics <s> Limitations of MapReduce <s> MapReduce programming model has simplified the implementation of many data parallel applications. The simplicity of the programming model and the quality of services provided by many implementations of MapReduce attract a lot of enthusiasm among distributed computing communities. From the years of experience in applying MapReduce to various scientific applications we identified a set of extensions to the programming model and improvements to its architecture that will expand the applicability of MapReduce to more classes of applications. In this paper, we present the programming model and the architecture of Twister an enhanced MapReduce runtime that supports iterative MapReduce computations efficiently. We also show performance comparisons of Twister with other similar runtimes such as Hadoop and DryadLINQ for large scale data parallel applications. <s> BIB003 </s> A survey on platforms for big data analytics <s> Limitations of MapReduce <s> Relational data are pervasive in many applications such as data mining or social network analysis. These relational data are typically massive containing at least millions or hundreds of millions of relations. This poses demand for the design of distributed computing frameworks for processing these data on a large cluster. MapReduce is an example of such a framework. However, many relational data based applications typically require parsing the relational data iteratively and need to operate on these data through many iterations. MapReduce lacks built-in support for the iterative process. This paper presents iMapReduce, a framework that supports iterative processing. iMapReduce allows users to specify the iterative operations with map and reduce functions, while supporting the iterative processing automatically without the need of users' involvement. More importantly, iMapReduce significantly improves the performance of iterative algorithms by (1) reducing the overhead of creating a new task in every iteration, (2) eliminating the shuffling of the static data in the shuffle stage of MapReduce, and (3) allowing asynchronous execution of each iteration, {it i.e.,} an iteration can start before all tasks of a previous iteration have finished. We implement iMapReduce based on Apache Hadoop, and show that iMapReduce can achieve a factor of 1.2 to 5 speedup over those implemented on MapReduce for well-known iterative algorithms. <s> BIB004 </s> A survey on platforms for big data analytics <s> Limitations of MapReduce <s> In this era of data abundance, it has become critical to process large volumes of data at much faster rates than ever before. Boosting is a powerful predictive model that has been successfully used in many real-world applications. However, due to the inherent sequential nature, achieving scalability for boosting is nontrivial and demands the development of new parallelized versions which will allow them to efficiently handle large-scale data. In this paper, we propose two parallel boosting algorithms, AdaBoost.PL and LogitBoost.PL, which facilitate simultaneous participation of multiple computing nodes to construct a boosted ensemble classifier. The proposed algorithms are competitive to the corresponding serial versions in terms of the generalization performance. We achieve a significant speedup since our approach does not require individual computing nodes to communicate with each other for sharing their data. In addition, the proposed approach also allows for preserving privacy of computations in distributed environments. We used MapReduce framework to implement our algorithms and demonstrated the performance in terms of classification accuracy, speedup and scaleup using a wide variety of synthetic and real-world data sets. <s> BIB005

One of the major drawbacks of MapReduce is its inefficiency in running iterative algorithms. MapReduce is not designed for iterative processes. Mappers read the same data again and again from the disk. Hence, after each iteration, the results have to be written to the disk to pass them onto the next iteration. This makes disk access a major bottleneck which significantly degrades the performance. For each iteration, a new mapper and reducer have to be initialized. Sometimes the MapReduce jobs are short-lived in which case the overhead of initialization of that task becomes a significant overhead to the task itself. Some workarounds such as forward scheduling (setting up the next MapReduce job before the previous one finishes) have been proposed. However, these approaches introduce additional levels of complexity in the source code. One such work called HaLoop BIB002 extends MapReduce with programming support for iterative algorithms and improves efficiency by adding caching mechanisms. CGL MapReduce BIB001 BIB005 is another work that focuses on improving the performance of MapReduce iterative tasks. Other examples of iterative MapReduce include Twister BIB003 and imapreduce BIB004 .

A survey on platforms for big data analytics <s> Berkeley data analytics stack (BDAS) <s> In this paper, we present BlinkDB, a massively parallel, approximate query engine for running interactive SQL queries on large volumes of data. BlinkDB allows users to trade-off query accuracy for response time, enabling interactive queries over massive data by running queries on data samples and presenting results annotated with meaningful error bars. To achieve this, BlinkDB uses two key ideas: (1) an adaptive optimization framework that builds and maintains a set of multi-dimensional stratified samples from original data over time, and (2) a dynamic sample selection strategy that selects an appropriately sized sample based on a query's accuracy or response time requirements. We evaluate BlinkDB against the well-known TPC-H benchmarks and a real-world analytic workload derived from Conviva Inc., a company that manages video distribution over the Internet. Our experiments on a 100 node cluster show that BlinkDB can answer queries on up to 17 TBs of data in less than 2 seconds (over 200 x faster than Hive), within an error of 2-10%. <s> BIB001 </s> A survey on platforms for big data analytics <s> Berkeley data analytics stack (BDAS) <s> From social networks to targeted advertising, big graphs capture the structure in data and are central to recent advances in machine learning and data mining. Unfortunately, directly applying existing data-parallel tools to graph computation tasks can be cumbersome and inefficient. The need for intuitive, scalable tools for graph computation has lead to the development of new graph-parallel systems (e.g., Pregel, PowerGraph) which are designed to efficiently execute graph algorithms. Unfortunately, these new graph-parallel systems do not address the challenges of graph construction and transformation which are often just as problematic as the subsequent computation. Furthermore, existing graph-parallel systems provide limited fault-tolerance and support for interactive data mining. We introduce GraphX, which combines the advantages of both data-parallel and graph-parallel systems by efficiently expressing graph computation within the Spark data-parallel framework. We leverage new ideas in distributed graph representation to efficiently distribute graphs as tabular data-structures. Similarly, we leverage advances in data-flow systems to exploit in-memory computation and fault-tolerance. We provide powerful new operations to simplify graph construction and transformation. Using these primitives we implement the PowerGraph and Pregel abstractions in less than 20 lines of code. Finally, by exploiting the Scala foundation of Spark, we enable users to interactively load, transform, and compute on massive graphs. <s> BIB002 </s> A survey on platforms for big data analytics <s> Berkeley data analytics stack (BDAS) <s> Machine learning (ML) and statistical techniques are key to transforming big data into actionable knowledge. In spite of the modern primacy of data, the complexity of existing ML algorithms is often overwhelming|many users do not understand the trade-os and challenges of parameterizing and choosing between dierent learning techniques. Furthermore, existing scalable systems that support machine learning are typically not accessible to ML researchers without a strong background in distributed systems and low-level primitives. In this work, we present our vision for MLbase, a novel system harnessing the power of machine learning for both end-users and ML researchers. MLbase provides (1) a simple declarative way to specify ML tasks, (2) a novel optimizer to select and dynamically adapt the choice of learning algorithm, (3) a set of high-level operators to enable ML researchers to scalably implement a wide range of ML methods without deep systems knowledge, and (4) a new run-time optimized for the data-access patterns of these high-level operators. <s> BIB003

The Spark developers have also proposed an entire data processing stack called Berkeley Data Analytics Stack (BDAS) [20] which is shown in Figure 2 . At the lowest level of this stack, there is a component called Tachyon [21] which is based on HDFS. It is a fault tolerant distributed file system which enables file sharing at memory-speed (data I/O speed comparable to system memory) across a cluster. It works with cluster frameworks such as Spark and MapReduce. The major advantage of Tachyon over Hadoop HDFS is its high performance which is achieved by using memory more aggressively. Tachyon can detect the frequently read files and cache them in memory thus minimizing the disk access by different jobs/queries. This enables the cached files to be read at memory speed. Another feature of Tachyon is its compatibility with Hadoop MapReduce. MapReduce programs can run over Tachyon without any modifications. The other advantage of using Tachyon is its support for raw tables. Tables with hundreds of columns can be loaded easily and the user can specify the frequently used columns to be loaded in memory for faster access. The second component in BDAS, which is the layer above Tachyon, is called Apache Mesos. Mesos is a cluster manager that provides efficient resource isolation and sharing across distributed applications/frameworks. It supports Hadoop, Spark, Aurora [22] , and other applications on a dynamically shared pool of resources. With Mesos, scalability can be increased to tens of thousands of nodes. APIs are available in java, python and C++ for developing new parallel applications. It also includes multi-resource scheduling capabilities. The third component running on top of Mesos is Spark which takes the place of Hadoop MapReduce in the BDAS architecture. On the top of the stack are many Spark wrappers such as Spark Streaming (Large Scale real-time stream processing), Blink DB (queries with bounded errors and bounded response times on very large data) BIB001 , GraphX (Resilient distributed Graph System on Spark) BIB002 and MLBase (distributed machine learning library based on Spark) BIB003 . Recently, BDAS and Spark have been receiving a lot of attention due to their performance gain over Hadoop. Now, it is even possible to run Spark on Amazon Elastic Map-Reduce [26] . Although BDAS consists of many useful components in the top layer (for various applications), many of them are still in the early stages of development and hence the support is rather limited. Due to the vast number of tools that are already available for Hadoop MapReduce, it is still the most widely used distributed data processing framework.

A survey on platforms for big data analytics <s> Multicore CPU <s> This paper examines simultaneous multithreading, a technique permitting several independent threads to issue instructions to a superscalar's multiple functional units in a single cycle. We present several models of simultaneous multithreading and compare them with alternative organizations: a wide superscalar, a fine-grain multithreaded processor, and single-chip, multiple-issue multiprocessing architectures. Our results show that both (single-threaded) superscalar and fine-grain multithreaded architectures are limited their ability to utilize the resources of a wide-issue processor. Simultaneous multithreading has the potential to achieve 4 times the throughput of a superscalar, and double that of fine-grain multithreading. We evaluate several cache configurations made possible by this type of organization and evaluate tradeoffs between them. We also show that simultaneous multithreading is an attractive alternative to single-chip multiprocessors; simultaneous multithreaded processors with a variety of organizations outperform corresponding conventional multiprocessors with similar execution resources.While simultaneous multithreading has excellent potential to increase processor utilization, it can add substantial complexity to the design. We examine many of these complexities and evaluate alternative organizations in the design space. <s> BIB001 </s> A survey on platforms for big data analytics <s> Multicore CPU <s> This tutorial gives a broad view of modern approaches for scaling up machine learning and data mining methods on parallel/distributed platforms. Demand for scaling up machine learning is task-specific: for some tasks it is driven by the enormous dataset sizes, for others by model complexity or by the requirement for real-time prediction. Selecting a task-appropriate parallelization platform and algorithm requires understanding their benefits, trade-offs and constraints. This tutorial focuses on providing an integrated overview of state-of-the-art platforms and algorithm choices. These span a range of hardware options (from FPGAs and GPUs to multi-core systems and commodity clusters), programming frameworks (including CUDA, MPI, MapReduce, and DryadLINQ), and learning settings (e.g., semi-supervised and online learning). The tutorial is example-driven, covering a number of popular algorithms (e.g., boosted trees, spectral clustering, belief propagation) and diverse applications (e.g., recommender systems and object recognition in vision). The tutorial is based on (but not limited to) the material from our upcoming Cambridge U. Press edited book which is currently in production. Visit the tutorial website at http://hunch.net/~large_scale_survey/ <s> BIB002

Multicore refers to one machine having dozens of processing cores BIB002 . They usually have shared memory but only one disk. Over the past few years, CPUs have gained internal parallelism. More recently, the number of cores per chip and the number of operations that a core can perform has increased significantly. Newer breeds of motherboards allow multiple CPUs within a single machine thereby increasing the parallelism. Until the last few years, CPUs were mainly responsible for accelerating the algorithms for big data analytics. Figure 3 (a) shows a high-level CPU architecture with four cores. The parallelism in CPUs is mainly achieved through multithreading BIB001 . All the cores share the same memory. The task has to be broken down into threads. Each thread is executed in parallel on different CPU cores. Most of the programming languages provide libraries to create threads and use CPU parallelism. The most popular choice of such programming languages is Java. Since multicore CPUs have been around for several years, a large number of software applications and programming environments are well developed for this platform. The developments in CPUs are not at the same pace compared to GPUs. The number of cores per CPU is still in double digits with the processing power close to 10Gflops while a single GPU has more than 2500 processing cores with 1000Tflops of processing power. This massive parallelism in GPU makes it a more appealing option for parallel computing applications. The drawback of CPUs is their limited number of processing cores and their primary dependence on the system memory for data access. System memory is limited to a few hundred gigabytes and this limits the size of the data that a CPU can process efficiently. Once the data size exceeds the system memory, disk access becomes a huge bottleneck. Even if the data fits into the system memory, CPU can process data at a much faster rate than the memory access speed which makes memory access a bottleneck. GPU avoids this by making use of DDR5 memory compared to a slower DDR3 memory used in a system. Also, GPU has high speed cache for each multiprocessor which speeds up the data access.

A survey on platforms for big data analytics <s> Graphics processing unit (GPU) <s> We introduce GPUMiner, a novel parallel data mining system that utilizes new-generation graphics processing units (GPUs). Our system relies on the massively multi-threaded SIMD (Single Instruction, Multiple-Data) architecture provided by GPUs. As specialpurpose co-processors, these processors are highly optimized for graphics rendering and rely on the CPU for data input/output as well as complex program control. Therefore, we design GPUMiner to consist of the following three components: (1) a CPU-based storage and buffer manager to handle I/O and data transfer between the CPU and the GPU, (2) a GPU-CPU co-processing parallel mining module, and (3) a GPU-based mining visualization module. We design the GPU-CPU co-processing scheme in mining depending on the complexity and inherent parallelism of individual mining algorithms. We provide the visualization module to facilitate users to observe and interact with the mining process online. We have implemented the k-means clustering and the Apriori frequent pattern mining algorithms in GPUMiner. Our preliminary results have shown significant speedups over state-of-the-art CPU implementations on a PC with a G80 GPU and a quad-core CPU. We will demonstrate the mining process through our visualization module. Code and documentation of GPUMiner are available at http://code.google.com/p/gpuminer/. <s> BIB001 </s> A survey on platforms for big data analytics <s> Graphics processing unit (GPU) <s> GPU architectures are increasingly important in the multi-core era due to their high number of parallel processors. Programming thousands of massively parallel threads is a big challenge for software engineers, but understanding the performance bottlenecks of those parallel programs on GPU architectures to improve application performance is even more difficult. Current approaches rely on programmers to tune their applications by exploiting the design space exhaustively without fully understanding the performance characteristics of their applications. To provide insights into the performance bottlenecks of parallel applications on GPU architectures, we propose a simple analytical model that estimates the execution time of massively parallel programs. The key component of our model is estimating the number of parallel memory requests (we call this the memory warp parallelism) by considering the number of running threads and memory bandwidth. Based on the degree of memory warp parallelism, the model estimates the cost of memory requests, thereby estimating the overall execution time of a program. Comparisons between the outcome of the model and the actual execution time in several GPUs show that the geometric mean of absolute error of our model on micro-benchmarks is 5.4% and on GPU computing applications is 13.3%. All the applications are written in the CUDA programming language. <s> BIB002

Graphics Processing Unit (GPUs) is a specialized hardware designed to accelerate the creation of images in a frame buffer intended for display output [30] . Until the past few years, GPUs were primarily used for graphical operations such as video and image editing, accelerating graphics-related processing etc. However, due to their massively parallel architecture, recent developments in GPU hardware and related programming frameworks have given rise to GPGPU (general-purpose computing on graphics processing units) . GPU has large number of processing cores (typically around 2500+ to date) as compared to a multicore CPU. In addition to the processing cores, GPU has its own high throughput DDR5 memory which is many times faster than a typical DDR3 memory. GPU performance has increased significantly in the past few years compared to that of CPU. Recently, Nvidia has launched Tesla series of GPUs which are specifically designed for high performance computing. Nvidia has released the CUDA framework which made GPU programming accessible to all programmers without delving into the hardware details. These developments suggest that GPGPU is indeed gaining more popularity. Figure 3(b) shows a high-level GPU architecture with 14 multiprocessors and 32 streaming processors per block. It usually has two levels of parallelism. At the first level, there are several multiprocessors (MPs) and within each multiprocessor there are several streaming processors (SPs). To use this setup, GPU program is broken down into threads which execute on SPs and these threads are grouped together to form thread blocks which run on a multiprocessor. Each thread within a block can communicate with each other and synchronize with other threads in the same block. Each of these threads has access to small but extremely fast shared cache memory and larger global main memory. Threads in one block cannot communicate with the threads in the other block as they may be scheduled at different times. This architecture implies that for any job to be run on GPU, it has to be broken into blocks of computation that can run independently without communicating with each other BIB002 . These blocks will have to be further broken down into smaller tasks that execute on an individual thread that may communicate with other threads in the same block. GPUs have been used in the development of faster machine learning algorithms. Some libraries such as GPUMiner BIB001 implement few machine learning algorithms on GPU using the CUDA framework. Experiments have shown many folds speedup using the GPU compared to a multicore CPU. GPU has its own drawbacks. The primary drawback is the limited memory that it contains. With a maximum of 12GB memory per GPU (as of current generation), it is not suitable to handle terabyte scale data. Once the data size is more than the size of the GPU memory, the performance decreases significantly as the disk access becomes the primary bottleneck. Another drawback is the limited amount of software and algorithms that are available for GPUs. Because of the way in which the task breakdown is required for GPUs, not many existing analytical algorithms are easily portable to GPUs.

A survey on platforms for big data analytics <s> Field programmable gate arrays (FPGA) <s> Summary form only given. An overview of how FPGAs are impacting education is given with an emphasis on how laboratory experiences are used to enhance learning. Courses employing these devices include: introductory logic, advanced logic (ASIC Prototyping), system-on-chip and platform design, HW/SW codesign of real-time embedded systems, network routing, and multidisciplinary capstone design. Project examples are presented along with specific ways that instructors can collaborate more to enhance the students' experiences and their own productivity. <s> BIB001 </s> A survey on platforms for big data analytics <s> Field programmable gate arrays (FPGA) <s> High end network security applications demand high speed operation and large rule set support. Packet classification is the core functionality that demands high throughput in such applications. This paper proposes a packet classification architecture to meet such high throughput. We have implemented a Firewall with this architecture in reconflgurable hardware. We propose an extension to Distributed Crossproducting of Field Labels (DCFL) technique to achieve scalable and high performance architecture. The implemented Firewall takes advantage of inherent structure and redundancy of rule set by using our DCFL Extended (DCFLE) algorithm. The use of DCFLE algorithm results in both speed and area improvement when it is implemented in hardware. Although we restrict ourselves to standard 5-tuple matching, the architecture supports additional fields. High throughput classification invariably uses Ternary Content Addressable Memory (TCAM) for prefix matching, though TCAM fares poorly in terms of area and power efficiency. Use of TCAM for port range matching is expensive, as the range to prefix conversion results in large number of prefixes leading to storage inefficiency. Extended TCAM (ETCAM) is fast and the most storage efficient solution for range matching. We present for the first time a reconfigurable hardware implementation of ETCAM. We have implemented our Firewall as an embedded system on Virtex-II Pro FPGA based platform, running Linux with the packet classification in hardware. The Firewall was tested in real time with 1 Gbps Ethernet link and 128 sample rules. The packet classification hardware uses a quarter of logic resources and slightly over one third of memory resources of XC2VP30 FPGA. It achieves a maximum classification throughput of 50 million packet/s corresponding to 16 Gbps link rate for the worst case packet size. The Firewall rule update involves only memory re-initialization in software without any hardware change. <s> BIB002 </s> A survey on platforms for big data analytics <s> Field programmable gate arrays (FPGA) <s> The aim of this paper is to review the state-of-the-art of Field Programmable Gate Array (FPGA) technologies and their contribution to industrial control applications. Authors start by addressing various research fields which can exploit the advantages of FPGAs. The features of these devices are then presented, followed by their corresponding design tools. To illustrate the benefits of using FPGAs in the case of complex control applications, a sensorless motor controller has been treated. This controller is based on the Extended Kalman Filter. Its development has been made according to a dedicated design methodology, which is also discussed. The use of FPGAs to implement artificial intelligence-based industrial controllers is then briefly reviewed. The final section presents two short case studies of Neural Network control systems designs targeting FPGAs. <s> BIB003 </s> A survey on platforms for big data analytics <s> Field programmable gate arrays (FPGA) <s> Given the rapid evolution of attack methods and toolkits, software-based solutions to secure the network infrastructure have become overburdened. The performance gap between the execution speed of security software and the amount of data to be processed is ever widening. A common solution to close this performance gap is through hardware implementation of security functions. Possessing the flexibility of software and high parallelism of hardware, reconfigurable hardware devices, such as Field Programmable Gate Arrays (FPGAs), have become increasingly popular for this purpose. FPGAs support the performance demands of security operations as well as enable architectural and algorithm innovations in the future. This paper presents a survey of the state-of-art in FPGA-based implementations that have been used in the network infrastructure security area, categorizing currently existing diverse implementations. Combining brief descriptions with intensive case-studies, we hope this survey will inspire more active research in this area. <s> BIB004

FPGAs are highly specialized hardware units which are custom-built for specific applications . FPGAs can be highly optimized for speed and can be orders of magnitude faster compared to other platforms for certain applications. They are programmed using Hardware descriptive language (HDL) [35] . Due to customized hardware, the development cost is typically much higher compared to other platforms. On the software side, coding has to be done in HDL with a low-level knowledge of the hardware which increases the algorithm development cost. User has to carefully investigate the suitability of a particular application for FPGA as they are effective only for a certain set of applications. FPGAs are used in a variety of real-world applications BIB003 BIB001 . One example where FPGA was successfully deployed is in the network security applications BIB004 . In one such application, FPGA is used as a hardware firewall and is much faster than the software firewalls in scanning large amounts of network data BIB002 . In the recent years, the speed of multicore processors is reaching closer to that of FPGAs.

A review of methods for spike sorting : the detection and classification of neural action potentials <s> Measuring neural activity <s> A tungsten microelectrode with several small holes burnt in the vinyl insulation enables the action potentials from several adjacent neurons to be observed simultaneously. A digital computer is used to separate the contributions of each neuron by examining and classifying the waveforms of the action potentials. These methods allow studies to be made of interactions between neurons that lie close together. <s> BIB001 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Measuring neural activity <s> A spike separation technique which combines data processing methods with extracellular probing techniques to allow simultaneous observation of multiple neural events is presented. A preparation, the locust ventral cord, allows spike separation. Experimental results and simulation indicate the usefulness of the method for this preparation. A feature of the data processing method allows the experimenter to direct the machine classification by an initial classification. Subsequently, the machine returns an indication of the quality of classification, allowing a reclassification or termination. <s> BIB002

The first link between neural communication and electrical signals was made by Luigi Galvani in 1791 when he showed that frog muscles could be stimulated by electricity. It was not until the 1920s, however, that the nerve impulses could be measured directly by the amplification of electrical signals recorded by microelectrodes. The basic electrical circuit is shown in figure 1 . The circuit amplifies the the potential between the ground (usually measured by placing a wire under the scalp) and the tip of the microelectrode. The potential changes measured at the tip reflect current flow in the extracellular medium. Typically the largest component of this current is that generated by the action potential, but there can be many other, less prominent components. Signals that look much like cellular action potentials can be picked up from axonal fibre bundles, also called fibres of passage. These signals are typically much more localized and small than cellular action potentials, which can usually be tracked while the electrode is advanced many tens of microns. Another signal source is the field potential. This is typically seen in layered structures and results from the synchronous flow of current into a parallel set of dendrites. This signal is typically of sufficiently low bandwidth that it can be filtered out from the neural actional potentials. The shape of the electrode has some effect on what types of signals are measured. To some extent, the larger the tip of the electrode the greater the number of signals recorded. If the electrode tip is too large it will be impossible to isolate any one particular neuron. If the electrode tip is too small it might be difficult to detect any signal at all. Additionally, the configuration of the tip can be an important factor in determining what signals can be measured. Current in the extracellular space tends to flow in the interstitial space between cells and does not necessarily flow regularly. A glass electrode which has an O-shaped tip may pick up different signals than a glass-coated platinum-iridium electrode with a bullet-shaped tip. As is often the case in neurophysiology, what is best must be determined empirically and even then is not necessarily reliable. For further discussions of issues related to electrical recording, see . The last step in the measurement is to amplify the electrical signal. A simple method of measuring the neural activity can be performed in hardware with a threshold detector, but with modern computers it is possible to analyse the waveform digitally and use algorithmic approaches to spike sorting BIB001 BIB002 . For a review on earlier efforts in this area, see . Previously software spike sorting involved considerable effort to set up and implement, but today the process is much more convenient. Several excellent software packages, many of which are publicly available, can do some of the more sophisticated analyses described here with minimal effort on the part of the user. Furthermore, the increased speed of modern computers makes it possible to use methods that in the past required prohibitive computational expense.

A review of methods for spike sorting : the detection and classification of neural action potentials <s> Feature analysis <s> Abstract Description of a method by which action potentials recorded simultaneously can be sorted in a moderate size machine in real-time and on-line. <s> BIB001 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Feature analysis <s> Classification of characteristic neural spike shapes in multi-unit recordings is performed in real time using a reduced feature set. A model of uncorrelated signal-related noise is used to reduce the feature set by choosing a subset of aperiodic samples which is effective for discrimination between signals by a nearest-mean algorithm. Initial signal classes are determined by an unsupervised clustering algorithm applied to the reduced features of the learning set events. Classification is carried out in real time using a distance measure derived for the reduced feature set. Examples of separation and correlation of multiunit activity from cat and frog visual systems are described. <s> BIB002 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Feature analysis <s> A number ofmultiunit neural signal classification techniques are compared in their theoretical separation properties and in their empirical performance in classifying two channel recordings from the ventral nerve cord of the cockroach. The techniques include: the use of amplitude and conduction time measures, template matching, the principal components method, optimal filtering, and maximin discrimination. The noise encountered under different situations is characterized, permitting the comparisons to be made as functions of the experimental conditions. Recommendations are made as to the appropriate use of the techniques. <s> BIB003

The traces in figure 3(b) show two clear action potentials that have roughly the same height but are different in shape. If the shape could be characterized, we could use this information to classify each spike. How do we characterize the shape? One approach is to measure features of the shape, such as spike height and width or peak-to-peak amplitude. This is one of the earliest approaches to spike sorting. It was common in these methods to put considerable effort into choosing the minimal set of features that yielded the best discrimination, because computer resources were very limited BIB001 BIB002 . For further discussions of feature analysis techniques, see BIB003 and . In general, the more features we have, the better we will be able to distinguish different spike shapes. Figure 6 (a) is a scatter plot of the maximum versus minimum spike amplitudes for each spike in the waveform used in figure 3(b). On this plot, there is a clear clustering of the two different spike shapes. The cluster positions indicate that the spikes have similar maximum amplitudes, but the minimum amplitudes fall into primarily two regions. The large cluster near the origin reflects both noise and the spikes of background neurons. It is also possible to measure different features, and somewhat better clustering is obtained with the spike height and width, as shown in figure 6(b). The vertical banding reflects the sampling frequency. How do we sort the spikes? A common method is a technique called cluster cutting. In this approach, the user defines a boundary for a particular set of features. If a data point falls within the boundary, it is classified as belonging to that cluster; if it falls outside the boundary, it is discarded. Figure 6 (b) shows an example of boundaries placed around the primary clusters. It should be evident that positioning of the boundaries for optimal classification can be quite difficult if the clusters are not distinct. There is also the same trade-off between false positives and missed spikes as there was for threshold detection, but now in two dimensions. Methods to position the cluster boundaries automatically will be discussed below. In off-line analysis the cluster boundaries are determined after the data have been collected by looking at all (or a sample from) the data over the collection period. This allows the experiment to verify that the spike shapes were stable for the duration of the collection period. Clustering can also be performed on-line (i.e. while the data are being collected) if the clusters are stable. Methods for addressing unstable clusters will be discussed below.

A review of methods for spike sorting : the detection and classification of neural action potentials <s> Clustering in higher dimensions and template matching <s> Abstract A heuristic method was developed to identify and to separate automatically unit nerve impulses from a multiunit recording. Up to 20 distinct units can be identified. The method can sequentially decompose superimposed nerve impulses if the rapidly changing region of at least one of them is relatively undistorted. The identification and separation procedure has been successfully applied to the extracellularly recorded neural activity associated with the shadow reflex pathway of the barnacle. The limitations of the procedure are discussed and additional applications of the technique are presented. <s> BIB001 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Clustering in higher dimensions and template matching <s> A system for neural spike detection and classification is presented which does not require a priori assumptions about spike shape or timing. The system is divided into two parts: a learning subsystem and a real-time detection and classification subsystem. The learning subsystem, comprising of feature learning phase and a template learning phase, extracts templates for each separate spike class. The real-time detection and classification subsystems identifies spikes in the noisy neural trace and sorts them into classes, based on the templates and the statistics of the background noise. Comparisons are made among three different schemes for the real-time detection and classification subsystem. Performance of the system is illustrated by using it to classify spikes in segments of neural activity recorded from monkey motor cortex and from guinea pig and ferret auditory cortexes. > <s> BIB002

Although convenient for display purposes, there is no reason to restrict the cluster space to two dimensions; the algorithms also work in higher dimensions. Figure 11 shows the results of clustering the whole spike waveform. The waveforms are the class means and correspond to the average spike waveform for each class. By adding more dimensions to the clustering, more information is available which can lead to more accurate classification. Using model spike shapes to classify new action potentials is also called template matching (Capowski 1976, Millecchia and BIB001 . Earlier methods of template matching relied on the user to choose a small set of spikes that would serve as the templates. In clustering procedures, the spike templates are chosen automatically BIB002 . If a Euclidean metric is used to calculate the distance to the template, then this corresponds to nearest-neighbour clustering and assumes a spherical cluster around the template (D'Hollander and Orban 1979). The Bayesian version of classification by spike templates has the advantage that the classification takes into account the variation around the mean spike shape to give the most accurate decision boundaries.

A review of methods for spike sorting : the detection and classification of neural action potentials <s> Choosing the number of classes <s> Neuronal noise sources and systematic variability in the shape of a spike limit the ability to sort multiple unit waveforms recorded from nervous tissue into their single neuron constituents. Here we present a procedure to efficiently sort spikes in the presence of noise that is anisotropic, i.e., dominated by particular frequencies, and whose amplitude distribution may be non-Gaussian, such as occurs when spike waveforms are a function of interspike interval. Our algorithm uses a hierarchical clustering scheme. First, multiple unit records are sorted into an overly large number of clusters by recursive bisection. Second, these clusters are progressively aggregated into a minimal set of putative single units based on both similarities of spike shape as well as the statistics of spike arrival times, such as imposed by the refractory period. We apply the algorithm to waveforms recorded with chronically implanted micro-wire stereotrodes from neocortex of behaving rat. Natural extensions of the algorithm may be used to cluster spike waveforms from records with many input channels, such as those obtained with tetrodes and multiple site optical techniques. <s> BIB001 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Choosing the number of classes <s> We discuss Bayesian methods for model averaging and model selection among Bayesian-network models with hidden variables. In particular, we examine large-sample approximations for the marginal likelihood of naive-Bayes models in which the root node is hidden. Such models are useful for clustering or unsupervised learning. We consider a Laplace approximation and the less accurate but more computationally efficient approximation known as the Bayesian Information Criterion (BIC), which is equivalent to Rissanen's (1987) Minimum Description Length (MDL). Also, we consider approximations that ignore some off-diagonal elements of the observed information matrix and an approximation proposed by Cheeseman and Stutz (1995). We evaluate the accuracy of these approximations using a Monte-Carlo gold standard. In experiments with artificial and real examples, we find that (1) none of the approximations are accurate when used for model averaging, (2) all of the approximations, with the exception of BIC/MDL, are accurate for model selection, (3) among the accurate approximations, the Cheeseman–Stutz and Diagonal approximations are the most computationally efficient, (4) all of the approximations, with the exception of BIC/MDL, can be sensitive to the prior distribution over model parameters, and (5) the Cheeseman–Stutz approximation can be more accurate than the other approximations, including the Laplace approximation, in situations where the parameters in the maximum a posteriori configuration are near a boundary. <s> BIB002

One of the more difficult aspects of clustering approaches is choosing the number of classes. In Bayesian approaches, it is possible to estimate the probability of each model given the observed data , Gull 1988 BIB002 . If the assumptions of the model are accurate, this will give the relative probabilities of different numbers of classes. This approach was used by in the case of spherical Gaussian mixture models. The software package AutoClass (Cheeseman and Stutz 1996) , used in figures 9 and 11, estimates the relative probabilities for a general (multivariate) Gaussian mixture model. In figure 9 , for example, the probability of the nine-class model was e 160 times greater than the four-class model, suggesting overwhelming evidence in favour of the nine-class model. This procedure selects the most probable number of classes given the data and does not always favour models with more classes. In the same example, the probability of the nine-class model was e 16 times greater than that of an eleven-class model. These numbers are calculated given the assumptions of the model and thus should be considered accordingly, i.e. they are accurate to the extent that the assumptions are valid. Ideally, the number of classes would correspond to the number of neurons being observed, but there are several factors that prevent such a simple interpretation. The parameters of the classes are adapted to fit the distribution of the data. Individual neurons will not necessarily produce spikes that result in a distribution than can be well described by the model. In some special cases, such as with stationary spike shapes and uncorrelated noise, the clusters will be nearly spherical in which case the conclusions drawn from nearestneighbour or symmetric Gaussian models can be very accurate. Many less ideal situations, such as correlated noise or non-stationary spike shapes, can still be accurately modelled by general Gaussian mixture models. In more complicated situations, such as neurons that generate complex bursts or when the background noise is non-stationary, the structure of the data can be very difficult to capture with a mixture model and thus it will be difficult both to predict the number of units and to make accurate classifications. One approach to choosing the number of classes that avoids some of the assumptions of the simple cluster models was suggested by BIB001 . The idea behind this approach is to use the interspike interval histogram to guide decisions about whether a class represents a single unit. When a neuron generates an irregularly shaped spike, such as a bursting neuron, many clustering algorithms often fit the resulting data with two or more classes. The method of BIB001 groups multiple classes according to whether the interspike interval histogram of the group shows a significant number of spikes in the refractory period. Classification is done normally using the whole set of classes, but spikes classified as belonging to any of the classes in a group are labelled as the same unit. If overlapping action potentials are ignored, this approach can give biased results, because discarded overlaps could artificially create an interspike interval histogram that does not violate assumptions of the refractory period. It is important, then, with this approach, to calculate the interspike interval statistics in a region where overlaps can be accurately classified. Another potential drawback of this approach is that, because it relies on constructing interspike interval histograms, long collection periods may be required to achieve the desired degree of statistical certainty.

A review of methods for spike sorting : the detection and classification of neural action potentials <s> Filter-based methods <s> A number ofmultiunit neural signal classification techniques are compared in their theoretical separation properties and in their empirical performance in classifying two channel recordings from the ventral nerve cord of the cockroach. The techniques include: the use of amplitude and conduction time measures, template matching, the principal components method, optimal filtering, and maximin discrimination. The noise encountered under different situations is characterized, permitting the comparisons to be made as functions of the experimental conditions. Recommendations are made as to the appropriate use of the techniques. <s> BIB001 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Filter-based methods <s> Describes advanced protocols for the discrimination and classification of neuronal spike waveforms within multichannel electrophysiological recordings. The programs are capable of detecting and classifying the spikes from multiple, simultaneously active neurons, even in situations where there is a high degree of spike waveform superposition on the recording channels. The protocols are based on the derivation of an optimal linear filter for each individual neuron. Each filter is tuned to selectively respond to the spike waveform generated by the corresponding neuron, and to attenuate noise and the spike waveforms from all other neurons. The protocol is essentially an extension of earlier work (S. Andreassen et al., 1979; W.M. Roberts and D.K. Hartline, 1975; R.B. Stein et al., 1979). However, the protocols extend the power and utility of the original implementations in two significant respects. First, a general single-pass automatic template estimation algorithm was derived and implemented. Second, the filters were implemented within a software environment providing a greatly enhanced functional organization and user interface. The utility of the analysis approach was demonstrated on samples of multiunit electrophysiological recordings from the cricket abdominal nerve cord. > <s> BIB002

Another approach to spike sorting uses the methods of optimal filtering BIB002 . The idea behind this approach is to generate a set of filters that optimally discriminate a set of spikes from each other and from the background noise. This method assumes that both the noise power spectrum and the spike shapes can be estimated accurately. For each spike model, a filter is constructed that responds maximally to the spike shape of interest and minimally to the background noise, which may include the spikes of other units. The neural waveform is then convolved with the set of filters and spikes are classified according to which filter generates the largest response. This is analogous to the clustering methods above in which the metric used to calculate distance to the class mean is inversely related to the filter output. If the filters used to model the spike shapes were orthogonal, this would also be able to handle overlapping action potentials, but in practice this is rarely the case. Comparisons of spike classification on a common data set were carried out by BIB001 who found that optimal filtering methods did not classify as accurately as feature clustering using principal components or template matching.

A review of methods for spike sorting : the detection and classification of neural action potentials <s> Overlapping spikes <s> This paper develops the multidimensional binary search tree (or k -d tree, where k is the dimensionality of the search space) as a data structure for storage of information to be retrieved by associative searches. The k -d tree is defined and examples are given. It is shown to be quite efficient in its storage requirements. A significant advantage of this structure is that a single data structure can handle many types of queries very efficiently. Various utility algorithms are developed; their proven average running times in an n record file are: insertion, O (log n ); deletion of the root, O ( n ( k -1)/ k ); deletion of a random node, O (log n ); and optimization (guarantees logarithmic performance of searches), O ( n log n ). Search algorithms are given for partial match queries with t keys specified [proven maximum running time of O ( n ( k - t )/ k )] and for nearest neighbor queries [empirically observed average running time of O (log n ).] These performances far surpass the best currently known algorithms for these tasks. An algorithm is presented to handle any general intersection query. The main focus of this paper is theoretical. It is felt, however, that k -d trees could be quite useful in many applications, and examples of potential uses are given. <s> BIB001 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Overlapping spikes <s> An essential step in studying nerve cell interaction during information processing is the extracellular microelectrode recording of the electrical activity of groups of adjacent cells. The recording usually contains the superposition of the spike trains produced by a number of neurons in the vicinity of the electrode. It is therefore necessary to correctly classify the signals generated by these different neurons. This problem is considered, and a new classification scheme is developed which does not require human supervision. A learning stage is first applied on the beginning portion of the recording to estimate the typical spike shapes of the different neurons. As for the classification stage, a method is developed which specifically considers the case when spikes overlap temporally. The method minimizes the probability of error, taking into account the statistical properties of the discharges of the neurons. The method is tested on a real recording as well as on synthetic data. > <s> BIB002 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Overlapping spikes <s> Fast search algorithms are proposed and studied for vector quantization encoding using the K-dimensional (K-d) tree structure. Here, the emphasis is on the optimal design of the K-d tree for efficient nearest neighbor search in multidimensional space under a bucket-Voronoi intersection search framework. Efficient optimization criteria and procedures are proposed for designing the K-d tree, for the case when the test data distribution is available (as in vector quantization application in the form of training data) as well as for the case when the test data distribution is not available and only the Voronoi intersection information is to be used. The criteria and bucket-Voronoi intersection search procedure are studied in the context of vector quantization encoding of speech waveform. They are empirically observed to achieve constant search complexity for O(log N) tree depths and are found to be more efficient in reducing the search complexity. A geometric interpretation is given for the maximum product criterion, explaining reasons for its inefficiency with respect to the optimization criteria. > <s> BIB003 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Overlapping spikes <s> Neuronal noise sources and systematic variability in the shape of a spike limit the ability to sort multiple unit waveforms recorded from nervous tissue into their single neuron constituents. Here we present a procedure to efficiently sort spikes in the presence of noise that is anisotropic, i.e., dominated by particular frequencies, and whose amplitude distribution may be non-Gaussian, such as occurs when spike waveforms are a function of interspike interval. Our algorithm uses a hierarchical clustering scheme. First, multiple unit records are sorted into an overly large number of clusters by recursive bisection. Second, these clusters are progressively aggregated into a minimal set of putative single units based on both similarities of spike shape as well as the statistics of spike arrival times, such as imposed by the refractory period. We apply the algorithm to waveforms recorded with chronically implanted micro-wire stereotrodes from neocortex of behaving rat. Natural extensions of the algorithm may be used to cluster spike waveforms from records with many input channels, such as those obtained with tetrodes and multiple site optical techniques. <s> BIB004 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Overlapping spikes <s> Determination of single-unit spike trains from multiunit recordings obtained during extracellular recording has been the focus of many studies over the last two decades. In multiunit recordings, superpositions can occur with high frequency if the firing rates of the neurons are high or correlated, making superposition resolution imperative for accurate spike train determination. In this work, a connectionist neural network (NN) was applied to the spike sorting challenge. A novel training scheme was developed which enabled the NN to resolve some superpositions using single-channel recordings. Simulated multiunit spike trains were constructed from templates and noise segments that were extracted from real extracellular recordings. The simulations were used to determine the performances of the NN and a simple matched template filter (MTF), which was used as a basis for comparison. The network performed as well as the MTF in identifying nonoverlapping spikes, and was significantly better in resolving superpositions and rejecting noise. An on-line, real-time implementation of the NN discriminator, using a high-speed digital signal processor mounted inside an IBM-PC, is now in use in six laboratories. <s> BIB005

None of the methods described above explicitly deals with overlapping spikes. If two spikes are sufficiently separated in time, it is possible that the aforementioned methods will make the correct classification, but all of the methods reviewed thus far degrade severely when two spikes fire simultaneously. With the cluster cutting and Bayesian approaches to classification, it is possible to detect 'bad' overlaps as outliers. This gives the experimenter some gauge of the relative frequency of these events and whether they would compromise the results. There are many situations, however, where it would be desirable to both detect and accurately classify overlapping action potentials, e.g. investigations of local circuits or studies of spike-timing codes. One simple approach to overlaps is to subtract a spike from the waveform once it is classified, in the hope that this will improve the classification of subsequent spikes. This approach requires a model of the spike shape (or template). It yields reasonable results 0 1 2 3 4 msec Figure 13 . A high degree of overlap makes it difficult to identify the component spikes. when two spikes are separated well enough so that the first can be accurately classified, but fails when the spikes are closer together like those shown in figure 13. Another problem with this approach is that the subtraction can introduce more noise in the waveform if the spike model is not accurate. Another approach to the problem of overlaps is use neural networks to learn more general decision boundaries (Jansen 1990, Chandra and BIB005 . BIB005 reported that a trained neural network performed as well as a matched filter for classifying non-overlapping action potentials and showed improved performance for overlapping action potentials. A serious drawback of these approaches, however, is that the network must be trained using labelled spikes; thus the decision boundaries that are learned can only be as accurate as the initial labelling. Like the subtraction methods, these methods can only identify overlaps that have identifiable peaks. One potential problem with subtraction-based approaches is that it is possible to introduce spurious spike-like shapes if the spike occurrence time is not accurately estimated. Typically, spike occurrence time is estimated to a resolution of one sample period, but often this is not sufficient to prevent artifacts in the residual waveform due to misalignment of the spike model with the measured waveform. The minimal precision of the time alignment can be surprisingly small, often a fraction of a sample period. gave the following equation for error introduced by spike-time misalignment. For a given spike model, s(t), the maximum error resulting from a misalignment of δ is For values of equal to the RMS noise level, typical δ's range from 0.1 to 0.5 sample periods. This equation gives a discrete number of time-alignment positions that must be checked in order to ensure an error less than . A more robust approach for decomposing overlaps was proposed by BIB002 . When an overlap is detected, this approach compares all possible combinations of two spike models over a short range of spike occurrence times to find the combination with the highest likelihood. This approach can identify exact overlaps, but has the drawback of being computationally expensive, particularly for higher numbers of overlaps. introduced a computationally efficient overlap decomposition algorithm that addressed many of these problems. The idea behind the algorithm is to construct a special data structure that can be used for classification, time alignment, and overlap decomposition, all at the same time and with minimal computational expense. The data structure is constructed from the spike shapes, once they are determined, and then used repeatedly for classification and decomposition when new spikes are detected. In clustering and template-matching approaches, the largest computational expense is in comparing the observed spike to each of the clusters or templates. For single action potentials, this expense is insignificant, but if overlaps are considered then comparisons must be made for each spike combination (pair, triple, etc) and for all the alignments of the spikes with respect to each other. This quickly results in far too many possibilities to consider in a reasonable amount of time. It is possible, however, to avoid the expense of comparing the data from the observed spike to all possible cases. Using data structures and search techniques from computer science, it is possible to organize the cases in the data structure so that the spike combinations that most likely account for the data can be identified very quickly. The algorithm of used k-dimensional search trees BIB001 ) to quickly search the large space of possible combinations of spike shapes that could account for a given spike waveform. k-dimensional trees are a multidimensional extension of binary trees, where k refers to the number of dimensions in the cluster means. A simple method of constructing this type of search tree is to identify the dimension in the data with the largest variation and divide the data at the median of this dimension. This divides the data in two and determines the first division in the tree. This procedure is applied recursively to each subdivision until the tree extends down to the level of single data points. Each node in the tree stores what dimension is cut and the position of that cut. There are many algorithms for constructing these trees that use different strategies to ensure that the nodes in the tree are properly balanced BIB003 . To find the closest match in the tree to a new data point, the tree is traversed from top to bottom, comparing the appropriate dimensions at cutting points at each node. If each node divides on half of the subregion, then the closest match will be found in an average of O(log 2 N) comparisons, where N is the number of data points stored in the tree. In the case of spike sorting, these would correspond to the means of the models. To construct the tree requires O(N log 2 N) time, but once it is set up, each nearest-neighbour search is very fast. For purposes of calculating the relative probabilities of different clusters, it is not sufficient just to identify the closest cluster. For this calculation, it is necessary to find all the means within a certain radius (which is proportional to the background noise level) of the data point, and there are also algorithms that can perform this search using k-dimensional trees in O(log 2 N) time (Friedman et al 1977, Ramasubramanian and BIB003 . The overlap decomposition algorithm of is illustrated in figure 14 . The first step is to find a peak in the extracellular waveform. A region around the peak (indicated by the dashed lines) is selected. These data are classified with the k-dimensional tree which returns a list of spike sequence models and their relative probabilities. Each sequence model is a list of spikes (possibly only a single spike) and temporal positions relative to the waveform peak. The residual waveform (the raw waveform minus the model) of each remaining model is expanded until another peak is found. The relative probabilities of each sequence are recalculated using the entire waveform so far and the improbable sequences (e.g. probability < 0.001) are discarded. The cycle is repeated recursively, again using the k-dimensional tree to classify the waveform peak in each residual waveform. The algorithm terminates when no more peaks are found over the duration of the component spike models. The algorithm returns with list of spike model sequences and their relative probabilities. It is fast enough that it can be performed in real time with only modest computing requirements. Step 1 of the algorithm identifies all plausible spike models in a peak region (indicated by the dashed lines). Step 2 expands each spike model sequence in the current list until another peak is found in the residual error. Step 3 calculates the likelihood of each spike model sequence and prunes from the sequence list all those that are improbable. The steps are repeated on the next peak region in the residual waveform for each sequence in the list. The algorithm returns a list of spike sequences and their relative probabilities. (b, c, d) Three different decompositions of the same waveform. The decomposition in (b) is twice as probable as that in (c) even though the latter fits the data better. The decomposition in (d) has small probability, because it does not fit the data sufficiently well. One unforeseen consequence of a good decomposition algorithm is that there are actually many different ways to account for the same waveform. This is essentially the same overfitting problem that was mentioned in section 4.7: models with more degrees of freedom achieve better fits to the data, but can also result in less accurate predictions. This problem was addressed in Lewicki's algorithm by using Bayesian methods to determine which sequence is the most probable. For example, the four-spike sequence in figure 14(b) has twice the probability of the six-spike sequence in figure 14(c) , even though the latter fits the data better (i.e. has less residual error). This approach does not make use of spike firing times, but in principle this information could also be incorporated into the calculation. One limitation of this approach is that it assumes the clusters are spherical, which is equivalent to assuming a fixed spike shape with uncorrelated Gaussian noise. One approach for using this decomposition algorithm with non-spherical clusters is to use the approach of BIB004 which uses several spherical clusters to approximate more general types of cluster shapes.

A review of methods for spike sorting : the detection and classification of neural action potentials <s> Multiple electrodes <s> A new method is described for the recording and discrimination of extracellular action potentials in CNS regions with high cellular packing density or where there is intrinsic variation in action potential amplitude during burst discharge. The method is based on the principle that cells with different ratios of distances from two electrode tips will have different spike-amplitude ratios when recorded on two channels. The two channel amplitude ratio will remain constant regardless of intrinsic variation in the absolute amplitude of the signals. The method has been applied to the rat hippocampal formation, from which up to 5 units have been simultaneously isolated. The construction of the electrodes is simple, relatively fast, and reliable, and their low tip impedances result in excellent signal to noise characteristics. <s> BIB001 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Multiple electrodes <s> The majority of techniques for separating multiple single-unit spike trains from a multi-unit recording rely on the assumption that different cells exhibit action potentials having unique amplitudes and waveforms. When this assumption fails, due to the similarity of spike shape among different cells or to the presence of complex spikes with declining intra-burst amplitude, these methods lead to errors in classification. In an effort to avoid these errors, the stereotrode (McNaughton et al., 1983) and later the tetrode (O'Keefe and Reece, 1993; Wilson and McNaughton, 1993) recording techniques were developed. Because the latter technique has been applied primarily to the hippocampus, we sought to evaluate its performance in the neocortex. Multi-unit recordings, using single tetrodes, were made at 28 sites in area 17 of 3 anesthetized cats. Neurons were activated with moving bars and square wave gratings. Single units were separated by identification of clusters in 2-D projections of either peak-to-peak amplitude, spike width, spike area, or the 1st versus 2nd principal components of the waveforms recorded on each channel. Using tetrodes, we recorded a total of 154 single cells (mean = 5.4, max = 9). By cross-checking the performance of the tetrode with the stereotrode and electrode, we found that the best of the 6 possible stereotrode pairs and the best of 4 possible electrodes from each tetrode yielded 102 (mean = 3.6, max = 7) and 95 (mean = 3.4, max = 6) cells, respectively. Moreover, we found that the number of cells isolated at each site by the tetrode was greater than the stereotrode or electrode in 16/28 and 28/28 cases, respectively. Thus, both stereotrodes, and particularly electrodes, often lumped 2 or more cells in a single cluster that could be easily separated by the tetrode. We conclude that tetrode recording currently provides the best and most reliable method for the isolation of multiple single units in the neocortex using a single probe. <s> BIB002

There are many situations when two different neurons generate action potentials having very similar shapes in the recorded waveform. This happens when the neurons are similar in morphology and about equally distant from the recording electrode. One approach to circumventing this problem is to record from multiple electrodes in the same local area BIB001 . The idea is that if two recording electrodes are used, pairs of cells will be less likely to be equidistant from both electrodes (stereotrodes). This idea can be extended further to have four electrodes (tetrodes) that can provide four separate measurements of neural activity in the local area BIB001 , Wilson and McNaughton 1993 . Under the assumption that the extracellular space is electrically homogeneous, four electrodes provide the minimal number necessary to identify the spatial position of a source based only on the relative spike amplitudes on different electrodes. Having multiple recordings of the same unit from different physical locations allows additional information to be used for more accurate spike sorting. This can also reduce the problem of overlapping spikes: what appears as an overlap on one channel might be a isolated unit on another. BIB002 used recordings made with tetrodes in cat visual cortex to compare the performance of tetrodes with the best electrode pair and best single electrode. Using two-dimensional feature clustering, the tetrode recordings yielded an average of 5.4 isolated cells per site compared to 3.6 cells per site and 3.4 cells per site for the best electrode pair and best single electrode, respectively. Publicly available software for hand-clustering of tetrode data has been described by . Many of the spike-sorting techniques developed for single electrodes extend naturally to multiple electrodes. Principal component analysis can also be performed on multipleelectrode channels to obtain useful features for clustering. In this case, the principal components describe the directions of maximum variation on all channels simultaneously. It is also possible to do clustering of all the channels simultaneously using the raw waveforms. Here each cluster mean represents the mean spike shape as it appears on each of the channels. have applied Bayesian clustering methods to tetrode data which show improved classification accuracy compared to two-dimensional clustering methods.

A review of methods for spike sorting : the detection and classification of neural action potentials <s> Summary <s> A number ofmultiunit neural signal classification techniques are compared in their theoretical separation properties and in their empirical performance in classifying two channel recordings from the ventral nerve cord of the cockroach. The techniques include: the use of amplitude and conduction time measures, template matching, the principal components method, optimal filtering, and maximin discrimination. The noise encountered under different situations is characterized, permitting the comparisons to be made as functions of the experimental conditions. Recommendations are made as to the appropriate use of the techniques. <s> BIB001 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Summary <s> The majority of techniques for separating multiple single-unit spike trains from a multi-unit recording rely on the assumption that different cells exhibit action potentials having unique amplitudes and waveforms. When this assumption fails, due to the similarity of spike shape among different cells or to the presence of complex spikes with declining intra-burst amplitude, these methods lead to errors in classification. In an effort to avoid these errors, the stereotrode (McNaughton et al., 1983) and later the tetrode (O'Keefe and Reece, 1993; Wilson and McNaughton, 1993) recording techniques were developed. Because the latter technique has been applied primarily to the hippocampus, we sought to evaluate its performance in the neocortex. Multi-unit recordings, using single tetrodes, were made at 28 sites in area 17 of 3 anesthetized cats. Neurons were activated with moving bars and square wave gratings. Single units were separated by identification of clusters in 2-D projections of either peak-to-peak amplitude, spike width, spike area, or the 1st versus 2nd principal components of the waveforms recorded on each channel. Using tetrodes, we recorded a total of 154 single cells (mean = 5.4, max = 9). By cross-checking the performance of the tetrode with the stereotrode and electrode, we found that the best of the 6 possible stereotrode pairs and the best of 4 possible electrodes from each tetrode yielded 102 (mean = 3.6, max = 7) and 95 (mean = 3.4, max = 6) cells, respectively. Moreover, we found that the number of cells isolated at each site by the tetrode was greater than the stereotrode or electrode in 16/28 and 28/28 cases, respectively. Thus, both stereotrodes, and particularly electrodes, often lumped 2 or more cells in a single cluster that could be easily separated by the tetrode. We conclude that tetrode recording currently provides the best and most reliable method for the isolation of multiple single units in the neocortex using a single probe. <s> BIB002 </s> A review of methods for spike sorting : the detection and classification of neural action potentials <s> Summary <s> Neuronal noise sources and systematic variability in the shape of a spike limit the ability to sort multiple unit waveforms recorded from nervous tissue into their single neuron constituents. Here we present a procedure to efficiently sort spikes in the presence of noise that is anisotropic, i.e., dominated by particular frequencies, and whose amplitude distribution may be non-Gaussian, such as occurs when spike waveforms are a function of interspike interval. Our algorithm uses a hierarchical clustering scheme. First, multiple unit records are sorted into an overly large number of clusters by recursive bisection. Second, these clusters are progressively aggregated into a minimal set of putative single units based on both similarities of spike shape as well as the statistics of spike arrival times, such as imposed by the refractory period. We apply the algorithm to waveforms recorded with chronically implanted micro-wire stereotrodes from neocortex of behaving rat. Natural extensions of the algorithm may be used to cluster spike waveforms from records with many input channels, such as those obtained with tetrodes and multiple site optical techniques. <s> BIB003

Which method is best? An early comparison of feature-based methods was done by BIB001 who concluded that template-matching methods yielded the best classification accuracy compared to spike-shape features, principal components, and optimal filters. compared template-based, Bayesian clustering and classification to the commercial package Brainwaves, which relied on the user to define the two-dimensional cluster boundaries by hand. The methods gave similar results for well separated clusters, but the Bayesian methods were much more accurate for spike shapes that were similar. Template-based methods can fail for neurons that burst and can become increasingly inaccurate if there is electrode drift. The cluster grouping method of BIB003 gives better classification in this situation compared to template-based methods. For overlapping action potentials, the method of was shown to be nearly 100% accurate for action potentials that are significantly above the noise level. Perhaps the most promising of recent methods for measuring the activity of neural populations is not an algorithm, but the recording technique of using multiple electrodes. Many of the difficult problems encountered with single-electrode recording vanish with multiple-electrode recordings. BIB002 showed that tetrodes yielded about two more isolated cells per site compared to the best single electrode, when the data were sorted with a simple two-dimensional clustering procedure. Bayesian clustering and classification shows promise to improve this yield even more BIB003 . A more practical question might be: what is the simplest method that satisfies experimental demands? For many researchers this is still a single electrode with threshold detection. Although simple, this technique can be time consuming and biased. Not only can neurophysiologists waste hours searching for well isolated cells, but in the end this search is biased towards cells that produce the largest action potentials which may not be representative of the entire population. Software spike sorting can reduce these biases, but this approach is still not in widespread use because of the difficulty in implementing even the simplest algorithms and also the added time required for obtaining more data. With modern computers and software this is no longer the case. If the raw waveform data can be transferred to the computer for software analysis, many of the algorithms described here can be implemented with simple programs using software packages such as Matlab, Octave, or Mathematica. In the past several years, there has been much progress in spike sorting. It is now possible to replace much of the decision making and user interaction requirements of older methods with more accurate automated algorithms. There are still many problems that limit the robustness of many of the current methods. These include those discussed in section 7, such as non-stationary background noise, electrode drift and proper spike alignment. Possibly the most restrictive assumption of most methods is the assumption of stationary spike shapes. The method of BIB003 addresses this problem to some extent, as can methods that use multiple electrodes, but currently there are no methods that can accurately classify highly overlapping groups of bursting action potentials. Decomposing overlapping action potentials with non-stationary shapes is largely an unsolved problem. Techniques that use multiple electrodes and incorporate both spike shape and spike timing information show promise in surmounting this problem.

A Survey of Formal Verification for Business Process Modeling <s> Introduction <s> Diese Arbeit befasst sich mit den begrifflichen Grundlagen einer Theorie der Kommunikation. Die Aufgabe dieser Theorie soll es sein, moglichst viele Erscheinungen bei der Informationsubertragung und Informationswandlung in einheitlicher und exakter Weise zu beschreiben. ::: The theory of automata is shown not capable of representing the actual physical flow of information in the solution of a recursive problem. The argument proceeds as follows: ::: 1. We assume the following postulates: ::: a) there exists an upper bound on the speed of signals; ::: b) there exists an upper bound on the density with which information can be stored. ::: ::: 2. Automata of fixed, finite size can recognize, at best, only iteratively defined classes of input sequences. (See Kleene (11) and Copi, Elgot, and Wright (8).) ::: ::: 3. Recursively defined classes of input sequences that cannot be defined iteratively can be recognized only by automata of unbounded size. ::: ::: 4. In order for an automaton to solve a (soluble) recursive problem, the possibility must be granted that it can be extended unboundedly in whatever way might be required. ::: ::: 5. Automata (as actual hardware) formulated in accordance with automata theory will, after a finite number of extensions, conflict with at least one of the postulates named above. ::: Suitable conceptual structures for an exact theory of communication are then discussed, and a theory of communication proposed. ::: All of the really useful results of automata theory may be expressed by means of these new concepts. Moreover, the results retain their usefulness and the new nrocedure has definite advantages over the older ones. ::: The proposed representation differs from each of the presently known theories concerning information on at least one of the following essential points: ::: 1. The existence of a metric is assumed for either space nor time nor for other physical magnitudes. ::: 2. Time is introduced as a strictly local relation between states. ::: 3. The objects of the theory are discrete, and they are combined and produced only by means of strictly finite techniques. ::: ::: The following conclusions drawn from the results of this work may be cited as of some practical interest: ::: 1. The tolerance requirements for the response characteristics of computer components can be substantially weakened if the computer is suitably structured. ::: 2. It is possible to design computers structurally in such a way that they are asynchronous, all parts operating in parallel, and can be extended arbitrarily without interrupting their computation. ::: 3. For complicated organizational processes of any given sort the theory yields a means of representation that with equal rigor and simplicity accomplishes more than the theory of synchronous automata. <s> BIB001 </s> A Survey of Formal Verification for Business Process Modeling <s> Introduction <s> Glossary Part I. Communicating Systems: 1. Introduction 2. Behaviour of automata 3. Sequential processes and bisimulation 4. Concurrent processes and reaction 5. Transitions and strong equivalence 6. Observation equivalence: theory 7. Observation equivalence: examples Part II. The pi-Calculus: 8. What is mobility? 9. The pi-calculus and reaction 10. Applications of the pi-calculus 11. Sorts, objects and functions 12. Commitments and strong bisimulation 13. Observation equivalence and examples 14. Discussion and related work Bibliography Index. <s> BIB002

Recently, enterprise information systems are designed based on service-oriented architecture. The solution against the changing business environment is construction of flexible business processes, which is the core of enterprise information systems development. It is common knowledge that business process modeling (BPM) is effective for the development. Developers can generally model business processes with modeling notation, e.g., BPMN , activity diagrams of UML . The diagram, modeled with the notation, is simple and intuitively understandable at a glance. The notation is also designed so that anyone can easily model. Moreover, the notation is closely relevant to web services; the diagram can be converted into the BPEL XML format . However, work of general modeling includes arbitrariness and lacks strictness. A diagram modeled with the notation may have various interpretations and one or more different diagrams may denote one process. Thus, before utilizing BPM, we must define strict semantics of the models and verify formally them. There have been many efforts that validate strictness of the diagrams; automation tools which can debug grammatical errors of BPMN and convert diagrams into BPEL , formal methods for verifying diagrams based on the π calculus BIB002 or Petri Net BIB001 , techniques proving consistency with model-checking , and so on. In this paper we present a survey of existing proposals for formal verification techniques of business process diagrams and compare them among each other with respect to motivations, methods, and logics. We also discuss some conclusive considerations and our direction for future work. The most important purpose of BPM is to yield a profit for enterprise after the business reform. Thus, we should verify the profit which is generated by the model. In this paper we also discuss the value of business process models and properties for the evaluation. We hope the survey contributes to designers and developers of enterprise information systems for solving issues on their section and satisfying the industrial needs.

A Survey of Formal Verification for Business Process Modeling <s> Automata <s> This book is a rigorous exposition of formal languages and models of computation, with an introduction to computational complexity. The authors present the theory in a concise and straightforward manner, with an eye out for the practical applications. Exercises at the end of each chapter, including some that have been solved, help readers confirm and enhance their understanding of the material. This book is appropriate for upper-level computer science undergraduates who are comfortable with mathematical arguments. <s> BIB001 </s> A Survey of Formal Verification for Business Process Modeling <s> Automata <s> In this paper we show how we can translate Web Services described by WS-CDL into a timed automata orchestration, and more specifically we are interested in Web services with time restrictions. Our starting point are Web Services descriptions written in WSBPEL- WSCDL (XML-based description languages). These descriptions are then automatically translated into timed automata, and then, we use a well known tool that supports this formalism (UPPAAL) to simulate and analyse the system behaviour. As illustration we take a particular case study, an airline ticket reservation system. <s> BIB002 </s> A Survey of Formal Verification for Business Process Modeling <s> Automata <s> Recently, a promising programming model called Orc has been proposed to support a structured way of orchestrating distributed web services. Orc is intuitive because it offers concise constructors to manage concurrent communication, time-outs, priorities, failure of sites or communication and so forth. The semantics of Orc is also precisely defined. However, there is no verification tool available to verify critical properties against Orc models. Instead of building one from scratch, we believe the existing mature model-checkers can be reused. In this work, we first define a Timed Automata semantics for the Orc language, which we prove is semantically equivalent to the original operational semantics of Orc. Consequently, Timed Automata models are systematically constructed from Orc models. The practical implication of the construction is that tool supports for Timed Automata, e.g., UPPAAL, can be used to model check Orc models. An experimental tool is implemented to automate our approach. <s> BIB003

Automata are a public and base model of formal specifications for systems BIB001 . An automaton consists of a set of states, actions, transitions between states, and an initial state. Labels denote the transition from one state to another. Many specification models to express system behavior derive from automata. In the reference , the authors propose a framework to analyze and verify properties of BPMN diagrams converted into the BPEL format that communicate via asynchronous XML messages. The framework first converts the processes to a particular type of automata whose every transition is equipped with a guard in an XPath format, after which these guarded automata are translated into Promela (Process or Protocol Meta Language) for the SPIN model checker . Consequently, SPIN can be used to verify whether business process models satisfy properties formalized in LTL (Linear Time Temporal Logic). In the reference BIB002 , the authors show a case study to convert automatically business processes written in BPEL-WSCDL to timed automata and to verify subsequently them by the UPPAAL model checker [49] . The authors are currently implementing a tool for the automatic translation that utilizes UPPAAL. In the reference BIB003 , the authors propose a framework to verify automatically business processes that are modelled in Orc . The authors define a formal timedautomata semantics for Orc expressions, which verifies to the Orc's operational semantics. Accordingly, one can verify formally Orc models with UPPAAL. The paper also shows a simple case study. Thus, to verify business process diagrams the efforts utilizing automata convert the diagrams to XML formats (e.g., BPEL, XPDL, WS-CDL, Orc) for the present. After that, they accommodate automata to XML formats and then model-checking tools can verify them (Figure 1 ). Besides the above automata models, team automata and I/O automata may be helpful for the verification. Team automata allow one to specify separately the components of a system, to describe their interactions, and to reuse the components. Their advantage is a flexible description for communication services among distributed systems, extending I/O automata. This advantage enables team automata to describe the formal model of secure web service compositions.

A Survey of Formal Verification for Business Process Modeling <s> Petri Net <s> This paper suggests that input and output are basic primitives of programming and that parallel composition of communicating sequential processes is a fundamental program structuring method. When combined with a development of Dijkstra's guarded command, these concepts are surprisingly versatile. Their use is illustrated by sample solutions of a variety of familiar programming exercises. <s> BIB001 </s> A Survey of Formal Verification for Business Process Modeling <s> Petri Net <s> We present an axiom system ACP, for communicating processes with silent actions ('z-steps'). The system is an extension of ACP, Algebra of Communicating Processes, with Milner's z-laws and an explicit abstraction operator. By means of a model of finite acyclic process graphs for ACP, syntactic properties such as consistency and conservativity over ACP are proved. Furthermore, the Expansion Theorem for ACP is shown to carry over to ACP~. Finally, termination of rewriting terms according to the ACP~ axioms is proved using the method of recursive path orderings. <s> BIB002 </s> A Survey of Formal Verification for Business Process Modeling <s> Petri Net <s> Web services -- Web-accessible programs and devices - are a key application area for the Semantic Web. With the proliferation of Web services and the evolution towards the Semantic Web comes the opportunity to automate various Web services tasks. Our objective is to enable markup and automated reasoning technology to describe, simulate, compose, test, and verify compositions of Web services. We take as our starting point the DAML-S DAML+OIL ontology for describing the capabilities of Web services. We define the semantics for a relevant subset of DAML-S in terms of a first-order logical language. With the semantics in hand, we encode our service descriptions in a Petri Net formalism and provide decision procedures for Web service simulation, verification and composition. We also provide an analysis of the complexity of these tasks under different restrictions to the DAML-S composite services we can describe. Finally, we present an implementation of our analysis techniques. This implementation takes as input a DAML-S description of a Web service, automatically generates a Petri Net and performs the desired analysis. Such a tool has broad applicability both as a back end to existing manual Web service composition tools, and as a stand-alone tool for Web service developers. <s> BIB003 </s> A Survey of Formal Verification for Business Process Modeling <s> Petri Net <s> Web services composition is an emerging paradigm for application integration within and across organizational boundaries. A landscape of languages and techniques for web services composition has emerged and is continuously being enriched with new proposals from different vendors and coalitions. However, little effort has been dedicated to systematically evaluate the capabilities and limitations of these languages and techniques. The work reported in this paper is a step in this direction. It presents an in-depth analysis of the Business Process Execution Language for Web Services (BPEL4WS) with respect to a framework composed of workflow and communication patterns. <s> BIB004 </s> A Survey of Formal Verification for Business Process Modeling <s> Petri Net <s> The Internet is going through several major changes. It has become a vehicle of Web services rather than just a repository of information. Many organizations are putting their core business competencies on the Internet as a collection of Web services. An important challenge is to integrate them to create new value-added Web services in ways that could never be foreseen forming what is known as Business-to-Business (B2B) services. Therefore, there is a need for modeling techniques and tools for reliable Web service composition. In this paper, we propose a Petri net-based algebra, used to model control flows, as a necessary constituent of reliable Web service composition process. This algebra is expressive enough to capture the semantics of complex Web service combinations. <s> BIB005 </s> A Survey of Formal Verification for Business Process Modeling <s> Petri Net <s> Web services aim to support efficient integration of applications over Web. Most Web services are stateful, such as services for business processes, and they converse with each other via properly ordered interactions, instead of individual unrelated invocations. In order to address efficient integration of conversational Web services, we create a unified specification model for both conversation protocol and composition; we propose methods to integrate a partner service with complex conversation protocol into a composition of Web services; assure the correctness of composition by formal verification. The mapping between our model and BPEL4WS is also discussed. <s> BIB006 </s> A Survey of Formal Verification for Business Process Modeling <s> Petri Net <s> The emerging paradigm of Web services opens a new way of Web application design and development to quickly develop and deploy Web applications by integrating independently published Web services components to conduct new business transactions. As research aiming at facilitating Web services integration and verification, WS-Net is an executable architectural description language incorporating the semantics of colored Petri-net with the style and understandability of object-oriented concepts. WS-Net describes each Web services component in three layers: interface net declares the services that the component provides to other components; interconnection net specifies the services that the component acquires to accomplish its mission; and interoperation net describes the internal operational behaviors of the component. As an architectural model that formalizes the architectural topology and behaviors of each Web services component as well as the entire system, WS-Net facilitates the verification and monitoring of Web services integration. <s> BIB007 </s> A Survey of Formal Verification for Business Process Modeling <s> Petri Net <s> Whether two web services are compatible depends not only on static properties like the correct typing of their message parameters, but also on their dynamic behaviour. Providing a simple description of the service behaviour based on process-algebraic or automata-based formalisms can help detecting many subtle incompatibilities in their interaction. Moreover, this compatibility checking can to a large extent be automated if we define the notion of compatibility in a sufficiently formal way. Based on a simple behavioural representation, we survey, propose and compare a number of formal definitions of the compatibility notion, and we illustrate them on simple examples. <s> BIB008 </s> A Survey of Formal Verification for Business Process Modeling <s> Petri Net <s> The Business Process Execution Language for Web Service, known as BPEL4WS, more recently as WS-BPEL (or BPEL for short) [1], is a process definition language geared towards Service-Oriented Computing (SOC) and layered on top of the Web services technology stack. In BPEL, the logic of the interactions between a given service and its environment is described as a composition of communication actions. These communication actions are interrelated by control-flow dependencies expressed through constructs close to those found in workflow definition languages. In particular, BPEL incorporates two sophisticated branching and synchronisation constructs, namely “control links” and “join conditions”, which can be found in a class of workflow models known as synchronising workflows formalised in terms of Petri nets in [3]. <s> BIB009 </s> A Survey of Formal Verification for Business Process Modeling <s> Petri Net <s> We present a Petri net semantics for the Business Process Execution Language for Web Services (BPEL). Our semantics covers the standard behaviour of BPEL as well as the exceptional behaviour (e.g. faults, events, compensation). The semantics is implemented as a parser that translates BPEL specifications into the input language of the Petri net model checking tool LoLA. We demonstrate that the semantics is well suited for computer aided verification purposes. <s> BIB010

Petri Net is a framework to model concurrent systems. Petri Net can identify many basic aspects of concurrent systems simply, mathematically and conceptually. Therefore, many theories of concurrent systems derive from Petri Net. Moreover, because Petri Net has easily understandable and graphical notation, it has been widely applied. Petri Net often become a topic in BPM and is related to capturing process control flows BIB004 . Petri Net can specially detect the dead path of business process models whose preconditions are not satisfied. The paper shows how to correspond all BPMN diagrams constructs into labeled Petri Net. This output can subsequently be used to verify BPEL processes by the open source tools BPEL2PNML and WofBPEL BIB009 . In the reference BIB003 , the authors define the semantics of relation BPEL and OWL-S [51] in terms of first-order logic. Based on this semantics they formalize business processes in Petri Net, complete with an operational semantics. They also develop a tool to describe and automatically verify composition of business processes. In the reference BIB005 , the authors apply a Petri-net-based algebra to modeling business processes, based on control flows. The paper BIB006 proposes a Petri-net-based design and verification tool for web service composition. The tool can visualize, create, and verify business processes. The authors are now improving the graphical user interface which can be used to aid the business process modeling and to edit Petri Net and BPEL in a lump. The paper BIB007 introduce a Petri-net-based architectural description language, named WS-Net, in which web-service-oriented systems can be modeled, and presents a simple example. To handle real applications and to detect errors in business processes, the authors are currently developing an automatic translation tool from WSDL to WS-Net. The paper BIB010 proposes a formal Petri Net semantics for BPEL which assures exception handling and compensations. Moreover, the authors present the parser which can automatically convert business process diagrams into Petri Net. Consequently, the semantics enabled many Petri Net verification tools to automatically analyze business processes. In the reference , the authors propose a framework which can translate Orc into colored Petri Net. Colored Petri Net has been proposed to model large scale systems more effectively. The framework and tool deal with recursion and data handling. Moreover, because the framework and tool can simulate and verify the behavior of process models at the design phase of information systems, users of them can detect and correct errors beforehand. Therefore, they contribute to raise the reliability of business process diagrams. Petri Net is the traditional and well-established technique, thus there have been many verification methods and tools. The essentials of the above efforts are how to translate business process diagrams into Petri Net. After that, we have a rich variety of tools for the verification. However, all the components in business process modeling notation cannot change into Petri Net. For instance, BPMN has various gateways, event triggers, loop activities, control flows, and nested/embedded subprocesses. It is difficult to define the correspondence of these objects to Petri Net. There is room for argument on the translation. ), Hoare's Calculus of Sequential Processes (CSP BIB001 ), the Algebra of Communicating Processes (ACP BIB002 ) by Bergstra and Klop, and the Language of Temporal Ordered Systems (LOTOS ) ISO standard. Process algebras are strict and well-established theories that support the automatic verification of properties of systems behavior as well as Petri Net. They also provide a rich theory on bisimulation analysis. The analysis is helpful to verify whether a service can substitute another service in a composition or the redundancy of a service BIB008 .

A Survey of Formal Verification for Business Process Modeling <s> Figure 5 The Revised Process Model with Usability <s> We describe a representation and set of inference techniques for the dynamic construction of probabilistic and decision-theoretic models expressed as networks. In contrast to probabilistic reasoning schemes that rely on fixed models, we develop a representation that implicitly encodes a large number of possible model structures. Based on a particular query and state of information, the system constructs a customized belief net for that particular situation. We develop an interpretation of the network construction process in terms of the implicit networks encoded in the database. A companion method for constructing belief networks with decisions and values (decision networks) is also developed that uses sensitivity analysis to focus the model building process. Finally, we discuss some issues of control of model construction and describe examples of constructing networks. <s> BIB001 </s> A Survey of Formal Verification for Business Process Modeling <s> Figure 5 The Revised Process Model with Usability <s> Probabilistic graphical models and decision graphs are powerful modeling tools for reasoning and decision making under uncertainty. As modeling languages they allow a natural specification of problem domains with inherent uncertainty, and from a computational perspective they support efficient algorithms for automatic construction and query answering. This includes belief updating, finding the most probable explanation for the observed evidence, detecting conflicts in the evidence entered into the network, determining optimal strategies, analyzing for relevance, and performing sensitivity analysis. The book introduces probabilistic graphical models and decision graphs, including Bayesian networks and influence diagrams. The reader is introduced to the two types of frameworks through examples and exercises, which also instruct the reader on how to build these models. The book is a new edition of Bayesian Networks and Decision Graphs by Finn V. Jensen. The new edition is structured into two parts. The first part focuses on probabilistic graphical models. Compared with the previous book, the new edition also includes a thorough description of recent extensions to the Bayesian network modeling language, advances in exact and approximate belief updating algorithms, and methods for learning both the structure and the parameters of a Bayesian network. The second part deals with decision graphs, and in addition to the frameworks described in the previous edition, it also introduces Markov decision processes and partially ordered decision problems. The authors also provide a well-founded practical introduction to Bayesian networks, object-oriented Bayesian networks, decision trees, influence diagrams (and variants hereof), and Markov decision processes. give practical advice on the construction of Bayesian networks, decision trees, and influence diagrams from domain knowledge. give several examples and exercises exploiting computer systems for dealing with Bayesian networks and decision graphs. present a thorough introduction to state-of-the-art solution and analysis algorithms. The book is intended as a textbook, but it can also be used for self-study and as a reference book. <s> BIB002 </s> A Survey of Formal Verification for Business Process Modeling <s> Figure 5 The Revised Process Model with Usability <s> Stochastic logic programs (SLPs) are logic programs with parameterised clauses which define a log-linear distribution over refutations of goals. The log-linear distribution provides, by marginalisation, a distribution over variable bindings, allowing SLPs to compactly represent quite complex distributions.We analyse the fundamental statistical properties of SLPs addressing issues concerning infinite derivations, 'unnormalised’ SLPs and impure SLPs. After detailing existing approaches to parameter estimation for log-linear models and their application to SLPs, we present a new algorithm called failure-adjusted maximisation (FAM). FAM is an instance of the EM algorithm that applies specifically to normalised SLPs and provides a closed-form for computing parameter updates within an iterative maximisation approach. We empirically show that FAM works on some small examples and discuss methods for applying it to bigger problems. <s> BIB003

To verify such uncertain decision, various logics introducing probability into firstorder predicate logic have been proposed BIB003 These studies make it possible to generate Bayesian Network BIB002 from predicate logic expression based on knowledge-based model construction BIB001 . Since there are some business processes which flow with non-programmable decision , the business process diagrams with uncertainness have to be verified by such logics. If the properties of business process models for Bayesian Network is defined (e.g., Figure 6 ), we may verify the diagrams based on probabilistic inference.

A Survey of Formal Verification for Business Process Modeling <s> Concluding Remarks <s> Statechart Diagrams provide a graphical notation for describing dynamic aspects of system behaviour within the Unified Modelling Language (UML). In this paper we present a translation from a subset of UML Statechart Diagrams - covering essential aspects of both concurrent behaviour, like sequentialisation, parallelism, non-determinism and priority, and state refinement - into PROMELA, the specification language of the SPIN model checker. SPIN is one of the most advanced analysis and verification tools available nowadays. Our translation allows for the automatic verification of UML Statechart Diagrams. The translation is simple, proven correct, and promising in terms of state space representation efficiency. <s> BIB001 </s> A Survey of Formal Verification for Business Process Modeling <s> Concluding Remarks <s> The Unified Modelling Language (UML) is a standardised notation for describing object oriented software designs. We present vUML, a tool that automatically verifies UML models where the behaviour of the objects is described using UML Statecharts diagrams. The tool uses the SPIN model checker to perform the verification, but the user does not have to know how to use SPIN or the PROMELA language. If an error is found during the verification, the tool creates a UML sequence diagram showing how to reproduce the error in the model. <s> BIB002 </s> A Survey of Formal Verification for Business Process Modeling <s> Concluding Remarks <s> Abstract The Unified Modeling Language provides two complementary notations, state machines and collaborations, for the specification of dynamic system behavior. We describe a prototype tool, HUGO , that is designed to automatically verify whether the interactions expressed by a collaboration can indeed be realized by a set of state machines. We compile state machines into a PROMELA model and collaborations into sets of Buchi automata (“never claims”). The model checker SPIN is called upon to verify the model against the automata. <s> BIB003 </s> A Survey of Formal Verification for Business Process Modeling <s> Concluding Remarks <s> Chance discovery is to become aware of a chance and to explain its significance, especially if the chance is rare and its significance is unnoticed. This direction matches with various real requirements in human life. This paper presents the significance, viewpoints, theories, methods, and future work of chance discovery. Three keys for the progress are extracted from fundamental discussions on how to realize chance discovery: (1) communication, (2) imagination, and (3) data mining. As an approach to chance discovery, visualized data mining methods are formalized as tools aiding chance discoveries on the basis of these keys. <s> BIB004

In this paper, we have presented the formal verification techniques which simulate and verify one's business process models at the design phase of enterprise information systems. These techniques can detect and correct errors of the models as early as possible and in any case before implementation. We have also shown future work of the formal verification for BPM. However, the comparison in this paper surveyed only the basic logics and the aims of the verification, thus we must also define the other quantitative information in order to choose which logics or methods better suit the formal verification of BPM. Moreover, there are the well-established practices which verify UML state machine diagrams for behavior with modelchecking BIB001 BIB002 [31] BIB003 . We should compare BPM verification with such studies. A prospect of the researches that we would like to deepen in future work is to determine the financial characteristics that each of the languages and models is able to describe in order to define a profitable business process. We are now discussing whether the chance discovery process BIB004 can be applied to the verification from the financial and business administration viewpoint.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> C. Structured Data Capture <s> There is a growing need for patient-specific and holistic modelling of the heart to support comprehensive disease assessment and intervention planning as well as prediction of therapeutic outcomes. We propose a patient-specific model of the whole human heart, which integrates morphology, dynamics and haemodynamic parameters at the organ level. The modelled cardiac structures are robustly estimated from four-dimensional cardiac computed tomography (CT), including all four chambers and valves as well as the ascending aorta and pulmonary artery. The patient-specific geometry serves as an input to a three-dimensional Navier–Stokes solver that derives realistic haemodynamics, constrained by the local anatomy, along the entire heart cycle. We evaluated our framework with various heart pathologies and the results correlate with relevant literature reports. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> C. Structured Data Capture <s> The American Medical Association asked RAND Health to characterize the factors that affect physician professional satisfaction. RAND researchers sought to identify high-priority determinants of professional satisfaction by gathering data from 30 physician practices in six states, using a combination of surveys and semistructured interviews. This article presents the results of the subsequent analysis. <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> C. Structured Data Capture <s> BACKGROUND ::: Even though it takes up such a large part of all clinicians' working day the medical literature on documentation and its value is sparse. ::: ::: ::: METHODS ::: Medline searches combining the terms medical records, documentation, time, and value or efficacy or benefit yielded only 147 articles. This review is based on the relevant articles selected from this search and additional studies gathered from the personal experience of the authors and their colleagues. ::: ::: ::: RESULTS ::: Documentation now occupies a quarter to half of doctors' time yet much of the information collected is of dubious or unproven value. Most medical records departments still use the traditional paper chart, and there is considerable debate on the benefits of electronic medical records (EMRs). Although EMRs contains a lot more information than a paper record clinicians do not find it easy to getting useful information out of them. Unlike the paper chart narrative is difficult to enter into most EMRs so that they do not adequately communicate the patient's "story" to clinicians. Recent innovations have the potential to address these issues. ::: ::: ::: CONCLUSION ::: Although documentation is widespread throughout the health care industry there has been almost no formal research into its value, on how to enhance its value, or on whether the time spent on it has negative effects on patient care. <s> BIB003

EHRs can only achieve their full potential if time and cost associated with data capture can be kept under control. While a good deal of clinical data can be obtained from other venues such as laboratory or radiology systems or from devices (e.g., vital signs, ventilators), a significant amount of data must be entered by providers. Because of the time and effort required for providers to capture structured data, they often question if there is sufficient value to warrant the negative impact on productivity BIB003 , BIB002 . Contemporary EHRs are estimated to require additional 48 min per day, much of which is devoted to documentation , . Healthcare is complex, which is also reflected in the data: there are hundreds of thousands of clinical concepts that have to be represented. In order to accommodate this scale and simplify representations, coding systems have been adopted for clinical concepts. The concept of heart failure, for example, can be represented in the International Classification of Disease Version 9 Clinical Modification as "428.0." This approach facilitates using keyword value approaches to representing data. Unfortunately, there are multiple coding systems for most clinical concepts so heart failure can also be represented by I50 (ICD-10), 16209 ( DiseaseDB), D00633 (MESH), 42343007 (SNOMED), and others. Even more unfortunately, a good deal of data are coded using idiosyncratic clinical codes that are unique to a specific healthcare delivery system. This variation means that using the data often requires mapping or translation between coding systems which usually requires substantial human effort and, in some cases, a specific data model. In addition to direct entry by providers or their surrogates, structured data can be derived directly from unstructured data including free text, images, and other signals. Radiology involves the acquisition, analysis, storage, and handling of radiological images and certainly involves huge amounts of data, in particular, when the analysis involves time, as in angiography, or all three spatial dimensions, as in whole body screening. Pathology involves the analysis of tissue, cell, and body fluid samples, typically via microscopic imaging. As pathology is digitized, increasing amounts of digital data are generated and need to be handled and stored. The standard is that medical specialists interpret the radiological and pathological images and describe the findings in written free-text or unstructured reports, although there is a trend toward template-based semistructured reporting. The computerized analysis of radiological and pathological images is an established research area involving sophisticated algorithms and is becoming increasingly clinically relevant BIB001 - . The analysis typically involves some form of machine learning, and the emerging field of deep learning has an increasing impact . Analysis increasingly generates qualitative and quantitative labels or tabs, which can be used in integrated analytics studies . Written text is a major medium: The exact numbers vary, but a significant proportion of the clinically relevant information is only documented in a textual format. Besides radiological and pathological reports, medically relevant textual sources are reports from other departments, notes, referral letters, and discharge letters. Both researchers and commercial developers have devoted considerable effort to improve the efficiency of structured data capture from text and some hope that Natural Language Processing (NLP) will obviate the need for structured data capture; but advances have been incremental. While there is progress in focused areas, information extraction from clinical texts is notoriously difficult. Some of the reasons are that reports are ungrammatical, contain short phrases and nonstandardized and overloaded abbreviations, and employ an abundant use of negations and lists. Structured reporting, where the text is generated automatically and the physician simply enters keywords and short pieces of text, would be a great advance, but is currently not the standard , in part because it is typically more time consuming for the provider. Another issue is that the structured data entered by providers or extracted from text need to be represented such that the data can be "understood" by a computer, in other words, the healthcare system needs to be able to communicate effectively and in the same formalized language. Some languages are essentially simple taxonomies and vocabularies and are the basis for standards used in the billing process, such as ICD for diagnosis, CPT© for procedures, and SNOMED codes for diseases or conditions. For medications, there is the National Library of Medicine's RxNorm, the National Drug Code (NDC), and others. Logical Observation Identifiers Names and Codes (LOINC©) define universal standards for identifying medical laboratory and clinical observations. For billing purposes all involved players are highly motivated to employ the codes with great discipline. Implied statements in general take on simple forms, like "Patient X has Disease Y." This changes if one wants to express some detailed medical finding accurately. Consider the phrases "43 yo female with history of GERD woke up w/ SOB and LUE discomfort 1 day PTA. She presented to [**Hospital2 72**] where she was ruled out for MI by enzymes. She underwent stress test the following day at [**Hospital2 72**]. She developed SOB and shoulder pain during the test." In order to utilize the information represented in this text, an application would first need to map and code the entities in the phrases and then formulate statements relating the complex sequential observations with many subtle phrases, which only makes sense to a trained expert. This goes far beyond the expressiveness of currently used medical formal languages. Genomic, proteomic, and other molecular data (discussed more fully in Section VII), which are almost by their nature digital, will add an extensive amount and variety of structured data though, in current practice, an extremely limited subset derived from the molecular data will be all that is necessary for a particular application.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Clinical Data Integration Efforts <s> Informatics for Integrating Biology and the Bedside (i2b2) is one of seven projects sponsored by the NIH Roadmap National Centers for Biomedical Computing (http://www. ncbcs.org). Its mission is to provide clinical investigators with the tools necessary to integrate medical record and clinical research data in the genomics age, a software suite to construct and integrate the modern clinical research chart. i2b2 software may be used by an enterprise’s research community tofind sets of interesting patients from electronic patient medical record data, while preserving patient privacy through a query tool interface. Project-specific mini-databases (“data marts”) can be created from these sets to make highly detailed data available on these specific patients to the investigators on the i2b2 platform, as reviewed and restricted by the Institutional Review Board. The current version of this software has been released into the public domain and is available at the URL: http://www.i2b2.org/software. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Clinical Data Integration Efforts <s> tranSMART is an emerging global open source public private partnership community developing a comprehensive informatics-based analysis and data-sharing cloud platform for clinical and translational research. The tranSMART consortium includes pharmaceutical and other companies, not-for-profits, academic entities, patient advocacy groups, and government stakeholders. The tranSMART value proposition relies on the concept that the global community of users, developers, and stakeholders are the best source of innovation for applications and for useful data. Continued development and use of the tranSMART platform will create a means to enable “pre-competitive” data sharing broadly, saving money and, potentially accelerating research translation to cures. Significant transformative effects of tranSMART includes 1) allowing for all its user community to benefit from experts globally, 2) capturing the best of innovation in analytic tools, 3) a growing ‘big data’ resource, 4) convergent standards, and 5) new informatics-enabled translational science in the pharma, academic, and not-for-profit sectors. <s> BIB002

Some providers may have implemented a separate research data system such as i2b2 BIB001 or tranSMART BIB002 . These systems extract clinically relevant information from the EHR and from other clinical resources and databases and integrate them into the research database. A research database can be a great resource for data analytics project. Unfortunately installing a research database can be extremely demanding since it needs to access data that are in the data silos of the different departments. As discussed, these databases might all have different structures and use different terminologies. In contrast to clinical data, billing data-in part because of its simplicity and in part out of necessity-are consistently structured and are often part of a research database. Unfortunately, these data do not contain much of the clinically relevant information and may not accurately and fully reflect clinical reality. Providers may not be as careful in recording administrative data believing it is not critical to be exactly correct or, in some cases, billing data may be coded to maximize reimbursement rather than to most accurately reflect the patient's clinical status. Another important issue is that the temporal order of events is often not well documented in the data. To analyze the causal effects of a decision and to optimize decisions, it is important to know which information was available to the decision maker at the time of decision. At the current status of documentation, reconstructing the temporal order of events can be difficult.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> D. Indiana Network for Patient Care <s> BACKGROUND ::: There is great variation in choices of method and specific analytical details in epidemiological studies, resulting in widely varying results even when studying the same drug and outcome in the same database. Not only does this variation undermine the credibility of the research but it limits our ability to improve the methods. ::: ::: ::: METHODS ::: In order to evaluate the performance of methods and analysis choices we used standard references and a literature review to identify 164 positive controls (drug-outcome pairs believed to represent true adverse drug reactions), and 234 negative controls (drug-outcome pairs for which we have confidence there is no direct causal relationship). We tested 3,748 unique analyses (methods in combination with specific analysis choices) that represent the full range of approaches to adjusting for confounding in five large observational datasets on these controls. We also evaluated the impact of increasingly specific outcome definitions, and performed a replication study in six additional datasets. We characterized the performance of each method using the area under the receiver operator curve (AUC), bias, and coverage probability. In addition, we developed simulated datasets that closely matched the characteristics of the observational datasets into which we inserted data consistent with known drug-outcome relationships in order to measure the accuracy of estimates generated by the analyses. ::: ::: ::: DISCUSSION ::: We expect the results of this systematic, empirical evaluation of the performance of these analyses across a moderate range of outcomes and databases to provide important insights into the methods used in epidemiological studies and to increase the consistency with which methods are applied, thereby increasing the confidence in results and our ability to systematically improve our approaches. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> D. Indiana Network for Patient Care <s> The vision of creating accessible, reliable clinical evidence by accessing the clincial experience of hundreds of millions of patients across the globe is a reality. Observational Health Data Sciences and Informatics (OHDSI) has built on learnings from the Observational Medical Outcomes Partnership to turn methods research and insights into a suite of applications and exploration tools that move the field closer to the ultimate goal of generating evidence about all aspects of healthcare to serve the needs of patients, clinicians and all other decision-makers around the world. <s> BIB002

The Regenstrief Institute was an early advocate for clinical data interoperability based on information standards and leveraged that work to enable HIE both regionally and nationally. Regenstrief investigators implemented the Indianapolis Network for Patient Care (INPC) in 1995 with the goal of providing clinicians with data necessary for patient diagnosis and treatment at the point of care. In 2016, over 100 hospitals, thousands of physician practices, ambulance services, large local and the state public health departments, regional laboratories and imaging centers, and payors participated in the INPC. The federated data repository stores more than 4.7 billion records, including over 118 million text reports from almost 15 million unique patients. The data are stored in a standard format, with standardized demographic codes; laboratory test results are mapped to a set of common test codes with standard units of measure; medications, diagnoses, imaging studies, and report types are also mapped to standard terminologies. The flows of data that enable the INPC support results delivery, public health surveillance, results retrieval, quality improvement, research, and other services. Building on this experience, Regenstrief investigators have informed the development of the nationwide health information network program now called the eHealth Exchange ("Exchange"). The INPC data have been utilized by Regenstrief for many big data studies and projects including the following. • The Observational Medical Outcomes Partnership (OMOP) BIB001 and the subsequent Observational Health Data Science and Informatics (OHDSI) BIB002 projects to utilize large-scale observational data for drug safety studies. • The two projects were a basis for ConvergeHEALTH, an effort spearheaded by Deloitte that aims to offer comprehensive data sharing among key organizations. Deloitte has an analytics platform that allows hospital systems to compare results with tools designed to study certain patient outcomes: their OutcomesMiner tool helps users explore real-world outcomes for subpopulations of interest. • The Merck-Regenstrief Institute "Big Data" Partnership Academic-Industry Collaboration to Support Personalized Medicine was formed in 2012 to leverage the INPC to support a range of research studies that use clinical data to inform personalized healthcare. The partnership has funded 50 projects to date. Industry commentators have observed that such partnerships between industry and academia, and between and among other payers, are essential as neither sector alone can undertake such projects. • The Indiana Health Information, a nonprofit organization created to sustain the INPC's operations, entered into a partnership agreement with a commercial predictive analytics company, Predixion, to develop new predictive applications aimed at further supporting the patient and business needs of ACOs and hospitals. The INPC database supports Predixion's current and future solution development.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Clinical Data Intelligence <s> The amount of data in our world has been exploding, and analyzing large data sets—so-called big data— will become a key basis of competition, underpinning new waves of productivity growth, innovation, and consumer surplus, according to research by MGI and McKinsey's Business Technology Office. Leaders in every sector will have to grapple with the implications of big data, not just a few data-oriented managers. The increasing volume and detail of information captured by enterprises, the rise of multimedia, social media, and the Internet of Things will fuel exponential growth in data for the foreseeable future. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Clinical Data Intelligence <s> This article is about a new project that combines clinical data intelligence and smart data. It provides an introduction to the “Klinische Datenintelligenz” (KDI) project which is founded by the Federal Ministry for Economic Affairs and Energy (BMWi); we transfer research and development results (R&D) of the analysis of data which are generated in the clinical routine in specific medical domain. We present the project structure and goals, how patient care should be improved, and the joint efforts of data and knowledge engineering, information extraction (from textual and other unstructured data), statistical machine learning, decision support, and their integration into special use cases moving towards individualised medicine. In particular, we describe some details of our medical use cases and cooperation with two major German university hospitals. <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Clinical Data Intelligence <s> As a result of the recent trend towards digitization-- which increasingly affects evidence-based medicine, accountable care, personalized medicine, and medical "Big Data" analysis --growing amounts of clinical data are becoming available for analysis. In this paper, we follow the idea that one can model clinical processes based on clinical data, which can then be the basis for many useful applications. We model the whole clinical evolution of each individual patient, which is composed of thousands of events such as ordered tests, lab results and diagnoses. Specifically, we base our work on a dataset provided by the Charite University Hospital of Berlin which is composed of patients that suffered from kidney failure and either obtained an organ transplant or are still waiting for one. These patients face a lifelong treatment and periodic visits to the clinic. Our goal is to develop a system to predict the sequence of events recorded in the electronic medical record of each patient, and thus to develop the basis for a future clinical decision support system. For modelling, we use machine learning approaches which are based on a combination of the embedding of entities and events in a multidimensional latent space, in combination with Neural Network predictive models. Similar approaches have been highly successful in statistical models for recommendation systems, language models, and knowledge graphs. We extend existing embedding models to the clinical domain, in particular with respect to temporal sequences, long-term memories and personalization. We compare the performance of our proposed models with standard approaches such as K-nearest neighbors method, Naive Bayes classifier and Logistic Regression, and obtained favorable results with our proposed model. <s> BIB003 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Clinical Data Intelligence <s> In clinical data sets we often find static information (e.g. patient gender, blood type, etc.) combined with sequences of data that are recorded during multiple hospital visits (e.g. medications prescribed, tests performed, etc.). Recurrent Neural Networks (RNNs) have proven to be very successful for modelling sequences of data in many areas of Machine Learning. In this work we present an approach based on RNNs, specifically designed for the clinical domain, that combines static and dynamic information in order to predict future events. We work with a database collected in the Charit\'{e} Hospital in Berlin that contains complete information concerning patients that underwent a kidney transplantation. After the transplantation three main endpoints can occur: rejection of the kidney, loss of the kidney and death of the patient. Our goal is to predict, based on information recorded in the Electronic Health Record of each patient, whether any of those endpoints will occur within the next six or twelve months after each visit to the clinic. We compared different types of RNNs that we developed for this work, with a model based on a Feedforward Neural Network and a Logistic Regression model. We found that the RNN that we developed based on Gated Recurrent Units provides the best performance for this task. We also used the same models for a second task, i.e., next event prediction, and found that here the model based on a Feedforward Neural Network outperformed the other models. Our hypothesis is that long-term dependencies are not as relevant in this task. <s> BIB004

Clinical Data Intelligence ("Klinische Datenintelligenz") is a German project funded by the German Ministry or Economics and Energy (BMWi) and involves two integrated care providers, i.e., the University Hospital Erlangen and the Charité Berlin, two globally acting companies, i.e., Siemens AG and the Siemens Healthineers, and application and research centers from the University of Erlangen, the German Research Centre for Artificial Intelligence (DFKI), Fraunhofer, and Averbis , BIB002 . The project puts particular emphasis on terminologies and ontologies, on metadata extraction from textual sources and radiological images, and on the integration of medical guidelines as a form of prior knowledge. As part of the project, a central research database is installed which serves all research and application subprojects. The project also addresses business models and app infrastructures suitable for large-scale data analytics. The core functionalities are realized by an integrated learning and decision system (ILDS). The ILDS accesses all patient-specific data and provides analytics and predictive and prescriptive functionalities. The ILDS models and analyzes clinical decision processes by learning from the EHR's structured data such as diagnosis, procedures, and lab results. The ILDS also analyzes medical history, radiology, and pathology reports and includes guideline information. In addition, the ILDS considers genomic data, and molecular data in general, to explore personalized medicine in the context of other clinical data. The ILDS will immediately be able to make predictions about common practice of the form: "For a patient with properties and problems X, procedure Y is typically done (in your clinic system)." More difficult, since it involves a careful analysis of confounders, is a prescription of the form: "For a patient with properties and problems X, procedure Y is typically done (in your clinic system) but procedure Z will probably result in a better outcome." An important outcome of the project will be a set of requirements for a clinical documentation that will enable more powerful data analytics in the future. For example, BIB001 Deep learning is one of the most exciting developments in machine learning in recent years. It is a field that attracts amazing talents with stunning successes in a number of applications. One of the driving forces in deep learning is DeepMind, a London-based company owned by Google. DeepMind Health is a project in which U.K. NHS medical data are analyzed. The agreement gives DeepMind access to healthcare data on more than a million patients . The first outcome is the mobile app Streams, which presents timely information that helps nurses and doctors detect cases of acute kidney injury. Other notable commercial deep learning efforts with relevance to healthcare are Deep Genomics (http://www.deepgenomics.com/), Entlitic (http://www.enlitic.com/), and Atomwise (http://www.atomwise.com/). clinical outcome is not always well documented; readmission within a certain period of time (typically a month) is sometimes taken for a negative outcome. Alternatively, one might define a hospital stay of more than a certain number of days as a negative outcome, where the threshold is specific to the Diagnosis Related Group (DRG). In some cases, for example, after a kidney transplantation or mastectomy, the patient is closely observed, and outcome information is available, possibly over patient lifetime. The ILDS partially uses deep learning (more specifically recurrent neural networks) to model the sequential decision processes in clinics BIB003 . BIB001 The project addresses two use cases in detail. The first concerns nephrology. Kidney diseases cause a significant financial burden for the healthcare system. The aim of this work is to systematically investigate drug-drug interaction (DDI) and adverse drug reactions (ADRs) in patients after renal transplantation and to realize an integrated decision support system. The use case is particularly interesting since longitudinal data covering several decades are available and since outcome is usually reported. First ILDS results are reported in BIB003 and BIB004 . The second use case concerns breast cancer, the most common malignancy in women. Relevant events are screening, diagnosis, therapy, and follow-up care. Of special interest here is the determination of risk factors, the evaluation of the therapy, and the prediction of side effects.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> G. Comments on the Value of Big Data Studies <s> There is growing concern in the scientific community that many published scientific findings may represent spurious patterns that are not reproducible in independent data sets. A reason for this is that significance levels or confidence intervals are often applied to secondary variables or sub-samples within the trial, in addition to the primary hypotheses (multiple hypotheses). This problem is likely to be extensive for population-based surveys, in which epidemiological hypotheses are derived after seeing the data set (hypothesis fishing). We recommend a data-splitting procedure to counteract this methodological problem, in which one part of the data set is used for identifying hypotheses, and the other is used for hypothesis testing. The procedure is similar to two-stage analysis of microarray data. We illustrate the process using a real data set related to predictors of low back pain at 14-year follow-up in a population initially free of low back pain. “Widespreadness” of pain (pain reported in several other places than the low back) was a statistically significant predictor, while smoking was not, despite its strong association with low back pain in the first half of the data set. We argue that the application of data splitting, in which an independent party handles the data set, will achieve for epidemiological surveys what pre-registration has done for clinical studies. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> G. Comments on the Value of Big Data Studies <s> Big Data bring new opportunities to modern society and challenges to data scientists. On the one hand, Big Data hold great promises for discovering subtle population patterns and heterogeneities that are not possible with small-scale data. On the other hand, the massive sample size and high dimensionality of Big Data introduce unique computational and statistical challenges, including scalability and storage bottleneck, noise accumulation, spurious correlation, incidental endogeneity and measurement errors. These challenges are distinguished and require new computational and statistical paradigm. This paper gives overviews on the salient features of Big Data and how these features impact on paradigm change on statistical and computational methods as well as computing architectures. We also provide various new perspectives on the Big Data analysis and computation. In particular, we emphasize on the viability of the sparsest solution in high-confidence set and point out that exogenous assumptions in most statistical methods for Big Data cannot be validated due to incidental endogeneity. They can lead to wrong statistical inferences and consequently wrong scientific conclusions. <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> G. Comments on the Value of Big Data Studies <s> ABSTRACTPrecision medicine aims to combine comprehensive data collected over time about an individual’s genetics, environment, and lifestyle, to advance disease understanding and interception, aid drug discovery, and ensure delivery of appropriate therapies. Considerable public and private resources have been deployed to harness the potential value of big data derived from electronic health records, ‘omics technologies, imaging, and mobile health in advancing these goals. While both technical and sociopolitical challenges in implementation remain, we believe that consolidating these data into comprehensive and coherent bodies will aid in transforming healthcare. Overcoming these challenges will see the effective, efficient, and secure use of big data disrupt the practice of medicine. It will have significant implications for drug discovery and development as well as in the provisioning, utilization and economics of health care delivery going forward; ultimately, it will enhance the quality of care for the... <s> BIB003

Often the goal of big data studies is to draw causal conclusions, e.g., on the effectiveness of a drug or on a possible disease cause, and one needs to consider the value of an observational big data study versus classical randomized controlled trials (RCTs). Prospective RCTs are often cited as the gold standard for evidence since by a careful study design, effects of hidden confounders can be minimized. But RTCs also have their shortcomings, in particular, due to the way patients are selected for a study and due to the small sample size. RCTs are often done in relatively healthy homogeneous groups of patients chosen to be healthy except for the condition of interest and free of common diseases like diabetes or high blood pressure and neither extremely young or old . If patients have several problems, treating them as if they were mutually independent might be bad in general, and information on treatment-treatment interactions might not be easily assessable through RCTs. Also, interplay between diseases like hypertension, high cholesterol, and depression might not become apparent in RCTs. Since patients are difficult to recruit in general, and the management of clinical studies is costly, sample size is often small. For the same reasons, findings need to be general and not personalized and there are long delays until a result is certain and can become clinical practice. It has been suggested that patient-reported outcome measures are often better predictors of long-term prognosis . Nonrandomized, quasi-experimental studies are sometimes employed but provide less evidence than RCTs . Big data analyses, in contrast, consider data from a large variety of patients and potentially can draw conclusions from a much larger sample. They are based on the natural population of patients, and conclusions can be personalized. For instance, with depressed diabetic patients, one would want to compare hospitalization rates between those taking antidepressants and those who were not, to determine if more patients should receive psychiatric treatment to help them manage their health. Currently such studies involve great efforts. In future big data healthcare, these questions could be answered by a simple database query . Big data analysis mostly concerns observational studies (cohort studies, case-control studies) whose conclusions are considered by some to be statistically less reliable. The main reason is that hidden confounders might produce correlations, independent of a causal effect. Confounders are variables that both influence clinical decisions and, at the same time, outcome. Multivariate models should be considered where predictors contain all variables that were used in decision making. Unfortunately, some of these variables might not be available for analysis, such as patient symptoms and patient complains, which are often not well documented. Data collection might introduce various forms of biases. Examples are batch effects, which might occur in the merging of data from different institutions; batch effects can be addressed by a careful statistical analysis BIB003 , BIB002 . It is still unclear if physicians are ready to use evidence from big data. Generally accepted is the generation of novel hypotheses by big data studies, which are then clinically validated, although clinicians are critical toward hypothesis fishing BIB001 . Of course, clinical studies are very expensive and would only be initiated with significant evidence from data and with the prospect of large benefits. A desired and well-accepted outcome is the discovery of novel patient subgroups based on risk of disease, or response to therapy, using diagnostic tests enabling targeted therapy. This is the basis for a precision medicine (see Section VII). For example, asthma is largely regarded as a single disease and current treatment options tend to address its symptoms rather than its underlying cause. It is now accepted that asthma patients can be grouped according to patterns of differential gene expression and clinical phenotype with group-specific therapies . A predictive or prescriptive analysis might output a prediction (e.g., prediction of some clinical end point), or a ranking or prioritization of treatments. In these cases, the output might have been calculated based on many patient dimensions and this process might be difficult to interpret. Prioritization is currently still contrary to medical tradition and it remains to be seen if the medical profession will accept this aspect of a big data decision support system. It is important to understand why machine learning solutions typically work with many inputs. In a perfect situation, a diagnostic test can reveal the cause of a problem and the subsequent therapies solve the problem. In reality, even with all advances in diagnostics, we are often still very far from being able to completely describe the health status of an individual. Technically, the health status of a patient consists of may dimensions and only some of these dimensions (i.e., some infections, some cancer types) can be inferred by specific diagnostic tests. In big data analysis, one is partially doing "new medicine," i.e., one might address problems from new disease subgroups or syndromes that cannot be detected unambiguously with existing diagnostic tests. Since the statistical model then implicitly needs to infer the latent causes from observed proxies, the models often become high dimensional, and their predictions become difficult to interpret by humans, although predictive performance might be excellent. This is an effect observed in a multitude of predictive machine learning applications in and outside healthcare. The big data perspective is: If there are latent diseases, disease subgroups, or syndromes, they might be reflected by a large number of observed dimensions.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Data Accessible to Payers: Billing Data <s> New reimbursement policies and pay-for-performance programs to reward providers for producing better outcomes are proliferating. Although electronic health record (EHR) systems could provide essential clinical data upon which to base quality measures, most metrics in use were derived from administrative claims data. We compared commonly used quality measures calculated from administrative data to those derived from clinical data in an EHR based on a random sample of 125 charts of Medicare patients with diabetes. Using standard definitions based on administrative data (which require two visits with an encounter diagnosis of diabetes during the measurement period), only 75% of diabetics determined by manually reviewing the EHR (the gold standard) were identified. In contrast, 97% of diabetics were identified using coded information in the EHR. The discrepancies in identified patients resulted in statistically significant differences in the quality measures for frequency of HbA1c testing, control of blood pressure, frequency of testing for urine protein, and frequency of eye exams for diabetic patients. New development of standardized quality measures should shift from claims-based measures to clinically based measures that can be derived from coded information in an EHR. Using data from EHRs will also leverage their clinical content without adding burden to the care process. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Data Accessible to Payers: Billing Data <s> I. INTRODUCTION When Lind Weaver starting receiving collections demands for a foot amputation she never had, she assumed it was a clerical error.1 Unfortunately, the operation had been performed on someone pretending to be Weaver, causing Weaver's medical history to become entangled in the thief's.2 Media reports about identity theft show Weaver's experience is far from unique. For example, a Chicago man was arrested after using his friend's identity to obtain $350,000 worth of cardiovascular surgery at a local hospital.3 Hackers broke into the medical records of thousands of University of California students.4 A staff member left a laptop containing records of patients of a local AIDS clinic on Boston public transportation.5 Further opportunities for thieves lurk in every unshredded envelope, online transaction or credit card purchase. Breaches of financial data, often the result of hacking or theft or loss of sensitive computer equipment are routine fixtures of the news cycle.6 Consumers are encouraged to check their credit scores and monitor their accounts for any suspicious activity.7 In sum, we are being bombarded with warnings about the threat of identity theft. This media saturation focuses on the misuse of a data linked to a victim's identity to gain access to consumer credit tools such as credit cards and loans. Yet, medical identity theft, what Lind Weaver experienced, lurks in the background. Medical identity theft consists of the misuse of personal information to gain access to healthcare.8 A 2006 report by the Federal Trade Commission (FTC) estimated that there were at least 250,000 victims of medical identity theft for the period 2001-2006." The actual number is likely even higher.10 In a more recent survey of identity theft victims assisted in 2008 by the non-profit Identity Theft Resource Center, two thirds of the 100 victims surveyed reported being billed for medical services they did not receive.11 To some extent the emergence of medical identity theft is not surprising. First, healthcare providers are the largest compilers of personal data12 and are just as vulnerable to attack as the financial industry.13 Second, the high cost of health care creates an incentive to steal the identity of someone with insurance in order to obtain needed health care services, to further drug-seeking behavior, or to defraud third-party payers.14 In addition to financial harms such as being billed for services not rendered, medical identity theft can introduce inaccuracies into a victim's medical records, causing a cascade of clinical, insurance, and even reputational harms. Unlike victims of financial identity theft who can use the credit reporting system to recover from financial identity theft, victims of medical identity theft lack similar statutory resources, and there are few available private remedies. Further, structural and regulatory features of the healthcare system, including those governed by the Health Insurance Portability and Accountability Act of 1996 (HIPAA)15 make it extremely difficult for victims to discover and remedy the damage caused to their medical records by an identity thief. To put it simply, "[tjhere is no single place individuals can go to locate and correct inaccurate medical information."16 Current regulatory focus on increasing privacy and security through technological improvement, such as the HITECH Act amendments to HIPAA and the push to develop electronic health records (EHRs) do nothing to address victims' access problems to their own medical records. Further there is no private incentive to develop resources for victims. Finally, new regulations requiring health care providers to prevent fraud and new data breach notification rules do not resolve the basic problem of access. This note will argue that, given the fragmented nature of the healthcare market, a new federal regulatory initiative modeled on what is available to victims of financial identity theft is necessary to give victims an effective means of protecting the integrity of their personal health records. … <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Data Accessible to Payers: Billing Data <s> The amount of data in our world has been exploding, and analyzing large data sets—so-called big data— will become a key basis of competition, underpinning new waves of productivity growth, innovation, and consumer surplus, according to research by MGI and McKinsey's Business Technology Office. Leaders in every sector will have to grapple with the implications of big data, not just a few data-oriented managers. The increasing volume and detail of information captured by enterprises, the rise of multimedia, social media, and the Internet of Things will fuel exponential growth in data for the foreseeable future. <s> BIB003

The most common situation where data are leaving the clinic is when claims are filed with a payer, e.g., a health insurer or a health plan. Depending on the particular reimbursement rules in place, payers see data of varying levels of detail, quality, and biases. Unfortunately, claims data may not fully reflect a patient's burden of illness BIB001 , . While the appropriateness of billing data to clinical research is often debated, many, many studies have used these data to guide clinical care, policy, and reimbursement. Claims data provide a holistic view of the patient across providers for a specific period of time and these data permit a patient-centric view on health. Claims data also provide direct and indirect evidence of outcome, e.g., by analyzing readmissions, and inform on cost efficiencies and treatment quality across providers. Payer organizations are increasingly interested in better understanding their customers, in this case their patients. Surveys, questionnaires, call center data, and increasingly social media, including tweets and blogs, are analyzed for gaining insights to improve quality of services and to optimize offerings. A major concern is the detection and prevention of abuse and fraud. A 2011 McKinsey report stated that fighting healthcare fraud with big data analysis can be quite effective BIB003 . Healthcare fraud in the United States alone involves tens of billions of dollars of damages each year and fighting fraud is one of the obvious activities to immediately reducing healthcare costs. Note that some forms of fraud actually do not only harm the payer but directly the patient (e.g., by unnecessary surgery) BIB002 , . Naturally, there is a gray zone between charging for justified claims on the one side and abuse and fraud on the other side. Certainly, billing for services never provided, e.g., for fictitious patients or deceased patients, is clearly fraud, but if an expensive treatment is necessary or not in a case might be debatable. Technical solutions focus on the detection of known fraud patterns, the prioritization of suspicious cases, and the identification of new forms of fraud. A more sophisticated approach uses statistical models of clinical pathways and best practices to detect abnormal claims (against the population) and analyzes suspicious temporal changes in charging patterns within the same provider. In addition, one can analyze different kinds of provider networks, where nodes are the providers and the links are common patients, analyzing homophily or "guilt by association" patterns. Another measure is the black listing of providers. Most commercial systems use a combination of different strategies . Despite all these efforts, and mostly due to the fragmentation in the system and a huge gray zone, it is estimated that only a small percentage of the fraud actually occurring is currently being detected.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Analyzing Traces <s> An increasing number of public and commercial initiatives invite individuals to participate in scientific research via the internet (Table 1). People are asked to provide information about personal medical history, medications, physical traits and measurements, ethnicity/ancestry, lifestyle and environmental exposures, and to donate biological material, generally saliva or blood, for DNA analysis. Some initiatives, such as the Personal Genome Project, have been launched with the specific goal of conducting scientific research, whereas others perform scientific analyses using data that were at least partly collected for other purposes. For example, PatientsLikeMe is an online community where patients can share information on symptoms, health state, and treatments to learn from each others' experiences, and the company 23andMe sells personal genome tests to individuals who want to learn their genetic risks of common diseases, carrier status of rare diseases, response to drug treatment, and ancestry. Data are collected predominantly through self-report online questionnaires and some initiatives offer the opportunity to make data accessible for the public. For example, the Personal Genome Project publishes anonymized data online and participants of PatientsLikeMe can choose to publish all data publicly available on the web or make data accessible only to registered users. ::: ::: ::: ::: Table 1 ::: ::: Examples of online research initiatives. ::: ::: ::: ::: Strong claims regarding the benefits of research using these resources are often made in order to encourage individuals to provide personal (health) information. For example, 23andWe, the research arm of 23andMe “gives customers the opportunity to leverage their data by contributing it to studies of genetics. With enough data, we believe 23andWe can produce revolutionary findings that will benefit us all” [1]. PatientsLikeMe tells patients that sharing personal stories and health data does not only enable individuals to “put your disease experiences in context and find answers to the questions you have” but also gives “the opportunity to help uncover great ideas and new knowledge” [2]. But how valid are these claims? Can online data collection lead to major breakthroughs in health research? We worry that overstating the conclusions that can be drawn from these resources may impinge on individual autonomy and informed consent. Just as researchers must take care to accurately convey direct benefits to study participants (which, we argue, in these situations are often small), they should also describe the likely outcomes and known limitations of observational studies conducted using volunteers. Clarity regarding the benefits of research using solicited personal data is particularly important when the data collected are also used for other purposes (e.g., PatientsLikeMe may sell members' information to pharmaceutical and insurance companies [2]), lest the allure of participation in a scientific study be used as a Trojan horse to entice individuals to part with information they might not otherwise volunteer. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Analyzing Traces <s> For several years personal genome tests have been offered directly to consumers via the internet. Based on single genome scans, these direct-toconsumer (DTC) tests predict susceptibility to common multifactorial diseases, such as Type 2 diabetes, coronary heart disease and nonfamilial cancer, inform about predisposition to drug response, report carrier status for monogenic diseases, or provide all of the above. The market is served by a few major players, such as 23andMe and deCODEme, and numerous lesser-known companies such as YouScript, GenePlanet and Theranostics [101–105]. The market for DTC personal genome testing is steadily increasing, even though the evidence on the predictive ability and clinical utility of these tests is limited. The few available studies have shown that predicted risks of multifactorial diseases differed between companies and were sometimes even contradictory for the same individual [1,106], but large-scale studies on the predictive ability are lacking. From prediction studies that investigated genetic risk models based on different but comparable selections of SNPs, we know that the predictive ability of genetic testing for multifactorial diseases is low to moderate, except when one or more SNPs had substantial impact on disease risk [2]. From this indirect evidence it is concluded that the DTC offer of genetic testing for multifactorial diseases is premature. To date, most of the discussion about DTC personal genome tests has focused on the prediction of these multifactorial diseases and less attention has been given to the predictive ability and clinical utility of pharmacogenetic testing. Yet, many companies offer pharmacogenetic testing to inform about the genetic susceptibility to drug response and side effects of treatment [3], such as the efficacy of clopidogrel and the risk <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Analyzing Traces <s> In February 2013, Google Flu Trends (GFT) made headlines but not for a reason that Google executives or the creators of the flu tracking system would have hoped. Nature reported that GFT was predicting more than double the proportion of doctor visits for influenza-like illness (ILI) than the Centers for Disease Control and Prevention (CDC), which bases its estimates on surveillance reports from laboratories across the United States ( 1 , 2 ). This happened despite the fact that GFT was built to predict CDC reports. Given that GFT is often held up as an exemplary use of big data ( 3 , 4 ), what lessons can we draw from this error? <s> BIB003 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Analyzing Traces <s> Large-scale aggregate analyses of anonymized data can yield valuable results and insights that address public health challenges and provide new avenues for scientific discovery. These methods can extend our knowledge and provide new tools for enhancing health and wellbeing. However, they raise questions about how to best address potential threats to privacy while reaping benefits for individuals and to society as a whole. The use of machine learning to make leaps across informational and social contexts to infer health conditions and risks from nonmedical data provides representative scenarios for reflections on directions with balancing innovation and regulation. <s> BIB004

Statistics on anonymized search query logs and traces in social media can be analyzed to inform public health, epidemiologists, and policy makers. It can support the early detection of epidemics, the analysis and modeling of the flow of illness, and other purposes BIB004 . Infodemiology is a new term standing for the large-scale analyses of anonymized traces, which can potentially yield valuable results and insights. The analysis can address public health challenges and provide new avenues for scientific discovery BIB004 . A widely discussed example is the analysis of search query logs as indicators for disease outbreaks. The idea is that social media and search logs might indicate an outbreak of an infectious disease like a flu immediately, including detailed temporal-spatial information of its spread. Previously, such outbreaks might go unnoticed for days of even weeks. But models have proven difficult. Google flu, for example, predicted well initially but the fit was very poor later BIB003 , . Another application is the detection of adverse drug reactions, which could be improved by jointly analyzing data from the U.S. Food and Drug Administration's Adverse Event Reporting System, anonymized search logs and social media data BIB004 . The analysis of patients' traces has increasing importance in pharmacovigilance, which concerns the collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products. Still there is little experience yet in the quality, reliability, and biases in data generated from web query logs and social network sites and conclusions should be drawn with great caution BIB001 , BIB002 . There is also a danger in these developments: The same traces, when reidentified, can be aimed at making inferences about unique individuals that could be used to infer their health status. Many problems are associated, e.g., with social scoring in healthcare. BIB004 reports on a Twitter suicide prevention application called Good Samaritan that monitored individuals' tweets for words and phrases indicating a potential mental health crisis. The service was removed after increasing complaints about violations of privacy and imminent dangers of stalking and bullying. As pointed out in BIB004 , health issues can also be inferred from seemingly unrelated traces. Simply changing communication patterns on social networks and internet search might indicate a new mother at risk for postpartum depression. Another issue is that some companies are working together with analytic experts to track employees' search queries, medical claims, prescriptions, and even voting habits to get insight into their personal lives . Although HIPAA legislation forbids employers to view their employees' health information, this does not apply to third parties. A company which received public attention is Castlight, which gathers data on workers' medical information, such as who is considering pregnancy or who may need back surgery. Castlight's policy is to only inform and advice the individuals directly and only report statistics to employers. These issues are increasingly addressed by regulators, e.g., in the United States by the Americans with Disabilities Act (ADA) and the Genetic Information Non-Discrimination Act (GINA). Horvitz and Mulligan BIB004 point out the technical difficulties in protecting the citizens against violations, in the face of powerful machine learning algorithms which can "jump categories": Machine learning can enable inferences about health conditions from nonmedical data generated far outside the medical context BIB004 .

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> C. PatientsLikeMe <s> Background: This project investigates the ways in which patients respond to the shared use of what is often considered private information: personal health data. There is a growing demand for patient access to personal health records. The predominant model for this record is a repository of all clinically relevant health information kept securely and viewed privately by patients and their healthcare providers. While this type of record does seem to have beneficial effects for the patient-physician relationship, the complexity and novelty of these data coupled with the lack of research in this area means the utility of personal health information for the primary stakeholders -- the patients-is not well documented or understood. ::: Objective: PatientsLikeMe® is an online community built to support information exchange between patients. The site provides customized disease-specific outcome and visualization tools to help patients understand and share information about their condition. We begin this paper by describing the components and design of the online community. We then identify and analyze how users of this platform reference personal health information within patient-to-patient dialogues. ::: Methods: Patients diagnosed with amyotrophic lateral sclerosis (ALS) post data on their current treatments, symptoms, and outcomes. These data are displayed graphically within personal health profiles and are reflected in composite community-level symptom and treatment reports. Users review and discuss these data within the Forum, private messaging, and comments posted on each others' profiles. We analyzed member communications that referenced individual-level personal health data to determine how patient peers use personal health information within patient-to-patient exchanges. ::: Results: Qualitative analysis of a sample of 123 comments (about 2% of the total) posted within the community revealed a variety of commenting and questioning behaviors by patient members. Members referenced data to locate others with particular experiences to answer specific health-related questions, proffer personally acquired disease-management knowledge to those who are most likely to benefit from it, and foster and solidify relationships based on shared concerns. ::: Conclusions: Few studies examine the use of personal health information by patients themselves. This project suggests how patients who choose to explicitly share health data within a community may benefit from the process, helping patients engage in dialogues that may inform disease self-management. We recommend that future designs make each patient's health information as clear as possible, automate matching of people with similar conditions and using similar treatments, and integrate data into online platforms for health conversations. ::: Keywords: personal health records; data visualization; personal monitoring; technology; healthcare; self-help devices; personal tracking; social support; online support group; online health community; ::: Social Uses of Personal Health Information Within PatientsLikeMe (4 Aud 1000 Frost Massagli) View SlideShare presentation or Upload your own. (tags: medicine20 phr ) [] <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> C. PatientsLikeMe <s> PatientsLikeMe (PLM) is an online community where patients share their personal experiences with a disease, find other patients like them, and learn from each other. The company was founded by Jamie and Ben Heywood when their 29-year-old brother was diagnosed with ALS or Lou Gehrig's disease. In less than five years, PLM has grown to 15 patient communities where over 80,000 patients discuss 19 diseases. In December 2010, PLM is discussing its planned launch of a General Platform that would expand the number of diseases covered from 19 to over 3,500. Is it the right move, and what does PLM need to do to make it a success?Learning Objective: To understand how an online community is built and monetized and to highlight the challenges in growing the platform to a larger scale. <s> BIB002

An openly commercial social network initiative is PatientsLikeMe BIB002 , with several hundred thousands of patients using the platform and addressing more than a thousand diseases. The majority of users have neurological diseases such as ALS, multiple sclerosis, and Parkinson's, but PatientsLikeMe is also increasingly addressing AIDS and mood disorders BIB001 , . PatientsLikeMe is not merely a chat board with selfhelp news but also collects quantitative data. It has designed several detailed questionnaires which are circulated regularly to its members. For example, epileptics can enter their seizure information into a seizure monitor. It has a survey tool to measure how closely patients adhere to their treatment regimen, but also scans language in the chat boards for alarming words and expressions. Patients-LikeMe offers a number of services. For example, it created a contrast sensitivity test together with the Massachusetts Eye and Ear Hospital for people with Parkinson's and hallucinations that come with mood disorders. http://www.optimizedcare.net/ The business model of PatientsLikeMe is not based on advertising. Instead, the company has based its business model around aligning patient interests with industry interests, i.e., accelerated clinical research, improved treatments, and better patient care. To achieve these goals, Patients-LikeMe sells aggregated, deidentified data to its partners, including pharmaceutical companies and medical device makers. In this way, PatientsLikeMe aims to help partners in the healthcare industry better understand the real-world experiences of patients as well as the real-world course of disease. Some of PatientsLikeMe's past and present partners include UCB, Novartis, Sanofi, Avanir Pharmaceuticals, and Acorda Therapeutics.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> V I. CON T IN UOUS HE A LT HC A R E <s> The author presents information on mobile health (mHealth) technology and argues that mHealth applications could be used for biomedical research as of June 2012. Topics include cell phones and the wireless transmission of health data, the cost-effectiveness of health assessments with mobile devices, and how health practitioners and software developers should collaborate to create innovative mHealth technologies. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> V I. CON T IN UOUS HE A LT HC A R E <s> Objective The aim of this systematic review was to synthesize current knowledge of the factors influencing healthcare professional adoption of mobile health (m-health) applications. ::: ::: Methods Covering a period from 2000 to 2014, we conducted a systematic literature search on four electronic databases (PubMed, EMBASE, CINAHL, PsychInfo). We also consulted references from included studies. We included studies if they reported the perceptions of healthcare professionals regarding barriers and facilitators to m-health utilization, if they were published in English, Spanish, or French and if they presented an empirical study design (qualitative, quantitative, or mixed methods). Two authors independently assessed study quality and performed content analysis using a validated extraction grid with pre-established categorization of barriers and facilitators. ::: ::: Results The search strategy led to a total of 4223 potentially relevant papers, of which 33 met the inclusion criteria. Main perceived adoption factors to m-health at the individual, organizational, and contextual levels were the following: perceived usefulness and ease of use, design and technical concerns, cost, time, privacy and security issues, familiarity with the technology, risk-benefit assessment, and interaction with others (colleagues, patients, and management). ::: ::: Conclusion This systematic review provides a set of key elements making it possible to understand the challenges and opportunities for m-health utilization by healthcare providers. <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> V I. CON T IN UOUS HE A LT HC A R E <s> Background: Despite the recent explosion of the mobile health (mHealth) industry and consumer acquisition of mHealth tools such as wearable sensors and applications (apps), limited information is known about how this technology can sustain health behavior change and be integrated into health care. Objective: The objective of the study was to understand potential users’ views of mHealth technology, the role this technology may have in promoting individual activity goals aimed at improving health, and the value of integrating mHealth technology with traditional health care. Methods: Four focus groups were conducted with adults interested in sharing their views on how mHealth technology could support wellness programs and improve health. Participants (n=30) were enrolled from an employee population at an academic health institution. Qualitative thematic analysis was used to code transcripts and identify overarching themes. Results: Our findings suggest that tracking health data alone may result in heightened awareness of daily activity, yet may not be sufficient to sustain use of mHealth technology and apps, which often have low reuse rates. Participants suggested that context, meaning, and health care partnerships need to be incorporated to engage and retain users. In addition to these findings, drivers for mHealth technology previously identified in the literature, including integration and control of health data were confirmed in this study. Conclusions: This study explores ways that mHealth technologies may be used to not only track data, but to encourage sustained engagement to achieve individual health goals. Implications of these findings include recommendations for mHealth technology design and health care partnership models to sustain motivation and engagement, allowing individuals to achieve meaningful behavior change. [JMIR Mhealth Uhealth 2016;4(1):e5] <s> BIB003

With the tremendous technological progress and prevalence of mobile devices, the disruptive potential of mobile health, and also more general technology-enabled care, is frequently discussed BIB001 , . A new generation of affordable sensors is able to collect health data outside the clinic in an unprecedented quality and quantity. This enables the transition from episodic healthcare, dominated by occasional encounters with healthcare providers, to continuous healthcare, i.e., health monitoring and care, potentially anytime and anywhere! Continuous healthcare certainly has the potential to create a shift in the current care continuum from a treatmentbased healthcare to a more prevention-based system. At a first glance this seems like a distant goal but many health problems can be prevented by a healthy life style and the early detection of disease onset, in combination with early intervention. However, the full potential remains to be unlocked as a 2012 Pew Research Center study about mobile health reveals . While about half of smartphone owners use their phone to look up health information, only one in five smartphone users owns a health app. Currently, this exciting field is in a flux and opportunities, challenges, and crucial factors for the widespread adoption are discussed in current research BIB002 - BIB003 .

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> A. Technological Basis <s> Body Area Networks integrated into mHealth systems are becoming a mature technology with unprecedented opportunities for personalized health monitoring and management. Potential applications include early detection of abnormal conditions, supervised rehabilitation, and wellness management. Such integrated mHealth systems can provide patients with increased confidence and a better quality of life, and promote healthy behavior and health awareness. Automatic integration of collected information and user's inputs into research databases can provide medical community with opportunity to search for personalized trends and group patterns, allowing insights into disease evolution, the rehabilitation process, and the effects of drug therapy. A new generation of personalized monitoring systems will allow users to customize their systems and user interfaces and to interact with their social networks. With emergence of first commercial body area network systems, a number of system design issues are still to be resolved, such as seamless integration of information and ad-hoc interaction with ambient sensors and other networks, to enable their wider acceptance. In this paper we present state of technology, discuss promising new trends, opportunities and challenges of body area networks for ubiquitous health monitoring applications. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> A. Technological Basis <s> This work demonstrates that a full laboratory-quality immunoassay can be run on a smartphone accessory. This low-cost dongle replicates all mechanical, optical, and electronic functions of a laboratory-based enzyme-linked immunosorbent assay (ELISA) without requiring any stored energy; all necessary power is drawn from a smartphone. Rwandan health care workers used the dongle to test whole blood obtained via fingerprick from 96 patients enrolling into care at prevention of mother-to-child transmission clinics or voluntary counseling and testing centers. The dongle performed a triplexed immunoassay not currently available in a single test format: HIV antibody, treponemal-specific antibody for syphilis, and nontreponemal antibody for active syphilis infection. In a blinded experiment, health care workers obtained diagnostic results in 15 min from our triplex test that rivaled the gold standard of laboratory-based HIV ELISA and rapid plasma reagin (a screening test for syphilis), with sensitivity of 92 to 100% and specificity of 79 to 100%, consistent with needs of current clinical algorithms. Patient preference for the dongle was 97% compared to laboratory-based tests, with most pointing to the convenience of obtaining quick results with a single fingerprick. This work suggests that coupling microfluidics with recent advances in consumer electronics can make certain laboratory-based diagnostics accessible to almost any population with access to smartphones. <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> A. Technological Basis <s> Sickle cell disease affects 25% of people living in Central and West Africa and, if left undiagnosed, can cause life threatening “silent” strokes and lifelong damage. However, ubiquitous testing procedures have yet to be implemented in these areas, necessitating a simple, rapid, and accurate testing platform to diagnose sickle cell disease. Here, we present a label-free, sensitive, and specific testing platform using only a small blood sample (<1 μl) based on the higher density of sickle red blood cells under deoxygenated conditions. Testing is performed with a lightweight and compact 3D-printed attachment installed on a commercial smartphone. This attachment includes an LED to illuminate the sample, an optical lens to magnify the image, and two permanent magnets for magnetic levitation of red blood cells. The sample is suspended in a paramagnetic medium with sodium metabisulfite and loaded in a microcapillary tube that is inserted between the magnets. Red blood cells are levitated in the magnetic field based on equilibrium between the magnetic and buoyancy forces acting on the cells. Using this approach, we were able to distinguish between the levitation patterns of sickle versus control red blood cells based on their degree of confinement. <s> BIB003

The technological basis of mHealth includes smart sensors, smart apps and devices, advanced telemedicine networks such as the optimized care network 7 and supporting software platforms. There is a broad range of new devices that have entered the market: smartphones, smart watches, smart wrist bands, smart head sets, and Google Glass, among others. In the future, patient consumers might use a number of different devices that measure a multitude of different signals: "headsets that measure brain activity, chest bands for cardiac monitoring, motion sensors for seniors living alone, remote glucose monitors for diabetes patients, and smart diapers to detect urinary tract infections" [11] . A Body Area Networks (BAN) is another form of a technological enabler with sensors that measure physiological signals, physical activities, or environmental parameters and come along with an internet-like infrastructure. BANs are, e.g., used to monitor cardiac patients and help to diagnose cardiac arrhythmias BIB001 . Add-ons to mobile devices such as lab-on-a-chip technologies are particularly interesting technologies and might represent a new form of point-of-care devices. Laksanasopin et al. BIB002 present a laboratory-quality immunoassay that can be run on a smartphone accessory and Knowlton et al. BIB003 present a 3-D printed attachment for a smartphone for the detection of sickle cell disease. Especially for developing countries with a limited infrastructure, the potential of such technologies is tremendous. From an engineering perspective, continuous healthcare is related to condition monitoring and predictive maintenance, enabled by smart sensors, connectivity, and analytics-a combination often referred to as the Internet of Things (IoT). By measuring and aggregating the signals of many different persons, machine learning 9 http://www.alivecor.com/ 10 http://w w w.roche.com/media/store/roche_stories/rochestories-2015-08-10.htm 11 http://www.ctti-clinicaltrials.org/ algorithms can be trained to detect, e.g., anomalies and unexpected correlations that might generate new insights. Open source initiatives such as the Open mHealth initiative are important enablers that could pave the way to overcome the data integration challenge.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Use Case Types <s> Body Area Networks integrated into mHealth systems are becoming a mature technology with unprecedented opportunities for personalized health monitoring and management. Potential applications include early detection of abnormal conditions, supervised rehabilitation, and wellness management. Such integrated mHealth systems can provide patients with increased confidence and a better quality of life, and promote healthy behavior and health awareness. Automatic integration of collected information and user's inputs into research databases can provide medical community with opportunity to search for personalized trends and group patterns, allowing insights into disease evolution, the rehabilitation process, and the effects of drug therapy. A new generation of personalized monitoring systems will allow users to customize their systems and user interfaces and to interact with their social networks. With emergence of first commercial body area network systems, a number of system design issues are still to be resolved, such as seamless integration of information and ad-hoc interaction with ambient sensors and other networks, to enable their wider acceptance. In this paper we present state of technology, discuss promising new trends, opportunities and challenges of body area networks for ubiquitous health monitoring applications. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Use Case Types <s> The author presents information on mobile health (mHealth) technology and argues that mHealth applications could be used for biomedical research as of June 2012. Topics include cell phones and the wireless transmission of health data, the cost-effectiveness of health assessments with mobile devices, and how health practitioners and software developers should collaborate to create innovative mHealth technologies. <s> BIB002

1) Disease Prevention: Smartphones are increasingly being used for measuring, managing, and displaying health and lifestyle related parameters such as weight, physical activity, smoking, and diabetes, among others. Improving lifestyle and fitness of the general population has the potential to reduce healthcare costs dramatically, and thus this type of health monitoring might have dramatic positive impact on both population health and healthcare cost. In a recent statement, the American Heart Association (AHA) reviewed the current use of mobile technologies to reduce cardiovascular disease (CVD) risk behavior . CVD continues to be the leading cause of death, disability, and high healthcare costs and is thus a prime example for investigating the potential of mHealth technologies. The work investigates different tools available to consumers to prevent CVD ranging from text messages (e.g., smoking cessation support), wearable sensors, and other smartphone applications. While more evidence and studies are needed, it appears that mHealth in CVD prevention is promising. The AHA strongly encourages more research. 2) Early Detection: Many diseases can be treated best when discovered early and before they cause serious health consequences. Early detection can happen at the population level or at the individual level. Collins BIB002 highlights an early warning system for disease outbreaks caused by illness-related parameters such as environmental exposure or infectious agents. On the individual level, the previously mentioned BAN is a major enabler for early detection of abnormalities. So-called smart alarms can be understood as another form of early detection on the individual level. Smart alarms cover a range of applications and are especially relevant to the elderly and monitor heart activity, breathing, to potential falls BIB001 . The company AliveCor 9 is offering a mobile ECG that is attached to a mobile device (either a smartphone or a tablet). The attached device creates an ECG that is then recorded via an app. The mobile ECG is cleared by the FDA and can also detect atrial fibrillation, a leading cause of mortality and morbidity. AliveCor states that the device has been used to record over five million ECGs. These data are then the basis for training an anomaly detection algorithm. 3) Disease Management: Healthcare costs can be reduced when the patient can be monitored at home instead of in the clinic and if physicians can optimize care without the need to call in the patients for a medical visit. Some hospitals and clinics collect continuous data on various health parameters as part of research studies [11] . Especially the management of chronic diseases can benefit from continuous healthcare. In a recent review , Hamine et al. screen systematically for randomized clinical trials that give evidence about better treatment adherence when using mHealth technologies. The type of applications range from simple SMS services to video messaging with smartphones and other wireless devices. They conclude that there is, without doubt, high potential for these technologies but, as the evidence in the trials was mixed, further research is needed to improve usability, feasibility, and acceptability. 4) Support of Translational Research: With hundreds of millions of smartphones in use around the world, the way patients are recruited to participate in clinical studies might change dramatically. In the future, patients might be able to decide themselves if they want to participate in a medical study and they might be able to specify how their data are used and shared with others. Major research institutions have already developed apps for studies involving asthma, breast cancer, cardiovascular disease, diabetes, and Parkinson's disease. One interesting use case is the control of disease endpoints in clinical trials with mHealth technologies. As a concrete example, Roche developed an app to control or measure the clinical endpoints of Parkinson's disease. The app, which complements the traditional physician-led assessment, is currently used in a Phase I trial to measure in a continuous way disease and symptom severity. The app is based on the Unified Parkinson's Disease Rating Scale (UPDRS) which is the traditional measurement for the disease and symptom severity. The test, which takes about 30 s, investigates six endpoint-relevant parameters such as a voice test, balance test, gain test, dexterity test, rest tremor tests, and postural tremor. The Clinical Trials Transformation Initiative, 11 an association representing diverse stakeholders along the clinical trial space, works on the next generation of clinical trials. Recently, the initiative has launched a mobile clinical trials program to investigate how mobile technologies and other off-site remote technologies can further facilitate clinical trials.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> V II. GET TING PER SONA L A. Precision Medicine Is Changing Healthcare <s> The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> V II. GET TING PER SONA L A. Precision Medicine Is Changing Healthcare <s> Epigenetics acts as an interface between environmental / exogenous factors, cellular responses and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases, including non-neoplastic disorders (e.g., cardiovascular diseases, hypertension, diabetes mellitus, autoimmune diseases, and some infectious diseases) and neoplasms (e.g., leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc.) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. DNA methylation assays are widely applied to formalin-fixed paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiologic factors, cellular molecular characteristics, and disease evolution, the field of “Molecular Pathological Epidemiology (MPE)” has emerged as an interdisciplinary integration of “molecular pathology” and “epidemiology”, with a similar conceptual framework to systems biology and network medicine. In contrast to traditional epidemiologic research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle; that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macro-environment and tissue microenvironment. The widespread application of epigenomics (e.g., methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator phenotype, LINE-1 hypomethylation, etc.), and host-disease interactions. MPE may represent a logical evolution of GWAS, termed “GWAS-MPE approach”. Though epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell within one individual has a unique, time-varying epigenome. This article will illustrate increasing contribution of modern pathology to broader public health sciences, which attests pivotal roles of pathologists in the new integrated MPE science towards our ultimate goal of personalized medicine and prevention. <s> BIB002

Maximizing the positive effect of a healthcare intervention by concurrently minimizing adverse side effects has always been the dream of individualized healthcare. Over the last decades it became clear that this goal could not be achieved with insights from conventional studies alone, which have been focusing on empirical intervention efficacy and side effects in large patient study groups. The reason is that, due to the biological diversity of individuals, environment, and pathogenesis, any incident of a complex disease is like no other. Precision medicine, personalized medicine, individualized medicine, and stratified medicine-terms we will use interchangeably-all refer to the grouping of patients based on the risk of disease, or response to therapy, using diagnostic tests. Precision medicine refers to the idea to customize healthcare, with medical decisions, practices, and procedures being tailored to a patient group. In its most extreme interpretation, this leads to the " n = 1 " principle, meaning that therapy should be tailored to the patient's individual characteristics, sometimes referred to as the "unique disease principle" BIB002 . Without question, the most important milestone for the realization of a personalized medicine was the publication of the reference sequence of the human genome about 15 years ago BIB001 , . In the following years, the patient's genomic profile, supplemented with other molecular and cellular data, became the basis for a dramatic progress in the understanding of the molecular basis of disease. The impact of this knowledge is not limited to research: As new analytical methods like next-generation sequencing (NGS) and new proteomic platforms bring cost down, molecular data will increasingly become part of clinical practice. The main goal is to link the generated data to clinically actionable information. With growing data, increasingly complex phenomena even with weak associations can be discovered and validated. As a matter of fact, research and clinical applications go along with a huge increase in the volume and variety of data available to characterize the physiology and pathophysiology. Genome-wide association studies (GWASs) with more than a million attributes collected from up to several thousands individuals are good examples. The vision of a realtime personalized healthcare is the rapid and real-time analysis of biomaterials obtained from the patients based on newest research results in a network of research labs and clinics. The insights in the biological causes of disease might lead to a more meaningful categorization of disease, at some point in the future replacing medical codes, which were mostly developed based on clinical phenotyping . By far the greatest efforts in precision medicine have been devoted to cancer (oncology), but precision medicine becomes increasingly relevant to other medical domains, e.g., the central nervous system (e.g., Alzheimer's and depression), immunology/transplant, prenatal medicine, pediatrics, asthma, infectious diseases, and CVD .

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Understanding Disease on a Molecular Level <s> The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigated. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated. Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer. It retained its significance even when adjustments were made for other known prognostic factors. Moreover, HER-2/neu amplification had greater prognostic value than most currently used prognostic factors, including hormonal-receptor status, in lymph node-positive disease. These data indicate that this gene may play a role in the biologic behavior and/or pathogenesis of human breast cancer. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Understanding Disease on a Molecular Level <s> A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substitution, and an inferred regulatory mutation. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1863 amino acids. This protein contains a zinc finger domain in its amino-terminal region, but is otherwise unrelated to previously described proteins. Identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology. <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Understanding Disease on a Molecular Level <s> Many examples highlight the power of gene expression profiles, or signatures, to inform an understanding of biological phenotypes. This is perhaps best seen in the context of cancer, where expression signatures have tremendous power to identify new subtypes and to predict clinical outcomes. Although the ability to interpret the meaning of the individual genes in these signatures remains a challenge, this does not diminish the power of the signature to characterize biological states. The use of these signatures as surrogate phenotypes has been particularly important, linking diverse experimental systems that dissect the complexity of biological systems with the in vivo setting in a way that was not previously feasible. <s> BIB003 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Understanding Disease on a Molecular Level <s> This year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable. Only 5–10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90–95% have their roots in the environment and lifestyle. The lifestyle factors include cigarette smoking, diet (fried foods, red meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity. The evidence indicates that of all cancer-related deaths, almost 25–30% are due to tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc. Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations, and regular check-ups. In this review, we present evidence that inflammation is the link between the agents/factors that cause cancer and the agents that prevent it. In addition, we provide evidence that cancer is a preventable disease that requires major lifestyle changes. <s> BIB004 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Understanding Disease on a Molecular Level <s> The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs). These studies were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders. We start by giving a number of quotes from scientists and journalists about perceived problems with GWASs. We will then briefly give the history of GWASs and focus on the discoveries made through this experimental design, what those discoveries tell us and do not tell us about the genetics and biology of complex traits, and what immediate utility has come out of these studies. Rather than giving an exhaustive review of all reported findings for all diseases and other complex traits, we focus on the results for auto-immune diseases and metabolic diseases. We return to the perceived failure or disappointment about GWASs in the concluding section. <s> BIB005 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Understanding Disease on a Molecular Level <s> We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer. <s> BIB006 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Understanding Disease on a Molecular Level <s> The successful completion of the Human Genome Project (HGP) was an unprecedented scientific advance that has become an invaluable resource in the search for genes that cause monogenic and common (polygenic) diseases. Prior to the HGP, linkage analysis had successfully mapped many disease genes for monogenic disorders; however, the limitations of this approach were particularly evident for identifying causative genes in rare genetic disorders affecting lifespan and/or reproductive fitness, such as skeletal dysplasias. In this review, we illustrate the challenges of mapping disease genes in such conditions through the ultra-rare disorder fibrodysplasia ossificans progressiva (FOP) and we discuss the advances that are being made through current massively parallel (“next generation”) sequencing (MPS) technologies. <s> BIB007 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> B. Understanding Disease on a Molecular Level <s> BACKGROUND: The development of minimally-invasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital PCR-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. In particular we studied the plasma of 14 medulloblastoma, 13 WHO grade 2-3 glioma and 14 WHO grade IV astrocytoma cases for levels of ctDNA. METHODS: The basis of our approach is to differentiate DNA shed by normal cells from DNA derived from tumor cells. In order to distinguish the two populations of cell-free DNA, we first identify a tumor-specific alteration. We then query for that exact mutation in matching plasma from the same patient to generate a personalized tumor biomarker. Only DNA derived from the tumor will harbor the genetic alteration. We initially use targeted, exomic, or whole genome sequencing to identify sequence or structural alterations in tumor tissues of 410 individuals. DNA was extracted from less than 5 ml of plasma in each case. The majority of plasma samples were queried for levels of ctDNA using a high fidelity next-generation sequencing approach coined Safe-SeqS. RESULTS: We found that at least one tumor-specific mutant molecule could be identified in 75% of patients with advanced ovarian, colorectal, bladder, gastroesophoageal, pancreatic, breast, melanoma, hepatocellular and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. Approximately 40% of medulloblastoma and 10% of low or high grade glioma cases had detectable levels of ctDNA. In patients with localized non-CNS tumors, ctDNA was detected in 73%, 57%, 48% and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor (EGFR) blockade in 24 colorectal cancer patients who objectively responded to therapy but who subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase (MAPK) pathway. CONCLUSIONS: Taken together, these data suggest that ctDNA is a sensitive, specific and robust biomarker that can be used for a variety of clinical and research purposes in patients with several multiple different types of cancer. For individuals with CNS neoplasms, alternate strategies may need to be developed in order to detect cell-free tumor derived DNA at levels that are clinically meaningful. ABSTRACT CATEGORY: Neuropathology & Tumor Biomarkers. <s> BIB008

In the last decades, a lot of attention has been focusing on understanding the genetic causes of disease. Monogenetic disorders with a high penetrance have been linked to mutations of single genes in inherited genes. The causative genes of most monogenic genetic disorders have now been identified BIB007 . Monogenetic diseases are relatively rare and attention has shifted largely to complex diseases: Most common diseases, including most forms of cancer, are based on an interaction of several factors, including a number of inherited genetic variations, one or several mutations acquired during cell lifetime, as well as environmental factors. Consider, for example, that worldwide approximately 18% of cancers are related to infectious diseases BIB004 . Due to the complex interplay of several factors, these diseases show what has been termed "missing heritability." Insights into inherited genetic cell disorders are obtained from germline DNA, typically obtained from blood cells. GWASs examine the correlation between germline genetic variations and common phenotypic characteristics, such as breast cancer BIB005 . With the establishment of next generation sequencing (NGS), in the future the whole genome might be decoded for costs in the order of a few hundred U.S. dollars and this will make genome analysis much more common. Eventually, the increasing use of genome sequencing will lead to better insights into which diseases can be explained by genetic variance and could revolutionize molecular medicine for some diseases. The likelihood of a person developing a disease in their lifetime can sometimes be predicted according to germline DNA profiles, permitting early intervention and possibly preventing an outbreak of the disease. Additional genetic variations of interest are those acquired during the lifetime of somatic cells, which comprise all cells that form an organism's body, excluding the germ cells. As genetic alterations accumulate, the somatic cell can turn into a malignant cell and form a cancerous tumor. Genetic profiles (mutations and amplifications) of somatic cancer cells are obtained from analyses of tumor biopsies. Their distinct mutations and gene amplification patterns are linked to many clinically relevant characteristics, such as prognosis or therapy response BIB006 . In some cases, the tumor is easily accessible, however, in other cases like tumors or metastases of certain organs (e.g., brain, liver, lung), a biopsy is not standard of care. In those cancer patients, the access to the material from which the genomic information could be obtained is difficult. Recently, novel methods have been developed that permit the analysis of alternative sources of tumor material, such as circulating tumor cells (CTCs). These are cancer cells that have shed into the blood stream from a primary tumor. CTCs can constitute seeds for subsequent growth of additional tumors (metastasis) in distant organs, triggering a mechanism that is responsible for the vast majority of cancer-related deaths. Thus, CTC analysis could be considered a "liquid biopsy." Also circulating tumor DNA (ctDNA) was found to resemble the tumor's genomic profile, being useful for cancer detection and prediction of therapy efficacy BIB008 . So far we have been focusing on DNA. The transcription of RNA from DNA is called gene expression. This step plays a crucial functional role, because RNA is translated directly into functional proteins. Furthermore, RNA has regulatory functions, of which many are not yet understood. In some cancers, such as breast cancer, the expression of This is a test that uses antibodies and color change to identify a substance. http://www.genome.gov/27541319 17 http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/basics/causes/con-20023871 some genes has already been proven to be of great clinical relevance. Even genomewide gene expression analyzes are becoming available to characterize cancer diseases BIB003 . Transcriptomics is the study of transcriptomes (RNA molecules, including mRNA, miRNA, rRNA, tRNA, and other noncoding RNA), their structures, and functions. DNA microarrays (which, despite their name, really test for RNA) and RNA-seq (RNA sequencing) can reveal a snapshot of RNA presence and quantify cellular activities at a given moment in time. Whereas the genome contains the code, the proteins are the body's functional worker molecules. Several methods like immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) are used in clinical practice for protein analysis. In research and recently also in clinical tests, mass spectroscopy is used to determine many proteins in a tissue, opening this field for high throughput and big data approaches . Increasingly also protein microarrays are used as a high-throughput method to track the interactions and activities of many proteins at a time. While the transformation of genetic information into functional proteins is recognized as being clinically highly relevant, the clinical relevance of other "omics" fields is still under investigation. Epigenomics, metabolomics, and lipidomics are three further levels of systems biology which might be unraveled by big data analyses. Epigenetic changes modify genes on a molecular level, such that expression is altered; the effects of these modifications are still largely unclear. Metabolomics concerns chemical fingerprints that specific cellular processes leave behind, in particular, the study of their smallmolecule metabolite. Lipidomics focuses on cellular lipids, including the modifications made to a particular set of lipids, produced by an organism or a system. The environment is increasing the number of possible interactions that play a role in the etiology (i.e., disease cause) and pathogenesis of a disease. The exposome encompasses the totality of human environmental (i.e., nongenetic) exposures from conception onwards, complementing the genome. For example, scientists believe that, for most people, Alzheimer's disease results from a combination of genetic, lifestyle, and environmental factors that affect the brain over time. Only in less than 5% of cases, Alzheimer's is caused by specific genetic changes that, by themselves, virtually guarantee a person will develop the disease. As a medical field, molecular medicine is concerned with the molecular and genetic problems that lead to diseases and with the development of molecular interventions to correct them. A better understanding of the underlying molecular mechanisms of diseases can lead to great advances in diagnostics and therapy. In particular, cancer subgroups can be determined by omics profiles and the most effective treatment with smallest adverse effects can be determined for each subgroup. This concept is at the center of precision medicine. To give insight in what is clinically relevant today, consider the concrete example of breast cancer. Molecular techniques have changed our understanding of the basic biology of breast cancer and provide the foundation for new methods of "personalized" prognostic and predictive testing. Several molecular markers are already established in clinical practice such as high penetrance breast cancer causing genes (BRCA1 and BRCA2) BIB002 , . Also the characterization of the tumor is driven by molecular markers such as estrogen receptor, progesterone receptor, and a genetic alteration, the HER2 amplification BIB001 . Since the biological signals of those markers are quite strong, they were discovered already in the 1990s, even before high-throughput molecular analysis became a reality. Now, more than 15 years after the primary publication of the human genome, many levels of biology (DNA, RNA, Protein, Epigenetics, miRNA, etc.) can be analyzed at relatively low cost, revealing detailed and comprehensive insight into the biology of a cell, including single gene functions and pathways as an interaction of whole groups of proteins and regulatory mechanisms. The Cancer Genome Atlas plays a particular role in understanding breast cancer on the molecular level play the efforts around "The Cancer Genome Atlas" (TCGA). It was one of the first Big Data efforts that compared the genetic information of the tumor with the genetic information of the blood on a large scale for each single of the three billion base pairs. See also Section VII-E. This project could, for the first time, describe systematically, which genes will mutate in the course of the pathogenesis of a healthy mammary cell to a breast cancer cell BIB006 .

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> C. Molecular Diagnostics and Drug Therapy <s> Abstract Pharmacogenetics encompasses the involvement of genes in an individual's response to drugs. As such, the field covers a vast area including basic drug discovery research, the genetic basis of pharmacokinetics and pharmacodynamics, new drug development, patient genetic testing and clinical patient management. Ultimately, the goal of pharmacogenetics is to predict a patient's genetic response to a specific drug as a means of delivering the best possible medical treatment. By predicting the drug response of an individual, it will be possible to increase the success of therapies and reduce the incidence of adverse side effects. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> C. Molecular Diagnostics and Drug Therapy <s> New drug development costs between 500 million and 2 billion dollars and takes 10-15 years, with a success rate of less than 10%. Drug repurposing is the process of discovering new indications for existing drugs and is becoming an important component of drug development as success rates for novel drugs in clinical trials decrease and costs increase. In the period 2007-2009, drug repurposing led to the launching of 30-40% of new drugs. Typically, a new indication for an available drug is identified by accident. However, new technologies and a huge amount of available resources enable us to develop systematic approaches to identify and validate drug repurposing candidates with significantly lower cost. A variety of resources have been utilized to identify novel drug repurposing candidates such as biomedical literature, clinical notes, and genetic data. In this study, we plan to 1) assess the usability and usefulness of new resources, specifically social media and phenome-wise association studies in drug repurposing, and 2) improve some previous proposed approaches, by investigating more accurate methods to prioritize and rank the generated drug repurposing candidates by literature-based discovery. <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> C. Molecular Diagnostics and Drug Therapy <s> BACKGROUND ::: BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 "basket" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers. ::: ::: ::: METHODS ::: We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival. ::: ::: ::: RESULTS ::: In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma. ::: ::: ::: CONCLUSIONS ::: BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT01524978.). <s> BIB003 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> C. Molecular Diagnostics and Drug Therapy <s> The widespread dissemination of the idea of personalized oncology has spread faster than the underlying science. The authors argue that the principles of clinical investigation need to be applied to address the many unanswered questions. <s> BIB004 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> C. Molecular Diagnostics and Drug Therapy <s> Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics, and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF-7, and PC-3 cell lines from the LINCS Project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled data set of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both pathway and gene level classification, DNN achieved high classification accuracy and convincingly outperformed the support vector machine (SVM) model on every multiclass classification prob... <s> BIB005

The alignment of clinical and molecular data in integrative data systems and improvements using these data for disease understanding and patient treatment will be among the next great challenges. The need for a precision medicine is quite apparent when looking at the limited drug response rates from the early 2000s as published research reveals BIB001 . Thus, Reality is even more complex: there is also heterogeneity within a particular tumor. The hypothesized cancer stem cell model asserts that within a population of tumor cells, there is only a small subset of cells that are tumourigenic (able to form tumours). These cells are termed cancer stem cells (CSCs), and are marked by their ability to both self-renew and differentiate into nontumourigenic progeny. One assumes a process of natural selection in the cancer model, one assumes a process of natural selection within a given tumor which also would explain why cancer is so difficult to fight: a treatment might eliminate one strain giving room for another strain to develop. It has been argued that this could be a major problem for the vision on a personalized medicine BIB004 . An alternative but related explanation is the clonal evolution model . http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ InVitroDiagnostics/ucm407297.htm alternatives to the traditional "blockbuster" models are needed . The diagnostic part of precision medicine relies heavily on biomarkers. In molecular diagnostics, the term biomarker refers to any of a patient's molecules that can be measured to assess health and that can be obtained from blood, body fluids, or tissue. Biomarkers are of central importance and biomarker testing is at the center of personalized medicine and is specific, e.g., to DNA, RNA, or protein variations. Biomarkers may also test if certain proteins may be overactive, in particular, if they help to promote cancer growth. A companion diagnostic is a diagnostic test (biomarker) used as a companion to a therapeutic drug to determine its applicability, e.g., efficacy and safety, to a specific patient. Companion diagnostics are co-developed with drugs to aid in selecting or excluding patient groups for treatment. A therapy may be based on the identification of a molecule (a drug target), often a protein, whose activity needs to be modified by a drug. Pharmaceutical research tries to find drugs, so called targeted drugs, that bind the target with the goal to influence underlying disease mechanisms. Targeted therapy uses a number of different strategies to fight tumors. For example, antibodies might be generated (e.g., monoclonal antibodies) which are man-made versions of large immune system proteins that bind to very specific target proteins on cancer cell membranes. Some targeted drugs block (inhibit) proteins that are signals for cancer cells to grow. Drugs called angiogenesis inhibitors stop tumors from making new blood vessels, which greatly limits their growth. Immunotherapy is a treatment that uses the body's own immune system to help fight cancer, e.g., uses the patient's immune system to attack those cells. For example, the protein HER2 is a member of the human epidermal growth factor receptor family and its overexpression plays an important role in certain forms of breast cancer; HER2 is the target of the monoclonal antibody trastuzumab. While most drugs have been approved for very specific diseases, they might also sometimes be effective in other diseases. One reason is that the targets in both diseases might have the same alterations. The application of known drugs and compounds to treat new indications is called drug repurposing. Analytics can play a role in finding good candidates BIB002 , BIB005 . A well-known case is the pain medicine Aspirin, which was found to be effective in treating and preventing heart disease. In cancer, as another example, it could be shown that a drug that works against a mutated gene in melanoma is also active in other cancers if the respective mutation in BRAF is found BIB003 . The main advantage of drug repositioning over traditional drug development is that, since the repositioned drug has already passed a significant number of toxicity and other tests, its safety is known and the risk of failure for reasons of adverse toxicology is reduced. Thus, the introduction of a specific drug for a new disease is greatly simplified.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> D. Implementing Precision Medicine <s> Over the last decade there has been vast interest in and focus on the implementation of personalized genomic medicine. Although there is general agreement that personalized genomic medicine involves utilizing genome technology to assess individual risk and ensure the delivery of the “right treatment, for the right patient, at the right time,” different categories of stakeholders focus on different aspects of personalized genomic medicine and operationalize it in diverse ways. In order to move toward a clearer, more holistic understanding of the concept, this article begins by identifying and defining three major elements of personalized genomic medicine commonly discussed by stakeholders: molecular medicine, pharmacogenomics, and health information technology. The integration of these three elements has the potential to improve health and reduce health care costs, but it also raises many challenges. This article endeavors to address these challenges by identifying five strategic areas that will require significant investment for the successful integration of personalized genomics into clinical care: (1) health technology assessment; (2) health outcomes research; (3) education (of both health professionals and the public); (4) communication among stakeholders; and (5) the development of best practices and guidelines. While different countries and global regions display marked heterogeneity in funding of health care in the form of public, private, or blended payor systems, previous analyses of personalized genomic medicine and attendant technological innovations have been performed without due attention to this complexity. Hence, this article focuses on personalized genomic medicine in the United States as a model case study wherein a significant portion of health care payors represent private, nongovernment resources. Lessons learned from the present analysis of personalized genomic medicine could usefully inform health care systems in other global regions where payment for personalized genomic medicine will be enabled through private or hybrid public-private funding systems. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> D. Implementing Precision Medicine <s> The completion of the Human Genome Project in 2003 was surrounded by lots of excitement in the scientific and lay communities because it was a milestone, along with other advancements in technology that have revolutionized our understanding of the contributions of genetic variability in shaping health and disease. One mystery the Human Genome Project helped scientists and clinicians unravel from a health perspective was why some patients responded differently to medications from the rest of the general population. Pharmacogenomics is the study of how genes influence an individual’s response to medications. The term pharmacogenomics is often used interchangeably with the term pharmacogenetics, which usually refers to how polymorphisms in a single gene influence response to a single medication. For more than 150 FDA-approved drugs, pharmacogenomic information can be found in the product labeling describing risk for adverse drug events, genotype-specific dosing, and/or variations in pharmacokinetic and pharmacodynamic parameters. For a select group of medications, such as codeine and clopidogrel, pharmacogenomic information may even be highlighted in a black box warning further emphasizing the important role of our unique genetic makeup in response to medications. Inherited genome variations influence the function of gene products that determine the pharmacokinetic and pharmacodynamic properties of a particular medication. In cancer, somatically acquired genomic variations and inherited genome variations influence response to anticancer agents. In infectious diseases, genomic variations in the bacteria or virus influence antimicrobial sensitivity. Pharmacogenomic research endeavors have sought to uncover the relationship between treatment response and genomic differences since it was first characterized in the 1950s by Sir Archibald Garrod, and the term was coined in 1959 by Friedrich Vogel. Some early pharmacogenomic examples include NAT2 gene deficiency and isoniazid-induced neuropathy, G6PD gene deficiency and primaquine-induced acute hemolytic crisis, and BChE gene deficiency resulting in succinylcholine-induced prolonged apnea. The translation of these findings and others into clinical practice in a sustainable and scalable model is more of a recent initiative to further optimize patient care. <s> BIB002

As a major milestone, a first insurer has begun to cover the cost of the sequencing of the full germline and tumor genomes of cancer patients. Despite the great perspectives of precision medicine it still faces many challenges. The implementation will require changes and improvements on many levels, reaching from technology developments (one genome can comprise up to 400 GB of data) over social and ethical challenges to legal implications and the need for large-scale educational programs for patients, physicians, researchers, healthcare providers, insurance companies, and even politicians BIB002 . The abundance of data and possibilities to join information sources raises the question on whether current rules for intellectual property, reimbursement, and personal privacy have to be adapted to personalized medicine. Regulatory authorities have already acknowledged those challenges and released a report titled "Paving the Way for Personalized Medicine: FDA's role in a New Era of Medical Product Development" BIB001 . In this report, the FDA describes a framework of how to integrate genomic medicine into clinical practice and drug development. Steps to implement precision medicine include the development of regulatory scientific standards, research methods, reference material, and new tools BIB001 . Implementing and even commercializing precision medicine will demand new standards with regard to the protection of patients' privacy and that of their families. Issues arise especially for healthy individuals who have genetic predisposition for a disease or patients who have a genetic alteration (either germline or somatic) and who are thought to be nonresponsive to standard treatments. Until a clear benefit for those persons is established, these data will have to be protected. In some cases, the person, for which the molecular data were created, might not want to know the complete interpretation of those results. An important milestone regarding privacy issues in the U.S. was the Genetic Information Nondiscrimination Act (GINA) in 2008 that protects American citizens from being discriminated based on their genetic information with respect to employment and health insurance.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Big Data in Molecular Research <s> Biobanks correspond to different situations: research and technological development, medical diagnosis or therapeutic activities. Their status is not clearly defined. We aimed to investigate human biobanking in Europe, particularly in relation to organisational, economic and ethical issues in various national contexts. Data from a survey in six EU countries (France, Germany, the Netherlands, Portugal, Spain and the UK) were collected as part of a European Research Project examining human and non-human biobanking (EUROGENBANK, coordinated by Professor JC Galloux). A total of 147 institutions concerned with biobanking of human samples and data were investigated by questionnaires and interviews. Most institutions surveyed belong to the public or private non-profit-making sectors, which have a key role in biobanking. This activity is increasing in all countries because few samples are discarded and genetic research is proliferating. Collections vary in size, many being small and only a few very large. Their purpose is often research, or research and healthcare, mostly in the context of disease studies. A specific budget is very rarely allocated to biobanking and costs are not often evaluated. Samples are usually provided free of charge and gifts and exchanges are the common rule. Good practice guidelines are generally followed and quality controls are performed but quality procedures are not always clearly explained. Associated data are usually computerised (identified or identifiable samples). Biobankers generally favour centralisation of data rather than of samples. Legal and ethical harmonisation within Europe is considered likely to facilitate international collaboration. We propose a series of recommendations and suggestions arising from the EUROGENBANK project. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Big Data in Molecular Research <s> Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility. <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Big Data in Molecular Research <s> The American Medical Association asked RAND Health to characterize the factors that affect physician professional satisfaction. RAND researchers sought to identify high-priority determinants of professional satisfaction by gathering data from 30 physician practices in six states, using a combination of surveys and semistructured interviews. This article presents the results of the subsequent analysis. <s> BIB003 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Big Data in Molecular Research <s> BACKGROUND ::: Even though it takes up such a large part of all clinicians' working day the medical literature on documentation and its value is sparse. ::: ::: ::: METHODS ::: Medline searches combining the terms medical records, documentation, time, and value or efficacy or benefit yielded only 147 articles. This review is based on the relevant articles selected from this search and additional studies gathered from the personal experience of the authors and their colleagues. ::: ::: ::: RESULTS ::: Documentation now occupies a quarter to half of doctors' time yet much of the information collected is of dubious or unproven value. Most medical records departments still use the traditional paper chart, and there is considerable debate on the benefits of electronic medical records (EMRs). Although EMRs contains a lot more information than a paper record clinicians do not find it easy to getting useful information out of them. Unlike the paper chart narrative is difficult to enter into most EMRs so that they do not adequately communicate the patient's "story" to clinicians. Recent innovations have the potential to address these issues. ::: ::: ::: CONCLUSION ::: Although documentation is widespread throughout the health care industry there has been almost no formal research into its value, on how to enhance its value, or on whether the time spent on it has negative effects on patient care. <s> BIB004 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> E. Big Data in Molecular Research <s> Background: The use of next-generation sequencing has significantly advanced personalized medicine for patients (pts) with breast cancer. Despite this technological advancement, there remains the challenge of understanding how and if tumor heterogeneity can confound molecular analysis and treatment decisions. It has been shown that the expression of ER, PR, and HER2 can vary widely within different areas of the same tumor and between matched primary and metastatic lesions. The "Intensive Trial of OMics in Cancer"-001 (ITOMIC-001; NCT01957514) enrolls pts with metastatic TNBC who are platinum-naive and scheduled to receive cisplatin. Multiple biopsies of up to 7 metastatic sites are performed prior to cisplatin and repeated upon completion of cisplatin and following subsequent therapies. A subset of specimens is chosen for DNA sequencing, RNA sequencing, and quantitative proteomics. We explored the discordance of genomic and proteomic alterations for intrapatient and temporal heterogeneity in pts with TNBC, and the potential benefit of panomic analysis to better inform treatment decisions. Methods: Between 7 and 107 tumor samples/biopsy specimens were obtained from each pt from 1-23 different time points. Blood samples were collected for matched tumor-normal genomic analysis. DNA sequencing data were processed using Contraster; RNASeq data confirmed the presence of gene mutations and was used to identify mutational and transcript abundance. PARADIGM was used to determine associations between gene mutations and signaling pathways. Selected reaction monitoring-mass spectrometry (SRM-MS) was used for proteomics analysis. Results: Almost all pts had loss of TP53 (common in TNBC), and 5 pts had germline BRCA1/2 events, some exhibiting a signature of mutations corresponding to a mismatch repair defect in ≥1 pt. FGFR1/2/3 mutations/amplifications occurred in 5 pts. Three of 12 pts (25%) achieved partial responses after receiving treatments (post cisplatin) based on the molecular profile of their tumor: 1 pt with two FGFR2 activating mutations treated with ponatinib, 1 with a germline BRCA2 mutation treated with veliparib, and 1 with highly expressed Gpnmb treated with an antibody drug conjugate against Gpnmb. Tumor samples showed increased mutational and rearrangement burdens over time but shared mutational characteristics that were unique to each pt. Through the shared alterations across time points for 3 pts, it was possible to reconstruct the clonal history and heterogeneity of the tumors as various therapeutic approaches were attempted. Conclusions: Here we show in TNBC, intrapatient and temporal heterogeneity that may lead to a lack of response to identified targeted therapies. Tumor samples taken over time from the same pt become enriched for more complex genomic structures post therapy but share mutational characteristics, indicating the presence of recurrent tumor populations. This study enabled us to reconstruct the clonal history and heterogeneity of tumors across space (metastatic vs primary at t=0) and time, illustrating the need for comprehensive molecular analysis and combination/multi-targeted therapeutics for optimal treatment in TNBC. Citation Format: Soon-Shiong P, Rabizadeh S, Benz S, Cecchi F, Hembrough T, Mahen E, Burton K, Song C, Senecal F, Schmechel S, Pritchard C, Dorschner M, Blau S, Blau A. Integrating whole exome sequencing data with RNAseq and quantitative proteomics to better inform clinical treatment decisions in patients with metastatic triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-05-08. <s> BIB005

The aim is to use the newly gained insight into etiology, pathogenesis, and progression of diseases for novel treatments and prevention. Large international consortia were formed over the last years integrating data from not seldom several hundreds of thousands of individuals to compare genetic and environmental information of healthy individuals with diseased patients. Several of those consortia have built superconsortia merging data and biomaterials of several large-scale consortia together. One example is the OncoArray Network. BIB004 GWAS study, in which more than 400 000 individuals have been genotyped for more than 570 000 genetic variants. Diseases included in this effort are breast cancer, ovarian cancer, colon cancer, lung cancer, and prostate cancer. The GWAS studies examine the correlation between germline gene variations and phenotypic characteristics. Most of those studies explain a certain amount of attributable risk for a disease within a population. For an individual, the statistical effects are rather small and implementation into healthcare is highly dependent on programs which would utilize this information in an epidemiological way, i.e., by selecting patients for individualized prevention or early detection of a disease. This requires tens if not hundreds of thousands or millions individual decisions in a population, which will require highly scalable Big Data technology. For the case of breast cancer, GWAS led to the discovery of around 100 risk genes BIB002 . Biobanks are great sources for molecular research. Biobanks store biological samples (often cancerous tissue) for use in research like genomics and personalized medicine BIB001 . The 1000 Genomes Project [128], launched in 2008, was an effort to sequence the genomes of at least 1000 anonymous participants. Many rare variations were identified, and eight structural-variation classes were analyzed. It is followed by the 100 000 Genomes project, which was launched in 2013. It aims to sequence 100 000 genomes from U.K.'s NHS patients by 2017 and it focuses on patients with rare diseases and more common cancers. BIB003 An interesting and less costly alternative is the distributed collection of genomic data from patients who donate their decentrally analyzed genome to central projects. From a data management perspective, these decentralized approaches require innovative ways of storing and analyzing huge amounts of data employing distributed computing. As stated before, complex diseases involve a number of causes. Unfortunately, to study the interaction of disease causes involving, for example, several gene variations requires even larger sample sizes. Similarly, the study of complex patterns behind the spatiotemporal disease progression requires the acquisition and management of huge data samples BIB005 .

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> F. Digitization Challenges in Precision Medicine <s> There is a growing need for patient-specific and holistic modelling of the heart to support comprehensive disease assessment and intervention planning as well as prediction of therapeutic outcomes. We propose a patient-specific model of the whole human heart, which integrates morphology, dynamics and haemodynamic parameters at the organ level. The modelled cardiac structures are robustly estimated from four-dimensional cardiac computed tomography (CT), including all four chambers and valves as well as the ascending aorta and pulmonary artery. The patient-specific geometry serves as an input to a three-dimensional Navier–Stokes solver that derives realistic haemodynamics, constrained by the local anatomy, along the entire heart cycle. We evaluated our framework with various heart pathologies and the results correlate with relevant literature reports. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> F. Digitization Challenges in Precision Medicine <s> Objective Clinicians’ ability to use and interpret genetic information depends upon how those data are displayed in electronic health records (EHRs). There is a critical need to develop systems to effectively display genetic information in EHRs and augment clinical decision support (CDS). ::: ::: Materials and Methods The National Institutes of Health (NIH)-sponsored Clinical Sequencing Exploratory Research and Electronic Medical Records & Genomics EHR Working Groups conducted a multiphase, iterative process involving working group discussions and 2 surveys in order to determine how genetic and genomic information are currently displayed in EHRs, envision optimal uses for different types of genetic or genomic information, and prioritize areas for EHR improvement. ::: ::: Results There is substantial heterogeneity in how genetic information enters and is documented in EHR systems. Most institutions indicated that genetic information was displayed in multiple locations in their EHRs. Among surveyed institutions, genetic information enters the EHR through multiple laboratory sources and through clinician notes. For laboratory-based data, the source laboratory was the main determinant of the location of genetic information in the EHR. The highest priority recommendation was to address the need to implement CDS mechanisms and content for decision support for medically actionable genetic information. ::: ::: Conclusion Heterogeneity of genetic information flow and importance of source laboratory, rather than clinical content, as a determinant of information representation are major barriers to using genetic information optimally in patient care. Greater effort to develop interoperable systems to receive and consistently display genetic and/or genomic information and alert clinicians to genomic-dependent improvements to clinical care is recommended. <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> F. Digitization Challenges in Precision Medicine <s> ABSTRACTPrecision medicine aims to combine comprehensive data collected over time about an individual’s genetics, environment, and lifestyle, to advance disease understanding and interception, aid drug discovery, and ensure delivery of appropriate therapies. Considerable public and private resources have been deployed to harness the potential value of big data derived from electronic health records, ‘omics technologies, imaging, and mobile health in advancing these goals. While both technical and sociopolitical challenges in implementation remain, we believe that consolidating these data into comprehensive and coherent bodies will aid in transforming healthcare. Overcoming these challenges will see the effective, efficient, and secure use of big data disrupt the practice of medicine. It will have significant implications for drug discovery and development as well as in the provisioning, utilization and economics of health care delivery going forward; ultimately, it will enhance the quality of care for the... <s> BIB003 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> F. Digitization Challenges in Precision Medicine <s> The ever-increasing volume of scientific discoveries, clinical knowledge, novel diagnostic tools, and treatment options juxtaposed with rising costs in health care challenge physicians to identify, prioritize, and use new information rapidly to deliver efficient and high-quality care to a growing and aging patient population. CancerLinQ, a rapid learning health care system in oncology, is an initiative of the American Society of Clinical Oncology and its Institute for Quality that addresses these challenges by collecting information from the electronic health records of large numbers of patients with cancer. CancerLinQ is first and foremost a quality measurement and reporting system through which oncologists can harness the depth and power of their patients' clinical records and other data to assess, monitor, and improve the care they deliver. However, in light of privacy and security concerns with regard to collection, use, and disclosure of patient information, this article addresses the need to collect protected health information as defined under the Health Insurance Portability and Accountability Act of 1996 to drive rapid learning through CancerLinQ. <s> BIB004

Recent publications , estimate that storage needs for molecular data will exceed by far those of Twitter or YouTube, which is of great concern to researchers and healthcare professionals alike. This perception is supported by the many large-scale population-based initiatives (e.g., the aforementioned Genomics England 100K project or the NIH precision medicine initiative) that will collect genomic and other biomedical data from individuals for the next five to ten years. A comprehensive and recent overview of these cohort studies from publicly or private funded entities can be found in BIB003 . The experiences gained from these initiatives will reveal interesting insights and lessons learned about data management of genomic and other "omics" data (e.g., transcrpitomics, proteomics, metabolomoics, epigenomics), emerging standards, and data privacy topics such as informed consent. To consistently improve consistently patient outcome and medical value, it will become very important to bridge the gap between all the previously mentioned "omics" data and clinical outcome. Indeed clinical sequencing in the clinics for advanced patient diagnosis is becoming more and more common, but many questions still remain, e.g., how, where, and what to store from genomic data in the EHR records. Here, important consortia such as Electronic Medical Records and Genomics (emerge) and Clinical Sequencing Exploratory Research (CSER) will hopefully pave the way toward a more integrated view of genomics in the clinic BIB002 . Structuring, organizing, and synchronizing different terminologies across clinical data repositories is the prerequisite to make clinical data meaningful. In that context, companies such as Flatiron Health have developed powerful tools and processes to tackle this data integration challenge and offer structured knowledge bases that can yield new insights into the fight against cancer. BIB001 In many current efforts, data are aggregated across many patients with the goal of developing Clinical Decision Support (CDS) systems. The American Society of Clinical Oncology (ASCO) launched a program named CancerLinQ that envisions to learn not only from trial data but also from the mass of EHR records. A goal is that doctors get support in their decision making by matching their patients' data with outcomes of patients across the United States. Patients gain confidence if their treatment decisions are based on their personal profile and on the shared experiences of similar cancer cases across the country. Finally, researchers can access this massive amount of deidentified health information to generate new hypotheses for research. To make CancerLinQ's vision happen, several different data types and technologies have to be orchestrated ranging from longitudinal patient records, cohort analyses, quality metrics to interactive reporting and text analytics BIB004 . Interoperability between different EHR systems will be another crucial success factor for the CancerLinQ initiative.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> G. Traditional IT Players are Entering Precision Medicine <s> IBM has collaborated with several cancer care providers to develop and train the IBM supercomputer Watson to help clinicians make informed treatment decisions. When a patient is seen in clinic, the oncologist can input all of the clinical information into the computer system. Watson will then review all of the data and recommend treatment options based on the latest evidence and guidelines. Once the oncologist makes the treatment decision, this information can be sent directly to the insurance company for approval. Watson has the ability to standardize care and accelerate the approval process, a benefit to the healthcare provider and the patient. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> G. Traditional IT Players are Entering Precision Medicine <s> The ever-increasing volume of scientific discoveries, clinical knowledge, novel diagnostic tools, and treatment options juxtaposed with rising costs in health care challenge physicians to identify, prioritize, and use new information rapidly to deliver efficient and high-quality care to a growing and aging patient population. CancerLinQ, a rapid learning health care system in oncology, is an initiative of the American Society of Clinical Oncology and its Institute for Quality that addresses these challenges by collecting information from the electronic health records of large numbers of patients with cancer. CancerLinQ is first and foremost a quality measurement and reporting system through which oncologists can harness the depth and power of their patients' clinical records and other data to assess, monitor, and improve the care they deliver. However, in light of privacy and security concerns with regard to collection, use, and disclosure of patient information, this article addresses the need to collect protected health information as defined under the Health Insurance Portability and Accountability Act of 1996 to drive rapid learning through CancerLinQ. <s> BIB002

The outlined data management and analytics challenges in precision medicine are being addressed by a number of established IT companies. Here are some examples. https://connection.asco.org/magazine/features/cancerlinq% E2%84%A2-takes-big-leap-forward 27 https://www.genomeweb.com/informatics/ibm-nygc-expandpartnership-new-pilot-cancer-study https://www.whitehouse.gov/the-press-office/2016/02/25/factsheet-obama-administration-announces-key-actions-accelerate 29 https://www.whitehouse.gov/the-press-office/2016/02/25/factsheet-obama-administration-announces-key-actions-accelerate SAP has teamed up with the American Society of Clinical Oncology (ASCO) to implement CancerLinQ , BIB002 . SAP's in-memory technology platform SAP HANA will play a crucial role in providing the infrastructure and algorithms to analyze the vast amounts of diverse data to provide clinical decision support. IBM with its Watson technology , BIB001 has recently started a collaboration with the New York Genome Center (NYGC) to generate and analyze the exome, complete genome data, and epigenetic data linked to clinical outcomes from participating patients. The partners plan to generate an open knowledge base using the generated data. Dell is partnering with the Translational Genomics Research Institute (TGen) to tackle pediatric cancer in Europe and in the Middle East. In addition, Dell recently announced that its Cloud Clinical Archive-currently storing over 11 billion medical images and around 159 million clinical studies from multiple healthcare providers-will support storage and management of genomics data. The long-term goal will be to combine medical imaging diagnosis with advanced genomics to impact patient care. Intel is also looking into the precision medicine space. Saffron, a cognitive computing company that Intel acquired in 2015, is studying how users can gain additional insights from above mentioned Dell's Cloud Clinical Archive. The company is also offering NLP capabilities, and the platform can be compared to IBM Watson's offering. In addition, within the context of Barack Obama's Precision Medicine Initiative, Intel launched a Precision Medicine Acceleration Program. Microsoft also supports the U.S. Government's Precision Medicine Initiative by hosting genomic data sets in Microsoft's Azure cloud platform by the end of 2016 free of charge. Amazon Web Services (AWS) is offering HIPAA-compliant cloud storage and data security. Therefore, AWS often functions as a backbone of genomics data management platforms, and several companies such as Seven Bridges or DNAnexus rely on the AWS technology. As a concrete example, the Cancer Genomics Cloud (CGC) which includes the well-known "The Cancer Genome Atlas" (TCGA) is operated by Seven Bridges and runs on the AWS cloud. Alphabet Inc. is investing heavily in precision medicine. This happens mainly either through the many investments taken by Google Ventures or by own research and development activities from subsidiaries such as Verily or Calico. Investments in companies related to precision medicine from Google Ventures include Flatiron Health, Foundation Medicine, and DNAnexus among others. Among Google's initiatives are, e.g., Google Genomics or the Google Baseline Study. Google Genomics is Google's HIPAA-compliant cloud platform for storing and managing genomics data. Besides offering access to publicly available data sets such as the TCGA, customers can load their own genomic data sets and run analyses on the data through the offered API. The Google baseline study aims to collect different types of data such as molecular, imaging, clinical, and data related to patient engagement to understand patterns that are typical for healthy individuals. All these efforts illustrate that information technology is moving quickly into personalized healthcare and therefore will be a main enabler to realize the goals of precision medicine. The crucial challenge is to turn these vast amounts of data into knowledge and insights.

Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> H. A View to the Future: a Truly " n = 1 "-Medicine <s> First-generation, E1-deleted adenovirus subtype 5 (Ad5)-based vectors, although promising platforms for use as cancer vaccines, are impeded in activity by naturally occurring or induced Ad-specific neutralizing antibodies. Ad5-based vectors with deletions of the E1 and the E2b regions (Ad5 [E1-, E2b-]), the latter encoding the DNA polymerase and the pre-terminal protein, by virtue of diminished late phase viral protein expression, were hypothesized to avoid immunological clearance and induce more potent immune responses against the encoded tumor antigen transgene in Ad-immune hosts. Indeed, multiple homologous immunizations with Ad5 [E1-, E2b-]-CEA(6D), encoding the tumor antigen carcinoembryonic antigen (CEA), induced CEA-specific cell-mediated immune (CMI) responses with antitumor activity in mice despite the presence of preexisting or induced Ad5-neutralizing antibody. In the present phase I/II study, cohorts of patients with advanced colorectal cancer were immunized with escalating doses of Ad5 [E1-, E2b-]-CEA(6D). CEA-specific CMI responses were observed despite the presence of preexisting Ad5 immunity in a majority (61.3 %) of patients. Importantly, there was minimal toxicity, and overall patient survival (48 % at 12 months) was similar regardless of preexisting Ad5 neutralizing antibody titers. The results demonstrate that, in cancer patients, the novel Ad5 [E1-, E2b-] gene delivery platform generates significant CMI responses to the tumor antigen CEA in the setting of both naturally acquired and immunization-induced Ad5-specific immunity. <s> BIB001 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> H. A View to the Future: a Truly " n = 1 "-Medicine <s> The search for specificity in cancers has been a holy grail in cancer immunology. Cancer geneticists have long known that cancers harbor transforming and other mutations. Immunologists have long known that inbred mice can be immunized against syngeneic cancers, indicating the existence of cancer-specific antigens. With the technological advances in high-throughput DNA sequencing and bioinformatics, the genetic and immunologic lines of inquiry are now converging to provide definitive evidence that human cancers are vastly different from normal tissues at the genetic level, and that some of these differences are recognized by the immune system. The very vastness of genetic changes in cancers now raises different question. Which of the many cancer-specific genetic (genomic) changes are actually recognized by the immune system, and why? New observations are now beginning to probe these vital issues with unprecedented resolution and are informing a new generation of studies in human cancer immunotherapy. Cancer Immunol Res; 3(9); 969–77. ©2015 AACR . <s> BIB002 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> H. A View to the Future: a Truly " n = 1 "-Medicine <s> Massively parallel sequencing approaches are beginning to be used clinically to characterize individual patient tumors and to select therapies based on the identified mutations. A major question in these analyses is the extent to which these methods identify clinically actionable alterations and whether the examination of the tumor tissue alone is sufficient or whether matched normal DNA should also be analyzed to accurately identify tumor-specific (somatic) alterations. To address these issues, we comprehensively evaluated 815 tumor-normal paired samples from patients of 15 tumor types. We identified genomic alterations using next-generation sequencing of whole exomes or 111 targeted genes that were validated with sensitivities >95% and >99%, respectively, and specificities >99.99%. These analyses revealed an average of 140 and 4.3 somatic mutations per exome and targeted analysis, respectively. More than 75% of cases had somatic alterations in genes associated with known therapies or current clinical trials. Analyses of matched normal DNA identified germline alterations in cancer-predisposing genes in 3% of patients with apparently sporadic cancers. In contrast, a tumor-only sequencing approach could not definitively identify germline changes in cancer-predisposing genes and led to additional false-positive findings comprising 31% and 65% of alterations identified in targeted and exome analyses, respectively, including in potentially actionable genes. These data suggest that matched tumor-normal sequencing analyses are essential for precise identification and interpretation of somatic and germline alterations and have important implications for the diagnostic and therapeutic management of cancer patients. <s> BIB003 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> H. A View to the Future: a Truly " n = 1 "-Medicine <s> A phase 1/2 clinical trial evaluating dosing, safety, immunogenicity, and overall survival on metastatic colorectal cancer (mCRC) patients after immunotherapy with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine was performed. We report our extended observations on long-term overall survival and further immune analyses on a subset of treated patients including assessment of cytolytic T cell responses, T regulatory (Treg) to T effector (Teff) cell ratios, flow cytometry on peripheral blood mononuclear cells (PBMCs), and determination of HLA-A2 status. An overall survival of 20 % (median survival 11 months) was observed during long-term follow-up, and no long-term adverse effects were reported. Cytolytic T cell responses increased after immunizations, and cell-mediated immune (CMI) responses were induced whether or not patients were HLA-A2 positive or Ad5 immune. PBMC samples from a small subset of patients were available for follow-up immune analyses. It was observed that the levels of carcinoembryonic antigen (CEA)-specific CMI activity decreased from their peak values during follow-up in five patients analyzed. Preliminary results revealed that activated CD4+ and CD8+ T cells were detected in a post-immunization sample exhibiting high CMI activity. Treg to Teff cell ratios were assessed, and samples from three of five patients exhibited a decrease in Treg to Teff cell ratio during the treatment protocol. Based upon the favorable safety and immunogenicity data obtained, we plan to perform an extensive immunologic and survival analysis on mCRC patients to be enrolled in a randomized/controlled clinical trial that investigates Ad5 [E1-, E2b-]-CEA(6D) as a single agent with booster immunizations. <s> BIB004 </s> Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare <s> H. A View to the Future: a Truly " n = 1 "-Medicine <s> Somatic mutations binding to the patient9s MHC and recognized by autologous T cells (neoepitopes) are ideal cancer vaccine targets. They combine a favorable safety profile due to a lack of expression in healthy tissues with a high likelihood of immunogenicity, as T cells recognizing neoepitopes are not shaped by central immune tolerance. Proteins mutated in cancer (neoantigens) shared by patients have been explored as vaccine targets for many years. Shared (“public”) mutations, however, are rare, as the vast majority of cancer mutations in a given tumor are unique for the individual patient. Recently, the novel concept of truly individualized cancer vaccination emerged, which exploits the vast source of patient-specific “private” mutations. Concurrence of scientific advances and technological breakthroughs enables the rapid, cost-efficient, and comprehensive mapping of the “mutanome,” which is the entirety of somatic mutations in an individual tumor, and the rational selection of neoepitopes. How to transform tumor mutanome data to actionable knowledge for tailoring individualized vaccines “on demand” has become a novel research field with paradigm-shifting potential. This review gives an overview with particular focus on the clinical development of such vaccines. Clin Cancer Res; 22(8); 1885–96. ©2016 AACR . See all articles in this CCR Focus section, “Opportunities and Challenges in Cancer Immunotherapy.” <s> BIB005

Dramatic improvements in the quality and speed of genomic sequencing and analysis as a clinical diagnostic tool for individual patients combined with the innovations propelling immuno-oncology are paving a new era for truly personalizing the treatment of cancer. At the heart of this new hope is the newfound ability to rapidly identify and target tumor cells with specific DNA mutations unique to each cancer patient. The products of mutated genes encoding altered proteins are so-called "neoepitopes" which serve as the molecular address to direct and redirect immune cells for killing and to procure long-term immunity. Neoepitopes are defined as unique genetic alterations, which result in unique novel proteins. They are found specifically in a patient's tumor (but not normal tissue) which can be targeted by the immune system to attack the tumor with minimal off-target toxicity. Also, it is highly unlikely that the same neoepitopes occur in other patients, and if so only in small groups of patients. Therefore, a possible treatment of neoepitopes with medicine that is manufactured in real time is a vision of real-life " n = 1 " medicine BIB005 , BIB002 . Identifying neoepitopes for each patient is made possible by high-throughput whole genome or exome sequencing and by the direct comparison of abnormal tumor DNA with each patient's own normal DNA. The former widens the search for drugable targets (neoepitopes) in the >99% of the genome deemed untargetable or unimportant by panel sequencing. The latter reduces the significantly high false positive error rates associated with tumor-only sequencing techniques BIB003 . Precision in individualizing treatments targeting neoepitopes further requires confirmation of the expression of mutated genes, thus avoiding another potential pitfall of false positive errors, and the potential for the altered protein to induce immunogenicity. If a tumor is found to express neoepitopes, which are unique for the tumor, they can serve as a "molecular address" for the immune system. Therefore, there is a good rationale that the neoepitope can be delivered to the immune system by an immunogenic vehicle such as a vaccinating virus. One such vehicle is the adenovirus which may be engineered to express within its DNA many neoepitopes, and upon injection, can locally infect dendritic cells (as part of the immune system) which then present an identified neoepitope to the immune effector cells and trigger an immune response against the tumor cells. Despite great promise, the use of adenovirus or any other foreign delivery vehicles remains hindered due to the preexistence or the induction of neutralizing antibodies against them by the patient's immune system. This limitation has been overcome by engineered adenoviruses which are capable of safely vaccinating and revaccinating against hundreds of neoepitopes and tumorassociated antigens despite preexisting immunity against adenovirus BIB001 . Remarkable results have thus far been published demonstrating the delivery of tumor associated antigens by this engineered adenovirus in a cohort of latestage colorectal cancer patients BIB004 . A more recent development has been the engineering and application of immune cells (T-cells and NK-cells) that express antibodies on their surface as part of a chimeric antigen receptor (CAR) for direct targeting of tumor cells expressing their cognate antigens. One particular approach, an off-the-shelf human NK cell line dubbed NK-92, is engineerable to produce innumerable CARs. These cells are now being engineered to produce CARs (dubbed taNKs) targeting neoepitopes discovered to be expressed by individual cancer patients' tumor cells, thus enabling a novel, truly personalized immunotherapeutic approach to fight cancer. For this and many other reasons, the discovery of neoepitopes has the potential to be a watershed moment in the war against cancer. These examples show that the implementation and utilization of the immune system requires yet another layer of data, leading to a true " n = 1 " medicine. One of the challenges with neoepitope discovery and targeting will be the management of big data: teraFLOPS of compute resources in a cloud environment are required to generate terabytes of sequencing data, including whole genome and/or whole exome sequencing, RNA sequencing, and molecular modeling of immune presentation of neoepitopes. Meeting the demands of heterogeneity, analysis and long-term storage of data from multiple biopsies for each patient are further challenges. These activities require compute and storage under HIPAA, as well as high-speed and large-bandwidth connectivity for transiting sequence data from sequencing labs to supercompute/cloud environments rapidly, such that derivation and delivery of neoepitope targeting platforms are enabled in actionable time for each patient. These challenges require significant infrastructure and resources, which are already realized by some private, Big Data supercompute clouds interconnected by dedicated fiber infrastructure capable of transporting terabytes of data at terabits per second. Such infrastructures had originally been developed for financial trading markets, but are now retrofitted to meet the needs of sequencing analysis and neoepitope discovery.

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> INTRODUCTION <s> Academic failure among first-year university students has long fuelled a large number of debates. Many educational psychologists have tried to understand and then explain it. Many statisticians have tried to foresee it. Our research aims to classify, as early in the academic year as possible, students into three groups: the 'low-risk' students, who have a high probability of succeeding; the 'medium-risk' students, who may succeed thanks to the measures taken by the university; and the 'high-risk' students, who have a high probability of failing (or dropping out). This article describes our methodology and provides the most significant variables correlated to academic success among all the questions asked to 533 first-year university students during November of academic year 2003/04. Finally, it presents the results of the application of discriminant analysis, neural networks, random forests and decision trees aimed at predicting those students' academic success. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> INTRODUCTION <s> Applying data mining DM in education is an emerging interdisciplinary research field also known as educational data mining EDM. It is concerned with developing methods for exploring the unique types of data that come from educational environments. Its goal is to better understand how students learn and identify the settings in which they learn to improve educational outcomes and to gain insights into and explain educational phenomena. Educational information systems can store a huge amount of potential data from multiple sources coming in different formats and at different granularity levels. Each particular educational problem has a specific objective with special characteristics that require a different treatment of the mining problem. The issues mean that traditional DM techniques cannot be applied directly to these types of data and problems. As a consequence, the knowledge discovery process has to be adapted and some specific DM techniques are needed. This paper introduces and reviews key milestones and the current state of affairs in the field of EDM, together with specific applications, tools, and future insights. © 2012 Wiley Periodicals, Inc. <s> BIB002

Educational Data Mining (EDM) is an emerging field exploring data in educational context by applying different Data Mining (DM) techniques/tools. EDM inherits properties from areas like Learning Analytics, Psychometrics, Artificial Intelligence, Information Technology, Machine learning, Statics, Database Management System, Computing and Data Mining. It can be considered as interdisciplinary research field which provides intrinsic knowledge of teaching and learning process for effective education BIB002 . The exponential growth of educational data BIB001 from heterogeneous sources results an urgent need for research in EDM. This can help to meet the objectives and to determine specific goals of education. EDM objective can be classified in the following way: (1) Academic Objectives -Person oriented (related to direct participation in teaching and learning process) E.g.: Student learning, cognitive learning, modelling, behavior, risk, performance analysis, predicting right enrollment decision etc. both in traditional and digital environment and Faculty modelling-job performance and satisfaction analysis. -Department/Institutions oriented (related to particular department/institutions with respect to time, sequence and demand). E.g.: Redesign new courses according to industry requirements, identify realistic problems to effective research and learning process. -Domain Oriented (related to a particular branch/institutions) E.g.: Designing Methods-Tools, Techniques, Knowledge Discovery based Decision Support System (KDDS) for specific application, branch and institutions. (2) Administrative Objectives -Administrator Oriented (related to direct involvement of higher authorities/administrator) E.g.: Resource (Infrastructure as well as Human) utilization, Industry academia relationship, marketing for student enrollment in case of private institutions and establishment of network for innovative research and practices. -To explore heterogeneous educational data by analyzing the authors' views from traditional to intelligent educational systems in the decision making process. -To explore intelligent tools and techniques used in EDM and -To find out the various EDM challenges. To meet academic and administrative objectives, a survey of EDM is necessary which focus on cutting edge technologies for quality education delivery. This paper discusses the EDM components and research trends of DM in Educational System for the year 1998 to 2012 covering various issues and challenges on EDM. The rest of this paper is organized into 5 sections. Section-2 focuses on EDM Components such as Stakeholders, environments, data, methods, tools etc. Section-3 is about mining educational objectives. Section-4 highlights the research trends in EDM including various authors' views in educational outcomes, useful EDM Tools and Techniques. Section-5 is a discussion based on section 3 and 4, Section-6 concludes the paper with observations based on the survey work and the future scope of EDM.

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> EDM environments <s> The subject materials of most enterprise e-training programs were mainly developed by employees of the enterprises; therefore, it becomes a challenging issue to efficiently and effectively translate the knowledge and experiences of the employees to computerized subject materials, especially for those who are not an experienced teacher. In addition, to develop an e- training course, personal ignorance or incorrect concepts might significantly affect the quality of the course if only a single employee is asked to develop the subject materials. To cope with this problem, a multi- expert e-training course design model is proposed in this paper. Accordingly, an e-training course development system has been implemented. Moreover, a practical application has showed that of the novel approach not only can improve the quality of the e- training course, but also help the experts to organize their domain knowledge. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> EDM environments <s> Most e-Learning systems store data about the learner's actions in log files, which give us detailed information about learner behaviour. Data mining and machine learning techniques can give meaning to these data and provide valuable information for learning improvement. One area that is of particular importance in the design of e-Learning systems is learner motivation as it is a key factor in the quality of learning and in the prevention of attrition. One aspect of motivation is engagement, a necessary condition for effective learning. Using data mining techniques for log file analysis, our research investigates the possibility of predicting users' level of engagement, with a focus on disengaged learners. As demonstrated previously across two different e-Learning systems, HTML-Tutor and iHelp, disengagement can be predicted by monitoring the learners' actions (e.g. reading pages and taking test/quizzes). In this paper we present the findings of three studies that refine this prediction approach. Results from the first study show that two additional reading speed attributes can increase the accuracy of prediction. The second study suggests that distinguishing between two different patterns of disengagement (spending a long time on a page/test and browsing quickly through pages/tests) may improve prediction in some cases. The third study demonstrates the influence of exploratory behaviour on prediction, as most users at the first login familiarize themselves with the system before starting to learn. <s> BIB002

Formal Environment. Direct interaction with primary group stakeholder of education. E.g.: face to face classroom interaction. Informal Environment. Indirect interaction with primary group stakeholder of education. E.g.: web based education (e-learning BIB002 e-training used in Chu et al. BIB001 , online supported tasks)

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Computer Supported Environment (individual and interaction). <s> Recommender systems have been evaluated in many, often incomparable, ways. In this article, we review the key decisions in evaluating collaborative filtering recommender systems: the user tasks being evaluated, the types of analysis and datasets being used, the ways in which prediction quality is measured, the evaluation of prediction attributes other than quality, and the user-based evaluation of the system as a whole. In addition to reviewing the evaluation strategies used by prior researchers, we present empirical results from the analysis of various accuracy metrics on one content domain where all the tested metrics collapsed roughly into three equivalence classes. Metrics within each equivalency class were strongly correlated, while metrics from different equivalency classes were uncorrelated. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Computer Supported Environment (individual and interaction). <s> This paper consists of an in-depth summary and analysis of the research and development state of the art for intelligent tutoring system (ITS) authoring systems. A seven-part categorization of two dozen authoring systems is given, followed by a characterization of the authoring tools and the types of ITSs that are built for each category. An overview of the knowledge acquisition and authoring techniques used in these systems is given. A characterization of the design tradeoffs involved in building an ITS authoring system is given. Next the pragmatic questions of real use, productivity findings, and evaluation are discussed. Finally, I summarize the major unknowns and bottlenecks to having widespread use of ITS authoring tools. (http://aied.inf.ed.ac.uk/members99/archive/vol_10/murray/full.html) <s> BIB002 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Computer Supported Environment (individual and interaction). <s> In this chapter we discuss how recent advances in the field of Computer Supported Collaborative Learning (CSCL) have created the opportunity for new synergies between CSCL and ITS research. Three “hot” CSCL research topics are used as examples: analyzing individual’s and group’s interactions, providing students with adaptive intelligent support, and providing students with adaptive technological means. <s> BIB003 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Computer Supported Environment (individual and interaction). <s> Applying data mining DM in education is an emerging interdisciplinary research field also known as educational data mining EDM. It is concerned with developing methods for exploring the unique types of data that come from educational environments. Its goal is to better understand how students learn and identify the settings in which they learn to improve educational outcomes and to gain insights into and explain educational phenomena. Educational information systems can store a huge amount of potential data from multiple sources coming in different formats and at different granularity levels. Each particular educational problem has a specific objective with special characteristics that require a different treatment of the mining problem. The issues mean that traditional DM techniques cannot be applied directly to these types of data and problems. As a consequence, the knowledge discovery process has to be adapted and some specific DM techniques are needed. This paper introduces and reviews key milestones and the current state of affairs in the field of EDM, together with specific applications, tools, and future insights. © 2012 Wiley Periodicals, Inc. <s> BIB004

Direct and /or Indirect interaction with all the three groups (depends upon the objectives) stakeholder of education. E.g.: Intelligent Tutoring Systems-Tools such as DOCENT, IDE, ISD Expert, Expert CML related to curriculum development BIB002 . Tools such as such as Algebra Tutor, Mathematics Tutor, eTeacher, ZOSMAT , REALP, CIRCSlM-Tutor, Why2-Atlas, SmartTutor, AutoTutor, ActiveMath, Eon, GTE, REDEEM related to tutoring system. -Collaborative learning used in BIB003 -Adaptive Educational System [1] -Learning Management System, Cognitive Learning, Recommender System used in BIB001 and User Modeling BIB004 etc.

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Educational Data <s> education domain offers a fertile ground for many interesting and challenging data mining applications. These applications can help both educators and students, and improve the quality of education. In this paper, we present a real-life application for the Gifted Education Programme (GEP) of the Ministry of Education (MOE) in Singapore. The application involves many data mining tasks. This paper focuses only on one task, namely, selecting students for remedial classes. Traditionally, a cut-off mark for each subject is used to select the weak students. That is, those students whose scores in a subject fall below the cut-off mark for the subject are advised to take further classes in the subject. In this paper, we show that this traditional method requires too many students to take part in the remedial classes. This not only increases the teaching load of the teachers, but also gives unnecessary burdens to students, which is particularly undesirable in our case because the GEP students are generally taking more subjects than non-GEP students, and the GEP students are encouraged to have more time to explore advanced topics. With the help of data mining, we are able to select the targeted students much more precisely. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Educational Data <s> Application of data mining techniques to the WWW (World Wide Web), referred to as Web mining, has been the focus of several research projects and papers. One of several possibilities can be its application to distance education. Taken as a whole, the emerging trends in distance education are facilitating its usability on the Internet. With the explosive growth of information sources available on the WWW, Web mining has become suitable for keeping pace with the trends in education, such as mass customization. In this paper, we define Web mining and present an overview of distance education. We describe the possibilities of application of Web mining to distance education, and, consequently, show that the use of Web mining for educational purposes is of great interest. <s> BIB002 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Educational Data <s> Several approaches have been proposed for representing uncertain data in a database. These approaches have typically extended the relational model by incorporating probability measures to capture the uncertainty associated with data items. However, previous research has not directly addressed the issue of normalization for reducing data redundancy and data anomalies in probabilistic databases. We examine this issue. To that end, we generalize the concept of functional dependency to stochastic dependency and use that to extend the scope of normal forms to probabilistic databases. Our approach is a consistent extension of the conventional normalization theory and reduces to the latter. <s> BIB003 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Educational Data <s> In this chapter we discuss how recent advances in the field of Computer Supported Collaborative Learning (CSCL) have created the opportunity for new synergies between CSCL and ITS research. Three “hot” CSCL research topics are used as examples: analyzing individual’s and group’s interactions, providing students with adaptive intelligent support, and providing students with adaptive technological means. <s> BIB004 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Educational Data <s> Applying data mining DM in education is an emerging interdisciplinary research field also known as educational data mining EDM. It is concerned with developing methods for exploring the unique types of data that come from educational environments. Its goal is to better understand how students learn and identify the settings in which they learn to improve educational outcomes and to gain insights into and explain educational phenomena. Educational information systems can store a huge amount of potential data from multiple sources coming in different formats and at different granularity levels. Each particular educational problem has a specific objective with special characteristics that require a different treatment of the mining problem. The issues mean that traditional DM techniques cannot be applied directly to these types of data and problems. As a consequence, the knowledge discovery process has to be adapted and some specific DM techniques are needed. This paper introduces and reviews key milestones and the current state of affairs in the field of EDM, together with specific applications, tools, and future insights. © 2012 Wiley Periodicals, Inc. <s> BIB005

Decision-making in the field of academic planning involves extensive analysis of huge volumes of educational data . Data's are generated from heterogeneous sources like diverse and varied uses in BIB001 , diverse and distributed, structured and unstructured data. These data's are mostly generated from the offline or online source Offline Data. Offline Data are generated from traditional and modern classroom interaction interactive teaching/learning environments, learner/educators information, students attendance, emotional data, course information, data collected from the academic section of an institution BIB005 etc.. Online Data. Online Data are generated from the geographically separated stake holder of the education, distance educations used in , web based education used in BIB002 , computersupported collaborative learning used in BIB004 BIB003 , sensor generated data, privacy preservation process data, summarization of data .

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Classification <s> Recent research has indicated that misuse of intelligent tutoring software is correlated with substantially lower learning. Students who frequently engage in behavior termed “gaming the system” (behavior aimed at obtaining correct answers and advancing within the tutoring curriculum by systematically taking advantage of regularities in the software’s feedback and help) learn only 2/3 as much as similar students who do not engage in such behaviors. We present a machine-learned Latent Response Model that can identify if a student is gaming the system in a way that leads to poor learning. We believe this model will be useful both for re-designing tutors to respond appropriately to gaming, and for understanding the phenomenon of gaming better. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Classification <s> Academic failure among first-year university students has long fuelled a large number of debates. Many educational psychologists have tried to understand and then explain it. Many statisticians have tried to foresee it. Our research aims to classify, as early in the academic year as possible, students into three groups: the 'low-risk' students, who have a high probability of succeeding; the 'medium-risk' students, who may succeed thanks to the measures taken by the university; and the 'high-risk' students, who have a high probability of failing (or dropping out). This article describes our methodology and provides the most significant variables correlated to academic success among all the questions asked to 533 first-year university students during November of academic year 2003/04. Finally, it presents the results of the application of discriminant analysis, neural networks, random forests and decision trees aimed at predicting those students' academic success. <s> BIB002

It is a two way technique (training and testing) which maps data into a predefined class. This technique is useful for success analysis with low, medium, high risk students used in BIB002 , student monitoring systems , predicting student performance, misuse detection used in BIB001 etc.

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Clustering <s> With advances in information and communication technology, interactive multimedia learning systems are widely used to support teaching and learning. However, as human factors vary across users, they may prefer the design of interactive multimedia learning systems differently. To have a deep understanding of the influences of human factors, we apply a data mining approach to the investigation of users’ preferences in using interactive multimedia learning systems. More specifically, a clustering technique named K-modes is used to group users’ preferences. The results indicate that users’ preferences could be divided into four groups where computer experience is a key human factor that influences their preferences. Implications for the development of interactive multimedia learning systems are also discussed. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Clustering <s> Group work is widespread in education. The growing use of online tools supporting group work generates huge amounts of data. We aim to exploit this data to support mirroring: presenting useful high-level views of information about the group, together with desired patterns characterizing the behavior of strong groups. The goal is to enable the groups and their facilitators to see relevant aspects of the group's operation and provide feedback if these are more likely to be associated with positive or negative outcomes and indicate where the problems are. We explore how useful mirror information can be extracted via a theory-driven approach and a range of clustering and sequential pattern mining. The context is a senior software development project where students use the collaboration tool TRAC. We extract patterns distinguishing the better from the weaker groups and get insights in the success factors. The results point to the importance of leadership and group interaction, and give promising indications if they are occurring. Patterns indicating good individual practices were also identified. We found that some key measures can be mined from early data. The results are promising for advising groups at the start and early identification of effective and poor practices, in time for remediation. <s> BIB002 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Clustering <s> Data mining combines machine learning, statistics and visualization techniques to discover and extract knowledge. One of the biggest challenges that higher education faces is to improve student retention (National Audition Office, 2007). Student retention has become an indication of academic performance and enrolment management. Our project uses data mining and natural language processing technologies to monitor student, analyze student academic behaviour and provide a basis for efficient intervention strategies. Our aim is to identify potential problems as early as possible and to follow up with intervention options to enhance student retention. In this paper we discuss how data mining can help spot students ‘at risk’, evaluate the course or module suitability, and tailor the interventions to increase student retention. <s> BIB003

It is a technique to group similar data into clusters in a way that groups are not predefined. This technique is useful to distinguish learner with their preference in using interactive multimedia system used in BIB001 , Students comprehensive character analysis used in BIB003 and suitable for collaborative learning used in BIB002 .

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Prediction <s> The monitoring and support of university freshmen is considered very important at many educational institutions. In this paper we describe the results of the educational data mining case study aimed at predicting the Electrical Engineering (EE) students drop out after the first semester of their studies or even before they enter the study program as well as identifying success-factors specific to the EE program. Our experimental results show that rather simple and intuitive classifiers (decision trees) give a useful result with accuracies between 75 and 80%. Besides, we demonstrate the usefulness of cost-sensitive learning and thorough analysis of misclassifications, and show a few ways of further prediction improvement without having to collect additional data about the students. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Prediction <s> Data mining combines machine learning, statistics and visualization techniques to discover and extract knowledge. One of the biggest challenges that higher education faces is to improve student retention (National Audition Office, 2007). Student retention has become an indication of academic performance and enrolment management. Our project uses data mining and natural language processing technologies to monitor student, analyze student academic behaviour and provide a basis for efficient intervention strategies. Our aim is to identify potential problems as early as possible and to follow up with intervention options to enhance student retention. In this paper we discuss how data mining can help spot students ‘at risk’, evaluate the course or module suitability, and tailor the interventions to increase student retention. <s> BIB002 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Prediction <s> We conduct a data mining project to generate predictive models for student retention management on campus. Given new records of incoming students, these predictive models can produce short accurate prediction lists identifying students who tend to need the support from the student retention program most. The project is a component in our artificial intelligence class. Students in the class get involved in the entire process of modeling and problem solving using machine learning algorithms. We examine the quality of the predictive models generated by the machine learning algorithms. The results show that some of the machine learning algorithms are able to establish effective predictive models from the existing student retention data. <s> BIB003

It is a technique which predicts a future state rather than a current state.This technique is useful to predict success rate, drop out used in Dekker et al. BIB001 BIB002 , and retention management used in BIB003 of students.

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Neural Network <s> Academic failure among first-year university students has long fuelled a large number of debates. Many educational psychologists have tried to understand and then explain it. Many statisticians have tried to foresee it. Our research aims to classify, as early in the academic year as possible, students into three groups: the 'low-risk' students, who have a high probability of succeeding; the 'medium-risk' students, who may succeed thanks to the measures taken by the university; and the 'high-risk' students, who have a high probability of failing (or dropping out). This article describes our methodology and provides the most significant variables correlated to academic success among all the questions asked to 533 first-year university students during November of academic year 2003/04. Finally, it presents the results of the application of discriminant analysis, neural networks, random forests and decision trees aimed at predicting those students' academic success. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Neural Network <s> Student retention is an important issue for all university policy makers due to the potential negative impact on the image of the univer- sity and the career path of the dropouts. Although this issue has been thoroughly studied by many institutional researchers using parametric tech- niques, such as regression analysis and logit modeling, this article attempts to bring in a new perspective by exploring the issue with the use of three data mining techniques, namely, classification trees, multivariate adaptive regression splines (MARS), and neural networks. Data mining procedures identify transferred hours, residency, and ethnicity as crucial factors to re- tention. Carrying transferred hours into the university implies that the stu- dents have taken college level classes somewhere else, suggesting that they are more academically prepared for university study than those who have no transferred hours. Although residency was found to be a crucial predic- tor to retention, one should not go too far as to interpret this finding that retention is affected by proximity to the university location. Instead, this is a typical example of Simpson's Paradox. The geographical information system analysis indicates that non-residents from the east coast tend to be more persistent in enrollment than their west coast schoolmates. <s> BIB002 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Neural Network <s> In this paper we are proposing a new Attribute Selection Measure Function (heuristic) on existing C4.5 algorithm. The advantage of heuristic is that the split information never approaches zero, hence produces stable Rule set and Decision Tree. In ideal situation, in admission process in engineering colleges in India, a student takes admission based on AIEEE rank and family pressure. If the student does not get admission in the desired branch of engineering, then they find it difficult to take decision which will be the suitable branch. The proposed knowledge based decision technique will guide the student for admission in proper branch of engineering. Another approach is also made to analyze the accuracy rate for decision tree algorithm (C5.0) and back propagation algorithm (ANN) to find out which one is more accurate for decision making. In this research work we have used the AIEEE2007 Database. <s> BIB003 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Neural Network <s> Research highlights? Adaptive learning in TESL. ? Data mining in e-learning system. ? e-learning system for TESL. This study proposes an Adaptive Learning in Teaching English as a Second Language (TESL) for e-learning system (AL-TESL-e-learning system) that considers various student characteristics. This study explores the learning performance of various students using a data mining technique, an artificial neural network (ANN), as the core of AL-TESL-e-learning system. Three different levels of teaching content for vocabulary, grammar, and reading were set for adaptive learning in the AL-TESL-e-learning system. Finally, this study explores the feasibility of the proposed AL-TESL-e-learning system by comparing the results of the regular online course control group with the AL-TESL-e-learning system adaptive learning experiment group. Statistical results show that the experiment group had better learning performance than the control group; that is, the AL-TESL-e-learning system was better than a regular online course in improving student learning performance. <s> BIB004

It is a technique to improve the interpretability of the learned network by using extracted rules for learning networks. This technique is useful to determine residency, ethnicity used in BIB002 , to predict academic performance used in BIB001 , accuracy prediction in the branch selection used in BIB003 and explores learning performance in a TESL based e-learning system BIB004 .

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Association Rule Mining <s> A rechargeable aqueous metal-halogen cell is described which includes a casing, a pair of spaced apart porous electrode substrates in the casing, a micro-porous separator between the electrode substrates defining a positive and a negative electrode compartment, an aqueous electrolytic solution containing a zinc salt selected from the class consisting of zinc bromide, zinc iodide, and mixtures thereof in both compartments, and an organic halogen complexing additive of nitrobenzene in the electrolytic solution of at least the positive compartment. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Association Rule Mining <s> Over the years, several statistical tools have been used to analyze students’ performance from different points of view. This paper presents data mining in education environment that identifies students’ failure patterns using association rule mining technique. The identified patterns are analysed to offer a helpful and ::: constructive recommendations to the academic planners in higher institutions of learning to enhance their decision making process. This will also aid in the curriculum structure and modification in order to improve students’ academic performance and trim down failure rate. The software for mining student failed courses was developed and the analytical process was described. <s> BIB002

It is a technique to identify specific relationships among data.This technique is useful to identify students' failure patterns BIB002 , parameters related to the admission process, migration, contribution of alumni, student assessment, co-relation between different group of students, to guide a search for a better fitting transfer model of student learning etc. used in BIB001 .

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Web mining <s> Most e-Learning systems store data about the learner's actions in log files, which give us detailed information about learner behaviour. Data mining and machine learning techniques can give meaning to these data and provide valuable information for learning improvement. One area that is of particular importance in the design of e-Learning systems is learner motivation as it is a key factor in the quality of learning and in the prevention of attrition. One aspect of motivation is engagement, a necessary condition for effective learning. Using data mining techniques for log file analysis, our research investigates the possibility of predicting users' level of engagement, with a focus on disengaged learners. As demonstrated previously across two different e-Learning systems, HTML-Tutor and iHelp, disengagement can be predicted by monitoring the learners' actions (e.g. reading pages and taking test/quizzes). In this paper we present the findings of three studies that refine this prediction approach. Results from the first study show that two additional reading speed attributes can increase the accuracy of prediction. The second study suggests that distinguishing between two different patterns of disengagement (spending a long time on a page/test and browsing quickly through pages/tests) may improve prediction in some cases. The third study demonstrates the influence of exploratory behaviour on prediction, as most users at the first login familiarize themselves with the system before starting to learn. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> Web mining <s> Mining association rules from huge amounts of data is an important issue in data mining, with the discovered information often being commercially valuable. Moreover, companies that conduct similar business are often willing to collaborate with each other by mining significant knowledge patterns from the collaborative datasets to gain the mutual benefit. However, in a cooperative project, some of these companies may want certain strategic or private data called sensitive patterns not to be published in the database. Therefore, before the database is released for sharing, some sensitive patterns have to be hidden in the database because of privacy or security concerns. To solve this problem, sensitive-knowledge-hiding (association rules hiding) problem has been discussed in the research community working on security and knowledge discovery. The aim of these algorithms is to extract as much as nonsensitive knowledge from the collaborative databases as possible while protecting sensitive information. Sensitive-knowledge-hiding problem was proven to be a nondeterministic polynomial-time hard problem. After that, a lot of research has been completed to solve the problem. In this article, we will introduce and discuss the major categories of sensitive-knowledge-protecting methodologies. © 2011 Wiley Periodicals, Inc. <s> BIB002

It is a technique for mining web data. This technique is useful for building virtual community in computational Intelligence used in , to determine misconception of learners used in BIB002 and to explore cognitive sense. Apart from the above methods, mentioned two new methods i.e. distillation of data for human judgment and discovery with models to analyze the behavioral impact of students in learning environments BIB001 .

A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> education domain offers a fertile ground for many interesting and challenging data mining applications. These applications can help both educators and students, and improve the quality of education. In this paper, we present a real-life application for the Gifted Education Programme (GEP) of the Ministry of Education (MOE) in Singapore. The application involves many data mining tasks. This paper focuses only on one task, namely, selecting students for remedial classes. Traditionally, a cut-off mark for each subject is used to select the weak students. That is, those students whose scores in a subject fall below the cut-off mark for the subject are advised to take further classes in the subject. In this paper, we show that this traditional method requires too many students to take part in the remedial classes. This not only increases the teaching load of the teachers, but also gives unnecessary burdens to students, which is particularly undesirable in our case because the GEP students are generally taking more subjects than non-GEP students, and the GEP students are encouraged to have more time to explore advanced topics. With the help of data mining, we are able to select the targeted students much more precisely. <s> BIB001 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> Web usage mining is the application of data mining techniques to discover usage patterns from Web data, in order to understand and better serve the needs of Web-based applications. Web usage mining consists of three phases, namely preprocessing, pattern discovery, and pattern analysis. This paper describes each of these phases in detail. Given its application potential, Web usage mining has seen a rapid increase in interest, from both the research and practice communities. This paper provides a detailed taxonomy of the work in this area, including research efforts as well as commercial offerings. An up-to-date survey of the existing work is also provided. Finally, a brief overview of the WebSIFT system as an example of a prototypical Web usage mining system is given. <s> BIB002 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> Web-based learning environments are now used extensively as integral components of course delivery in tertiary education. To provide an effective learning environment, it is important that educators understand how these environments are used by their students. In conventional teaching environments educators are able to obtain feedback on student learning experiences in face-to-face interactions with their students, enabling continual evaluation of their teaching programs. However, when students work in electronic environments, this informal monitoring is not possible; educators must look for other ways to attain this information. Capturing and recording student interactions with a website provides a rich source of information from data that is gathered unobtrusively. The aim of this study was firstly to explore what information can be gained from analysing student interactions with Web-based learning environments and secondly to determine the value of this process in providing information about student learning behaviours and learning outcomes. This study has provided critical information to educators about the learning behaviour of their students, informing future enhancements and developments to a courseware website and the teaching program it supports. <s> BIB003 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> Abstract Social cognitive career theory ( Lent, Brown, & Hackett, 1994 ) was originally designed to help explain interest development, choice, and performance in career and educational domains. These three aspects of career/academic development were presented in distinct but overlapping segmental models. This article presents a fourth social cognitive model aimed at understanding satisfaction experienced in vocational and educational pursuits. The model posits paths whereby core social cognitive variables (e.g., self-efficacy, goals) function jointly with personality/affective trait and contextual variables that have been linked to job satisfaction. We consider the model’s implications for forging an understanding of satisfaction that bridges the often disparate perspectives of organizational and vocational psychology. <s> BIB004 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> One of the biggest challenges that higher learning institutions face today is to improve the quality of managerial decisions. The managerial decision making process becomes more complex as the complexity of educational entities increase. Educational institute seeks more efficient technology to better manage and support decision making procedures or assist them to set new strategies and plan for a better management of the current processes. One way to effectively address the challenges for improving the quality is to provide new knowledge related to the educational processes and entities to the managerial system. This knowledge can be extracted from historical and operational data that reside in the educational organization's databases using the techniques of data mining technology. Data mining techniques are analytical tools that can be used to extract meaningful knowledge from large data sets. This paper presents the capabilities of data mining in the context of higher educational system by i) proposing an analytical guideline for higher education institutions to enhance their current decision processes, and ii) applying data mining techniques to discover new explicit knowledge which could be useful for the decision making processes. <s> BIB005 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> In this study, the authors developed and factor analyzed the Norwegian Teacher Self-Efficacy Scale. They also examined relations among teacher self-efficacy, perceived collective teacher efficacy, external control (teachers' general beliefs about limitations to what can be achieved through education), strain factors, and teacher burnout. Participants were 244 elementary and middle school teachers. The analysis supported the conceptualization of teacher self-efficacy as a multidimensional construct. They found strong support for 6 separate but correlated dimensions of teacher self-efficacy, which were included in the following subscales: Instruction, Adapting Education to Individual Students' Needs, Motivating Students, Keeping Discipline, Cooperating With Colleagues and Parents, and Coping With Changes and Challenges. They also found support for a strong 2nd-order self-efficacy factor underlying the 6 dimensions. Teacher self-efficacy was conceptually distinguished from perceived collective teacher efficacy and external control. Teacher self-efficacy was strongly related to collective teacher efficacy and teacher burnout. <s> BIB006 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> A novel personalized instructing recommendation system (PIRS) is designed for Web-based learning. This system recognizes different patterns of learning style and Web using habits through testing the learning styles of students and mining their Web browsing logs. Firstly, it processes the sparse data by item-based top-N recommendation algorithm in the course of testing the learning styles. Then it analyzes the habits and the interests of the Web users through mining the frequent sequences in the Web browsing logs by AprioriAll algorithm. Finally, this system completes personalized recommendation of the learning content based on the learning style and the habit of Web usage. Experiment shows that the recommendation model, proposed in this paper, is not only satisfied with the urgent need of the users, but also feasible and effective. <s> BIB007 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> The concept map proposed by Novak is a good tool to portray knowledge structure and to diagnose students' misconception in education. However, most of the learning concept maps have to be constructed through the suggestions of experts or scholars in related realm. It is really a complicated and time-consuming knowledge acquisition process. The study proposed to apply the algorithm of Apriori for Concept Map to develop an intelligent concept diagnostic system (ICDS). It provides teachers with constructed concept maps of learners rapidly, and enables teachers to diagnose the learning barriers and misconception of learners instantly. The best Remedial-Instruction Path (RIP) can be reached through the algorithm of RIP suggested in this study. Furthermore, RIP can be designed to provide remedial learning to learners. Moreover, by using statistical method, the study analyzed 245 students' data to investigate whether the learning performance of learners can be significantly enhanced after they have been guided by the RIP. <s> BIB008 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> The purpose of this paper is to propose an adaptive system analysis for optimizing learning sequences. The analysis employs a decision tree algorithm, based on students' profiles, to discover the most adaptive learning sequences for a particular teaching content. The profiles were created on the basis of pretesting and posttesting, and from a set of five student characteristics: gender, personality type, cognitive style, learning style, and the students' grades from the previous semester. This paper address the problem of adhering to a fixed learning sequence in the traditional method of teaching English, and recommend a rule for setting up an optimal learning sequence for facilitating students' learning processes and for maximizing their learning outcome. By using the technique proposed in this paper, teachers will be able both to lower the cost of teaching and to achieve an optimally adaptive learning sequence for students. The results show that the power of the adaptive learning sequence lies in the way it takes into account students' personal characteristics and performance; for this reason, it constitutes an important innovation in the field of Teaching English as a Second Language (TESL). <s> BIB009 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> Student retention is an important issue for all university policy makers due to the potential negative impact on the image of the univer- sity and the career path of the dropouts. Although this issue has been thoroughly studied by many institutional researchers using parametric tech- niques, such as regression analysis and logit modeling, this article attempts to bring in a new perspective by exploring the issue with the use of three data mining techniques, namely, classification trees, multivariate adaptive regression splines (MARS), and neural networks. Data mining procedures identify transferred hours, residency, and ethnicity as crucial factors to re- tention. Carrying transferred hours into the university implies that the stu- dents have taken college level classes somewhere else, suggesting that they are more academically prepared for university study than those who have no transferred hours. Although residency was found to be a crucial predic- tor to retention, one should not go too far as to interpret this finding that retention is affected by proximity to the university location. Instead, this is a typical example of Simpson's Paradox. The geographical information system analysis indicates that non-residents from the east coast tend to be more persistent in enrollment than their west coast schoolmates. <s> BIB010 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> This paper presents an applied study in data mining and knowledge discovery. It aims at discovering patterns within historical students' academic and financial data at UST (University of Science and Technology) from the year 1993 to 2005 in order to contribute improving academic performance at UST. Results show that these rules concentrate on three main issues, students' academic achievements (successes and failures), students' drop out, and students' financial behavior. Clustering (by K-means algorithm), association rules (by Apriori algorithm) and decision trees by (J48 and Id3 algorithms) techniques have been used to build the data model. Results have been discussed and analyzed comprehensively and then well evaluated by experts in terms of some criteria such as validity, reality, utility, and originality. In addition, practical evaluation using SQL queries have been applied to test the accuracy of produced model (rules). <s> BIB011 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> In this paper we are proposing a new Attribute Selection Measure Function (heuristic) on existing C4.5 algorithm. The advantage of heuristic is that the split information never approaches zero, hence produces stable Rule set and Decision Tree. In ideal situation, in admission process in engineering colleges in India, a student takes admission based on AIEEE rank and family pressure. If the student does not get admission in the desired branch of engineering, then they find it difficult to take decision which will be the suitable branch. The proposed knowledge based decision technique will guide the student for admission in proper branch of engineering. Another approach is also made to analyze the accuracy rate for decision tree algorithm (C5.0) and back propagation algorithm (ANN) to find out which one is more accurate for decision making. In this research work we have used the AIEEE2007 Database. <s> BIB012 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> This special issue of JEDM was dedicated to bridging work done in the disciplines of educational and psychological assessment and educational data mining (EDM) via the assessment design and implementation framework of evidence-centered design (ECD). It consisted of a series of five papers: one conceptual paper on ECD, three applied case studies that use ECD and EDM tools, and one simulation study that relies on ECD for its design and EDM for its implementation. In this reflection piece we discuss some of the key lessons that we have learned from the articles in this special issue with respect to the instructional utility of the digital learning environments, the nature of the statistical methodologies used, and the added value of the ECD framework for the work conducted in these projects. <s> BIB013 </s> A SURVEY ON EDUCATIONAL DATA MINING AND RESEARCH TRENDS <s> MINING EDUCATIONAL OBJECTIVIES <s> Abstract The study empirically tests an integrative model of work satisfaction ( Lent and Brown, 2006 , Duffy and Lent, 2009 , Lent et al., 2008 , Lent et al., 2011 ) in a sample of 5,022 teachers in Abu Dhabi in the United Arab Emirates. The study provided more support for the Lent and Brown (2006) model. Results revealed that this model was a strong fit for the data and accounted for 82% of the variance in work satisfaction. Of the five predictor classes, work conditions, goal progress, and positive affect were each found to explain unique predictive variance. This suggests that teachers who are most satisfied with their jobs see their work environment as supportive, experience positive goal progress, and report high levels of trait positive affect. Self-efficacy was related indirectly to work satisfaction (via work conditions and via goal progress). Goal support was also related indirectly to work satisfaction (via work conditions, and via self efficacy, but through goal progress. Implications of the findings for future research and efforts to promote teachers’ job satisfaction in Abu Dhabi are discussed. <s> BIB014

This survey focused on mining academic objectives of EDM in context of traditional to dynamic environments. In traditional teaching and learning environment Performance and Behavior analysis are performed on the basis of observation and paper records used in . BIB003 . This process is static used in BIB001 . This system has the drawbacks such as it cannot meet the need of the individual learner as well as lacking dynamic learning which can be improved by using five steps of an academic analytics process such as capture, report, predict, act and refine [36] . Learning and assessment process in a virtual environment using sophisticated DM methods in a digital learning environment is presented by BIB013 . This research focused on individual learners by "information-processing narratives" and group learners by "socio-cognitive narratives". To enhance the quality in higher learning institutions, the concept of predictive and descriptive models discussed by BIB005 . Predictive model predicts the success rate for individual students; individual lecturer and Descriptive model describe the pattern modeling of student course enrollment, course assignment policy making, behavior analysis etc. In Web-based education system learner behaviors, access patterns are recorded in a log file described in BIB002 , hence able to analyze the need of the individual learner. To better design and modification of web sites by analyzing the access patterns in weblogs are described in . The limitation of the log file is the authenticity of the user. In BIB010 provides the different way to log record process by keeping record of learning path. This approach is suitable only for small log files. To accumulate large log file in a real or virtual environment, an approach given by where recording of all activities of learning such as reading, writing, appearing test, communicate with peer groups are possible. To enhance this concept, BIB007 added collaborative learning approach between learner groups and educators which provides an easy way to analysis learner learning behavior. E-learning is one way of mining online data. Importance of DM in e-learning, concept map in elearning described in BIB008 learning management and Moodle system was described in . Researchers BIB007 BIB009 consider the "perception behavior" of learners and analysis with the help of sequential pattern mining technique which is able to analysis the data in a time sequence of actions. The researchers mixed up the different DM techniques to validate the Predictive and Descriptive model so it is not clearly visible which technique/algorithm is to discover the appropriate quality in higher education. To overcome this issue, an approach given by BIB011 , trying to discover the vital patterns of students by analyzing academic and financial data in terms of validity, reality, utility and originality. The researcher used clustering algorithm (k-means), Association Rules (Apriori algorithm) and DT algorithm (J48, ID3) and WEKA data mining tool to validate the data model. In this research, researcher focuses on vital pattern analysis in higher education system. But researcher did not mention which algorithm/technique is best to analyze vital patterns for quality education. Knowledge based decision technique by comparative study of the DM algorithms (C5.0 CART, ANN) and DM Tool (SPSS Clementine) was given by . Attribute mainly considered in this research work was enrollment decision making parameters such as parental pressure, demand of industry and historical placement record. To enhance the accuracy of the analysis real data set of AIEEE 2007 was used in this work. This research work concluded that C5.0 has the highest accuracy rate to predict the enrollment decision. Another approach given by BIB012 , proposing a new Attribute Selection Measure Function (heuristic) on existing C4.5 algorithm. The advantage of heuristic is that the split information never approaches zero, hence produces stable Rule Set and Decision Tree. Most of the above discussed researches try to meet student perspectives, where as analyses of satisfaction levels of teachers were not discussed which is also important in the educational system. To analyze this matter BIB004 proposed a model which comprises of five attributes i.e. Positive affect, Goal support, Self efficacy, Work conditions and Goal progress. This model tested on the sample data of Abu Dhabi employed teachers and it was found that most of the teachers satisfied with their supportive work conditions/ environments. Other parameters like Student's behavior, parent-teacher relationship, administrative satisfaction BIB006 , social culture, stress, demographic variables are also important to evaluate the teacher's satisfaction. In recent research, BIB014 enhanced the concept of BIB004 using hypothesis (22no) testing using 5022 samples of Abu Dhabi employed teachers. This study results a strong bond between the parameters "Positive affect" and "Work condition". "Goal progress" and "Self efficacy" are essential component where as goal support improves the goal performance if a teacher has high confidence in the work place. Apart from the teachers' job satisfaction; it is necessary to mine teachers' research interest including interdisciplinary areas to create a knowledge hub and hence transforming to world class institutions. In presents a methodology for managing educational capacity utilization, simulating various academic proposals and ultimately building a Decision Support System (DSS) that gives a comprehensive framework for systematic and efficient management of the university resources

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> I. INTRODUCTION TO NANONETWORKS <s> This chapter contains sections titled: Introduction Silicon-Based CMOS Scaling Nanoelectronic Materials and Devices Three-Dimensional (3D) Integration Summary References ]]> <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> I. INTRODUCTION TO NANONETWORKS <s> Nanotechnologies promise new solutions for several applications in biomedical, industrial and military fields. At nano-scale, a nano-machine can be considered as the most basic functional unit. Nano-machines are tiny components consisting of an arranged set of molecules, which are able to perform very simple tasks. Nanonetworks. i.e., the interconnection of nano-machines are expected to expand the capabilities of single nano-machines by allowing them to cooperate and share information. Traditional communication technologies are not suitable for nanonetworks mainly due to the size and power consumption of transceivers, receivers and other components. The use of molecules, instead of electromagnetic or acoustic waves, to encode and transmit the information represents a new communication paradigm that demands novel solutions such as molecular transceivers, channel models or protocols for nanonetworks. In this paper, first the state-of-the-art in nano-machines, including architectural aspects, expected features of future nano-machines, and current developments are presented for a better understanding of nanonetwork scenarios. Moreover, nanonetworks features and components are explained and compared with traditional communication networks. Also some interesting and important applications for nanonetworks are highlighted to motivate the communication needs between the nano-machines. Furthermore, nanonetworks for short-range communication based on calcium signaling and molecular motors as well as for long-range communication based on pheromones are explained in detail. Finally, open research challenges, such as the development of network components, molecular communication theory, and the development of new architectures and protocols, are presented which need to be solved in order to pave the way for the development and deployment of nanonetworks within the next couple of decades. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> I. INTRODUCTION TO NANONETWORKS <s> Abstract This paper provides an in-depth view on nanosensor technology and electromagnetic communication among nanosensors. First, the state of the art in nanosensor technology is surveyed from the device perspective, by explaining the details of the architecture and components of individual nanosensors, as well as the existing manufacturing and integration techniques for nanosensor devices. Some interesting applications of wireless nanosensor networks are highlighted to emphasize the need for communication among nanosensor devices. A new network architecture for the interconnection of nanosensor devices with existing communication networks is provided. The communication challenges in terms of terahertz channel modeling, information encoding and protocols for nanosensor networks are highlighted, defining a roadmap for the development of this new networking paradigm. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> I. INTRODUCTION TO NANONETWORKS <s> Development of targeted drug delivery systems using magnetic microrobots increases the therapeutic indices of drugs. These systems have to be incorporated with precise motion controllers. We demonstrate closed-loop motion control of microrobots under the influence of controlled magnetic fields. Point-to-point motion control of a cluster of iron oxide nanoparticles (diameter of 250 nm) is achieved by pulling the cluster towards a reference position using magnetic field gradients. Magnetotactic bacterium (MTB) is controlled by orienting the magnetic fields towards a reference position. MTB with membrane length of 5 μm moves towards the reference position using the propulsion force generated by its flagella. Similarly, self-propelled microjet with length of 50 μm is controlled by directing the microjet towards a reference position by external magnetic torque. The microjet moves along the field lines using the thrust force generated by the ejecting oxygen bubbles from one of its ends. Our control system positions the cluster of nanoparticles, an MTB and a microjet at an average velocity of 190 μm/s, 28 μm/s, 90 μm/s and within an average region-of-convergence of 132 μm, 40 μm, 235 μm, respectively. <s> BIB004

In upcoming years, the advancement in nanotechnology is expected to accelerate the development of integrated devices with the size ranging from one to a few hundred nanometers BIB002 , BIB003 . With the aim of shrinking traditional machines and creating nano-devices with new functionality, nanotechnologies have produced some novel nano-materials and nano-particles with novel behaviours and properties which are not observed at the microscopic level. The links and connectivity between nano-devices distributed through collaborative effort lead to the vision of nanonetworks, after the concept of nano-machine is proposed. The limited capabilities of nano-machines in terms of processing power, complexity and range of operations can be expanded by this collaborative communication. It is changing the paradigm from the Internet of Things (IoT) to Internet of Nano-Things (IoNTs) which shares the same development path as the nanonetworks. Communication between nano-machines in IoNTs can be set up through nano-mechanical, acoustic, chemical, electromagnetic (EM) and molecular communication approaches BIB002 . Unfortunately, traditional communication technologies are not suitable mainly due to the limitations, such as size, complexity and energy consumption of transmitters, receivers and other components at nano-scale BIB001 ; thus, novel and suitable communication techniques from physical layer to higher layers are required to develop for each paradigm. The molecular and EM communication schemes are envisioned as two most promising paradigms and numerous researches have been done in these two paradigms. This review focuses on molecular and EM approaches and presents their backgrounds, applications, recent developments and challenges. We mainly present a comprehensive survey on the researches that have already been done to enable the communication in nanonetworks. Moreover, several aspects of the integration of nanonetworks have been identified. We propose to implement a hybrid communication taking advantage of both paradigms to enhance the communication performance and aim to broaden and realize more applications. The feasibility of the novel hybrid communication is discussed based on the requirements and enabling technologies from both micro and macro perspectives, and the open challenges are explored as a source if inspiration towards future developments of this inter-connectivity. This paper provides a structured and comprehensive review arXiv:1912.09424v1 [eess.SP] BIB004 Dec 2019 on the recent literature on Body-Centric nanonetworks, an effectual foundation of IoNTs. The main contributions of this survey are summarized as follows. • The various applications are classified and summarized. • The latest advancement in physical, link, MAC, network and application layers have been comprehensively reviewed in addition to security changes. • The hybrid communication scheme by collaboratively employing EM-based nano-communication and molecular communication together is introduced. • Open issues and challenges for such hybrid networks are introduced. The rest of the paper is organized as follows. Section II presents an overview of various communication paradigms, numerous applications and standardization. Section III discusses the general requirements and performance metrics of the envisioned body-centric nanonetworks, while Section IV illustrates the enabling and concomitant technologies which would help the development of nanonetworks from EM and bio perspective, respectively. The architecture of the network and performance of EM and molecular communication is discussed in Section V and Section VI, respectively. The connectivity of both communication methods are discussed in Section VII. In Section VIII, the researches related to the security issues are discussed. In the end, the challenges and open problems are discussed with a brief conclusion.

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> II. AN OVERVIEW OF NANONETWORKS <s> Nanotechnologies promise new solutions for several applications in biomedical, industrial and military fields. At nano-scale, a nano-machine can be considered as the most basic functional unit. Nano-machines are tiny components consisting of an arranged set of molecules, which are able to perform very simple tasks. Nanonetworks. i.e., the interconnection of nano-machines are expected to expand the capabilities of single nano-machines by allowing them to cooperate and share information. Traditional communication technologies are not suitable for nanonetworks mainly due to the size and power consumption of transceivers, receivers and other components. The use of molecules, instead of electromagnetic or acoustic waves, to encode and transmit the information represents a new communication paradigm that demands novel solutions such as molecular transceivers, channel models or protocols for nanonetworks. In this paper, first the state-of-the-art in nano-machines, including architectural aspects, expected features of future nano-machines, and current developments are presented for a better understanding of nanonetwork scenarios. Moreover, nanonetworks features and components are explained and compared with traditional communication networks. Also some interesting and important applications for nanonetworks are highlighted to motivate the communication needs between the nano-machines. Furthermore, nanonetworks for short-range communication based on calcium signaling and molecular motors as well as for long-range communication based on pheromones are explained in detail. Finally, open research challenges, such as the development of network components, molecular communication theory, and the development of new architectures and protocols, are presented which need to be solved in order to pave the way for the development and deployment of nanonetworks within the next couple of decades. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> II. AN OVERVIEW OF NANONETWORKS <s> Untethered robots miniaturized to the length scale of millimeter and below attract growing attention for the prospect of transforming many aspects of health care and bioengineering. As the robot size goes down to the order of a single cell, previously inaccessible body sites would become available for high-resolution in situ and in vivo manipulations. This unprecedented direct access would enable an extensive range of minimally invasive medical operations. Here, we provide a comprehensive review of the current advances in biome dical untethered mobile milli/microrobots. We put a special emphasis on the potential impacts of biomedical microrobots in the near future. Finally, we discuss the existing challenges and emerging concepts associated with designing such a miniaturized robot for operation inside a biological environment for biomedical applications. <s> BIB002

According to Feynman, there is plenty of room at the bottom . Based on such statement and the considerable development of nano-technology, Prof. Metin Sitti has proposed that in the near future the network would go down to the nanoscale if the nano robots and molecular machine are adopted as its elements BIB002 . Thus, the concept of nano-networks was proposed. However, the connection between nano-devices in such networks would be a challenge, leading to the study on nano-communication , BIB001 . Therefore, nano-communication can be defined as the communication between nano-devices where the communication principles should be novel and modified to meet the demands in the nano-world. To make it clearer, four requirements are summarized in IEEE P1906.1 in the aspects of components, system structure, communication principles and etc.,

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Nano-communication paradigms <s> Nanotechnologies promise new solutions for several applications in biomedical, industrial and military fields. At nano-scale, a nano-machine can be considered as the most basic functional unit. Nano-machines are tiny components consisting of an arranged set of molecules, which are able to perform very simple tasks. Nanonetworks. i.e., the interconnection of nano-machines are expected to expand the capabilities of single nano-machines by allowing them to cooperate and share information. Traditional communication technologies are not suitable for nanonetworks mainly due to the size and power consumption of transceivers, receivers and other components. The use of molecules, instead of electromagnetic or acoustic waves, to encode and transmit the information represents a new communication paradigm that demands novel solutions such as molecular transceivers, channel models or protocols for nanonetworks. In this paper, first the state-of-the-art in nano-machines, including architectural aspects, expected features of future nano-machines, and current developments are presented for a better understanding of nanonetwork scenarios. Moreover, nanonetworks features and components are explained and compared with traditional communication networks. Also some interesting and important applications for nanonetworks are highlighted to motivate the communication needs between the nano-machines. Furthermore, nanonetworks for short-range communication based on calcium signaling and molecular motors as well as for long-range communication based on pheromones are explained in detail. Finally, open research challenges, such as the development of network components, molecular communication theory, and the development of new architectures and protocols, are presented which need to be solved in order to pave the way for the development and deployment of nanonetworks within the next couple of decades. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Nano-communication paradigms <s> Medical nanorobotics exploits nanometer-scale components and phenomena with robotics to provide new medical diagnostic and interventional tools. Here, the architecture and main specifications of a novel medical interventional platform based on nanorobotics and nanomedicine, and suited to target regions inaccessible to catheterization are described. The robotic platform uses magnetic resonance imaging (MRI) for feeding back information to a controller responsible for the real-time control and navigation along pre-planned paths in the blood vessels of untethered magnetic carriers, nanorobots, and/or magnetotactic bacteria (MTB) loaded with sensory or therapeutic agents acting like a wireless robotic arm, manipulator, or other extensions necessary to perform specific remote tasks. Unlike known magnetic targeting methods, the present platform allows us to reach locations deep in the human body while enhancing targeting efficacy using real-time navigational or trajectory control. The paper describes several versions of the platform upgraded through additional software and hardware modules allowing enhanced targeting efficacy and operations in very difficult locations such as tumoral lesions only accessible through complex microvasculature networks. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Nano-communication paradigms <s> A remarkable feature of modern silicon electronics is its ability to remain physically invariant, almost indefinitely for practical purposes. Although this characteristic is a hallmark of applications of integrated circuits that exist today, there might be opportunities for systems that offer the opposite behavior, such as implantable devices that function for medically useful time frames but then completely disappear via resorption by the body. We report a set of materials, manufacturing schemes, device components, and theoretical design tools for a silicon-based complementary metal oxide semiconductor (CMOS) technology that has this type of transient behavior, together with integrated sensors, actuators, power supply systems, and wireless control strategies. An implantable transient device that acts as a programmable nonantibiotic bacteriocide provides a system-level example. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Nano-communication paradigms <s> Development of targeted drug delivery systems using magnetic microrobots increases the therapeutic indices of drugs. These systems have to be incorporated with precise motion controllers. We demonstrate closed-loop motion control of microrobots under the influence of controlled magnetic fields. Point-to-point motion control of a cluster of iron oxide nanoparticles (diameter of 250 nm) is achieved by pulling the cluster towards a reference position using magnetic field gradients. Magnetotactic bacterium (MTB) is controlled by orienting the magnetic fields towards a reference position. MTB with membrane length of 5 μm moves towards the reference position using the propulsion force generated by its flagella. Similarly, self-propelled microjet with length of 50 μm is controlled by directing the microjet towards a reference position by external magnetic torque. The microjet moves along the field lines using the thrust force generated by the ejecting oxygen bubbles from one of its ends. Our control system positions the cluster of nanoparticles, an MTB and a microjet at an average velocity of 190 μm/s, 28 μm/s, 90 μm/s and within an average region-of-convergence of 132 μm, 40 μm, 235 μm, respectively. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Nano-communication paradigms <s> Recent progress in bioresorbable radio frequency electronics has promised the prospect of realizing a transient microbot system (TMS) for therapeutic applications. In this paper, we investigate simulation tools for the analysis of a TMS-oriented nano-communication (NC) model for targeted drug delivery, where the physically transient microbots are remotely controllable and trackable through an applied electromagnetic field (EMF), and are responsible for transportation of drug particles (channel in the NC context). Our approach is illustrated with a study case of drug delivery for breast cancer treatment by using the proposed analytical framework integrating robotics and communications at small length scales. <s> BIB005

To make the network work well, the communication between the nano-devices needs to be linked. In BIB001 , nanocommunication is studied in two scenarios: BIB001 Communication between the nano-devices to the micro/macro-system, and (2) Communication between nano-devices. Furthermore, molecular, electromagnetic, acoustic, nano-mechanical communication can be modified to nano-networks [10] , summarized in our previous work in . Based on the burgeoning of the nanotechnology, a fresh model of mechanical communication, i.e. touch communication (TouchCom), was also proposed in , where bunches of nano-robots were adopted to play as the message carriers. In TouchCom, transient microbots (TMs) BIB003 - BIB002 were used to carry the drug particles and they are controlled and guided by the external macro-unit (MAU) BIB004 , BIB005 . These TMs would stay in the body for some time whose pathway is the channel and the operations of loading and unloading of drugs can be treated as the transmitting and receiving process. The channel model of TouchCom could be described by the propagation delay, loss of the signal strength in the aspects of the angular/delay spectra . A simulation tool was also introduced to characterize the action of the nanorobots in the blood vessel BIB005 .

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> PHYSICAL PRINCIPLES. Classical Magnitudes and Scaling Laws. Potential Energy Surfaces. Molecular Dynamics. Positional Uncertainty. Transitions, Errors, and Damage. Energy Dissipation. Mechanosynthesis. COMPONENTS AND SYSTEMS. Nanoscale Structural Components. Mobile Interfaces and Moving Parts. Intermediate Subsystems. Nanomechanical Computational Systems. Molecular Sorting, Processing, and Assembly. Molecular Manufacturing Systems. IMPLEMENTATION STRATEGIES. Macromolecular Engineering. Paths to Molecular Manufacturing. Appendices. Afterword. Symbols, Units, and Constants. Glossary. References. Index. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> A cholesterol biosensors fabricated by immobilization of cholesterol oxidase (ChOx) in a layer of silicic sol-gel matrix on the top of a Prussian Blue-modified glassy carbon electrode was prepared. It is based on the detection of hydrogen peroxide produced by ChOx at −0.05 V. The half-lifetime of the biosensor is about 35 days. Cholesterol can be determined in the concentration range of 1×10−6−8×10−5 mol/L with a detection limit of 1.2×10−7 mol/L. Normal interfering compounds, such as ascorbic acid and uric acid do not affect the determination. The high sensitivity and outstanding selectivity are attributed to the Prussian Blue film modified on the sensor. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> This paper discusses the technological advancement in nanotechnology and some aspects of applications in engineering devices and biotechnologies. The lecture outlines the logical development of technology and engineering following (1) initiation of idea and visualization, (2) ability to control and measurements and (3) intense effort in engineering developments. The paper includes a brief review of the historical development in biology, nano and potential applications of electro-magnetic phenomena. The paper also describes the activities in the Center for Nanomagnetics and Biotechnology for clinical applications using nanomagnetic particles. Several magnetic phenomena in life sciences are illustrated. Brief discussions of nano materials are introduced. The paper then concludes with possible near term applications and long term developments of nanotechnology in biomedical and bioengineering. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Recently the technology of capsule endoscopy has developed dramatically and many researchers are making efforts to combine surgical function into the capsule type endoscope. In this paper, the micro biopsy module which is a part of the capsule endoscope is proposed. The proposed module is less than 2 mm in thickness and has a diameter of 10 mm. It consists of a trigger with paraffin block, rotational tissue-cutting razor with a torsion spring and controller. This module makes it possible for the capsule endoscope to obtain a sample tissue inside the small intestine which can not be reached by a conventional biopsy device. Through dedicated experiments, tissue samples were successfully extracted using the proposed biopsy module and the cells in samples were extracted and tested by a microscope. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> A capsule endoscope is a swallowable wireless miniature camera for getting images of the gastrointestinal (GI) mucosa. The initial capsule endoscope model was developed by Given Imaging and approved in Western countries in 2001. Before the introduction of capsule endoscopy (CE) and double-balloon endoscopy (DBE), there was no effective modality for the evaluation and management of patients with obscure GI bleeding. Obscure GI bleeding is defined as bleeding of unknown origin that persists or recurs after a negative initial or primary endoscopy (colonoscopy or upper endoscopy) result. The first capsule endoscope model, which is now regarded as a first-line tool for the detection of abnormalities of the small bowel, was the PillCam SB. It was approved in Japan in April 2007. The main indication for use of the PillCam SB is obscure GI bleeding. Almost the only complication of CE is capsule retention, which is the capsule remaining in the digestive tract for a minimum of 2 weeks. A retained capsule can be retrieved by DBE. There are some limitations of CE in that it cannot be used to obtain a biopsy specimen or for endoscopic treatment. However, the combination of a PillCam SB and DBE seems to be the best strategy for management of obscure GI bleeding. Recently, several new types of capsule endoscope have been developed, such as Olympus CE for the small bowel, PillCam ESO for investigation of esophageal diseases, and PillCam COLON for detection of colonic neoplasias. In the near future, CE is expected to have a positive impact on many aspects of GI disease evaluation and management. <s> BIB005 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> A novel algorithm to accurately determine the location of an ultrasound source within heterogeneous media is presented. The method obtains a small spacial error of 748 microm+/-310 microm for 100 different measurements inside a circular area with 140 mm diameter. The new algorithm can be used in targeted drug delivery for cancer therapies as well as to accurately locate any kind of ultrasound sources in heterogeneous media, such as ultrasonically marked medical devices or tumors. <s> BIB006 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Nanotechnologies promise new solutions for several applications in biomedical, industrial and military fields. At nano-scale, a nano-machine can be considered as the most basic functional unit. Nano-machines are tiny components consisting of an arranged set of molecules, which are able to perform very simple tasks. Nanonetworks. i.e., the interconnection of nano-machines are expected to expand the capabilities of single nano-machines by allowing them to cooperate and share information. Traditional communication technologies are not suitable for nanonetworks mainly due to the size and power consumption of transceivers, receivers and other components. The use of molecules, instead of electromagnetic or acoustic waves, to encode and transmit the information represents a new communication paradigm that demands novel solutions such as molecular transceivers, channel models or protocols for nanonetworks. In this paper, first the state-of-the-art in nano-machines, including architectural aspects, expected features of future nano-machines, and current developments are presented for a better understanding of nanonetwork scenarios. Moreover, nanonetworks features and components are explained and compared with traditional communication networks. Also some interesting and important applications for nanonetworks are highlighted to motivate the communication needs between the nano-machines. Furthermore, nanonetworks for short-range communication based on calcium signaling and molecular motors as well as for long-range communication based on pheromones are explained in detail. Finally, open research challenges, such as the development of network components, molecular communication theory, and the development of new architectures and protocols, are presented which need to be solved in order to pave the way for the development and deployment of nanonetworks within the next couple of decades. <s> BIB007 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Inflammation occurs in episodic flares in Crohn's disease, which are part of the waxing and waning course of the disease. Healing between flares allows the intestine to reconstitute its epithelium, but this healing results in the deposition of fibrotic scar tissue as part of the healing process. Repeated cycles of flares and healing often lead to clinically significant fibrosis and stenosis of the intestine. Patients are treated empirically with steroids, with their many side effects, in the hope that they will respond. Many patients would be better treated with surgery if we could identify which patients truly have intestinal fibrosis. Ultrasound elasticity imaging (UEI) offers the potential to radically improve the diagnosis and management of local tissue elastic property, particularly intestinal fibrosis. This method allows complete characterization of local intestine tissue with high spatial resolution. The feasibility of UEI on Crohn's disease is demonstrated by directly applying this technique to an animal model of inflammatory bowel disease (IBD). Five female Lewis rats (150-180g) were prepared with phosphate buffered solution (PBS) as a control group and six were prepared with repeated intrarectal administration of trinitrobenzenesulfonic acid (TNBS) as a disease group. Preliminary strain measurements differentiate the diseased colons from the normal colons (p < 0.0002) and compared well with direct mechanical measurements and histology (p < 0.0005). UEI provides a simple and accurate assessment of local severity of fibrosis. The preliminary results on an animal model also suggest the feasibility of translating this imaging technique directly to human subjects for both diagnosis and monitoring. <s> BIB008 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> The influence of oxygen on various ophthalmological complications is not completely understood and intraocular oxygen measurements are essential for better diagnosis and treatment. A magnetically controlled wireless sensor device is proposed for minimally invasive intraocular oxygen concentration measurements. This device will make it possible to make measurements at locations that are currently too invasive for human intervention by integrating a luminescence optical sensor and a magnetic steering system. The sensor works based on quenching of luminescence in the presence of oxygen. A novel iridium phosphorescent complex is designed and synthesized for this system. A frequency-domain lifetime measurement approach is employed because of the intrinsic nature of the lifetime of luminescence. Experimental results of the oxygen sensor together with magnetic and hydrodynamic characterization of the sensor platform are presented to demonstrate the concept. In order to use this sensor for in vivo intraocular applications, the size of the sensor must be reduced, which will require an improved signal-to-noise ratio. <s> BIB009 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Plants use inducible defence mechanisms to fend off harmful organisms. Resistance that is induced in response to local attack is often expressed systemically, that is, in organs that are not yet damaged. In the search for translocated defence signals, biochemical studies follow the physical movement of putative signals, and grafting experiments use mutants that are impaired in the production or perception of these signals. Long-distance signals can directly activate defence or can prime for the stronger and faster induction of defence. Historically, research has focused on the vascular transport of signalling metabolites, but volatiles can play a crucial role as well. We compare the advantages and constraints of vascular and airborne signals for the plant, and discuss how they can act in synergy to achieve optimised resistance in distal plant parts. <s> BIB010 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Filtration of molecules by nanometer-sized structures is ubiquitous in our everyday life, but our understanding of such molecular filtration processes is far less than desired. Until recently, one of the main reasons was the lack of experimental methods that can help provide detailed, microscopic pictures of molecule–nanostructure interactions. Several innovations in experimental methods, such as nuclear track-etched membranes developed in the 70s, and more recent development of nanofluidic molecular filters, played pivotal roles in advancing our understanding. With the ability to make truly molecular-scale filters and pores with well-defined sizes, shapes, and surface properties, now we are well positioned to engineer better functionality in molecular sieving, separation and other membrane applications. Reviewing past theoretical developments (often scattered across different fields) and connecting them to the most recent advances in the field would be essential to get a full, unified view on this important engineering question. <s> BIB011 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> New methods to identify trace amount of infectious pathogens rapidly, accurately and with high sensitivity are in constant demand to prevent epidemics and loss of lives. Early detection of these pathogens to prevent, treat and contain the spread of infections is crucial. Therefore, there is a need and urgency for sensitive, specific, accurate, easy-to-use diagnostic tests. Versatile biofunctionalized engineered nanomaterials are proving to be promising in meeting these needs in diagnosing the pathogens in food, blood and clinical samples. The unique optical and magnetic properties of the nanoscale materials have been put to use for the diagnostics. In this review, we focus on the developments of the fluorescent nanoparticles, metallic nanostructures and superparamagnetic nanoparticles for bioimaging and detection of infectious microorganisms. The various nanodiagnostic assays developed to image, detect and capture infectious virus and bacteria in solutions, food or biological samples in vitro and in vivo are presented and their relevance to developing countries is discussed. <s> BIB012 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> This chapter is a brief description of the state of the art of the field of targeted drug delivery using magnetic implants. It describes the advantages and drawbacks of the use of internal magnets to concentrate magnetic nanoparticles near tumor locations, and the different approaches to this task performed in vitro and in vivo reviewed in literature are presented. <s> BIB013 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Mechanical forces play important roles in the regulation of various biological processes at the molecular and cellular level, such as gene expression, adhesion, migration, and cell fate, which are essential to the maintenance of tissue homeostasis. In this review, we discuss emerging bioengineered tools enabled by microscale technologies for studying the roles of mechanical forces in cell biology. In addition to traditional mechanobiology experimental techniques, we review recent advances of microelectromechanical systems (MEMS)-based approaches for cell mechanobiology and discuss how microengineered platforms can be used to generate in vivo-like micromechanical environment in in vitro settings for investigating cellular processes in normal and pathophysiological contexts. These capabilities also have significant implications for mechanical control of cell and tissue development and cell-based regenerative therapies. <s> BIB014 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> BACKGROUND ::: Capsule endoscopy (CE) has been widely used in clinical practice. ::: ::: ::: OBJECTIVE ::: To provide systematically pooled results on the indications and detection, completion, and retention rates of small-bowel CE. ::: ::: ::: DESIGN ::: A systematic review. ::: ::: ::: MAIN OUTCOME MEASUREMENTS ::: We searched the PubMed database (2000-2008) for original articles relevant to small-bowel CE for the evaluation of patients with small-bowel signs and symptoms. Data on the total number of capsule procedures, the distribution of different indications for the procedures, the percentages of procedures with positive detection (detection rate), complete examination (completion rate), or capsule retention (retention rate) were extracted and/or calculated, respectively. In addition, the detection, completion, and retention rates were also extracted and/or calculated in relation to indications such as obscure GI bleeding (OGIB), definite or suspected Crohn's disease (CD), and neoplastic lesions. ::: ::: ::: RESULTS ::: A total of 227 English-language original articles involving 22,840 procedures were included. OGIB was the most common indication (66.0%), followed by the indication of only clinical symptoms reported (10.6%), and definite or suspected CD (10.4%). The pooled detection rates were 59.4%; 60.5%, 55.3%, and 55.9%, respectively, for overall, OGIB, CD, and neoplastic lesions. Angiodysplasia was the most common reason (50.0%) for OGIB. The pooled completion rate was 83.5%, with the rates being 83.6%, 85.4%, and 84.2%, respectively, for the 3 indications. The pooled retention rates were 1.4%, 1.2%, 2.6%, and 2.1%, respectively, for overall and the 3 indications. ::: ::: ::: LIMITATIONS ::: Inclusion and exclusion criteria were loosely defined. ::: ::: ::: CONCLUSIONS ::: The pooled detection, completion, and retention rates are acceptable for total procedures. OGIB is the most common indication for small-bowel CE, with a high detection rate and low retention rate. In addition, angiodysplasia is the most common finding in patients with OGIB. A relatively high retention rate is associated with definite or suspected CD and neoplasms. <s> BIB015 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Triggerable drug delivery systems enable on-demand controlled release profiles that may enhance therapeutic effectiveness and reduce systemic toxicity. Recently, a number of new materials have been developed that exhibit sensitivity to visible light, near-infrared (NIR) light, ultrasound, or magnetic fields. This responsiveness can be triggered remotely to provide flexible control of dose magnitude and timing. Here we review triggerable materials that range in scale from nano to macro, and are activated by a range of stimuli. <s> BIB016 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Wireless capsule endoscopy (WCE) offers a feasible noninvasive way to detect the whole gastrointestinal (GI) tract and revolutionizes the diagnosis technology. However, compared with wired endoscopies, the limited working time, the low frame rate, and the low image resolution limit the wider application. The progress of this new technology is reviewed in this paper, and the evolution tendencies are analyzed to be high image resolution, high frame rate, and long working time. Unfortunately, the power supply of capsule endoscope (CE) is the bottleneck. Wireless power transmission (WPT) is the promising solution to this problem, but is also the technical challenge. Active CE is another tendency and will be the next geneion of the WCE. Nevertheless, it will not come true shortly, unless the practical locomotion mechanism of the active CE in GI tract is achieved. The locomotion mechanism is the other technical challenge, besides the challenge of WPT. The progress about the WPT and the active capsule technology is reviewed. <s> BIB017 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> magnetic fi elds. [ 20 ] These helical microrobots have been used to transport a single microsphere in three dimensions. The microrobots were coated with a thin titanium (Ti) layer for better biocompatibility and affi nity with the cells; this was confi rmed by culturing cells on the helical microrobots. Similarly, microspheres can be transported in the fl owing streams of microfl uidic channels, which enable the microrobots to swim in the <s> BIB018 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Transport of individual cells or chemical payloads on a subcellular scale is an enabling tool for the study of cellular communication, cell migration, and other localized phenomena. We present a magnetically actuated robotic system capable of fully automated manipulation of cells and microbeads. Our strategy uses autofluorescent robotic transporters and fluorescently labeled microbeads to aid tracking and control in optically obstructed environments. We demonstrate automated delivery of microbeads infused with chemicals to specified positions on neurons. This system is compatible with standard upright and inverted light microscopes and is capable of applying forces less than 1 pN for precision positioning tasks. <s> BIB019 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Abstract Wirelessly interconnected nanorobots, i.e., engineered devices of sizes ranging from one to a few hundred nanometers, are promising revolutionary diagnostic and therapeutic medical applications that could enhance the treatment of major diseases. Each nanorobot is usually designed to perform a set of basic tasks such as sensing and actuation. A dense wireless network of nano-devices, i.e., a nanonetwork, could potentially accomplish new and more complex functionalities, e.g., in-vivo monitoring or adaptive drug-delivery, thus enabling revolutionary nanomedicine applications. Several innovative communication paradigms to enable nanonetworks have been proposed in the last few years, including electromagnetic communications in the terahertz band, or molecular and neural communications. In this paper, we propose and discuss an alternative approach based on establishing intra-body opto-ultrasonic communications among nanorobots. Opto-ultrasonic communications are based on the optoacoustic effect, which enables the generation of high-frequency acoustic waves by irradiating the medium with electromagnetic energy in the optical frequency range. We first discuss the fundamentals of nanoscale opto-ultrasonic communications in biological tissues by modeling the generation, propagation and detection of opto-ultrasonic waves, and we explore important tradeoffs. Then, we discuss potential research challenges for the design of opto-ultrasonic nanonetworks of implantable devices at the physical, medium access control, and network layers of the protocol stack. <s> BIB020 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> The assembly of three-dimensional, complex functional materials at micro- or nanoscales for various applications is challenging. Tasoglu et al. develop a magnetic micro-robot system that is capable of programmable coding of soft and rigid building blocks to build heterogeneous materials. <s> BIB021 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> As we move towards the miniaturization of devices to perform tasks at the nano and microscale, it has become increasingly important to develop new methods for actuation, sensing, and control. Over the past decade, bio-hybrid methods have been investigated as a promising new approach to overcome the challenges of scaling down robotic and other functional devices. These methods integrate biological cells with artificial components and therefore, can take advantage of the intrinsic actuation and sensing functionalities of biological cells. Here, the recent advancements in bio-hybrid actuation are reviewed, and the challenges associated with the design, fabrication, and control of bio-hybrid microsystems are discussed. As a case study, focus is put on the development of bacteria-driven microswimmers, which has been investigated as a targeted drug delivery carrier. Finally, a future outlook for the development of these systems is provided. The continued integration of biological and artificial components is envisioned to enable the performance of tasks at a smaller and smaller scale in the future, leading to the parallel and distributed operation of functional systems at the microscale. <s> BIB022 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> This paper proposes a new wireless biopsy method where a magnetically actuated untethered soft capsule endoscope carries and releases a large number of thermo-sensitive, untethered microgrippers (μ-grippers) at a desired location inside the stomach and retrieves them after they self-fold and grab tissue samples. We describe the working principles and analytical models for the μ-gripper release and retrieval mechanisms, and evaluate the proposed biopsy method in ex vivo experiments. This hierarchical approach combining the advanced navigation skills of centimeter-scaled untethered magnetic capsule endoscopes with highly parallel, autonomous, submillimeter scale tissue sampling μ-grippers offers a multifunctional strategy for gastrointestinal capsule biopsy. <s> BIB023 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Untethered robots miniaturized to the length scale of millimeter and below attract growing attention for the prospect of transforming many aspects of health care and bioengineering. As the robot size goes down to the order of a single cell, previously inaccessible body sites would become available for high-resolution in situ and in vivo manipulations. This unprecedented direct access would enable an extensive range of minimally invasive medical operations. Here, we provide a comprehensive review of the current advances in biome dical untethered mobile milli/microrobots. We put a special emphasis on the potential impacts of biomedical microrobots in the near future. Finally, we discuss the existing challenges and emerging concepts associated with designing such a miniaturized robot for operation inside a biological environment for biomedical applications. <s> BIB024 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> B. Applications of nanonetworks <s> Thank you for reading carbon nanotubes synthesis structure properties and applications. Maybe you have knowledge that, people have search hundreds times for their favorite readings like this carbon nanotubes synthesis structure properties and applications, but end up in infectious downloads. Rather than reading a good book with a cup of tea in the afternoon, instead they are facing with some infectious virus inside their laptop. <s> BIB025

Nano-communication spans a wide area such as military, ubiquitous health care, sport, entertainment and many other areas, detailed description of which has been summarized and classified in BIB007 , shown in Table I . The main characteristic in all applications is to improve people's life quality and nanonetworks are generally believed as the perfect candidate for bio-medical fields due to bio-compatibility, bio-stability and its dimension. Generally, the applications are classified into two general categories, medical and non-medical as below. 1) Medical Applications: There are many biomedical application in literature, e.g, intraocular pressure (IOP) for vision BIB024 and nano robotos for cancer cells in BIB020 . Moreover, nanonetworks will monitor the body status in real time and some nano-devices can be used as tissue substitutes, i.e., biohybrid implants. In the following, we present two interesting BIB024 , BIB007 Biomedical Environmental Industrial Military • Active Visual Imaging for Disease Diagnosis BIB015 BIB005 BIB017 BIB006 BIB008 Health Monitor • Mobile Sensing for Disease Diagnosis BIB009 [25] BIB002 BIB012 Bio-Degradation Product Quality Control Nuclear, Biological and Chemical Defences BIB025 • Tissue Engineering BIB021 [32] BIB018 • Bio-Hybrid Implant BIB001 • Targeted Therapy/Drug Delivery BIB013 [37] BIB016 [39] BIB022 • Cell Manipulation BIB003 [19] BIB019 [43] BIB014 Therapy • Minimally Invasive Surgery BIB004 [46] BIB023 Bio-Control BIB010 [49] BIB011 Intelligent Office Nano-Fictionalized Equipment [10] Location of James Status of SmartBlood Health Status of James examples that come from movies, which shows the limitless possibilities of nano network medical applications. a) Health-Monitoring: In the movie The Circle, an example of the health-monitor system which is installed in the body of the lead actress May has been displayed. The whole system consists of two parts: digestible nano-sensors and a wristband. At first, the doctor asked May to drink a bag of green solution with the nano-sensors in and then gave her a wristband which should be worn all the time, shown in Fig. 1a . The medium band would sync up with the sensors May has swallowed while both equipments would collect data of the heart rate, blood pressure, cholesterol, sleep duration, sleep quality, digestive efficiency, and so on. The capture of the movie in Fig. 1b shows the related information on the wall. Through the wristband, all the data can be stored anywhere May wants. Also, all the data would be shared with the related people, like the doctor or the nutritionist. b) Real-Time Detection: In the movie of 007: Spectre, a technology called Smart Blood was illustrated, which is a bunch of nano-machines/micro-chips capable of tracking Mr. Bond's movement in the field. They were injected into Bond's blood system, and the institute would monitor Bond's vital signs from anywhere on the planet, shown in Fig. 2 . It is not just a scientific idea in the movie because several researchers are working on various kinds of injectable substances that can identify cancer cells. The folks at Seattle-based Blaze Bioscience are among the pioneers. c) Drug Delivery: It is believed that the nanonetworks can not only sense the information but also make some actions when needed. The most trustworthy application would go for real-time glucose control. The nano-sensors spreading in blood vessels can monitor the glucose level; at the same time, the nano-machines could release the insulin to regulate the glucose level (shown in Fig. 3 ). With such technologies, people with diabetes would not need to needle themselves and inject the medicine in public which would cause the embarrassment and infection if the operation is not correct. Also, the signal can also be sent to related people through wearable devices or smart phones to let them help the patients build a healthy habit.

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In this paper, the authors review the fundamental issues arising when nanoscale devices are meant to be interconnected to transmit information. The possibility of manipulating and assembling objects at the atomic scale has paved the way for a future generation of computing machines, where nanoscale devices substitute silicon-based transistors. Interconnections, needed to perform complex operations, are expected to be the driving factor in terms of performance and costs of the resulting systems. In view of the current research on nanomachines, the authors are interested in understanding which may be the limits of communications at the nanoscale level. Our research stems from a few, simple and yet unanswered questions, like "what is the capacity of a nanowire/nanotube?", "what is the capacity of molecular-based communication systems?" etc. While we do not answer to such questions directly, we shed some light on possible approaches based on information-theoretical concepts <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In this paper, the problem of communicating using chemical messages propagating using Brownian motion, rather than electromagnetic messages propagating as waves in free space or along a wire, is considered. This problem is motivated by nanotechnological and biotechnological applications, where the energy cost of electromagnetic communication might be prohibitive. Models are given for communication using particles that propagate with Brownian motion, and achievable capacity results are given. Under conservative assumptions, it is shown that rates exceeding one bit per particle are achievable. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In molecular communication, messages are conveyed from a transmitter to a receiver by releasing a pattern of molecules at the transmitter, and allowing those molecules to propagate through a fluid medium towards a receiver. In this paper, achievable information rates are estimated for a molecular communication system when information is encoded using a set of distinct molecules, and when the molecules propagate across the medium via Brownian motion. Results are provided which indicate large gains in information rate over the case where the released molecules are indistinguishable from each other. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Molecular communication is a novel communication paradigm which allows nanomachines to communicate using molecules as a carrier. Controlled molecule delivery between two nanomachines is one of the most important challenges which must be addressed to enable the molecular communication. Therefore, it is essential to develop an information theoretical approach to find out molecule delivery capacity of the molecular channel. In this paper, we develop an information theoretical approach for capacity of a molecular channel between two nanomachines. We first introduce a molecular communication model. Then, using the principles of mass action kinetics we give a molecule delivery model for the molecular communication between two nanomachines called as Transmitter Nanomachine (TN) and Receiver Nanomachine (RN). Then, we derive a closed form expression for capacity of the channel between TN and RN. Numerical results show that selecting appropriate molecular communication parameters such as temperature of environment, concentration of emitted molecules, distance between nanomachines and duration of molecule emission, it can be possible to achieve maximum capacity for the molecular communication channel between two nanomachines. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Molecular communication is a biologically-inspired method of communication with attractive properties for microscale and nanoscale devices. In molecular communication, messages are transmitted by releasing a pattern of molecules at a transmitter, which propagate through a fluid medium towards a receiver. In this paper, molecular communication is formulated as a mathematical communication problem in an information-theoretic context. Physically realistic models are obtained, with sufficient abstraction to allow manipulation by communication and information theorists. Although mutual information in these channels is intractable, we give sequences of upper and lower bounds on the mutual information which trade off complexity and performance, and present results to illustrate the feasibility of these bounds in estimating the true mutual information. <s> BIB005 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Using a single layer of electrically controlled metamaterial, researchers have achieved active control of the phase of terahertz waves and demonstrated high-speed broadband modulation. <s> BIB006 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Molecular communication is a new paradigm for communication between biological nanomachines over a nano- and microscale range. As biological nanomachines (or nanomachines in short) are too small and simple to communicate through traditional communication mechanisms (e.g., through sending and receiving of radio or infrared signals), molecular communication provides a mechanism for a nanomachine (i.e., a sender) to communicate information by propagating molecules (i.e., information molecules) that represent the information to a nanomachine (i.e., a receiver). This paper describes the design of an in vitro molecular communication system and evaluates various approaches to maximize the probability of information molecules reaching a receiver(s) and the rate of information reaching the receiver(s). The approaches considered in this paper include propagating information molecules (diffusion or directional transport along protein filaments), removing excessive information molecules (natural decay or receiver removal of excessive information molecules), and encoding and decoding approaches (redundant information molecules to represent information and to decode information). Two types of molecular communication systems are considered: a unicast system in which a sender communicates with a single receiver and a broadcast system in which a sender communicates with multiple receivers. Through exploring tradeoffs among the various approaches on the two types of molecular communication systems, this paper identifies promising approaches and shows the feasibility of an in vitro molecular communication system. <s> BIB007 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Inspired by biological communication systems, molecular communication has been proposed as a viable scheme to communicate between nano-sized devices separated by a very short distance. Here, molecules are released by the transmitter into the medium, which are then sensed by the receiver. This paper develops a preliminary version of such a communication system focusing on the release of either one or two molecules into a fluid medium with drift. We analyze the mutual information between transmitter and the receiver when information is encoded in the time of release of the molecule. Simplifying assumptions are required in order to calculate the mutual information, and theoretical results are provided to show that these calculations are upper bounds on the true mutual information. Furthermore, optimized degree distributions are provided, which suggest transmission strategies for a variety of drift velocities. <s> BIB008 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Abstract Abstract Molecular communication is a new communication paradigm that uses molecules for information transmission between nanomachines. Similar to traditional communication systems, several factors constitute limits over the performance of this communication system. One of these factors is the energy budget of the transmitter. It limits the rate at which the transmitter can emit symbols, i.e., produce the messenger molecules. In this paper, an energy model for the communication via diffusion system is proposed. To evaluate the performance of this communication system, first a channel model is developed, and also the probability of correct decoding of the information is evaluated. Two optimization problems are set up for system analysis that focus on channel capacity and data rate. Evaluations are carried out using the human insulin hormone as the messenger molecule and a transmitter device whose capabilities are similar to a pancreatic β -cell. Results show that distance between the transmitter and receiver has a minor effect on the achievable data rate whereas the energy budget’s effect is significant. It is also shown that selecting appropriate threshold and symbol duration parameters are crucial to the performance of the system. <s> BIB009 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Nanotechnologies promise new solutions for several applications in the biomedical, industrial and military fields. At the nanoscale, a nanomachine is considered as the most basic functional unit which is able to perform very simple tasks. Communication among nanomachines will allow them to accomplish more complex functions in a distributed manner. In this paper, the state of the art in molecular electronics is reviewed to motivate the study of the Terahertz Band (0.1-10.0 THz) for electromagnetic (EM) communication among nano-devices. A new propagation model for EM communications in the Terahertz Band is developed based on radiative transfer theory and in light of molecular absorption. This model accounts for the total path loss and the molecular absorption noise that a wave in the Terahertz Band suffers when propagating over very short distances. Finally, the channel capacity of the Terahertz Band is investigated by using this model for different power allocation schemes, including a scheme based on the transmission of femtosecond-long pulses. The results show that for very short transmission distances, in the order of several tens of millimeters, the Terahertz channel supports very large bit-rates, up to few terabits per second, which enables a radically different communication paradigm for nanonetworks. <s> BIB010 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> This paper characterizes intersymbol interference (ISI) in a unicast molecular communication between a pair of nanomachines in a nanonetwork. Correspondingly, a transmission-controlled approach based on reduced pulse-width transmission has been proposed in order to mitigate ISI. Binary amplitude modulation has been assumed for the concentration-encoded signaling. Characteristics of interference signal strength (as a fraction of total available signal strength at the location of receiving nanomachine) have been explained in terms of communication range, pulse-width, and data rate of the system. Performance evaluation has been explained in the form of improvement by reducing interference with a reduced pulse-width approach. Results based on numerical analyses with three suitable propagation media (air, water, and human blood plasma) have been shown for the sake of potential applications in the field of nano-bio-communication and healthcare nanomedicine. Finally, it is concluded that ISI is a significant issue in molecular communication, and the proposed reduced pulse-width based approach saves signal energy and improves ISI performance in concentration-encoded molecular communication. <s> BIB011 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Abstract Currently, Communication via Diffusion (CvD) is one of the most prominent systems in nanonetworks. In this paper, we evaluate the effects of two major interference sources, Intersymbol Interference (ISI) and Co-channel Interference (CCI) in the CvD system using different modulation techniques. In the analysis of this paper, we use two modulation techniques, namely Concentration Shift Keying (CSK) and Molecule Shift Keying (MoSK) that we proposed in our previous paper. These techniques are suitable for the unique properties of messenger molecule concentration waves in nanonetworks. Using a two transmitting couple simulation environment, the channel capacity performances of the CvD system utilizing these modulation techniques are evaluated in terms of communication range, distance between interfering sources, physical size of devices, and average transmission power. <s> BIB012 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Abstract Designing an optimum receiver for diffusion-based molecular communication in nano-networks needs a well justified channel model. In this paper, we present a linear and time invariant signal propagation model and an additive noise model for the diffusion-based molecular communication channel. These models are based on Brownian motion molecular statistics. Using these models, we develop the first optimal receiver design for diffusion-based molecular communication scenarios with and without inter-symbol interference. We evaluate the performance of our proposed receiver by investigating the bit error rate for small and large transmission rates. <s> BIB013 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Diffusion-based molecular communications emerges due to the need for communication and networking among nanomachines, and molecular biological signaling networks. Inspired by the special molecular channel characteristics, we reveal the communication theoretical analogs with and differences from well-known wireless communications, particularly channel coding, intersymbol interference, multiple-input multipleoutput, and new design concepts in this article. <s> BIB014 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> We review different techniques for modulation of the electromagnetic properties of terahertz (THz) waves. We discuss various approaches for electronic, optical, thermal and nonlinear modulation in distinct material systems such as semiconductors, graphene, pho- tonic crystals and metamaterials. The modulators are classified and compared with respect to modulation speed, modulation depth and categorized by the physical quantity they control as e.g. amplitude, phase, spectrum, spatial and temporal properties of the THz wave. Based on the review paper, the reader should obtain guidelines for the proper choice of a specific modulation technique in view of the targeted application. <s> BIB015 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> We model the ligand-receptor molecular communication channel with a discrete-time Markov model, and show how to obtain the capacity of this channel. We show that the capacity-achieving input distribution is iid; further, unusually for a channel with memory, we show that feedback does not increase the capacity of this channel. <s> BIB016 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Molecular communications emerges as a promising scheme for communications between nanoscale devices. In diffusion-based molecular communications, molecules as information symbols diffusing in the fluid environments suffer from molecule crossovers, i.e., the arriving order of molecules is different from their transmission order, leading to intersymbol interference (ISI). In this paper, we introduce a new family of channel codes, called ISI-free codes, which improve the communication reliability while keeping the decoding complexity fairly low in the diffusion environment modeled by the Brownian motion. We propose general encoding/decoding schemes for the ISI-free codes, working upon the modulation schemes of transmitting a fixed number of identical molecules at a time. In addition, the bit error rate (BER) approximation function of the ISI-free codes is derived mathematically as an analytical tool to decide key factors in the BER performance. Compared with the uncoded systems, the proposed ISI-free codes offer good performance with reasonably low complexity for diffusion-based molecular communication systems. <s> BIB017 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In the Molecular Communication (MC), molecules are utilized to encode, transmit, and receive information. Transmission of the information is achieved by means of diffusion of molecules and the information is recovered based on the molecule concentration variations at the receiver location. The MC is very prone to intersymbol interference (ISI) due to residual molecules emitted previously. Furthermore, the stochastic nature of the molecule movements adds noise to the MC. For the first time, we propose four methods for a receiver in the MC to recover the transmitted information distorted by both ISI and noise. We introduce sequence detection methods based on maximum a posteriori (MAP) and maximum likelihood (ML) criterions, a linear equalizer based on minimum mean-square error (MMSE) criterion, and a decision-feedback equalizer (DFE) which is a nonlinear equalizer. We present a channel estimator to estimate time varying MC channel at the receiver. The performances of the proposed methods based on bit error rates are evaluated. The sequence detection methods reveal the best performance at the expense of computational complexity. However, the MMSE equalizer has the lowest performance with the lowest computational complexity. The results show that using these methods significantly increases the information transmission rate in the MC. <s> BIB018 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> This paper studies the mitigation of intersymbol interference in a diffusive molecular communication system using enzymes that freely diffuse in the propagation environment. The enzymes form reaction intermediates with information molecules and then degrade them so that they cannot interfere with future transmissions. A lower bound expression on the expected number of molecules measured at the receiver is derived. A simple binary receiver detection scheme is proposed where the number of observed molecules is sampled at the time when the maximum number of molecules is expected. Insight is also provided into the selection of an appropriate bit interval. The expected bit error probability is derived as a function of the current and all previously transmitted bits. Simulation results show the accuracy of the bit error probability expression and the improvement in communication performance by having active enzymes present. <s> BIB019 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Abstract In this paper, a novel error control strategy for electromagnetic nanonetworks, based on the utilization of low-weight channel codes and aimed at the prevention of channel errors, is proposed. In particular, it is first analytically shown that both the molecular absorption noise and the multi-user interference in nanonetworks can be mitigated by reducing the channel code weight, which results into a lower channel error probability. Then, the relation between the channel code weight and the code word length is analyzed for the case of utilizing constant weight codes. Finally, the performance of the proposed strategy is analytically and numerically investigated in terms of the achievable information rate after coding and the Codeword Error Rate (CER). Two different receiver architectures are considered, namely, an ideal soft-receiver and a hard receiver. An accurate Terahertz Band channel model and novel stochastic models for the molecular absorption noise and the multi-user interference, validated with COMSOL, are utilized. The results show that low-weight channel codes can be used to reduce the CER without compromising the achievable information rate or even increasing it, especially for the hard-receiver architecture. Moreover, it is shown that there is an optimal code weight, for which the information rate is maximized. <s> BIB020 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> The memoryless additive inverse Gaussian noise channel model describing communication based on the exchange of chemical molecules in a drifting liquid medium is investigated for the situation of simultaneously an average-delay and a peak-delay constraint. Analytical upper and lower bounds on its capacity in bits per molecule use are presented. These bounds are shown to be asymptotically tight, i.e., for the delay constraints tending to infinity with their ratio held constant (or for the drift velocity of the fluid tending to infinity), the asymptotic capacity is derived precisely. Moreover, characteristics of the capacity-achieving input distribution are derived that allow accurate numerical computation of capacity. The optimal input appears to be a mixed continuous and discrete distribution. <s> BIB021 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> The design of biologically-inspired wireless communication systems using bacteria as the basic element of the system is initially motivated by a phenomenon called Quorum Sensing. Due to high randomness in the individual behavior of a bacterium, reliable communication between two bacteria is almost impossible. Therefore, we have recently proposed that a population of bacteria in a cluster is considered as a bio node in the network capable of molecular transmission and reception. This proposition enables us to form a reliable bio node out of many unreliable bacteria. In this paper, we study the communication between two nodes in such a network where information is encoded in the concentration of molecules by the transmitter. The molecules produced by the bacteria in the transmitter node propagate through the diffusion channel. Then, the concentration of molecules is sensed by the bacteria population in the receiver node which would decode the information and output light or fluorescent as a result. The uncertainty in the communication is caused by all three components of communication, i.e., transmission, propagation and reception. We study the theoretical limits of the information transfer rate in the presence of such uncertainties. Finally, we consider M-ary signaling schemes and study their achievable rates and corresponding error probabilities. <s> BIB022 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Particulate Drug Delivery Systems (PDDS) are ther- apeutic methods that use nanoparticles to achieve their healing effects at the exact time, concentration level of drug nanoparti- cles, and location in the body, while minimizing the effects on other healthy locations. The Molecular Communication (MC) paradigm, where the transmitted message is the drug injection process, the channel is the cardiovascular system, and the received message is the drug reception process, has been investigated as a tool to study nanoscale biological and medical systems in recent years. In this paper, the various noise effects that cause uncertainty in the cardiovascular system are analyzed, modeled, and evaluated from the information theory perspective. Analytical MC noises are presented to include all end-to-end noise effects, from the drug injection, to the absorption of drug nanoparticles by the diseased cells, in the presence of a time-varying and turbulent blood flow. The PDDS capacity is derived analytically including all these noise effects and the constraints on the drug injection. The proposed MC noise is validated by using the kinetic Monte-Carlo simulation technique. Analytical expressions of the noise and the capacity are derived, and MC is presented as a framework for the optimization of particulate drug delivery systems (PDDS). Index Terms—Drug delivery systems, nanonetworks, molecu- lar communication, time-varying channels, communication chan- nels, intra-body communication, noise modeling, capacity, kinetic Monte-Carlo. <s> BIB023 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Within the domain of molecular communications, researchers mimic the techniques in nature to come up with alternative communication methods for collaborating nanomachines. This letter investigates the channel transfer function for molecular communications via diffusion. In nature, information-carrying molecules are generally absorbed by the target node via receptors. Using the concentration function, without considering the absorption process, as the channel transfer function implicitly assumes that the receiver node does not affect the system. In this letter, we propose a solid analytical formulation and analyze the signal metrics (attenuation and propagation delay) for molecular communication via diffusion channel with an absorbing receiver in a 3-D environment. The proposed model and the formulation match well with the simulations without any normalization. <s> BIB024 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In this paper, we consider a multi-hop molecular communication network consisting of one nanotransmitter, one nanoreceiver, and multiple nanotransceivers acting as relays. We consider three different relaying schemes to improve the range of diffusion-based molecular communication. In the first scheme, different types of messenger molecules are utilized in each hop of the multi-hop network. In the second and third schemes, we assume that two types of molecules and one type of molecule are utilized in the network, respectively. We identify self-interference, backward intersymbol interference (backward-ISI), and forward-ISI as the performance-limiting effects for the second and third relaying schemes. Furthermore, we consider two relaying modes analogous to those used in wireless communication systems, namely full-duplex and half-duplex relaying. We propose the adaptation of the decision threshold as an effective mechanism to mitigate self-interference and backward-ISI at the relay for full-duplex and half-duplex transmission. We derive closed-form expressions for the expected end-to-end error probability of the network for the three considered relaying schemes. Furthermore, we derive closed-form expressions for the optimal number of molecules released by the nanotransmitter and the optimal detection threshold of the nanoreceiver for minimization of the expected error probability of each hop. <s> BIB025 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> This paper studies a three-node network in which an intermediate nano-transceiver, acting as a relay, is placed between a nano-transmitter and a nano-receiver to improve the range of diffusion-based molecular communication. Motivated by the relaying protocols used in traditional wireless communication systems, we study amplify-and-forward (AF) relaying with fixed and variable amplification factor for use in molecular communication systems. To this end, we derive a closed-form expression for the expected end-to-end error probability. Furthermore, we derive a closed-form expression for the optimal amplification factor at the relay node for minimization of an approximation of the expected error probability of the network. Our analytical and simulation results show the potential of AF relaying to improve the overall performance of nano-networks. <s> BIB026 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In this paper, the capacity of a diffusion based molecular communication network under the model of a Linear Time Invarient-Poisson (LTI-Poisson) channel is studied. Introduced in the context of molecular communication, the LTI-Poisson model is a natural extension of the conventional memoryless Poisson channel to include memory. Exploiting prior art on linear ISI channels, a computable finite-letter characterization of the capacity of single-hop LTI-Poisson networks is provided. Then, the problem of finding more explicit bounds on the capacity is examined, where lower and upper bounds for the point to point case are provided. Furthermore, an approach for bounding mutual information in the low SNR regime using the symmetrized KL divergence is introduced and its applicability to Poisson channels is shown. To best of our knowledge, the first non-trivial upper bound on the capacity of Poisson channel with a maximum transmission constraint in the low SNR regime is found. Numerical results show that the proposed upper bound is of the same order as the capacity in the low SNR regime. <s> BIB027 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In this paper, we present an analytical model for the diffusive molecular communication (MC) system with a reversible adsorption receiver in a fluid environment. The widely used concentration shift keying (CSK) is considered for modulation. The time-varying spatial distribution of the information molecules under the reversible adsorption and desorption reaction at the surface of a receiver is analytically characterized. Based on the spatial distribution, we derive the net number of newly-adsorbed information molecules expected in any time duration. We further derive the number of newly-adsorbed molecules expected at the steady state to demonstrate the equilibrium concentration. Given the number of newly-adsorbed information molecules, the bit error probability of the proposed MC system is analytically approximated. Importantly, we present a simulation framework for the proposed model that accounts for the diffusion and reversible reaction. Simulation results show the accuracy of our derived expressions, and demonstrate the positive effect of the adsorption rate and the negative effect of the desorption rate on the error probability of reversible adsorption receiver with last transmit bit-1. Moreover, our analytical results simplify to the special cases of a full adsorption receiver and a partial adsorption receiver, both of which do not include desorption. <s> BIB028 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Nanocommunications via Forster Resonance Energy Transfer (FRET) is a promising means of realising collaboration between photoactive nanomachines to implement advanced nanotechnology applications. The method is based on exchange of energy levels between fluorescent molecules by the FRET phenomenon which intrinsically provides a virtual nanocommunication link. In this work, further to the extensive theoretical studies, we demonstrate the first information transfer through a FRET-based nanocommunication channel. We implement a digital communication system combining macroscale transceiver instruments and a bulk solution of fluorophore nanoantennas. The performance of the FRET-based Multiple-Input and Multiple-Output (MIMO) nanocommunication channel between closely located mobile nanoantennas in the sample solution is evaluated in terms of Signal-to-Noise Ratio (SNR) and Bit Error Rate (BER) obtained for the transmission rates of 50 kbps, 150 kbps and 250 kbps. The results of the performance evaluation are very promising for the development of high-rate and reliable molecular communication networks at nanoscale. <s> BIB029 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Molecular communication is a promising approach to realize the communication between nanoscale devices. In a diffusion-based molecular communication network, transmitters and receivers communicate by using signalling molecules. The transmitter uses different time-varying functions of concentration of signalling molecules (called emission patterns) to represent different transmission symbols. The signalling molecules diffuse freely in the medium. The receiver is assumed to consist of a number of receptors, which can be in ON or OFF state. When the signalling molecules arrive at the receiver, they react with the receptors and switch them from OFF to ON state probabilistically. The receptors remain ON for a random amount of time before reverting to the OFF state. This paper assumes that the receiver uses the continuous history of receptor state to infer the transmitted symbol. Furthermore, it assumes that the transmitter uses two transmission symbols and approaches the decoding problem from the maximum a posteriori (MAP) framework. Specifically, the decoding is realized by calculating the logarithm of the ratio of the posteriori probabilities of the two transmission symbols, or log-MAP ratio. A contribution of this paper is to show that the computation of log-MAP ratio can be performed by an analog filter. The receiver can therefore use the output of this filter to decide which symbol has been sent. This analog filter provides insight on what information is important for decoding. In particular, the timing at which the receptors switch from OFF to ON state, the number of OFF receptors and the mean number of signalling molecules at the receiver are important. Numerical examples are used to illustrate the property of this decoding method. <s> BIB030 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In vivo wireless nanosensor networks (iWNSNs) consist of nanosized communicating devices, which can operate inside the human body in real time. iWNSNs are at the basis of transformative healthcare techniques, ranging from intra-body health-monitoring systems to drug-delivery applications. Plasmonic nanoantennas are expected to enable the communication among nanosensors in the near infrared and optical transmission window. This result motivates the analysis of the phenomena affecting the propagation of such electromagnetic (EM) signals inside the human body. In this paper, a channel model for intra-body optical communication among nanosensors is developed. The total path loss is computed by taking into account the absorption from different types of molecules and the scattering by different types of cells. In particular, first, the impact of a single cell on the propagation of an optical wave is analytically obtained, by modeling a cell as a multi-layer sphere with complex permittivity. Then, the impact of having a large number of cells with different properties arranged in layered tissues is analyzed. The analytical channel model is validated by means of electromagnetic simulations and extensive numerical results are provided to understand the behavior of the intra-body optical wireless channel. The result shows that, at optical frequencies, the scattering loss introduced by cells is much larger than the absorption loss from the medium. This result motivates the utilization of the lower frequencies of the near-infrared window for communication in iWNSNs. <s> BIB031 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Nanonetworks consist of nano-sized communicating devices which are able to perform simple tasks at the nanoscale. The limited capabilities of individual nanomachines and the Terahertz (THz) band channel behavior lead to error-prone wireless links. In this paper, a cross-layer analysis of error-control strategies for nanonetworks in the THz band is presented. A mathematical framework is developed and used to analyze the tradeoffs between Bit Error Rate, Packet Error Rate, energy consumption and latency, for five different error-control strategies, namely, Automatic Repeat reQuest (ARQ), Forward Error Correction (FEC), two types of Error Prevention Codes (EPC) and a hybrid EPC. The cross-layer effects between the physical and the link layers as well as the impact of the nanomachine capabilities in both layers are taken into account. At the physical layer, nanomachines are considered to communicate by following a time-spread on-off keying modulation based on the transmission of femtosecond-long pulses. At the link layer, nanomachines are considered to access the channel in an uncoordinated fashion, by leveraging the possibility to interleave pulse-based transmissions from different nodes. Throughout the analysis, accurate path loss, noise and multi-user interference models, validated by means of electromagnetic simulation, are utilized. In addition, the energy consumption and latency introduced by a hardware implementation of each error control technique, as well as, the additional constraints imposed by the use of energy-harvesting mechanisms to power the nanomachines, are taken into account. The results show that, despite their simplicity, EPCs outperform traditional ARQ and FEC schemes, in terms of error correcting capabilities, which results in further energy savings and reduced latency. <s> BIB032 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In this paper, a graphene-based plasmonic phase modulator for Terahertz band (0.1–10 THz) communication is proposed, modeled and analyzed. The modulator is based on a fixed-length graphene-based plasmonic waveguide, and leverages the possibility to tune the propagation speed of Surface Plasmon Polariton (SPP) waves on graphene by modifying the Fermi energy of the graphene layer. An analytical model for the modulator is developed starting from the dynamic complex conductivity of graphene and a revised dispersion equation for SPP waves in gated graphene structures. By utilizing the model, the performance of the modulator is analyzed in terms of symbol error rate when utilized to implement a M-ary digital phase shift keying modulation. The model is validated by means of electromagnetic simulations, and numerical results are provided to illustrate the performance of the modulator. <s> BIB033 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> This paper studies the problem of receiver modeling in molecular communication systems. We consider the diffusive molecular communication channel between a transmitter nano-machine and a receiver nano-machine in a fluid environment. The information molecules released by the transmitter nano-machine into the environment can degrade in the channel via a first-order degradation reaction and those that reach the receiver nano-machine can participate in a reversible bimolecular reaction with receiver receptor proteins. Thereby, we distinguish between two scenarios. In the first scenario, we assume that the entire surface of the receiver is covered by receptor molecules. We derive a closed-form analytical expression for the expected received signal at the receiver, i.e., the expected number of activated receptors on the surface of the receiver. Then, in the second scenario, we consider the case where the number of receptor molecules is finite and the uniformly distributed receptor molecules cover the receiver surface only partially. We show that the expected received signal for this scenario can be accurately approximated by the expected received signal for the first scenario after appropriately modifying the forward reaction rate constant. The accuracy of the derived analytical results is verified by Brownian motion particle-based simulations of the considered environment, where we also show the impact of the effect of receptor occupancy on the derived analytical results. <s> BIB034 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In active transport molecular communication (ATMC), information particles are actively transported from a transmitter to a receiver using special proteins. Prior work has demonstrated that ATMC can be an attractive and viable solution for on-chip applications. The energy consumption of an ATMC system plays a central role in its design and engineering. In this work, an energy model is presented for ATMC and the model is used to provide guidelines for designing energy efficient systems. The channel capacity per unit energy is analyzed and maximized. It is shown that based on the size of the symbol set and the symbol duration, there is a vesicle size that maximizes rate per unit energy. It is also demonstrated that maximizing rate per unit energy yields very different system parameters compared to maximizing the rate only. <s> BIB035 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> The performance of communication systems is fundamentally limited by the loss of energy through propagation and circuit inefficiencies. In this article, we show that it is possible to achieve ultra low energy communications at the nano-scale, if diffusive molecules are used for carrying data. Whilst the energy of electromagnetic waves will inevitably decay as a function of transmission distance and time, the energy in individual molecules does not. Over time, the receiver has an opportunity to recover some, if not all of the molecular energy transmitted. The article demonstrates the potential of ultra-low energy simultaneous molecular information and energy transfer (SMIET) through the design of two different nano-relay systems, and the discusses how molecular communications can benefit more from crowd energy harvesting than traditional wave-based systems. <s> BIB036 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> The opportunity to control and fine-tune the behavior of biological cells is a fascinating possibility for many diverse disciplines, ranging from medicine and ecology, to chemical industry and space exploration. While synthetic biology is providing novel tools to reprogram cell behavior from their genetic code, many challenges need to be solved before it can become a true engineering discipline, such as reliability, safety assurance, reproducibility and stability. This paper aims to understand the limits in the controllability of the behavior of a natural (non-engineered) biological cell. In particular, the focus is on cell metabolism, and its natural regulation mechanisms, and their ability to react and change according to the chemical characteristics of the external environment. To understand the aforementioned limits of this ability, molecular communication is used to abstract biological cells into a series of channels that propagate information on the chemical composition of the extracellular environment to the cell's behavior in terms of uptake and consumption of chemical compounds, and growth rate. This provides an information-theoretic framework to analyze the upper bound limit to the capacity of these channels to propagate information, which is based on a well-known and computationally efficient metabolic simulation technique. A numerical study is performed on two human gut microbes, where the upper bound is estimated for different environmental compounds, showing there is a potential for future practical applications. <s> BIB037 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Information delivery using chemical molecules is an integral part of biology at multiple distance scales and has attracted recent interest in bioengineering and communication theory. Potential applications include cooperative networks with a large number of simple devices that could be randomly located (e.g., due to mobility). This paper presents the first tractable analytical model for the collective signal strength due to randomly placed transmitters in a 3-D large-scale molecular communication system, either with or without degradation in the propagation environment. Transmitter locations in an unbounded and homogeneous fluid are modeled as a homogeneous Poisson point process. By applying stochastic geometry, analytical expressions are derived for the expected number of molecules absorbed by a fully absorbing receiver or observed by a passive receiver. The bit error probability is derived under ON/OFF keying and either a constant or adaptive decision threshold. Results reveal that the combined signal strength increases proportionately with the transmitter density, and the minimum bit error probability can be improved by introducing molecule degradation. Furthermore, the analysis of the system can be generalized to other receiver designs and other performance characteristics in large-scale molecular communication systems. <s> BIB038 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> Molecular communication via diffusion (MCvD) is inherently an energy efficient transportation paradigm, which requires no external energy during molecule propagation. Inspired by the fact that the emitted molecules have a finite probability to reach the receiver, this letter introduces an energy efficient scheme for the information molecule synthesis process of MCvD via a simultaneous molecular information and energy transfer (SMIET) relay. With this SMIET capability, the relay can decode the received information as well as generate its emission molecules using its absorbed molecules via chemical reactions. To reveal the advantages of SMIET, approximate closed-form expressions for the bit error probability and the synthesis cost of this two-hop molecular communication system are derived and then validated by particle-based simulation. Interestingly, by comparing with a conventional relay system, the SMIET relay system can be shown to achieve a lower minimum bit error probability via molecule division, and a lower synthesis cost via molecule type conversion or molecule division. <s> BIB039 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> III. REQUIREMENTS AND PERFORMANCE METRICS OF BODY-CENTRIC NANONETWORKS <s> In multi-cellular organisms, molecular signaling spans multiple distance scales and is essential to tissue structure and functionality. Molecular communications is increasingly researched and developed as a key subsystem in the Internet-of-Nano-Things paradigm. While short range microscopic diffusion communications is well understood, longer range channels can be inefficient and unreliable. Static and mobile relays have been proposed in both conventional wireless systems and molecular communication contexts. In this paper, our main contribution is to analyze the information delivery energy efficiency of bacteria mobile relays. We discover that these mobile relays offer superior energy efficiency compared with pure diffusion information transfer over long diffusion distances. This paper has widespread implications ranging from understanding biological processes to designing new efficient synthetic biology communication systems. <s> BIB040

A. EM-Based Body-Centric Nanonetworks 1) Achievable Information Rates: The maximum achievable information rate, I R max(sym) , with the unit of bit/symbol based on a specific modulation scheme in a communication system has been defined as : where X and Y denote the message sent by the transmitter and its noisy version at the receiver, respectively. Here, H(X) represents the entropy of message X, while H(X|Y) is the conditional entropy of X given Y. Represent the transmitted information over the asymmetric THz band channel without coding as a discrete binary random variable, x 0 and x 1 ; then, H(X) is given as : where p X (x m ) indicates the probability of transmitted symbol x 0 named as silence and x 1 named as pulse. Assuming Additive Coloured Gaussian Noise (ACGN) BIB010 at the receiver, and a Binary Asymmetric Channel (BAC) with Y being a discrete random variable, the information rate (in bits/second) is given as BIB020 : where B represents the bandwidth of channel. β is the ratio of the symbol interval T s and the pulse length T p . And the rate of the symbols transmitted is defined as R = 1 / T s = 1 (βT p ) . Note that the requirements on the transceiver can be greatly relaxed by reducing the single-user rate to increase β. Fig. 9 studies the trade-off between the information rate and the transmission distance, for three different human body tissues (with an EM channel of bandwidth 1 THz . 2) Bit Error Rate: Since EM waves propagate through the frequency-dependent materials inside the human body, the operating frequency has an important effect on the communication channel. BIB031 shows that the scattering from cells is the major phenomenon affecting the propagation of EM waves at Fig. 9 : The trade-off between Information rate and transmission distance for three different human tissues . optical frequencies inside the human body. BIB032 does the error analysis (at the physical layer and link layer) of an EM system operating in THz band. 3) Symbol Error Rate: BIB015 studies different types of modulators capable of setting the amplitude or phase of the THz wave. A meta-material-based modulator was employed to control the phase of THz wave in BIB006 . BIB033 proposes and validates an analytic model for the plasmonic phase modulator that starts from the dynamic complex conductivity of graphene. By applying the model, the symbol error rate performance of the plasmonic modulator is studied when it is utilized to implement an M-array phase shift keying modulation. B. MC-Based Body-Centric Nanonetworks 1) Achievable Information Rates: The discussion of the performance limits of the MC-based nanonetworks in terms of achievable information rates was first initiated by BIB001 . Later, Eckford computed the mutual information (i.e., the maximum achievable information rate) for an MC channel whereby the information was encoded into the release time of molecules BIB002 , and by a set of distinct molecules BIB003 . In a followup work, Eckford also provided tractable lower and upper bounds on information rate of one-dimensional MC system BIB005 . In another work BIB008 , Kadloor et. al. considered an MC system inside a blood vessel and introduced a drift component into the MC channel to take into account the blood flow, and computed the information rate for the case when pulse-position modulation is used by the emitter. Last but not the least, reported an important finding whereby it was proved that the noise in the one-dimensional MC channel with positive drift velocity is additive with inverse Gaussian (IG) distribution. Below, we summarize the information rates achieved by some very prominent MC channels. • Timing Channel: In a timing channel, the point transmitter encodes a message in the release time of a molecule, and once a molecule reaches the receiver, it is fully absorbed, thus the first arrival time determines the actual arrival time of the molecule. For a single molecule released at time X, its actual arrival time Y will be expressed as , BIB021 where N T is the first arrival time at the receiver boundary. For the positive drift v > 0, N T follows AIGN distribution IG( l v , 2l 2 D ) with the communication distance l and diffusion coefficient D. Based on [70] bounded from above and below the capacity of additive IG noise channel with a constraint on the mean of the transmitted message X. Extended from , the authors in BIB021 studied the capacity of the same additive IG noise channel under either an average-and a peakdelay constraint or a peak-delay constraint, and the authors in revisited the capacity bounds of diffusionbased timing channel (without drift) with finite particle's time. • Concentration-encoded Channel: In this channel, concentration of molecules is varied to convey information BIB004 - . The authors in BIB004 studied the mutual information of a more specific molecular communication system with ligand-binding receptors, where the molecules can bind or unbind from the receiver, but without taking into account the diffusion propagation and channel memory. The authors in BIB007 modeled and measured the information rate of various molecular communication systems with diffusion, connected, or hybrid-aster propagation approaches, and noise-free, all-noise, exponential decay, and receiver removal noise model. The achievable rates of the diffusion-based MC channel, under two different coding schemes were studied in BIB012 . considered concentration encoding at the emitter, a diffusion-based MC channel with memory and noise at the receiver, and derived the closed-form expression for the channel capacity. To account for memory, the bounds on capacity of the conventional memoryless Poisson channel was extended to that of the Linear Time Invarient-Poisson channel of diffusion-based single-hop networks BIB027 . However, the reception process has not been treated in , BIB027 . • Biological System: In BIB016 and BIB022 , the capacities of an inter-cellular signal transduction channel and bacterial communication were studied by modelling the ligandreception processes as a discrete-time Markov model, and a Binomial Channel for a bacterial colony, respectively. The capacity analysis of molecular communication channel in a drug delivery system BIB023 and cell metabolism BIB037 were studied using COMSOL Multiphysics and KBase (Department of Energy Systems Biology Knowledgebase) software application suite, respectively. More detailed literature review on information theoretic study of molecular commmunication can be found in . 2) Bit Error Rate: During each slot, the receiver will receive the molecules due to the current slot as well as from the previous slots (due to brownian motion of molecules). This phenomenon is known as inter-symbol interference (ISI). As the main bottleneck of bit error performance of molecular communication system, the ISI is first characterized in BIB011 , and increasing attention has been focused on the bit error rate performance characterization from then on. • Single-Hop System with the Passive Receiver: Initial MC works have focused on a passive (spherical) receiver that just counts the number of received molecules in its close vicinity without interacting with them. The bit error rate of the MC system with a passive receiver under ISI and no ISI was studied in BIB013 where the receiver implements the optimal maximum a-posteriori probability (MAP) rule. To improve the BER performance of the MC systems, BIB017 introduced a new family of ISI-free coding with fairly low decoding complexity. While, BIB018 did the MAP based, maximum likelihood (ML) based, linear equalizer/minimum mean-square error (MMSE) based, and a decision-feedback equalizer (DFE) based sequence detection. BIB019 introduced the enzyme reactions to the diffusion, derived the average BER, and verified it via the realistic particle-based simulation. All these works point to the undesirable effect of ISI on the performance of an MC system with a passive receiver. • Single-Hop System with the Active Receiver: In a real biological system, the receiver actually consists of receptors that react to some specific molecules (e.g., peptides or calcium ions). Thus, research efforts have shifted to the simulation and modelling of the active receivers, such as the fully absorbing receiver BIB024 , the reversible absorbing receiver BIB028 , and the ligand-binding receiver BIB034 . BIB024 derived a simple expression for the channel impulse response of an MC system with an fully absorbing receiver, and validated it by the particle-based simulation simulator (MUCIN). BIB028 and BIB034 derived the analytical expressions for the expected received signal and the average BER for an MC system with reversible absorbing receiver, and for an MC system with the ligand-binding receiver, respectively. The expressions obtained were then verified by particle-based simulation algorithms. • Multi-Hop System and Large-scale System: The average BER of the multi-hop decode-and-forward relay and amplify-and-forward relay MC systems were derived and simulated in BIB025 and BIB026 to extend the transmission range and improve the reliability of MC systems. Using the three-dimensional stochastic geometry, the average BER with large number of transmitters perfrom joint transmission to the fully absorbing receiver were analyzed and simulated via particle-based simulation and Pseudo-Random simulation in BIB038 , which provided an analytical model of BER evaluation for large-scale MC system with all kinds of active receivers. • Experimental System: The BER performance of the F orster Resonance Energy Transfer (FRET) nanoscale MIMO communication channel has been tested and examined in BIB029 , which was shown to provide acceptable reliability with BER about 5.7×10 −5 bit −1 for nanonetworks up to 150 kbps transmission rates. 3) Symbol Error Rate: The symbol error rate (SER) of molecular communication system was first mentioned in BIB014 , then the SERs of an MC system with absorbing receiver under the binary concentration keying (BCSK), the quadrature CSK (QCSK), the binary molecular frequency shift keying (BMFSK), and the quadrature MFSK (QMFSK) were simu-lated in using MUCIN simulator. In BIB030 , the SER of diffusion-based MC system with receiver having periodically ON and OFF receptors and analog filter for computing the logarithm of the MAP ratio was studied. 4) Energy Cost: BIB009 develops an energy model for the MC system whereby the energy costs in the messenger molecule synthesizing process, the secretory vesicle production process, the secretory vesicle carrying process, and the molecule releasing process were defined based on molecular cell biology. The energy model of vesicle-based active transport MC system was described in BIB035 , where the energy costs of the vesicle synthesis, the intranode transportation, the DNA hybridization, the vesicle anchoring, loading, unloading, and the micro-tubule motion were defined. In BIB039 , BIB036 , a detailed mathematical model for the molecule synthesis cost in MC system with the absorbing receiver was provided to examine the energy efficiency of different relay schemes. In BIB040 , the energy costs in the encoding and synthesizing plasmid, the plasmid transportation, the carrier bacterial transportation, the decapsulation and decoding were defined and examined within bacterial relay MC networks.

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> The dielectric properties of tissues have been extracted from the literature of the past five decades and presented in a graphical format. The purpose is to assess the current state of knowledge, expose the gaps there are and provide a basis for the evaluation and analysis of corresponding data from an on-going measurement programme. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> A parametric model was developed to describe the variation of dielectric properties of tissues as a function of frequency. The experimental spectrum from 10 Hz to 100 GHz was modelled with four dispersion regions. The development of the model was based on recently acquired data, complemented by data surveyed from the literature. The purpose is to enable the prediction of dielectric data that are in line with those contained in the vast body of literature on the subject. The analysis was carried out on a Microsoft Excel spreadsheet. Parameters are given for 17 tissue types. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Multicellular organisms create complex patterned structures from identical, unreliable components. Learning how to engineer such robust behavior is important to both an improved understanding of computer science and to a better understanding of the natural developmental process. Earlier work by our colleagues and ourselves on amorphous computing demonstrates in simulation how one might build complex patterned behavior in this way. This work reports on our first efforts to engineer microbial cells to exhibit this kind of multicellular pattern directed behavior. We describe a specific natural system, the Lux operon of Vibrio fischeri, which exhibits density dependent behavior using a well characterized set of genetic components. We have isolated, sequenced, and used these components to engineer intercellular communication mechanisms between living bacterial cells. In combination with digitally controlled intracellular genetic circuits, we believe this work allows us to begin the more difficult process of using these communication mechanisms to perform directed engineering of multicellular structures, using techniques such as chemical diffusion dependent behavior. These same techniques form an essential part of our toolkit for engineering with life, and are widely applicable in the field of microbial robotics, with potential applications in medicine, environmental monitoring and control, engineered crop cultivation, and molecular scale fabrication. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Terahertz technology is continually evolving and much progress has been made in recent years. Many new applications are being discovered and new ways to implement terahertz imaging investigated. In this review, we limit our discussion to biomedical applications of terahertz imaging such as cancer detection, genetic sensing and molecular spectroscopy. Our discussion of the development of new terahertz techniques is also focused on those that may accelerate the progress of terahertz imaging and spectroscopy in biomedicine. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> The complex refractive indices of freshly excised healthy breast tissue and breast cancers collected from 20 patients were measured in the range of 0.15 - 2.0 THz using a portable terahertz pulsed transmission spectrometer. Histology was performed to classify the tissue samples as healthy adipose tissue, healthy fibrous breast tissue, or breast cancers. The average complex refractive index was determined for each group and it was found that samples containing cancer had a higher refractive index and absorption coefficient. The terahertz properties of the tissues were also used to simulate the impulse response functions expected when imaging breast tissue in a reflection geometry as in terahertz pulsed imaging (TPI). Our results indicate that both TPS and TPI can be used to distinguish between healthy adipose breast tissue, healthy fibrous breast tissue and breast cancer due to the differences in the fundamental optical properties. <s> BIB005 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Nanotechnology is enabling the development of devices in a scale ranging from one to a few hundred nanometers. Coordination and information sharing among these nano-devices will lead towards the development of future nanonetworks, boosting the range of applications of nanotechnology in the biomedical, environmental and military fields. Despite the major progress in nano-device design and fabrication, it is still not clear how these atomically precise machines will communicate. Recently, the advancements in graphene-based electronics have opened the door to electromagnetic communications in the nano-scale. In this paper, a new quantum mechanical framework is used to analyze the properties of Carbon Nanotubes (CNTs) as nano-dipole antennas. For this, first the transmission line properties of CNTs are obtained using the tight-binding model as functions of the CNT length, diameter, and edge geometry. Then, relevant antenna parameters such as the fundamental resonant frequency and the input impedance are calculated and compared to those of a nano-patch antenna based on a Graphene Nanoribbon (GNR) with similar dimensions. The results show that for a maximum antenna size in the order of several hundred nanometers (the expected maximum size for a nano-device), both a nano-dipole and a nano-patch antenna will be able to radiate electromagnetic waves in the terahertz band (0.1–10.0 THz). <s> BIB006 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> We have previously demonstrated that terahertz pulsed imaging is able to distinguish between rat tissues from different healthy organs. In this paper we report our measurements of healthy and cirrhotic liver tissues using terahertz reflection spectroscopy. The water content of the fresh tissue samples was also measured in order to investigate the correlations between the terahertz properties, water content, structural changes and cirrhosis. Finally, the samples were fixed in formalin to determine whether water was the sole source of image contrast in this study. We found that the cirrhotic tissue had a higher water content and absorption coefficient than the normal tissue and that even after formalin fixing there were significant differences between the normal and cirrhotic tissues' terahertz properties. Our results show that terahertz pulsed imaging can distinguish between healthy and diseased tissue due to differences in absorption originating from both water content and tissue structure. <s> BIB007 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption. <s> BIB008 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Ubiquitous healthcare (u-healthcare) applications typically require the frequent transmission of small data sets, e.g., from patient monitors, over wireless networks. We consider the transmissions of such u-healthcare data over an LTE-Advanced network, where each small data set must complete the standardized random access (RA) procedure. We mathematically analyze the delay of the RA procedure and verify our analysis with simulations. We find that our delay analysis, which is the first of its kind, gives reasonably accurate delay characterization. Thus, the presented delay characterization may form the basis for network management mechanisms that ensure reliable delivery of small frequent u-health\-care data sets within small delays. <s> BIB009 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> The Internet is continuously changing and evolving. The main communication form of present Internet is human-human. The Internet of Things (IoT) can be considered as the future evaluation of the Internet that realizes machine-to-machine (M2M) learning. Thus, IoT provides connectivity for everyone and everything. The IoT embeds some intelligence in Internet-connected objects to communicate, exchange information, take decisions, invoke actions and provide amazing services. This paper addresses the existing development trends, the generic architecture of IoT, its distinguishing features and possible future applications. This paper also forecast the key challenges associated with the development of IoT. The IoT is getting increasing popularity for academia, industry as well as government that has the potential to bring significant personal, professional and economic benefits. <s> BIB010 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Recently there has been quite a number of independent research activities that investigated the potentialities of integrating social networking concepts into Internet of Things (IoT) solutions. The resulting paradigm, named Social Internet of Things (SIoT), has the potential to support novel applications and networking services for the IoT in more effective and efficient ways. In this context, the main contributions of this paper are the following: (i) we identify appropriate policies for the establishment and the management of social relationships between objects in such a way that the resulting social network is navigable; (ii) we describe a possible architecture for the IoT that includes the functionalities required to integrate things into a social network; (iii) we analyze the characteristics of the SIoT network structure by means of simulations. <s> BIB011 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Nanonetworks, i.e., networks of nano-sized devices, are the enabling technology of long-awaited applications in the biological, industrial and military fields. For the time being, the size and power constraints of nano-devices limit the applicability of classical wireless communication in nanonetworks. Alternatively, nanomaterials can be used to enable electromagnetic (EM) communication among nano-devices. In this paper, a novel graphene-based nano-antenna, which exploits the behavior of Surface Plasmon Polariton (SPP) waves in semi-finite size Graphene Nanoribbons (GNRs), is proposed, modeled and analyzed. First, the conductivity of GNRs is analytically and numerically studied by starting from the Kubo formalism to capture the impact of the electron lateral confinement in GNRs. Second, the propagation of SPP waves in GNRs is analytically and numerically investigated, and the SPP wave vector and propagation length are computed. Finally, the nano-antenna is modeled as a resonant plasmonic cavity, and its frequency response is determined. The results show that, by exploiting the high mode compression factor of SPP waves in GNRs, graphene-based plasmonic nano-antennas are able to operate at much lower frequencies than their metallic counterparts, e.g., the Terahertz Band for a one-micrometer-long ten-nanometers-wide antenna. This result has the potential to enable EM communication in nanonetworks. <s> BIB012 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Embedding nanosensors in the environment would add a new dimension to the Internet of Things, but realizing the IoNT vision will require developing new communication paradigms and overcoming various technical obstacles. <s> BIB013 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> This paper is concerned with parameter extraction for the double Debye model, which is used for analytically determining human skin permittivity. These parameters are thought to be the origin of contrast in terahertz (THz) images of skin cancer. The existing extraction methods could generate Debye models, which track their measurements accurately at frequencies higher than 1 THz but poorly at lower frequencies, where the majority of permittivity contrast between healthy and diseased skin tissues is actually observed. We propose a global optimization-based parameter extraction, which results in globally accurate tracking and thus supports the full validity of the Debye model for simulating human skin permittivity in the whole usable THz frequencies. Numerical results confirm viability of our novel methodology. <s> BIB014 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> In this work, we describe the first modular, and programmable platform capable of transmitting a text message using chemical signalling - a method also known as molecular communication. This form of communication is attractive for applications where conventional wireless systems perform poorly, from nanotechnology to urban health monitoring. Using examples, we demonstrate the use of our platform as a testbed for molecular communication, and illustrate the features of these communication systems using experiments. By providing a simple and inexpensive means of performing experiments, our system fills an important gap in the molecular communication literature, where much current work is done in simulation with simplified system models. A key finding in this paper is that these systems are often nonlinear in practice, whereas current simulations and analysis often assume that the system is linear. However, as we show in this work, despite the nonlinearity, reliable communication is still possible. Furthermore, this work motivates future studies on more realistic modelling, analysis, and design of theoretical models and algorithms for these systems. <s> BIB015 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Bacterial populations housed in microfluidic environments can serve as transceivers for molecular communication, but the data-rates are extremely low (e.g., 10-5 bits per second.). In this work, genetically engineered Escherichia coli bacteria were maintained in a microfluidic device where their response to a chemical stimulus was examined over time. The bacteria serve as a communication receiver where a simple modulation such as on-off keying (OOK) is achievable, although it suffers from very poor data-rates. We explore an alternative communication strategy called time-elapse communication (TEC) that uses the time period between signals to encode information. We identify the limitations of TEC under practical non-zero error conditions and propose an advanced communication strategy called smart time-elapse communication (TEC-SMART) that achieves over a 10x improvement in data-rate over OOK. We derive the capacity of TEC and provide a theoretical maximum data-rate that can be achieved. <s> BIB016 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Microfluidics deals with manipulation and control of fluids which flow in constrained sub-millimetric media. In this paper communication concepts and networking approaches, typical of telecommunications, are extended to the microfluidic domain. The work illustrated in this paper investigates on possible approaches to information encoding and evaluation of the corresponding channel capacity as well as design of switching solutions. Based on the results of this study, the Hydrodynamic Controlled Microfluidic Network (HCN) paradigm is proposed, which is based on a pure hydrodynamic microfluidic switching function. The HCN paradigm can be applied to interconnect Labs-on-a-Chip (LoCs) in a microfluidic network in which chemical/biological samples are routed between the LoCs by exploiting hydrodynamic effects only. The resulting LoCs are expected to be highly flexible and inexpensive, and thus to become extremely useful in chemical/biological analysis and synthesis. <s> BIB017 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Based on the properties of graphene nano-patch antennas, we propose a reconfigurable multiple-input multiple-output (MIMO) antenna system for Terahertz (THz) communications. First, the characteristics of the graphene are analyzed and a beam reconfigurable antenna is designed. The beamwidth and direction can be controlled by the states of each graphene patch in the antenna. Then the path loss and reflection models of the THz channel are discussed. We combine the graphene-based antenna and the THz channel model, and propose a new MIMO antenna design. The radiation directions of the transmit antennas can be programmed dynamically, leading to different channel state matrices. Finally, the path loss and the channel capacity are numerically calculated and compared with those of the Gigahertz (GHz) channel. The results show that for short range communications, the proposed MIMO antenna design can enlarge the channel capacity by both increasing the number of antennas and choosing the best channel state matrices. <s> BIB018 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Nearly all existing nanoelectronic sensors are based on charge detection, where molecular binding changes the charge density of the sensor and leads to sensing signal. However, intrinsically slow dynamics of interface-trapped charges and defect-mediated charge-transfer processes significantly limit those sensors' response to tens to hundreds of seconds, which has long been known as a bottleneck for studying the dynamics of molecule-nanomaterial interaction and for many applications requiring rapid and sensitive response. Here we report a fundamentally different sensing mechanism based on molecular dipole detection enabled by a pioneering graphene nanoelectronic heterodyne sensor. The dipole detection mechanism is confirmed by a plethora of experiments with vapour molecules of various dipole moments, particularly, with cis- and trans-isomers that have different polarities. Rapid (down to ~0.1 s) and sensitive (down to ~1 ppb) detection of a wide range of vapour analytes is achieved, representing orders of magnitude improvement over state-of-the-art nanoelectronics sensors. <s> BIB019 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Cloud computing is ever stronger converging with the Internet of Things (IoT) offering novel techniques for IoT infrastructure virtualization and its management on the cloud. However, system designers and operations managers face numerous challenges to realize IoT cloud systems in practice, mainly due to the complexity involved with provisioning large-scale IoT cloud systems and diversity of their requirements in terms of IoT resources consumption, customization of IoT capabilities and runtime governance. In this paper, we introduce the concept of software-defined IoT units--a novel approach to IoT cloud computing that encapsulates fine-grained IoT resources and IoT capabilities in well-defined APIs in order to provide a unified view on accessing, configuring and operating IoT cloud systems. Our software-defined IoT units are the fundamental building blocks of software-defined IoT cloud systems. We present our framework for dynamic, on-demand provisioning and deploying such software-defined IoT cloud systems. By automating provisioning processes and supporting managed configuration models, our framework simplifies provisioning and enables flexible runtime customizations of software-defined IoT cloud systems. We demonstrate its advantages on a real-world IoT cloud system for managing electric fleet vehicles. <s> BIB020 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> A log-periodic toothed nanoantenna based on graphene is proposed, and its multi-resonance properties with respect to the variations of the chemical potential are investigated. The field enhancement and radar cross-section of the antenna for different chemical potentials are calculated, and the effect of the chemical potential on the resonance frequency is analyzed. In addition, the dependence of the resonance frequency on the substrate is also discussed. It is shown that large modulation of resonance intensity in log-periodic toothed nanoantenna can be achieved via turning the chemical potential of graphene. The tunability of the resonant frequencies of the antenna can be used to broad tuning of spectral features. The property of tunable multi-resonant field enhancement has great prospect in the field of graphene-based broadband nanoantenna, which can be applied in non-linear spectroscopy, optical sensor, and near-field optical microscopy. <s> BIB021 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> This paper provides an overview of the Internet of Things (IoT) with emphasis on enabling technologies, protocols, and application issues. The IoT is enabled by the latest developments in RFID, smart sensors, communication technologies, and Internet protocols. The basic premise is to have smart sensors collaborate directly without human involvement to deliver a new class of applications. The current revolution in Internet, mobile, and machine-to-machine (M2M) technologies can be seen as the first phase of the IoT. In the coming years, the IoT is expected to bridge diverse technologies to enable new applications by connecting physical objects together in support of intelligent decision making. This paper starts by providing a horizontal overview of the IoT. Then, we give an overview of some technical details that pertain to the IoT enabling technologies, protocols, and applications. Compared to other survey papers in the field, our objective is to provide a more thorough summary of the most relevant protocols and application issues to enable researchers and application developers to get up to speed quickly on how the different protocols fit together to deliver desired functionalities without having to go through RFCs and the standards specifications. We also provide an overview of some of the key IoT challenges presented in the recent literature and provide a summary of related research work. Moreover, we explore the relation between the IoT and other emerging technologies including big data analytics and cloud and fog computing. We also present the need for better horizontal integration among IoT services. Finally, we present detailed service use-cases to illustrate how the different protocols presented in the paper fit together to deliver desired IoT services. <s> BIB022 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> The journey of IoT from Arpanet to state of art wireless communication in vehicles is presented. The history of the wireless standards used in IoT is described which gives the path followed by the community of IoT using different communication modes. It is observed that Wi-Fi is the speediest of all the wireless standards used for IoT. A special observation here, which is design constraint, is that internet connectivity is mandatory for information communication. Extensive usage of IoT in Vehicle communication has impacted the research work to develop new routing and data gathering protocols. The growth of internet of things in vehicular communication is discussed. Surveys of the routing protocols are presented. It is interesting to note that present smart vehicles have data sensing and gathering (DSG) modules and data fusing models to improve the services provided to user community. The survey depicts the advancement in the IoT trends up to date till the year 2015. A brief overview of the IoT system design is presented with some typical issues that have to be seen during deployment phase. <s> BIB023 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> The double Debye model has been used to understand the dielectric response of different types of biological tissues at terahertz (THz) frequencies but fails in accurately simulating human breast tissue. This leads to limited knowledge about the structure, dynamics, and macroscopic behavior of breast tissue, and hence, constrains the potential of THz imaging in breast cancer detection. The first goal of this paper is to propose a new dielectric model capable of mimicking the spectra of human breast tissue's complex permittivity in THz regime. Namely, a non-Debye relaxation model is combined with a single Debye model to produce a mixture model of human breast tissue. A sampling gradient algorithm of nonsmooth optimization is applied to locate the optimal fitting solution. Samples of healthy breast tissue and breast tumor are used in the simulation to evaluate the effectiveness of the proposed model. Our simulation demonstrates exceptional fitting quality in all cases. The second goal is to confirm the potential of using the parameters of the proposed dielectric model to distinguish breast tumor from healthy breast tissue, especially fibrous tissue. Statistical measures are employed to analyze the discrimination capability of the model parameters while support vector machines are applied to assess the possibility of using the combinations of these parameters for higher classification accuracy. The obtained analysis confirms the classification potential of these features. <s> BIB024 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Nanocommunications via Forster Resonance Energy Transfer (FRET) is a promising means of realising collaboration between photoactive nanomachines to implement advanced nanotechnology applications. The method is based on exchange of energy levels between fluorescent molecules by the FRET phenomenon which intrinsically provides a virtual nanocommunication link. In this work, further to the extensive theoretical studies, we demonstrate the first information transfer through a FRET-based nanocommunication channel. We implement a digital communication system combining macroscale transceiver instruments and a bulk solution of fluorophore nanoantennas. The performance of the FRET-based Multiple-Input and Multiple-Output (MIMO) nanocommunication channel between closely located mobile nanoantennas in the sample solution is evaluated in terms of Signal-to-Noise Ratio (SNR) and Bit Error Rate (BER) obtained for the transmission rates of 50 kbps, 150 kbps and 250 kbps. The results of the performance evaluation are very promising for the development of high-rate and reliable molecular communication networks at nanoscale. <s> BIB025 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> This paper presents experimental study of real human skin material parameter extraction based on terahertz (THz) time-domain spectroscopy in the band 0.1–2.5 THz. Results in this paper show that electromagnetic properties of the human skin distinctively affect the path loss and noise temperature parameters of the communication link, which are vital for channel modeling of in-body nanonetworks. Refractive index and absorption coefficient values are evaluated for dermis layer of the human skin. Repeatability and consistency of the data are accounted for in the experimental investigation and the morphology of the skin tissue is verified using a standard optical microscope. Finally, the results of this paper are compared with the available work in the literature, which shows the effects of dehydration on the path loss and noise temperature. The measured parameters, i.e., the refractive index and absorption coefficient are 2.1 and 18.45 cm−1, respectively, at 1 THz for a real human skin, which are vital for developing and optimizing future in-body nanonetworks. <s> BIB026 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> In diffusion-based molecular communication, information transport is governed by diffusion through a fluid medium. The achievable data rates for these channels are very low compared to the radio-based communication system, since diffusion can be a slow process. To improve the data rate, a novel multiple-input multiple-output (MIMO) design for molecular communication is proposed that utilizes multiple molecular emitters at the transmitter and multiple molecular detectors at the receiver (in RF communication these all correspond to antennas). Using particle-based simulators, the channel’s impulse response is obtained and mathematically modeled. These models are then used to determine interlink interference (ILI) and intersymbol interference (ISI). It is assumed that when the receiver has incomplete information regarding the system and the channel state, low complexity symbol detection methods are preferred since the receiver is small and simple. Thus, four detection algorithms are proposed—adaptive thresholding, practical zero forcing with channel models excluding/including the ILI and ISI, and Genie-aided zero forcing. The proposed algorithms are evaluated extensively using numerical and analytical evaluations. <s> BIB027 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> Stochastic resonance (SR) is an intrinsic noise usage system for small-signal sensing found in various living creatures. The noise-enhanced signal transmission and detection system, which is probabilistic but consumes low power, has not been used in modern electronics. We demonstrated SR in a summing network based on a single-walled carbon nanotube (SWNT) device that detects small subthreshold signals with very low current flow. The nonlinear current-voltage characteristics of this SWNT device, which incorporated Cr electrodes, were used as the threshold level of signal detection. The adsorption of redox-active polyoxometalate molecules on SWNTs generated additional noise, which was utilized as a self-noise source. To form a summing network SR device, a large number of SWNTs were aligned parallel to each other between the electrodes, which increased the signal detection ability. The functional capabilities of the present small-size summing network SR device, which rely on dense nanomaterials and exploit i... <s> BIB028 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> This paper focuses on the analysis of cultivated collagen samples at the terahertz (THz) band using double debye model parameter extraction. Based on measured electrical and optical parameters, we propose a model to describe such parameters extracted with a global optimisation method, namely, particle swarm optimisation. Comparing the measured data with ones in the open literature, it is evident that using only cultivated collagen is not sufficient to represent the performance of the epidermis layer of the skin tissue at the THz band of interest. The results show that the differences between the measured data and published ones are as high as 14 and 6 for the real and imaginary values of the dielectric constant, respectively. Our proposed double debye model agrees well with the measured data. <s> BIB029 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> We propose an adaptive sampling algorithm to improve the acquisition efficiency for terahertz time-domain spectroscopy (THz-TDS). Most THz-TDS measurements scan the delay line with constant speed and the data acquired have constant time steps. Our algorithm exploits the fact that the useful information within THz signals tends to cluster at certain positions: efficient sampling can be done by adaptively increasing the sample rate in regions containing more interesting features. The algorithm was implemented by programming a linear optical delay line. Depending on the experiment parameters, the sampling time of a pulse can be reduced by a factor of 2–3 with only slight degradation in accuracy, possible sources of error are discussed. We show how adaptive sampling algorithms can improve the acquisition time in applications where the main pulse is the primary concern. <s> BIB030 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> The design of communication systems capable of processing and exchanging information through molecules and chemical processes is a rapidly growing interdisciplinary field, which holds the promise to revolutionize how we realize computing and communication devices. While molecular communication (MC) theory has had major developments in recent years, more practical aspects in the design and prototyping of components capable of MC functionalities remain less explored. In this paper, motivated by a bulk of MC literature on information transmission via molecular pulse modulation, the design of a pulse generator is proposed as an MC component able to output a predefined pulse-shaped molecular concentration upon a triggering input. The chemical processes at the basis of this pulse generator are inspired by how cells generate pulse-shaped molecular signals in biology. At the same time, the slow-speed, unreliability, and non-scalability of these processes in cells are overcome with a microfluidic-based implementation based on standard reproducible components with well-defined design parameters. Mathematical models are presented to demonstrate the analytical tractability of each component, and are validated against a numerical finite element simulation. Finally, the complete pulse generator design is implemented and simulated in a standard engineering software framework, where the predefined nature of the output pulse shape is demonstrated together with its dependence on practical design parameters. <s> BIB031 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> IV. ENABLING AND CONCOMITANT TECHNOLOGIES <s> The nervous system holds a central position among the major in-body networks. It comprises of cells known as neurons that are responsible to carry messages between different parts of the body and make decisions based on those messages. In this work, further to the extensive theoretical studies, we demonstrate the first controlled information transfer through an in vivo nervous system by modulating digital data from macro-scale devices onto the nervous system of common earthworms and conducting successful transmissions. The results and analysis of our experiments provide a method to model networks of neurons, calculate the channel propagation delay, create their simulation models, indicate optimum parameters such as frequency, amplitude and modulation schemes for such networks, and identify average nerve spikes per input pulse as the nervous information coding scheme. Future studies on neuron characterization and artificial neurons may benefit from the results of our work. <s> BIB032

A. EM Aspects 1) Nano-Devices: Advances in nanotechnology have paralleled developments in Internet and sensing technology. The development routine is summarised in Fig. 10 . At the same time, due to the general belief that graphene/CNT would be the future star of the nano-technology world since its appearance, more attentions has been put on such novel materials and great advances have been achieved. Antenna, as the basic element in communication system, is firstly fully investigated with numerous papers on the design of the antenna made of graphene or CNT in the last five years. First, the possibility of the applications of graphene and CNT was investigated and the wave performance on a graphene sheet was also studied in . Then, various antennas like graphene patch antenna with different shapes - , CNT dipole antenna , , BIB006 , and so on were proposed. Furthermore, a nanoantenna with the shape of log-periodic tooth made of graphene was proposed in BIB021 and a novel graphene-based nanoantenna, which exploits the behaviour of Surface Plasmon Polariton waves in semi-finite sized Graphene Nanoribons (GNRs) was proposed in BIB012 . Recently, a beam reconfigurable multiple input multiple output (MIMO) antenna system based on graphene nano-patch antenna is proposed in BIB018 , whose radiation pattern can be steered dynamically, leading to different channel state matrices. Meanwhile, the design of the sensors made of graphene is also introduced. Reference BIB019 introduces a graphene-based wearable sensor which can be used to detect airborne chemicals and its concentration level like acetone (an indicator of diabetes) or nitric oxide and oxygen (a bio-marker for high blood pressure, anemia, or lung disease). Later, the sensor made of graphene is designed with higher accuracy to detect HIV-related DNA hybridization at picomolar concentrations, which is a charge detector fabricated of graphene capable of detecting extremely low concentration of charges close to its surface . A Stochastic Resonance based (SR-based) electronic device, consisting of singlewalled carbon nanotubes (SWNTs) and phosphomolybdic acid (PMo12) molecules, has been developed at Osaka University to apply in bio-inspired sensor BIB028 . It is believed by the authors that by using such devices neural networks capable of spontaneous fluctuation can be developed. 2) Internet-of-Things: Internet-of-Things (IoT) refers to a network of devices with Internet connectivity to communicate directly without human-intervention in order to provide smart services to users BIB022 . The Internet-of-Things shares the same development route with nanonetworks, and it is believed that the ultimate goal is to emerge both technologies to form the Internet-of-Nano-Things (IoNT) BIB013 . It is generally believed that the achievements in IoT can also be applied to nanonetworks with minor modification. In IoT, the number of sensors/devices could achieve as high as tons BIB022 , many challenges related to addressing and identification of the connected devices would appear, same as nanonetworks. Furthermore, huge amount of data would be produced by such high numbers of sensors which requires high bandwidth and real-time access. Furthermore, implementation of IoT is complex, as it includes cooperation among massive, distributed, autonomous and heterogeneous components at various levels of granularity and abstraction . Applications in health BIB009 , smart security, and smart cities found their way to the market and realize the potential benefits of this technology BIB023 . In addition, many other applications of IoT can be enumerated such as agriculture, industry, natural resources (water, forests, etc.) monitoring, transport system design, and military applications BIB010 . Network densification is considered as an enabler for the successful diffusion of IoT services and application in the society. In reality, millions of simultaneous connections would be built in IoT, involving a variety of devices, connected homes, smart grids and smart transportation systems BIB010 . The concept of cloud and fog computing is introduced to offer large storage, high computation and networking capabilities BIB020 . Also, a high level design of cloud assisted, intelligent, software agent-based IoT architecture is proposed in . Besides of the concept of IoNT, Social Internet of Things (SIoT) is also proposed recently BIB011 . To advocate a common standard, IoT Global Standards (IoT-GSI) are proposed by ITU-T . 3) Bio-Tissue Characterization: Characterization of channel medium is an essential part to investigate the channel; therefore, it is important to obtain the parameters of biotissues if the body-centric communication is under study. Usually, the electromagnetic parameters, i.e., permittivity and permiability µ, are used to describe medium in microwave and RF frequency; while at optical frequency, the material is usually described by refractive index (or index of refraction). The techniques such as resonant cavity perturbation method, Transmission-Reflection-Method (TRM), and THz Time Domain Spectroscopy system have been applied to obtain the dielectric property of human tissues BIB029 . In , the database of the parameters for human tissues (skin, muscle blood bone and etc.) from 10 Hz to 100 GHz are illustrated, mainly on the basis of Gabriel's work BIB001 - BIB002 . THZ TDS system is fully studied by E. Pickwell BIB004 - BIB030 and has been applied to measure the dielectric parameters of bio-tissues like livers BIB007 , human colonic tissues BIB008 , human breast tissues BIB005 , etc.. Both basal cell carcinoma and normal skin are measured by C.Bao to investigate the possibility of the detection of skin cancer at early stage based on the work of parameter extraction of skin with global optimization method BIB014 . And also, the model of human breast tissue in THz band is studied in BIB024 . Recently, the performance of DED samples and collagen have been investigated in BIB026 , and the corresponding model has been studied as well to investigate the possibility of adoption of collagen and DED sample as the phantom during the measurement BIB029 . More work needs to be done to build the database and the appropriate phantom should be sought to use in the measurement setup. B. Molecular Aspects 1) Molecular Test-beds: Until now, one fundamental challenge in the application of molecular communication is that we still do not have well studied nano-size biological friendly molecular communication transceivers, despite the existing research efforts in designing and building MC test-beds BIB025 , BIB015 - BIB032 , and in engineering biological MC systems BIB003 , . • Macroscale MC Test-beds: The first macro-scale experimental test-bed for molecular communication was shown in BIB015 , where the text messages were converted to binary sequence, and transmitted via alcohol particles based on a time-slotted on-off-keying modulation. In this tabletop MC test-bed the messages transmission and detection were realized via the alcohol spray and the alcohol metal-oxide sensor, and the message generation and interpretation were electronically controlled via the Arduino micro-controllers. They shown that a transmission data rate of 0.3 bit/s with the bit error rates of 0.01 to 0.03 can be achieved using this Later on, this SISO test-bed was duplicated to form a multiple-input-multiple-output (MIMO) tabletop MC test-bed with multiple sprays and sensors in BIB027 , which achieved 1.7 times higher transmission data rates than that of the SISO test-bed. • Nanoscale MC Test-bed: The first nanoscale molecular communication based on the F orster Resonance Energy Transfer (FRET) was implemented and tested in BIB025 , where the information was encoded on the energy states of fluorescent molecules, and the energy states were exchanged via FRET. • Microfludic MC Test-beds: In BIB016 , the genetically engineered Escherichia coli (E. coli) bacteria population housed in micrometer sized chambers were used as MC transceivers connected via microfluidic pathways, and the message molecule (N-(3-Oxyhexanoyl)-L-homoserine lactone, or C6-HSL) generation and detection were realized via the LuxI enzyme catalyzes and the LuxR receptor protein with fluorescent light based on On-Off Keying (OOK). To improve the achievable data rates of this testbed with OOK, the time-elapse communication (TEC) was proposed by encoding the information in the time interval between two consecutive pulses, which shown an order of magnitude data-rate improvement. In BIB017 , the Hydrodynamic Controlled microfluidic Network (HCN) fabricated in poly(dimethylsiloxane) (PDMS) polymer was proposed, where the information was encoded and decoded based on the distance between consecutive droplets, and droplets carrying information were controlled and transported in HCN to realize molecular communication. The maximum information rate of HCN was analyzed, the noise effect in HCN was simulated using OpenFOAM, and a HCN prototype was fabricated in poly(dimethylsiloxane) (PDMS) polymer. Inspired by the biological circuits in synthetic biology, a chemical circuits based on a series of faster chemical reactions were designed to achieve the transformation of the timing varying information molecules flow from the digital signal to the analog signal inside a designed microfluidic devices in BIB031 . This work provides a novel research direction for performing signal processing using chemical circuits inside microfluidic device, and also an alternative method for proof-of-concept analogues of biological circuits with potentially higher speed.

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 2) Molecular Experiments: <s> Multicellular organisms create complex patterned structures from identical, unreliable components. Learning how to engineer such robust behavior is important to both an improved understanding of computer science and to a better understanding of the natural developmental process. Earlier work by our colleagues and ourselves on amorphous computing demonstrates in simulation how one might build complex patterned behavior in this way. This work reports on our first efforts to engineer microbial cells to exhibit this kind of multicellular pattern directed behavior. We describe a specific natural system, the Lux operon of Vibrio fischeri, which exhibits density dependent behavior using a well characterized set of genetic components. We have isolated, sequenced, and used these components to engineer intercellular communication mechanisms between living bacterial cells. In combination with digitally controlled intracellular genetic circuits, we believe this work allows us to begin the more difficult process of using these communication mechanisms to perform directed engineering of multicellular structures, using techniques such as chemical diffusion dependent behavior. These same techniques form an essential part of our toolkit for engineering with life, and are widely applicable in the field of microbial robotics, with potential applications in medicine, environmental monitoring and control, engineered crop cultivation, and molecular scale fabrication. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 2) Molecular Experiments: <s> This study presents a self organized control of nano sensor's mobility based on the particle swarm optimization (PSO) algorithm. PSO models the set of potential problem solutions as a swarm of particles moving about in a virtual search space by adapting self organizing concept. The study is based on the premise that the deployment of nanosensors and used for investigating within human body. The spatially distributed nanosensors collect information about the target environment by moving throughout the body. Movement of sensors will be addressed how sensors are perimeter covered to the target environment. There may be two kinds of issues for coverage such that insufficient coverage and covered by too many sensors in certain areas without necessary. If there is not enough coverage, the required information may not get properly. If there are more sensors than necessary, there may be some redundant nodes and it may consume more energy. Therefore, the sensors should move to the next target, which has proper coverage criteria. The simulation results have approved that the proposed scheme effectively constructs a self organized mobility within the optimized coverage area. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 2) Molecular Experiments: <s> Abstract Nanotechnology has the potential to have a significant impact on a number of application areas. The possibility of building components at the nanoscale revolutionized the way we think about systems by enabling myriad possibilities, that were simply impossible otherwise. At the same time, countless challenges were raised in system design. One such challenge is to build components that act together to handle complex tasks that require physically separate components to work in unison. To achieve coordination, these components have to be capable of communicating reliably, either with a central controller or amongst themselves. In this research, we propose to build analytical foundations to analyze and design nanonetworks, consisting of individual stations communicating over a wireless medium using nanotransceivers with nanotube antennas. We give a simple nanoreceiver design and analyze its basic limitations. Based on the insights drawn, we propose a communication-theoretic framework to design reliable and robust nanoreceivers. With the basic limitations of the nanocommunications via nanoantennas in mind, it is possible to develop mathematical tools to help construct nanonetworks that execute basic sequential tasks in a reliable manner with minimal amount of communication and computation required. In this paper, we present a communication-theoretic analysis of networks of nanoscale nodes equipped with carbon nanotube-based receivers and transmitters. Our objective is to analyze the performance characteristics of nanoscale nodes and expose their fundamental capabilities and limitations. The presented analysis is intended to serve as the basis of nanonetwork design enabling various applications. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 2) Molecular Experiments: <s> Embedding nanosensors in the environment would add a new dimension to the Internet of Things, but realizing the IoNT vision will require developing new communication paradigms and overcoming various technical obstacles. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 2) Molecular Experiments: <s> Emerging nanotechnology presents great potential to change human society. Nanoscale devices are able to be included with Internet. This new communication paradigm, referred to as Internet of Nanothings (IoNT), demands very short-range connections among nanoscale devices. IoNT raises many challenges to realize it. Current network protocols and techniques may not be directly applied to communicate with nanosensors. Due to the very limited capability of nanodevices, the devices must have simple communication and simple medium sharing mechanism in order to collect the data effectively from nanosensors. Moreover, nanosensors may be deployed at organs of the human body, and they may produce large data. In this process, the data transmission from nanosensors to gateway should be controlled from the energy efficiency point of view. In this paper, we propose a wireless nanosensor network (WNSN) at the nanoscale that would be useful for intrabody disease detection. The proposed conceptual network model is based on On-Off Keying (OOK) protocol and TDMA framework. The model assumes hexagonal cell-based nanosensors deployed in cylindrical shape 3D hexagonal pole. We also present in this paper the analysis of the data transmission efficiency, for the various combinations of transmission methods, exploiting hybrid, direct, and multi-hop methods. <s> BIB005 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 2) Molecular Experiments: <s> Nano-communication is considered to become a major building block for many novel applications in the health care and fitness sector. Given the recent developments in the scope of nano machinery, coordination and control of these devices becomes the critical challenge to be solved. In-Body Nano-Communication based on either molecular, acoustic, or RF radio communication in the terahertz band supports the exchange of messages between these in-body devices. Yet, the control and communication with external units is not yet fully understood. In this paper, we investigate the challenges and opportunities of connecting Body Area Networks and other external gateways with in-body nano-devices, paving the road towards more scalable and efficient Internet of Nano Things (IoNT) systems. We derive a novel network architecture supporting the resulting requirements and, most importantly, investigate options for the simulation based performance evaluation of such novel concepts. Our study is concluded by a first look at the resulting security issues considering the high impact of potential misuse of the communication links. <s> BIB006 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 2) Molecular Experiments: <s> Terahertz frequency band, 0.1–10THz, is envisioned as one of the possible resources to be utilized for wireless communications in networks beyond 5G. Communications over this band will be feature a number of attractive properties, including potentially terabit-per-second link capacities, miniature transceivers and, potentially, high energy efficiency. Meanwhile, a number of specific research challenges have to be addressed to convert the theoretical estimations into commercially attractive solutions. Due to the diversity of the challenges, the research on THz communications at its early stages was mostly performed by independent communities from different areas. Therefore, the existing knowledge in the field is substantially fragmented. In this paper, an attempt to address this issue and provide a clear and easy to follow introduction to the THz communications is performed. A review on the state-of-the-art in THz communications research is given by identifying the target applications and major open research challenges as well as the recent achievements by industry, academia, and the standardization bodies. The potential of the THz communications is presented by illustrating the basic tradeoffs in typical use cases. Based on the given summary, certain prospective research directions in the field are identified. <s> BIB007 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 2) Molecular Experiments: <s> The nervous system holds a central position among the major in-body networks. It comprises of cells known as neurons that are responsible to carry messages between different parts of the body and make decisions based on those messages. In this work, further to the extensive theoretical studies, we demonstrate the first controlled information transfer through an in vivo nervous system by modulating digital data from macro-scale devices onto the nervous system of common earthworms and conducting successful transmissions. The results and analysis of our experiments provide a method to model networks of neurons, calculate the channel propagation delay, create their simulation models, indicate optimum parameters such as frequency, amplitude and modulation schemes for such networks, and identify average nerve spikes per input pulse as the nervous information coding scheme. Future studies on neuron characterization and artificial neurons may benefit from the results of our work. <s> BIB008

• In Vivo Nervous System Experiment: The first controlled information transfer through an in vivo nervous system was demonstrated in BIB008 . Modulated signals were transmitted into nervous systems of earthworms from anterior end, and propagated through earthworms' nerve cord. Although the network of neurons, i.e., the channel response, were considered as a black-box, the authors found the received signals can be decoded as the number of average nerve spikes per input pulse counted in the posterior end. In addition, the MC system was optimized in terms of frequency, amplitude, and modulation scheme, and the authors showed that the data rate can reach 52.6646 bps with a 7.2 × 10 −4 bit error rate when employing a 4FSK modulation and square shaped pulse. • Biological MC Experiments: The first engineered intercellular MC experiment between living bacterial cells was reported in BIB001 , where the plasmid pSND-1 was the sender constructed to produce the autoinducer chemical (VAI) via the LuxI gene expression inside E. coli. Then, the VAI (information messenger) migrates through the cell membranes and medium to interact with the LuxR gene of the receiver-plasmid pRCV-3 inside E. coli, and produces Green fluorescent protein (GFP) for information decoding. Using the protein engineering and synthetic biology, a simple MC based on baterial quorum sensing (QS) was engineered in , where a multidomain fusion protein with QS molecular signal generation capability was fabricated as the sender, and an E. coli was engineered as the receiver to receive and report this QS signal. These research demonstrated the great potential of biofabrication of MC devices. V. ARCHITECTURE OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS Generally, it is believed that both EM and MC should share the same network architecture, but will have minor differences according to various specific applications. 1) Network Deployment: Aligned with the IEEE P1906.1 framework, the authors of provided an overview of the nanonetworks and is divided in to nano-routers, nano-nodes, gateway and nano-micro interfaces. The work proposed in BIB005 attempts to investigate the ideal number of devices, optimal edge length relative to horizontal length of a general human body organ. The proposed scheme assumes nanosensors are distributed in a 3-dimensional space in the nanonetworks according to a homogeneous spatial Poisson process as shown in Fig. 11 . Authors represent the network deployment as cylindrical 3D hexagonal pole, claiming that the cylindrical shape is closer to the shape of human body organs. They assume that they can put as many nano-sensors as possible and there is only one active nano-sensor in each hexagonal cell. They proposed a scheme for each sensor duty cycle with the assumption that only one sensor is active in each cell. A cell is defined as the smallest living unit of an organ. The ideal number of nano-sensors is calculated using an equation derived by the authors. The equation describes the diameter of the cylinder, the width of the organ in relation to the edge length of the cylinder. The work of BIB005 is considered a step forward in realizing the nano-sensors deployment; however, the authors assume that all the nano-sensors may recognize other neighbouring nano-sensors. The authors also assume that network deployment also includes routeing nodes; however, they did not state how to calculate the number of routers or micro-interfaces and the positioning technique for these nodes. Emre et. al. BIB003 debates that the first step in network design and deployment is highly tied to the parameters of the nano-antenna, hence nano-antenna design is a critical component of the network design. The reason behind this is their observation that there is a clear trade-off between the number of different tasks the nanonetworks can execute and the reliable communication over the network. Hence, the authors proposed a network of nano-devices that are able to carry out binary tasks and proved that it is possible to construct multi-hop nanonetworks using simple individual nodes activated simultaneously over a shared medium without a significant detriment in reliability. The number of nodes depends on the number of complex tasks for the nanonetworks. The authors did not provide a mechanism describing the process of choosing the appropriate number of nano-nodes or interfaces. Additionally, the authors did not provide an analysis of the nano-router or interfaces as they did for nano-sensors. Dressler and Fischer BIB006 discussed the requirements and challenges of designing the gateway or the interface between the nanonetwork and the macro/micro network to bridge the gap of the gateway or interface void. They stated that multiple gateways are required in IoNT deployment such that each one of them is associated with one or more nanonetworks. They also suggested that a gateway should operate at the application layer and recognize the right nanonetwork to receive a message. They also suggested that the gateway being equipped with one or more nano communication interface should contain the molecular and terahertz interface. As a molecular network may prove to be a significant challenge, a reasonable approach might be to make the gateway an implantable micro device that uses electromagnetic wireless communication to interface the molecular network to the Internet. While the study in BIB006 discussed the requirement and challenges of gateway deployment, they did not provide any solution. Similar to BIB006 , the study presented in BIB004 discussed the challenges and requirements for the gateway deployment. The study concluded that the gateway will be an implantable device equipped to enable communication with the molecular interface as well as the EM nanonetworks. However, the study remarked that the high ratio of nano-sensors to gateways could lead to swift energy depletion if gateways process information from every nano-sensor. They suggested to thereby distribute the sink architecture and develop a twolayered hierarchy consisting of gateways and nanonetworks. The aforementioned research attempts to address the network deployment, however, the proposed schemes provide partial solutions to the network deployment; some focused on nano-sensor deployment, while others discussed the requirements and challenges of gateway deployment. However, no all-encompassing solution has been provided in literature yet. Additionally, deployment that achieves essential goals such as survivability, reliability, accuracy or latency intolerance remains an unexplored area of research in nanonetworks deployment. 2) Network Mobility: Nano sensors (NS) are dynamic components in their applications whereby they are forced to move and each move is dictated by their environment. Environmental NS will move according to wind direction and force, which in turns will act to adjust their controller association, location and link quality. Comparatively, the motion of blood monitoring NS will be influenced by its surroundings, whereby speed and turbidity of blood flow and vessel thickness will affect NS link communication quality, velocity and location. This effect is highly pronounced in nanonetworks when compared to traditional sensor networks due to the unique nature of the NS and the used modulation used in nanonetwork communication. Nanonetworks communicate using TS-OOK. This requires nodes to be highly synchronized, an aspect that can be significantly affected by changes in NS mobility. TS-OOK synchronizes transmissions between sender and receiver by requiring the receiver to listen to transmissions on fixed time intervals, thereby ensuring that transmitted bits are received. Distance between the receiver and sender has the largest impact on this process and deciding the time intervals at which the receiver should listen. This distance may change due to NS movement and might result in missing a transmission. The work in studied the effect of NS movements on the communication link. The authors studied the pulse time-shift, which is defined by the authors as the distance in time between the actual arrival of the signal and its estimated arrival (in case of no movement), taking into account the Doppler effect, information reduction, and error rate increase. The authors concluded that the doppler effect can be negligible; however, the pulse time-shift can introduce inter-symbol interference (ISI), and the NS movement influences the maximum information rate and the attainable error rate. The work presented in provides a good insight on the effect of mobility in nanosensors networks. However, the assumption of the authors that the transmitter is static while the receiver is mobile, and NSs are moving with the speed of light may limit the scope of the results and their adaptability into applications. Even though the mobility of NSs may pause a major challenge on practical deployment of nanosensors, this area is still severely under-researched. References BIB007 remarked that there is an eminent need to come up with mobility perdition models; a reactive response to NS movement is no longer satisfactory. The authors of BIB002 proposed a movement control method for nanonetworks which is self-organised. The algorithm uses the localization of a particle and its neighbouring paticles to optimise the location of particles and enhance movement positions fo NS through the use of particle swarm optimisation. The proposed algorithm cannot be considered a general mobility model for nanosensors because the algorithm is proposed for homogeneous networks, which is not the norm of a nanonetwork; they are expected to consist of heterogeneous devices with diverse capabilities. Additionally, the model is designed based on the unit disk coverage thereby inheriting the advantages and disadvantages of using this method. In , the authors proposed a scheme for the hand-off of mobile sensors to the most appropriate nano-controller to conserve energy consumption and reduce the unsuccessful transmission rates. The authors presented a TDMA-based MAC protocol simple fuzzy logic system to control the mobility procedure. They used locally available metrics at each nano-node consisting of the distance of mobile nano-node from nano-controller, traffic load and residual energy of nano-controller, which are considered as fuzzy input variables to control the hand-off decision procedure. The scope of the offered solution is limited by the assumption of constant velocity of the nanosensors and the unit disk transmission similarly to the other proposed schemes. Additionally, the practicality of the system deployment is highly dependent of the trade-off between accuracy and complexity of the algorithm. Hence, the problem of NSs mobility modeling still stands as an urgent area of research for practical deployment of nanonetworkss.

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Nanotechnology is enabling the development of devices in a scale ranging from one to a few hundred nanometers. Coordination and information sharing among these nano-devices will lead towards the development of future nanonetworks, rising new applications of nanotechnology in the medical, environmental and military fields. Despite the major progress in nano-device design and fabrication, it is still not clear how these atomically precise machines will communicate. The latest advancements in graphene- based electronics have opened the door to electromagnetic communication among nano-devices in the terahertz band (0.1-10 THz). This frequency band can potentially provide very large bandwidths, ranging from the entire band to several gigahertz- wide windows, depending on the transmission distance and the molecular composition of the channel. In this paper, the capacity of the terahertz channel is numerically evaluated by using a new terahertz propagation model, for different channel molecular compositions, and under different power allocation schemes. A novel communication technique based on the transmission of ultra-short pulses, less than one picosecond long, is motivated and quantitatively compared to the capacity- optimal power allocation scheme. The results show that for the very short range, up to a few tens of millimeters, the transmission of short pulses offer a realistic and still efficient way to exploit the terahertz channel. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Nanotechnology is providing the engineering community with a new set of tools to design and manufacture integrated devices just a few hundred nanometers in total size. Communication among these nano-devices will boost the range of applications of nanotechnology in several fields, ranging from biomedical research to military technology or environmental science. Within the different alternatives for communication in the nanoscale, recent developments in nanomaterials point to the Terahertz band (0.1-10 THz) as the frequency range of operation of future electromagnetic nano-transceivers. This frequency band can theoretically support very large bit-rates in the short range, i.e., for distances below one meter. Due to the limited capabilities of individual nano-devices, pulse-based communications have been proposed for electromagnetic nanonetworks in the Terahertz band. However, the expectedly very large number of nano-devices and the unfeasibility to coordinate them, can make interference a major impairment for the system. In this paper, low-weight channel coding is proposed as a novel mechanism to reduce interference in pulse-based nanonetworks. Rather than utilizing channel codes to detect and correct transmission errors, it is shown that by appropriately choosing the weight of a code, interference can be mitigated. The performance of the proposed scheme is analytically and numerically investigated both in terms of overall interference reduction and achievable information rate, by utilizing a new statistical interference model. The results show that this type of network-friendly channel coding schemes can be used to alleviate the interference problem in nanonetworks without compromising the individual user information rate. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Nanotechnology is enabling the development of sensing devices just a few hundreds of nanometers in size, which are able to measure new types of events in the nanoscale by exploiting the properties of novel nanomaterials. Wireless communication among these nanosensors will boost the range of applications of nanotechnology in the biomedical, environmental and military fields, amongst others. Within the different alternatives for communication in the nanoscale, recent advancements in nanomaterials point to the Terahertz band (0.1–10.0 THz) as the frequency range of operation of future electronic nano-devices. This still unlicensed band can theoretically support very large transmission bit-rates in the short range, i.e., for distances below one meter. More importantly, the Terahertz band also enables very simple communication mechanisms suited to the very limited capabilities of nanosensors. In this paper, a new communication paradigm called TS-OOK (Time Spread On-Off Keying) for Electromagnetic Wireless Nanosensor Networks (WNSNs) is presented. This new technique is based on the transmission of femtosecond-long pulses by following an on-off keying modulation spread in time. The performance of this scheme is assessed in terms of information capacity for the single-user case as well as aggregated network capacity for the multiuser case. The results show that by exploiting the peculiarities of the Terahertz band, this scheme provides a very simple but robust communication technique for WNSNs. Moreover, it is shown that, due to the peculiar behavior of the noise in the Terahertz band, the single-user capacity and the aggregated network capacity can exceed those of the AWGN channel classical wireless networks, when the appropriate channel codes are used. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Wireless nanosensor networks (WNSNs), which are collections of nanosensors with communication units, can be used for sensing and data collection with extremely high resolution and low power consumption for various applications. In order to realize WNSNs, it is essential to develop energy-efficient communication techniques, since nanonodes are severely energy-constrained. In this paper, a novel minimum energy coding scheme (MEC) is proposed to achieve energy-efficiency in WNSNs. Unlike the existing minimum energy codes, MEC maintains the desired Hamming distance, while minimizing energy, in order to provide reliability. It is analytically shown that, with MEC, codewords can be decoded perfectly for large code distance, if source set cardinality, M is less than inverse of symbol error probability, 1/ps. Performance analysis shows that MEC outperforms popular codes such as Hamming, Reed-Solomon and Golay in average energy per codeword sense. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Bio-nanosensors and communication at the nanoscale are a promising paradigm and technology for the development of a new class of ehealth solutions. While recent communication technologies such as mobile and wireless combined with medical sensors have allowed new successful eHealth applications, another level of innovation is required to deliver scalable and cost-effective solutions via developing devices that operate and communicate directly inside the body. This work presents the application of nano technology for the development of miniaturized bio-nanosensors that are able to communicate and exchange information about sensed molecules or chemical compound concentration and therefore draw a global response in the case of health anomalies. Two communication techniques are reviewed: electromagnetic wireless communication in the terahertz band and molecular communication. The characteristics of these two modes of communication are highlighted, and a general architecture for bio-nanosensors is proposed along with examples of cooperation schemes. An implementation of the bio-nanosensor part of the nanomachine is presented along with some experimental results of sensing biomolecules. Finally, a general example of coordination among bio-nanomachines using both communication technologies is presented, and challenges in terms of communication protocols, data transmission, and coordination among nanomachines are discussed. <s> BIB005 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Wireless NanoSensor Networks (WNSNs), i.e., networks of nanoscale devices with unprecedented sensing capabilities, are the enabling technology of long-awaited applications such as advanced health monitoring systems or surveillance networks for chemical and biological attack prevention. The peculiarities of the Terahertz Band, which is the envisioned frequency band for communication among nano-devices, and the extreme energy limitations of nanosensors, which require the use of nanoscale energy harvesting systems, introduce major challenges in the design of MAC protocols for WNSNs. This paper aims to design energy and spectrum-aware MAC protocols for WNSNs with the objective to achieve fair, throughput and lifetime optimal channel access by jointly optimizing the energy harvesting and consumption processes in nanosensors. Towards this end, the critical packet transmission ratio (CTR) is derived, which is the maximum allowable ratio between the transmission time and the energy harvesting time, below which a nanosensor can harvest more energy than the consumed one, thus achieving perpetual data transmission. Based on the CTR, first, a novel symbol-compression scheduling algorithm, built on a recently proposed pulse-based physical layer technique, is introduced. The symbol-compression solution utilizes the unique elasticity of the inter-symbol spacing of the pulse-based physical layer to allow a large number of nanosensors to transmit their packets in parallel without inducing collisions. In addition, a packet-level timeline scheduling algorithm, built on a theoretical bandwidth-adaptive capacity-optimal physical layer, is proposed with an objective to achieve balanced single-user throughput with infinite network lifetime. The simulation results show that the proposed simple scheduling algorithms can enable nanosensors to transmit with extremely high speed perpetually without replacing the batteries. <s> BIB006 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> It is essential to develop energy-efficient communication techniques for nanoscale wireless communications. In this paper, a new modulation and a novel minimum energy coding scheme (MEC) are proposed to achieve energy efficiency in wireless nanosensor networks (WNSNs). Unlike existing studies, MEC maintains the desired code distance to provide reliability, while minimizing energy. It is analytically shown that, with MEC, codewords can be decoded perfectly for large code distances, if the source set cardinality is less than the inverse of the symbol error probability. Performance evaluations show that MEC outperforms popular codes such as Hamming, Reed-Solomon and Golay in the average codeword energy sense. <s> BIB007 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Wireless nanosensor networks (WNSNs), which consist of a lot of nanosensors with size of just a few hundred nanometers and are able to detect and sense new types of events at the nanoscale, are promising for a lot of unique applications like intrabody drug delivery systems, air pollution surveillance, etc. One important feature of WNSNs is that the nanosensors are highly energy-constrained, which makes it essential to develop energy efficient protocols for different layers of such networks. This paper focuses on a WNSN with on-off keying (OOK) modulation and explores the problem of transmission energy minimization in it. We first propose a general minimum transmission energy (MTE) coding scheme, which maps m-bit symbols into n-bit codewords with the least number of high-bits and thus results in the lowest energy consumption per symbol for any given m and n. We further determine the optimal setting of symbol length m and codeword length n in the MTE coding scheme so as to achieve the minimum energy consumption per data bit, which serves as the lower bound of transmission energy consumption in such WNSNs. Numerical results are provided to demonstrate the efficiency of the MTE coding scheme. <s> BIB008 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> The progress of nanotechnology is paving the way to the emerging concept of wireless nanosensor network (WNSN). In fact, it is now possible to create integrated machines at the nano scale, which interact on cooperative basis using wireless communications. The research in this field is still in an embryonal stage and the design of the WNSN protocol suite represents a fundamental issue to address. Therefore, an open source simulation framework for WNSN would be highly beneficial to let research activities converge towards participated design methodologies. In an our recent work, we presented a new NS-3 module, namely Nano-Sim, modeling WNSNs based on electromagnetic communications in the Terahertz band. In its preliminary version, Nano-Sim provides a simple network architecture and a protocol suite for such an emerging technology. In this paper, we significantly improved our previous work in several directions. First, we have extended the tool by developing a new routing algorithm and a more efficient MAC protocol. Moreover, focusing the attention on a WNSN operating in a health monitoring scenario, we have investigated how the density of nodes, the transmission range of nanomachines, and the adoption of specific combinations of routing and MAC strategies may affect the network behavior. Finally, a study on Nano-Sim computational requirements has been also carried out, thus demonstrating how the developed module guarantees great achievements in terms of scalability. <s> BIB009 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Nanonetworks consist of nano-sized communicating devices which are able to perform simple tasks at the nanoscale. Nanonetworks are the enabling technology of long-awaited applications such as advanced health monitoring systems or high-performance distributed nano-computing architectures. The peculiarities of novel plasmonic nano-transceivers and nano-antennas, which operate in the Terahertz Band (0.1-10 THz), require the development of tailored communication schemes for nanonetworks. In this paper, a modulation and channel access scheme for nanonetworks in the Terahertz Band is developed. The proposed technique is based on the transmission of one-hundred-femtosecond-long pulses by following an asymmetric On-Off Keying modulation Spread in Time (TS-OOK). The performance of TS-OOK is evaluated in terms of the achievable information rate in the single-user and the multi-user cases. An accurate Terahertz Band channel model, validated by COMSOL simulation, is used, and novel stochastic models for the molecular absorption noise in the Terahertz Band and for the multi-user interference in TS-OOK are developed. The results show that the proposed modulation can support a very large number of nano-devices simultaneously transmitting at multiple Gigabits-per-second and up to Terabits-per-second, depending on the modulation parameters and the network conditions. <s> BIB010 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Wireless NanoSensor Networks (WNSNs) will allow novel intelligent nanomaterial-based sensors, or nanosensors, to detect new types of events at the nanoscale in a distributed fashion over extended areas. Two main characteristics are expected to guide the design of WNSNs architectures and protocols, namely, their Terahertz Band wireless communication and their nanoscale energy harvesting process. In this paper, a routing framework for WNSNs is proposed to optimize the use of the harvested energy to guarantee the perpetual operation of the WNSN while, at the same time, increasing the overall network throughput. The proposed routing framework, which is based on a previously proposed medium access control protocol for the joint throughput and lifetime optimization in WNSNs, uses a hierarchical cluster-based architecture that offloads the network operation complexity from the individual nanosensors towards the cluster heads, or nano-controllers. This framework is based on the evaluation of the probability of saving energy through a multi-hop transmission, the tuning of the transmission power of each nanosensor for throughput and hop distance optimization, and the selection of the next hop nanosensor on the basis of their available energy and current load. The performance of this framework is also numerically evaluated in terms of energy, capacity, and delay, and compared to that of the single-hop communication for the same WNSN scenario. The results show how the energy per bit consumption and the achievable throughput can be jointly maximized by exploiting the peculiarities of this networking paradigm. <s> BIB011 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> This paper presents the characteristics of electromagnetic waves propagating inside human body at Terahertz frequencies and an initial study of the system performance of nano-network. It has been observed that the path loss is not only the function of distance and frequency but also related to the dielectric loss of human tissues. Numerical results have been compared with analytical studies and a good match has been found which validates the proposed numerical model. Based on the calculation of path losses and noise level for THz wave propagation, the channel capacity is studied to give an insight of future nano-communications within the human body. Results show that at the distance of millimeters, the capacity can reach as high as 100 Terabits per second (Tbps) depending on the environment and exciting pulse types. <s> BIB012 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Wireless Nano-scale Sensor Networks (WNSNs) are very simple and energy restricted networks that operate over terahertz band ranging from 0.1–10 THz, which faces significant molecular absorption noise and attenuation. Given these challenges, reliability, energy efficiency, and simplicity constitute the main criteria in designing communication protocols for WNSNs. Due to its simplicity and energy efficiency, carrier-less pulse based modulation is considered the best candidate for WNSNs. In this paper, we compare the performance of four different carrier-less modulations, PAM, OOK, PPM, and BPSK, in the context of WNSNs operating within the terahertz band. Our study shows that although BPSK is relatively more complex in terms of decoding logic at the receiver, it provides the highest reliability and energy efficiency among all the contenders. PAM has the worst performance in terms of reliability as well as energy efficiency. OOK and PPM have simpler decoding logic, but perform worse than BPSK in both reliability and energy efficiency. <s> BIB013 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Nano-communication is considered to become a major building block for many novel applications in the health care and fitness sector. Given the recent developments in the scope of nano machinery, coordination and control of these devices becomes the critical challenge to be solved. In-Body Nano-Communication based on either molecular, acoustic, or RF radio communication in the terahertz band supports the exchange of messages between these in-body devices. Yet, the control and communication with external units is not yet fully understood. In this paper, we investigate the challenges and opportunities of connecting Body Area Networks and other external gateways with in-body nano-devices, paving the road towards more scalable and efficient Internet of Nano Things (IoNT) systems. We derive a novel network architecture supporting the resulting requirements and, most importantly, investigate options for the simulation based performance evaluation of such novel concepts. Our study is concluded by a first look at the resulting security issues considering the high impact of potential misuse of the communication links. <s> BIB014 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> The present paper introduces a joint coordinate and routing system (CORONA) which can be deployed dynamically on a 2D ad-hoc nanonetwork. User-selected nodes are used as anchor-points at the setup phase. All nodes then measure their distances, in number of hops, from these anchors, obtaining a sense of geolocation. At operation phase, the routing employs the appropriate subset of anchors, selected by the sender of a packet. CORONA requires minimal setup overhead and simple integer-based calculations only, imposing limited requirements for trustworthy operation. Once deployed, it operates efficiently, yielding a very low packet retransmission and packet loss rate, promoting energy-efficiency and medium multiplexity. <s> BIB015 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Electromagnetic-based Wireless NanoSensor Networks (EM-WNSNs) operating in the TeraHertz (THz) band (0.1 THz--10 THz) has been in focus recently because of potential applications in nano-scale scenarios. However, one major hurdle for advancing nano-scale communications is the lack of suitable networking protocols to address current and future needs of nanonetworks. Working together with routing that finds the path from a source to destination, forwarding is a networking task of sending a packet to the next-hop along its path to the destination. While forwarding has been straightforward in traditional wired networks, forwarding schemes now play a vital role in determining wireless network performance. In this paper, we propose a channel-aware forwarding scheme and compare it against traditional forwarding schemes for wireless sensor networks. To fit the peculiarity of EM-WNSNs, the channel-aware forwarding scheme makes forwarding decision considering the frequency selective pecularities of the THz channel which are undesirable from a networking perspective. It is shown through simulation that the proposed channel-aware forwarding scheme outperforms traditional forwarding schemes in terms of the end-to-end capacity while maintaining comparable performance for delay. <s> BIB016 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Wireless networks of nano-nodes will play a critical role in future medical, quality control, environmental monitoring and military applications. Nano-nodes are invisible/marginally visible to the human eye, ranging in size from approximately 100 $\mu \text{m}$ to few nanometers. Nano-networking poses unique challenges, requiring ground-breaking solutions. First, the nano-scale imposes severe restrictions to the computational and communication capabilities of the nodes. Second, nano-nodes are not accessible for programming, configuration and debugging in the classical sense. Thus, a nano-network should be self-configuring, resilient and adaptive to environmental changes. Finally, all nano-networking protocols should be ultra-scalable, since a typical nano-network may comprise billions of nodes. The study contributes a novel paradigm for data dissemination in networking nano-machines, addressing these unique challenges. Relying on innovative analytical results on lattice algebra and nature-inspired processes, a novel data dissemination method is proposed. The nano-nodes exploit their environmental feedback and mature adaptively into network backbone or remain single network users. Such a process can be implemented as an ultra-scalable, low complexity, multi-modal nano-node architecture (physical layer), providing efficient networking and application services at the same time. Requiring existing manufacturing technology, the proposed architecture constitutes the first candidate solution for realizable nano-networking. <s> BIB017 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Abstract Body Area Nano-NETworks (BANNETs) consist of integrated nano-machines, diffused in the human body for collecting diagnostic information and tuning medical treatments. Endowed with communication capabilities, such nano-metric devices can interact with each other and the external micro/macro world, thus enabling advanced health-care services (e.g., therapeutic, monitoring, sensing, and telemedicine tasks). Due to limited computational and communication capabilities of nano-devices, as well as their scarce energy availability, the design of powerful BANNET systems represents a very challenging research activity for upcoming years. Starting from the most significant and recent findings of the research community, this work provides a further step ahead by proposing a hierarchical network architecture, which integrates a BANNET and a macro-scale health-care monitoring system and two different energy-harvesting protocol stacks that regulate the communication among nano-devices during the execution of advanced nano-medical applications. The effectiveness of devised solutions and the comparison with the common flooding-based communication technique have been evaluated through computer simulations. Results highlight pros and cons of considered approaches and pave the way for future activities in the Internet of Nano-Things and nano-medical research fields. <s> BIB018 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Abstract This paper focuses on molecular absorption noise caused by molecular absorption in the higher frequency bands, such as THz band (0.1–10 THz). This transmission induced noise has been predicted to exist in the THz band, since the conservation of energy requires the conservation of the absorbed energy in the medium. There exist multiple models for the molecular absorption noise. Most of them focus only on the transformation of the absorbed energy directly into antenna temperature. This paper aims at giving additional perspectives to the molecular absorption noise. It is shown that the molecular absorption noise can be investigated with multiple different approaches, strongly affecting on the predicted strength and behavior of the noise. The full molecular absorption noise model is not given in this paper. Instead, we study the molecular absorption noise from different perspectives and give their derivations and the general ideas behind the noise modeling. <s> BIB019 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Nanosized devices operating inside the human body open up new prospects in the healthcare domain. Invivo wireless nanosensor networks (iWNSNs) will result in a plethora of applications ranging from intrabody health-monitoring to drug-delivery systems. With the development of miniature plasmonic signal sources, antennas, and detectors, wireless communications among intrabody nanodevices will expectedly be enabled at both the terahertz band (0.1-10 THz) as well as optical frequencies (400-750 THz). This result motivates the analysis of the phenomena affecting the propagation of electromagnetic signals inside the human body. In this paper, a rigorous channel model for intrabody communication in iWNSNs is developed. The total path loss is computed by taking into account the combined effect of the spreading of the propagating wave, molecular absorption from human tissues, as well as scattering from both small and large body particles. The analytical results are validated by means of electromagnetic wave propagation simulations. Moreover, this paper provides the first framework necessitated for conducting link budget analysis between nanodevices operating within the human body. This analysis is performed by taking into account the transmitter power, medium path loss, and receiver sensitivity, where both the THz and photonic devices are considered. The overall attenuation model of intrabody THz and optical frequency propagation facilitates the accurate design and practical deployment of iWNSNs. <s> BIB020 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> The envisioned dense nano-network inside the human body at terahertz (THz) frequency suffers a communication performance degradation among nano-devices. The reason for this performance limitation is not only the path loss and molecular absorption noise, but also the presence of multi-user interference and the interference caused by utilising any communication scheme, such as time spread ON—OFF keying (TS-OOK). In this paper, an interference model utilising TS-OOK as a communication scheme of the THz communication channel inside the human body has been developed and the probability distribution of signal-to-interference-plus-noise ratio (SINR) for THz communication within different human tissues, such as blood, skin, and fat, has been analyzed and presented. In addition, this paper evaluates the performance degradation by investigating the mean values of SINR under different node densities in the area and the probabilities of transmitting pulses. It results in the conclusion that the interference restrains the achievable communication distance to approximate 1 mm, and more specific range depends on the particular transmission circumstance. Results presented in this paper also show that by controlling the pulse transmission probability and node density, the system performance can be ameliorated. In particular, SINR of in vivo THz communication between the deterministic targeted transmitter and the receiver with random interfering nodes in the medium improves about 10 dB, when the node density decreases one order. The SINR increases approximate 5 and 2 dB, when the pulse transmitting probability drops from 0.5 to 0.1 and 0.9 to 0.5. <s> BIB021 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Abstract Micro and nanorobotics represents one of the most challenging sectors of modern robotics. Through batch fabrication of Micro Electro-Mechanical Systems (MEMS), advanced small scale sensing and actuating tasks in a wide area of applications can be performed. Most miniaturized electro-mechanical devices are characterized by low-power and low-memory capacity. The huge number of modular robots introduces the need to explore novel self-reconfiguration algorithms to optimize movement and communication performances in terms of efficiency, parallelism and scalability. Nano-transceivers and nano-antennas operating in the Terahertz Band are already a well acquainted communication paradigm, enforcing nano-wireless networking that can be directly integrated in MEMS microrobots. Several logical topology shape-shifting algorithms are already implemented and tested in literature, along with performance evaluation on nano-wireless use. This article aims to provide an algorithm to reconnect groups of microrobots, along with a novel movement model for microrobotics ensembles introduced to enforce more realistic simulations. Special emphasis is given on the need of novel movement algorithms for swarms of microrobots. <s> BIB022 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Abstract We discuss the combination of in-body nano communication with the Internet of Things (IoT) as the Internet of Nano Things (IoNT). This combination enables a wide range of new applications and opportunities – particularly in the biomedical domain – but it also entails a number of new challenges. One of many research challenges in functional and non-functional aspects is the addressing and naming of nodes in a nano network. Our study in this area not only includes traditional techniques driven from today’s IoT, but also new unconventional ideas, originating from molecular level communication. We come up with a summary of either theoretical, simulated or realized ideas to draw conclusions about implementations and performance potential, with a focus on medical in-body communication scenarios, before we present our concept, Function Centric Nano-Networking (FCNN). FCNN allows us to address groups of interchangeable nano machines in a network by using location information and functional capabilities of the machines. This concept does not rely on the durability and uniqueness of individual nodes. We are comparing the novel concept of FCNN with similar ones and highlight elementary differences between them as well advantages and disadvantages. <s> BIB023 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> VI. COMMUNICATION AND NETWORKING OF EM AND MOLECULAR BODY-CENTRIC NANONETWORKS <s> Researchers consider wireless nanosensor networks (WNSNs) as a revolutionary emerging network paradigm from the point of its diversified applications and contributions to the humanity. Existing research in this field is still in elementary stage and performance enhancement via designing protocol suit represents a potential issue to address for this field. However, most of the studies in the literature mainly focus on lower layers, i.e., Physical and MAC layer protocols leaving upper layers such as Network layer and Transport layer protocols still unexplored. Therefore, in this paper, we explore performance enhancement in WNSNs via modifications in the existing network and transport layers protocols. In this paper, we devise a hierarchical AODV routing protocol and an acknowledgement-based UDP protocol for WNSNs. We perform rigorous simulation in ns−2 to prove the efficacy and efficiency of our proposed mechanisms. Our simulation results reveal significant performance enhancement in wireless nanosensor networks for our proposed protocols. <s> BIB024

A. EM-Based Body-Centric Nanonetworks 1) Physical Layer and MAC Layer: a) Path Loss Model: Studies on THz channel modelling of nano-communication is conducted in BIB012 - , based on the researches of the one in the air BIB001 - BIB010 . From the above studies, it can be concluded that there are three parts in the path loss of the THz wave inside human tissues: the spread path loss PL spr , the absorption path loss PL abs and the scattering path loss PL sca : where f is the frequency while r stands for the path length. The spread path loss, caused by the expansion of the wave in the medium, is defined as where λ g = λ o /n r represents the wavelength in medium with free-space wavelength λ o , and r stands for the transmission distance of the wave. Generally, the electromagnetic power is considered to travel spherically. 4πr 2 denotes the isotropic expansion term and 4π( n r f c ) 2 is the frequency dependent receiver antenna aperture term. The absorption path loss represents the attenuation absorbed by the molecular of the medium. It is assumed that part of the energy would convert into internal kinetic energy to excite the molecules in the medium. By reversing the the transmittance of the medium τ( f , d), we can obtain the absorption loss: where α is the absorption coefficient while r is the distance. The scattering path loss accounts for the loss of the signals caused by the deflection of the beam because of the nonuniformity's of the environment. Take human as an example, there are tons of molecules, cells, organs with various shapes and EM properties. The effects are dependent not only on the size, shape and EM properties of the particles but also on the wavelength of the transmitting signal. In BIB020 , the detailed phenomenon was discussed and it can be written as where µ sca refers to the scattering coefficient and r is the travelling distance. In BIB020 , the effects of all three path loss have been fully discussed for the in-body nano-communication. It is stated that the scattering path loss is almost negligible compared with the absorption path loss at the THz band. b) Noise model: The molecular absorption noise is the main element of the noises at Terahertz band, which is introduced by the molecular vibration, partially re-radiated the energy absorbed from the EM waves . Therefore, such noises are dependent on the transmitted signal. In BIB006 , noise model was investigated while in BIB021 noise of the human tissues was studied. The total molecular absorption noise p.s.d. S N can considered as the summation of the atmospheric noise S N 0 , the selfinduced noise S N 1 and others originating from other sources like devices S N o : where r refers to the propagation distance, f stands for the frequency of the EM wave, k B is the Boltzmann constant, T 0 is the reference temperature of the medium, α( f ) is the absorption coefficient, c is the speed of light in vacuum, f 0 is the design centre frequency, and S is the p.s.d of the transmitted signal. The atmosphere can be seen as an effective black body radiatior in the homogeneously absorbing medium; thus, the absorbing atmosphere with any temperature would produce the atmospheric noise BIB019 . Such atmospheric noise is called as the background noise, independent on the transmitted signal. However, the noise model of Eq. (11) only describes a special case for THz wave in air. Without loss of the generality, the term k B T 0 should be replaced with the Planck's law, which describes the general radiation of the black body BIB019 . Therefore, the molecular absorption noise contains three main contributors: the background noise S N b (r, f ), the self-induced noise S N s (r, f ) and other noise S N o (r, f ): The detailed discussions were conducted in BIB021 , and it is found that the molecular absorption noise would be the essential part of the contributors to the noise at the receiver. Meanwhile, p.s.d of human tissues on the sef-induced noise and background noise are investigated as well, where the following trends were observed: • The background noise p.s.d stay steady for all three tissue types because of the slight difference of refractive index. • The induced noise p.s.d change slowly with frequency, different from the fierce fluctuations of THz communication in air . • The self-induced noise p.s.d is way bigger than the background noise for all three human tissues, leading to the conclusion that the background noise could be neglected in vivo. c) Modulation Technique: Because the limitation of the size, nano-devices are power-limited; thus, it is not possible to adopt the traditional modulation techniques which would cause energy. Based on such situations, the modulation of carrier-less pulse based modulation is investigated in BIB013 . And a pulse modulation technique, , named TS-OOK, is studied in BIB002 and improved in BIB010 to fully exploit the potential of the nano-devices made of graphene. So far, TS-OOK is the most promising communication scheme for resource-constrained nanonetworks. To investigate the collision between symbols in body-centric nano-communication, reference BIB021 investigated the feasibility of TS-OOK as a communication scheme at THz band for the in-body communication of nanonetwork where not only the noise but also the interference is investigated. It shows that the received signal power is closely related to the transmitted signal power; thus we need to choose the transmitted power carefully to make the difference of the received power with the silence pulse large enough to make the detection accurate. In BIB003 , TS-OOK is introduced and femto-second pulse is used as the communication signal between nano-devices . Reference BIB010 analysed this pulse-based modulation where the transmitted pulse length is 100 f s. Meanwhile, the channel access scheme of nano networks at THz band was proposed and analyzed. In the paper, interference-free scenario and multi-user scenario were both discussed. In the end, the model was evaluated by COMSOL Multi-physics . The results showed that such modulation schemes were suitable for nanonetworks and by choosing suitable parameters the rates would go from a few Gbps to a few Tbps. Later, Rate Division Time-Spread On-Off Keying (RD TS-OOK) is studied in and the PHysical Layer Aware MAC protocol for Electromagnetic nanonetworks in the Terahertz Band (PHLAME) is first proposed. The proposal of these two concept is to support the extremely high density of nanodevices in nanonetworks and enable the network throughput to go up to tens of Gbps. In 2013, the critical packet transmission ratio (CTR) was derived in BIB006 to introduce an energy and spectrum aware MAC protocol which can make nano-sensors transmit with high speed with little energy consumption. d) Coding Technique: Due to the simple structure, nanonodes only have limited power storage. Thus, to save the transmitted energy, numerous coding methods were discussed. Fixed-length codewords with a constant weight can be used not only reduce the power consumption, but also to reduce the interference BIB002 . Kocaoglu et al. BIB004 , BIB007 proposed a fixed-length coding methods later to keep the Hamming distance of codewords which would make the Average Code Weight (ACW) lowest. The performance study of the fixedlength code at the aspects on ACW and code length was conducted in BIB008 . Based on this research, variable-length low weight codes for OOK modulation was investigated in which would lower the transmission energy while keep the desired throughput. 2) Network Layer: • Addressing The IEEE 1906 standard defines the specificity as the technique that enables a reception of a message carrier by a target and maps it to an address in classical communication systems. However, it does not provide any discussion on how to generate, manage, or assign specificity component to nanonodes in molecular or EM nanonetworks. Individualized network addresses and conventional addressing are not feasible nor practical due to the nano-scale of the nanonetworks. Therefore, the use of cluster-based addressing is advantageous over node-base addressing. It provides the ability to address a group of nodes with a specific function in monitoring health or in a specific biological organ BIB005 . Additionally, addressing may be safely assumed to be required in inbound direction within the nanonetworks to inform a cluster or a nanonetwork performing a specific function (application) on its next action. However, in outbound direction, no addressing is necessary since the outbound device is the sink of communication of the nanonetworks; whenever a gateway receives a message from inside, it will simply forward it to that device BIB014 . Hence, conventional addressing is not necessary for nanonetworks. It may be sufficient to reach a destination just to know the right direction, since it may be the only possible option as discussed above or any member of cluster in that direction is a suitable destination. Addressing in its conventional meaning may not be needed. For example, broadcasting a message in nanonetworks may be a solution for data dissemination because of the low possibility of collision in THz band due to the wide bandwidth and transmission time. A receiver overhearing the message decides if the message is of interest. This method can be naturally implemented in molecular nanonetworks. Direct connectivity between nanodevices is another example, where a guided communication can be provided via antenna aperture, resonant frequency, or impedance match in EM nanonetworks and shape or affinity of molecule to a particular target, complementary DNA for hybridization, etc in molecular networks. In literature, several authors in the context of proposing routing or MAC protocols for EM nanonetworks assumed that the nanonodes are assigned addresses without discussing how (for e.g BIB022 , BIB009 ). Few studies discuss nanonetwork addressing. Stelzner et.al. BIB023 proposed an addressing scheme that is based on the function of the nanosensor and its location rather than focussing on individual nodes. The authors proposed employing known protocols like IPv6 or overhead-reduced variants like 6LoWPAN for the control station and gateways. In the proposed scheme, it is irrelevant which specific sensor detects an event or which node executes a service as long as the right function is performed at the right location. However, this scheme is challenged when exact and specific quantities are required such as the case in releasing a certain amount of a drug. Addressing a partial number of nodes based on the required quantity with the lack of individual addressing of node continues to be an open area of research. • Routing One of the most fundamental concerns for Body-Centric nanonetworkss is accurate routing in order to transmit signal promptly and precisely. Some challenges affect the routing protocol, including energy, complexity, latency and throughput. Thinking of the limited resourceequipped nano-sensors, one of the most important requirement is to reduce the energy consumption. There have been a few attempts towards achieving energy efficiency in such networks by multi-hop networking BIB011 - BIB015 . A routing framework for WNSNs is proposed to guarantee the perpetual operation while increase the overall network throughput BIB011 . The framework uses a hierarchical cluster-based architecture. The choice between direct and multi-hop transmission is determined based on the probability of energy savings through the transmission process. It is concluded that multi-hop performs better for varying distance. However, only two hop counts are considered which requires more hops consideration in the performance evaluation. Besides, it mainly focuses on WNSNs and does not solve the requirements and constraints of BCNN. The primary task of networking protocol is forwarding, which is sending packets to the next-hop along its path to the destination. In traditional wireless sensor networks (WSN), multi-hop forwarding schemes including the nearest hop forwarding, the longest hop forwarding and the random forwarding schemes as well as the single-hop end-to-end transmission are utilised. For long range THz wireless nano-sensor networks (WNSN) with absorption-defined windows, in order to overcome the frequency-selective feature, a channel-aware forwarding scheme is proposed in BIB016 . The selection of the next hop is a trade-off between minmising the transmission distance and the hop count. Nevertheless, all the relay nodes are assumed to have sufficient energy and computation capacity which is impractical. Moreover, authors in BIB015 , propose a geographic routing protocol. User-selected nodes are used as anchor-points at the setup phase, and all nodes measure their distances from these anchors to obtain address. The routing then employs the appropriate subset of anchors which is selected by the sender of a packet. However, the proposed scheme is based on fixed topology neglecting the mobility and dynamic of nano-nodes. A flood-based data dissemination scheme is introduced in BIB017 . This scheme classifies each node as infrastructure or network user after processing the reception quality. Only infrastructure nodes can act as re-transmitters, while the remaining nodes revert to receiving-only mode. This approach improves the energy efficiency by avoiding the unconditional broadcast and reliving the serious redundancy and collisions. Nonetheless, this dynamicallyforming infrastructure requires topology-dependent optimisation and digital signal processing capabilities of nano-nodes. BCNN routing protocols design provides a challenge with no real solutions despite the growing research tackling this area. Two kinds of energy-harvesting protocol stacks that regulate the communication among nano-devices are proposed in BIB018 . The greedy energy-harvesting scheme simply delivers the packet to the node with the higher energy level, while the optimal energy-harvesting scheme selects the node that can maximise the overall energy level within each cluster. Both schemes shown better performance compared with the traditional flooding-based scheme. However, the optimal routing strategy cannot be easily employed because of its high computational capacity requirement. Besides, the transmission distance is not taken into consideration, which makes the selection of relay path inappropriate only based on the energy level. Recently, a cognitive routing named enhanced energy-efficient approach is proposed for IoNT . An analytic-hierarchy process is implemented as the reasoning element to make the cognitive decision based on observing the dynamically changing topology of the network. 3) Transport Layer: IEEE P1906.1 standard in mapping the nanonetwork to the conventional layering system ignored the transport layer as shown in Table II . Reliable transmission is a requirement for practical implementation of nanonetworks. Due to the peculiar characteristics of the nanonetworks, researchers agree that reliability at the MAC layer or the transport layer is sufficient but not necessary in both. Hence, the IEEE P1906.1 framework assumes the existence of the MAC layer and the absence of the transport layer. Piro et. al. BIB009 implemented two types of MAC protocols, transparent MAC and Smart MAC, in designing their nano simulator. Transparent MAC pushes packets from the network layer to the physical interface without any processing at the MAC layer. Smart MAC enqueues a packet in reception to discover the neighboring nodes before sending the packet through a handshaking procedure. For transparent MAC, researches assume that the reliability service is shifted to the transport layer, thereby advocating for the existence of transport layer. The authors of proposed adapting the Optimized Exchange Protocol (OEP) protocol, which is part of the IEEE 11073-20601 standard and is particularly important in telemedicine to provide access points to services from the application layer to the transport layer. The OEP protocol is flexible and lightweight, which makes it suitable for implementation in constraint processing power and storage nano devices. However, the authors did not propose any technique on how to adapt or implement the OEP protocol for nanonetworks. Tairin et. al. BIB024 proposed an acknowledgement-based UDP protocol to improve the packet delivery ratio in a nanonetwork. The proposed protocol utilizes timeout timer in UDP to double check whether the packet gets delivered to the destination. The authors evaluated the performance of the protocol via simulation and found that the proposed protocol improved the delivery ratio of packets but introduced additional delay to the network. Few proposals addressed transport layer protocol design. This area remains unexplored in academia and industrial research. The interaction of congestion avoidance and reliability between the MAC layer and the transport layer along with the trade-off of induced delay and energy consumption is yet to be explored.

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> This book is a lucid, straightforward introduction to the concepts and techniques of statistical physics that students of biology, biochemistry, and biophysics must know. It provides a sound basis for understanding random motions of molecules, subcellular particles, or cells, or of processes that depend on such motion or are markedly affected by it. Readers do not need to understand thermodynamics in order to acquire a knowledge of the physics involved in diffusion, sedimentation, electrophoresis, chromatography, and cell motility--subjects that become lively and immediate when the author discusses them in terms of random walks of individual particles. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> Molecular communication is a biologically-inspired method of communication with attractive properties for microscale and nanoscale devices. In molecular communication, messages are transmitted by releasing a pattern of molecules at a transmitter, which propagate through a fluid medium towards a receiver. In this paper, molecular communication is formulated as a mathematical communication problem in an information-theoretic context. Physically realistic models are obtained, with sufficient abstraction to allow manipulation by communication and information theorists. Although mutual information in these channels is intractable, we give sequences of upper and lower bounds on the mutual information which trade off complexity and performance, and present results to illustrate the feasibility of these bounds in estimating the true mutual information. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> Abstract Abstract Molecular communication is a new communication paradigm that uses molecules for information transmission between nanomachines. Similar to traditional communication systems, several factors constitute limits over the performance of this communication system. One of these factors is the energy budget of the transmitter. It limits the rate at which the transmitter can emit symbols, i.e., produce the messenger molecules. In this paper, an energy model for the communication via diffusion system is proposed. To evaluate the performance of this communication system, first a channel model is developed, and also the probability of correct decoding of the information is evaluated. Two optimization problems are set up for system analysis that focus on channel capacity and data rate. Evaluations are carried out using the human insulin hormone as the messenger molecule and a transmitter device whose capabilities are similar to a pancreatic β -cell. Results show that distance between the transmitter and receiver has a minor effect on the achievable data rate whereas the energy budget’s effect is significant. It is also shown that selecting appropriate threshold and symbol duration parameters are crucial to the performance of the system. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> Abstract Currently, Communication via Diffusion (CvD) is one of the most prominent systems in nanonetworks. In this paper, we evaluate the effects of two major interference sources, Intersymbol Interference (ISI) and Co-channel Interference (CCI) in the CvD system using different modulation techniques. In the analysis of this paper, we use two modulation techniques, namely Concentration Shift Keying (CSK) and Molecule Shift Keying (MoSK) that we proposed in our previous paper. These techniques are suitable for the unique properties of messenger molecule concentration waves in nanonetworks. Using a two transmitting couple simulation environment, the channel capacity performances of the CvD system utilizing these modulation techniques are evaluated in terms of communication range, distance between interfering sources, physical size of devices, and average transmission power. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> This paper studies the mitigation of intersymbol interference in a diffusive molecular communication system using enzymes that freely diffuse in the propagation environment. The enzymes form reaction intermediates with information molecules and then degrade them so that they cannot interfere with future transmissions. A lower bound expression on the expected number of molecules measured at the receiver is derived. A simple binary receiver detection scheme is proposed where the number of observed molecules is sampled at the time when the maximum number of molecules is expected. Insight is also provided into the selection of an appropriate bit interval. The expected bit error probability is derived as a function of the current and all previously transmitted bits. Simulation results show the accuracy of the bit error probability expression and the improvement in communication performance by having active enzymes present. <s> BIB005 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> In this letter, a new molecular modulation scheme for nanonetworks is proposed. To evaluate the scheme, a system model based on the Poisson distribution is introduced. The error probability of the proposed scheme as well as that of two previously known schemes, the concentration and molecular shift keying modulations, are derived for the Poisson model by taking into account the error propagation effect of previously decoded symbols. The proposed scheme is shown to outperform the previously introduced schemes. This is due to the fact that the decoding of the current symbol in the proposed scheme does not encounter propagation of error, as the decoding of the current symbol does not depend on the previously transmitted and decoded symbols. Finally, fundamental limits on the probability of error of a practical set of encoders and decoders are derived using information theoretical tools. <s> BIB006 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> Molecular communication is an emerging communication paradigm for biological nanomachines. It allows biological nanomachines to communicate through exchanging molecules in an aqueous environment and to perform collaborative tasks through integrating functionalities of individual biological nanomachines. This paper develops the layered architecture of molecular communication and describes research issues that molecular communication faces at each layer of the architecture. Specifically, this paper applies a layered architecture approach, traditionally used in communication networks, to molecular communication, decomposes complex molecular communication functionality into a set of manageable layers, identifies basic functionalities of each layer, and develops a descriptive model consisting of key components of the layer for each layer. This paper also discusses open research issues that need to be addressed at each layer. In addition, this paper provides an example design of targeted drug delivery, a nanomedical application, to illustrate how the layered architecture helps design an application of molecular communication. The primary contribution of this paper is to provide an in-depth architectural view of molecular communication. Establishing a layered architecture of molecular communication helps organize various research issues and design concerns into layers that are relatively independent of each other, and thus accelerates research in each layer and facilitates the design and development of applications of molecular communication. <s> BIB007 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> The memoryless additive inverse Gaussian noise channel model describing communication based on the exchange of chemical molecules in a drifting liquid medium is investigated for the situation of simultaneously an average-delay and a peak-delay constraint. Analytical upper and lower bounds on its capacity in bits per molecule use are presented. These bounds are shown to be asymptotically tight, i.e., for the delay constraints tending to infinity with their ratio held constant (or for the drift velocity of the fluid tending to infinity), the asymptotic capacity is derived precisely. Moreover, characteristics of the capacity-achieving input distribution are derived that allow accurate numerical computation of capacity. The optimal input appears to be a mixed continuous and discrete distribution. <s> BIB008 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> Within the domain of molecular communications, researchers mimic the techniques in nature to come up with alternative communication methods for collaborating nanomachines. This letter investigates the channel transfer function for molecular communications via diffusion. In nature, information-carrying molecules are generally absorbed by the target node via receptors. Using the concentration function, without considering the absorption process, as the channel transfer function implicitly assumes that the receiver node does not affect the system. In this letter, we propose a solid analytical formulation and analyze the signal metrics (attenuation and propagation delay) for molecular communication via diffusion channel with an absorbing receiver in a 3-D environment. The proposed model and the formulation match well with the simulations without any normalization. <s> BIB009 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> This article examines recent research in molecular communications from a telecommunications system design perspective. In particular, it focuses on channel models and state-of-the-art physical layer techniques. The goal is to provide a foundation for higher layer research and motivation for research and development of functional prototypes. In the first part of the article, we focus on the channel and noise model, comparing molecular and radio-wave pathloss formulae. In the second part, the article examines, equipped with the appropriate channel knowledge, the design of appropriate modulation and error correction coding schemes. The third reviews transmitter and receiver side signal processing methods that suppress inter-symbol interference. Taken together, the three parts present a series of physical layer techniques that are necessary to produce reliable and practical molecular communications. <s> BIB010 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> In this paper, we present an analytical model for the diffusive molecular communication (MC) system with a reversible adsorption receiver in a fluid environment. The widely used concentration shift keying (CSK) is considered for modulation. The time-varying spatial distribution of the information molecules under the reversible adsorption and desorption reaction at the surface of a receiver is analytically characterized. Based on the spatial distribution, we derive the net number of newly-adsorbed information molecules expected in any time duration. We further derive the number of newly-adsorbed molecules expected at the steady state to demonstrate the equilibrium concentration. Given the number of newly-adsorbed information molecules, the bit error probability of the proposed MC system is analytically approximated. Importantly, we present a simulation framework for the proposed model that accounts for the diffusion and reversible reaction. Simulation results show the accuracy of our derived expressions, and demonstrate the positive effect of the adsorption rate and the negative effect of the desorption rate on the error probability of reversible adsorption receiver with last transmit bit-1. Moreover, our analytical results simplify to the special cases of a full adsorption receiver and a partial adsorption receiver, both of which do not include desorption. <s> BIB011 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> Molecular communication via diffusion (MCvD) is a new field of communication where molecules are used to transfer information. One of the main challenges in MCvD is the intersymbol interference (ISI), which inhibits communication at high data rates. Furthermore, at nanoscale, energy efficiency becomes an essential problem. Before addressing these problems, a pre-determined threshold for the received signal must be calculated to make a decision. In this paper, an analytical technique is proposed to determine the optimum threshold, whereas in the literature, these thresholds are calculated empirically. Since the main goal of this paper is to build an MCvD system suitable for operating at high data rates without sacrificing quality, new modulation and filtering techniques are proposed to decrease the effects of ISI and enhance energy efficiency. As a transmitter-based solution, a modulation technique, molecular transition shift keying (MTSK), is proposed in order to increase the data rate by suppressing ISI. Furthermore, for energy efficiency, a power adjustment technique that utilizes the residual molecules is proposed. Finally, as a receiver-based solution, a new energy efficient decision feedback filter (DFF) is proposed as a substitute for the conventional decoders in the literature. The error performance of DFF and MMSE equalizers are compared in terms of bit error rates, and it is concluded that DFF may be more advantageous when energy efficiency is concerned, due to its lower computational complexity. <s> BIB012 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> This paper studies the problem of receiver modeling in molecular communication systems. We consider the diffusive molecular communication channel between a transmitter nano-machine and a receiver nano-machine in a fluid environment. The information molecules released by the transmitter nano-machine into the environment can degrade in the channel via a first-order degradation reaction and those that reach the receiver nano-machine can participate in a reversible bimolecular reaction with receiver receptor proteins. Thereby, we distinguish between two scenarios. In the first scenario, we assume that the entire surface of the receiver is covered by receptor molecules. We derive a closed-form analytical expression for the expected received signal at the receiver, i.e., the expected number of activated receptors on the surface of the receiver. Then, in the second scenario, we consider the case where the number of receptor molecules is finite and the uniformly distributed receptor molecules cover the receiver surface only partially. We show that the expected received signal for this scenario can be accurately approximated by the expected received signal for the first scenario after appropriately modifying the forward reaction rate constant. The accuracy of the derived analytical results is verified by Brownian motion particle-based simulations of the considered environment, where we also show the impact of the effect of receptor occupancy on the derived analytical results. <s> BIB013 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 1) Propagation Channel Model: <s> Information delivery using chemical molecules is an integral part of biology at multiple distance scales and has attracted recent interest in bioengineering and communication theory. Potential applications include cooperative networks with a large number of simple devices that could be randomly located (e.g., due to mobility). This paper presents the first tractable analytical model for the collective signal strength due to randomly placed transmitters in a 3-D large-scale molecular communication system, either with or without degradation in the propagation environment. Transmitter locations in an unbounded and homogeneous fluid are modeled as a homogeneous Poisson point process. By applying stochastic geometry, analytical expressions are derived for the expected number of molecules absorbed by a fully absorbing receiver or observed by a passive receiver. The bit error probability is derived under ON/OFF keying and either a constant or adaptive decision threshold. Results reveal that the combined signal strength increases proportionately with the transmitter density, and the minimum bit error probability can be improved by introducing molecule degradation. Furthermore, the analysis of the system can be generalized to other receiver designs and other performance characteristics in large-scale molecular communication systems. <s> BIB014

• In the free-diffusion channel, the information molecules (such as hormones, pheromones, DNA) move in the fluid medium via Brownian motion. In this case, the propagation is often assumed to follow the Wiener process, and the propagation model can be mathematically described using Fick's second law BIB001 : where the diffusion coefficient D is governed by the Einstein relation as where T is temperature in kelvin, η is the viscosity of the fluid environment, r m is the radius of information molecule, and k B is the Boltmann constant. This Einstein relation may lose accuracy in most realistic scenarios, and the diffusion coefficient of which is usually obtained via experiment . • In the diffusion with drift channel, the propagation model in a 3D environment can be mathematically expressed as BIB001 Ch. 4 ] where v x , v y , and v z are the constant drift velocities in the +x, +y, and +z directions, respectively. Different from the EM wave propagation model, the molecular propagation has the advantages of not sufferring from the diffraction loss under the shadow of objects, and not restricting by the cut-off frequency in pipe, aperture, and mesh environments BIB010 . 2) Noise Model: • The inherent noise is usually contributed by the random arrival of emitted molecules at the previous bit intervals. In the timing channel, the noise N T is the first arrival time at the receiver boundary given as with the communication distance l and diffusion coefficient D for the positive drift v > 0. In the concentration-encoded channel, the number of left over molecules belonging to the previous bit to the current bit duration follows the binomial distributions, and the noise at the n b th bit interval due to previous (n b − 1) bit intervals is described as BIB011 , BIB003 where N is the number of transmit molecules at the start of the first bit interval, n b is the number bit intervals, T b is the length of one bit interval, d is the distance between the transmitter and the receiver, and F (·, ·, ·) is the fraction number of molecules counted at the receiver. • The external noise usually includes the biochemical noise, the thermal noise, the physical noise, the sampling noise, and the counting noise. The biochemical noise is the biochemically interaction between the information molecules/bio-nanomachines and the surrouding molecules and environment. The thermal noise is the varied activity levels of the thermally activated processes or stochastic thermal motion due to the changing surrounding temperature, and the physical noise is the physical force on the molecules movement due to the viscosity of fluid environment BIB007 . The counting noise arises when measuring the molecular concentration at the receiver location, and it is due to the randomness in the molecules movement and to the discreteness of the molecules, whereas the sampling noise arises when modulating the molecular concentration at the emission of molecules, and is due to the discreteness of the molecules and the unwanted perturbation at the emission process . 3) Modulation Techniques: Different from the modulation in radio frequency (RF) wireless communication systems where the information is modulated on the amplitude, frequency, and phase of the radio waves, the molecular communication transmitters modulate the information on the type/structure, the emitting time, and the number of releasing molecules. • In the timing channel, the information was modulated on the emitting time of molecules as in BIB002 - BIB008 . • In the concentration-encoded channel, two types of modulation schemes for binary MC system was first described in , which are the ON-OFF modulation and the Multilevel amplitude modulation (M-AM). In the ON-OFF modulation scheme, the concentration of information molecules during the bit interval is Q to represent bit-1, and the concentration of information molecules during the bit interval is 0 to represent bit-0. In the M-AM scheme, the concentration of information molecules is continuous sinusoidal wave, where the amplitude and the frequency can be encoded. The Concentration shift keying (CSK) was proposed for modulating the number of information molecules, and Molecule Shift Keying (MoSK) was proposed for modulating on different types of information molecules BIB004 . Due to the constraints in the accurate time arrival of molecules in random walks, and the limited types of molecules in MC system, the Binary CSK modulation based on the number of releasing molecules have been widely applied BIB004 , BIB009 , BIB011 , BIB014 , , BIB005 , , where the molecules concentration is considered as the signal amplitude. In more detail, in the Binary CSK, the transmitter emits N 1 molecules at the start of the bit interval to represent the bit-1 transmission, and emits N 2 molecules at the start of the bit interval to represent the bit-0 transmission. In most works, N 1 can be set as zero to reduce the energy consumption and make the received signal more distinguishable. The hybrid modulation based on the number as well as the types of releasing moleules were proposed and studied in BIB006 , BIB012 . 4) Reception Model: For the same single point transmitter located at − → r relative to the center of a receiver with radius r r , the received number of molecules will be different depending on the types of receivers. • For the passive receiver, the local point concentration at the center of the passive receiver at time t due to a single pulse emission by the transmitter occurring at t = 0 is given as [207, Eq. (4.28)] C Ω r r , t − → r = 1 where − → r = [x, y, z], and [x, y, z] are the coordinates along the three axes. • For the fully absorbing receiver with spherical symmetry, the reception process can be described as [208, Eq. (3.64) ] where k is the absorption rate (in length×time −1 ). The molecule distribution function of the fully absorbing receiver at time t due to a single pulse emission by the transmitter occurring at t = 0 is presented as • For the reversible adsorption receiver with spherical symmetry, the boundary condition of the information molecules at its surface is [209, Eq. (4)] D ∂ (C (r, t| r 0 )) ∂r where k 1 is the adsorption rate (length×time −1 ) and k −1 is the desorption rate (time −1 ), and its molecule distribution function was derived in [210, Eq. (8)]. • For the ligand binding receiver with spherical symmetry, the boundary condition of the information molecules at its surface is where S ( t| r 0 ) is the probability that the information molecules released at distance r 0 given as and its molecule distribution function was derived in BIB013 Eq. (23) ].

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 5) Coding <s> Communication between nanoscale devices is an area of considerable importance as it is essential that future devices be able to form nanonetworks and realise their full potential. Molecular communication is a method based on diffusion, inspired by biological systems and useful over transmission distances in the nm to m range. The propagation of messenger molecules via diffusion implies that there is thus a probability that they can either arrive outside of their required time slot or ultimately, not arrive at all. Therefore, in this paper, the use of a error correcting codes is considered as a method of enhancing the performance of future nanonetworks. Using a simple block code, it is shown that it is possible to deliver a coding gain of ∼ 1.7dB at transmission distances of 1 m. Nevertheless, energy is required for the coding and decoding and as such this paper also considers the code in this context. It is shown that these simple error correction codes can deliver a benefit in terms of energy usage for transmission distances of upwards of 25 m for receivers of a 5 m radius. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 5) Coding <s> Molecular communications emerges as a promising scheme for communications between nanoscale devices. In diffusion-based molecular communications, molecules as information symbols diffusing in the fluid environments suffer from molecule crossovers, i.e., the arriving order of molecules is different from their transmission order, leading to intersymbol interference (ISI). In this paper, we introduce a new family of channel codes, called ISI-free codes, which improve the communication reliability while keeping the decoding complexity fairly low in the diffusion environment modeled by the Brownian motion. We propose general encoding/decoding schemes for the ISI-free codes, working upon the modulation schemes of transmitting a fixed number of identical molecules at a time. In addition, the bit error rate (BER) approximation function of the ISI-free codes is derived mathematically as an analytical tool to decide key factors in the BER performance. Compared with the uncoded systems, the proposed ISI-free codes offer good performance with reasonably low complexity for diffusion-based molecular communication systems. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 5) Coding <s> Owing to the limitations of molecular nanomachines, it is essential to develop reliable, yet energy-efficient communication techniques. Two error correction coding techniques are compared under a diffusive molecular communication mechanism, namely, Hamming codes and minimum energy codes (MECs). MECs, which previously have not been investigated in a diffusive channel, maintain the desired code distance to keep reliability while minimising energy. Results show that MECs outperform the Hamming codes, both in aspects of bit error rate and energy consumption. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 5) Coding <s> Future applications for nano-machines, such as drug-delivery and health monitoring, will require robust communications and nanonetworking capabilities. This is likely to be enabled via the use of molecules, as opposed to electromagnetic waves, acting as the information carrier. To enhance the reliability of the transmitted data, Euclidean geometry low density parity check (EG-LDPC) and cyclic Reed-Muller (C-RM) codes are considered for use within a molecular communication system for the first time. These codes are compared against the Hamming code to show that an $\boldsymbol{s}=4$ LDPC (integer $\boldsymbol{s}\ge 2$ ) has a superior coding gain of 7.26 dBs. Furthermore, the critical distance and energy cost for a coded system are also taken into account as two other performance metrics. It is shown that when considering the case of nano–to nano-machines communication, a Hamming code with $\boldsymbol{m}=4$ , (integer $\boldsymbol{m}\ge 2$ ) is better for a system operating between $10^{-6}$ and $10^{-3}$ bit error rate (BER) levels. Below these BERs, $\boldsymbol{s}=2$ LDPC codes are superior, exhibiting the lowest energy cost. For communication between nano–to macro-machines, and macro–to nano-machines, $\boldsymbol{s}=3$ LDPC and $\boldsymbol{s}=2$ LDPC are the best options respectively. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 5) Coding <s> Molecular communication (MC) has recently emerged as a novel paradigm for nano-scale communication utilizing molecules as information carriers. In diffusion-based molecular communication, the system performance is constrained by the inter-symbol-interference caused by the crossover of information carrying molecules in consecutive bits. To cope with this, we propose the Reed-Solomon (RS) codes as an error recovery tool, to improve the transmission reliability in diffusion-based MC systems. To quantify the performance improvement due to RS codes, we derive the analytical expression for the approximate bit error probability (BEP) of the diffusion-based MC system with the full absorption receiver. We further develop the particle-based simulation framework to simulate the proposed system with RS code to verify the accuracy of our derived analytical results. Our results show that, as the number of molecules per bit increases, the BEP of the system with RS codes exhibits a substantial improvement than that of non-coded systems. Furthermore, the BEP of the proposed system with RS codes can be greatly improved by increasing the minimum distance of the codeword. <s> BIB005 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 5) Coding <s> Molecular Communication (MC) is an enabling paradigm for the interconnection of future devices and networks in the biological environment, with applications ranging from bio-medicine to environmental monitoring and control. The engineering of biological circuits, which allows to manipulate the molecular information processing abilities of biological cells, is a candidate technology for the realization of MC-enabled devices. In this paper, inspired by recent studies favoring the efficiency of analog computation over digital in biological cells, an analog decoder design is proposed based on biological circuit components. In particular, this decoder computes the a-posteriori log-likelihood ratio of parity-check-encoded bits from a binary-modulated concentration of molecules. The proposed design implements the required L-value and the box-plus operations entirely in the biochemical domain by using activation and repression of gene expression, and reactions of molecular species. Each component of the circuit is designed and tuned in this paper by comparing the resulting functionality with that of the corresponding analytical expression. Despite evident differences with classical electronics, biochemical simulation data of the resulting biological circuit demonstrate very close performance in terms of Mean Squared Error (MSE) and Bit Error Rate (BER), and validate the proposed approach for the future realization of MC components. <s> BIB006 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 5) Coding <s> Abstract Real-time monitoring of medical test parameters as well as biological and chemical substances inside the human body is an aspiration which might facilitate the control of pathologies and would ensure better effectiveness in diagnostics and treatments. Future Body Area NanoNetworks (BANN) represent an ongoing effort to complement these initiatives, although due to its early stage of development, further research is required. This paper contributes with a hierarchical BANN architecture consisting of two types of nanodevices, namely, nanonodes and a nanorouter, which are conceptually designed using technologically available electronic components. A straightforward communication scheme operating at the THz band for the exchange of information among nanodevices is also proposed. Communications are conducted in a human hand scenario since, unlike other parts of the human body, the negative impact of path loss and molecular absorption noise on the propagation of electromagnetic waves in biological tissues is mitigated. However, data transmission is restricted by the tiny size of nanodevices and their extremely limited energy storing capability. To overcome this concern, nanodevices must be powered through the bloodstream and external ultrasound energy harvesting sources. Under these conditions, the necessary energy and its management have been thoroughly examined and assessed. The results obtained reveal the outstanding ability of nanonodes to recharge, thus enabling each pair of nanonode–nanorouter to communicate every 52 min. This apparently long period is compensated by the considerably high number of nanonodes in the network, which satisfies a quasi-constant monitoring of medical parameter readings. <s> BIB007 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 5) Coding <s> Inspired by nature, molecular communications (MC), i.e., the use of molecules to encode, transmit, and receive information, stands as the most promising communication paradigm to realize the nanonetworks. Even though there has been extensive theoretical research toward nanoscale MC, there are no examples of implemented nanoscale MC networks. The main reason for this lies in the peculiarities of nanoscale physics, challenges in nanoscale fabrication, and highly stochastic nature of the biochemical domain of envisioned nanonetwork applications. This mandates developing novel device architectures and communication methods compatible with MC constraints. To that end, various transmitter and receiver designs for MC have been proposed in the literature together with numerable modulation, coding, and detection techniques. However, these works fall into domains of a very wide spectrum of disciplines, including, but not limited to, information and communication theory, quantum physics, materials science, nanofabrication, physiology, and synthetic biology. Therefore, we believe it is imperative for the progress of the field that an organized exposition of cumulative knowledge on the subject matter can be compiled. Thus, to fill this gap, in this comprehensive survey, we review the existing literature on transmitter and receiver architectures toward realizing MC among nanomaterial-based nanomachines and/or biological entities and provide a complete overview of modulation, coding, and detection techniques employed for MC. Moreover, we identify the most significant shortcomings and challenges in all these research areas and propose potential solutions to overcome some of them. <s> BIB008

Techniques: Similar to traditional wireless communication systems, many coding schemes have been studied for molecular paradigm to improve transmission reliability. Hamming codes were used as the error control coding (ECC) for DMC in BIB001 , where the coding gain can achieve 1.7dB with transmission distance being 1µm. Meanwhile, the authors modelled the energy consumption of coding and decoding to show that the proposed coding scheme is energy inefficient at shorter transmission distances. In their subsequent work, the minimum energy codes (MECs) were investigated and outperformed the Hamming codes in bit error rate and energy consumption BIB003 . Moreover, the authors of BIB004 compared and evaluated the Hamming codes, Euclidean geometry low density parity check (EG-LDPC) and cyclic Reed-Muller (C-RM) codes. In order to mitigate the inter-symbol-interference (ISI) caused by the overlap of two consecutive symbols for DMC, Reed Solomon (RS) codes were investigated in BIB005 . Compared with the Hamming codes capable of correcting one bit error, the RS codes are highly effective against burst and random errors. The results showed that the bit error probability (BEP) increases as either the number of molecules per bit increases or the codeword minimum distance decreases. Besides these frequently used wireless communication codes, new coding schemes were developed to tailor MC channel characteristics, such as the coding based on molecular coding (MoCo) distance function and the ISI-free code for DMC channels with a drift BIB002 . Further to these, the authors of BIB006 considered coding implementation and designed a parity check analog decoder using biological components. The decoding process depends on the computation of aposteriori log-likelihood ratio involving L-value and box-plus calculation. The calculations are completed with the help of chemical reactions and the gene regulation mechanism whose input-output relation can be described by Hill function. Through carefully choosing the parameters in Hill function, the Hill function is able to approximate some mathematical operations, such as the hyperbolic operation and logarithmic operation, and finally leads to the successfully bits decoding. More details on coding schemes for MC could refer to , BIB008 . (a) The proposed scheme in (b) The proposed scheme in BIB007 . Fig. 12 : Two nanonetworks schemes that adopt electromagnetic paradigm as their in-body and body-area communication method.

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Requirements and Opportunities <s> In this study, we propose and simulate a high-sensitivity carbon nanotube sensor, capable of transducing protein-ligand binding, or more generally, macromolecular-recognition into a frequency variation of an electric current. In conjunction with small proteins like streptavidin the nanosensor can reach the sensitivity threshold, i.e. detecting a single molecule binding. For heavier, virus-sized particles the same device can provide a relatively accurate measure of their mass. In a first step, we focus on mechanical issues and characterize the sensor under several aspects both by molecular dynamics and continuous shell theory. The second part focuses on the transduction of the cantilever deflection into an electrical signal, and is achieved through a combination of Green's functions and spatial domain decomposition. The influence of thermal effects on the proper operation of the sensor is also discussed in conjunction with the construction of the current-displacement characteristic. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Requirements and Opportunities <s> Abstract This paper provides an in-depth view on nanosensor technology and electromagnetic communication among nanosensors. First, the state of the art in nanosensor technology is surveyed from the device perspective, by explaining the details of the architecture and components of individual nanosensors, as well as the existing manufacturing and integration techniques for nanosensor devices. Some interesting applications of wireless nanosensor networks are highlighted to emphasize the need for communication among nanosensor devices. A new network architecture for the interconnection of nanosensor devices with existing communication networks is provided. The communication challenges in terms of terahertz channel modeling, information encoding and protocols for nanosensor networks are highlighted, defining a roadmap for the development of this new networking paradigm. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Requirements and Opportunities <s> Approaches, Derivatives and Applications Vasilios Georgakilas,† Michal Otyepka,‡ Athanasios B. Bourlinos,‡ Vimlesh Chandra, Namdong Kim, K. Christian Kemp, Pavel Hobza,‡,§,⊥ Radek Zboril,*,‡ and Kwang S. Kim* †Institute of Materials Science, NCSR “Demokritos”, Ag. Paraskevi Attikis, 15310 Athens, Greece ‡Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic Center for Superfunctional Materials, Department of Chemistry, Pohang University of Science and Technology, San 31, Hyojadong, Namgu, Pohang 790-784, Korea Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo naḿ. 2, 166 10 Prague 6, Czech Republic <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Requirements and Opportunities <s> In molecular communication, a group of biological nanomachines communicates through exchanging molecules and collectively performs application dependent tasks. An open research issue in molecular communication is to establish interfaces to interconnect the molecular communication environment (e.g., inside the human body) and its external environment (e.g., outside the human body). Such interfaces allow conventional devices in the external environment to control the location and timing of molecular communication processes in the molecular communication environment and expand the capability of molecular communication. In this paper, we first describe an architecture of externally controllable molecular communication and introduce two types of interfaces for biological nanomachines; bio-nanomachine to bio-nanomachine interfaces (BNIs) for bio-nanomachines to interact with other biological nanomachines in the molecular communication environment, and inmessaging and outmessaging interfaces (IMIs and OMIs) for bio-nanomachines to interact with devices in the external environment. We then describe a proof-of- concept design and wet laboratory implementation of the IMI and OMI, using biological cells. We further demonstrate, through mathematical modeling and numerical experiments, how an architecture of externally controllable molecular communication with BNIs and IMIs/OMIs may apply to pattern formation, a promising nanomedical application of molecular communication. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Requirements and Opportunities <s> Nano-communication is considered to become a major building block for many novel applications in the health care and fitness sector. Given the recent developments in the scope of nano machinery, coordination and control of these devices becomes the critical challenge to be solved. In-Body Nano-Communication based on either molecular, acoustic, or RF radio communication in the terahertz band supports the exchange of messages between these in-body devices. Yet, the control and communication with external units is not yet fully understood. In this paper, we investigate the challenges and opportunities of connecting Body Area Networks and other external gateways with in-body nano-devices, paving the road towards more scalable and efficient Internet of Nano Things (IoNT) systems. We derive a novel network architecture supporting the resulting requirements and, most importantly, investigate options for the simulation based performance evaluation of such novel concepts. Our study is concluded by a first look at the resulting security issues considering the high impact of potential misuse of the communication links. <s> BIB005 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Requirements and Opportunities <s> Abstract Real-time monitoring of medical test parameters as well as biological and chemical substances inside the human body is an aspiration which might facilitate the control of pathologies and would ensure better effectiveness in diagnostics and treatments. Future Body Area NanoNetworks (BANN) represent an ongoing effort to complement these initiatives, although due to its early stage of development, further research is required. This paper contributes with a hierarchical BANN architecture consisting of two types of nanodevices, namely, nanonodes and a nanorouter, which are conceptually designed using technologically available electronic components. A straightforward communication scheme operating at the THz band for the exchange of information among nanodevices is also proposed. Communications are conducted in a human hand scenario since, unlike other parts of the human body, the negative impact of path loss and molecular absorption noise on the propagation of electromagnetic waves in biological tissues is mitigated. However, data transmission is restricted by the tiny size of nanodevices and their extremely limited energy storing capability. To overcome this concern, nanodevices must be powered through the bloodstream and external ultrasound energy harvesting sources. Under these conditions, the necessary energy and its management have been thoroughly examined and assessed. The results obtained reveal the outstanding ability of nanonodes to recharge, thus enabling each pair of nanonode–nanorouter to communicate every 52 min. This apparently long period is compensated by the considerably high number of nanonodes in the network, which satisfies a quasi-constant monitoring of medical parameter readings. <s> BIB006 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Requirements and Opportunities <s> The nervous system holds a central position among the major in-body networks. It comprises of cells known as neurons that are responsible to carry messages between different parts of the body and make decisions based on those messages. In this work, further to the extensive theoretical studies, we demonstrate the first controlled information transfer through an in vivo nervous system by modulating digital data from macro-scale devices onto the nervous system of common earthworms and conducting successful transmissions. The results and analysis of our experiments provide a method to model networks of neurons, calculate the channel propagation delay, create their simulation models, indicate optimum parameters such as frequency, amplitude and modulation schemes for such networks, and identify average nerve spikes per input pulse as the nervous information coding scheme. Future studies on neuron characterization and artificial neurons may benefit from the results of our work. <s> BIB007

Besides the five components discussed in Sec. II-C, the IEEE P1906.1 framework also defined the element of the interface between the In-Body Network and the Body-Area Network which is an important part for the application implementation of nanonetworks, especially for medical-related applications. However, as the goal of the standard is to highlight the minimum required components and their corresponding functions necessary to deploy a nanonetwork, which communication paradigm is adopted inside the human body and outside people, and what is the interface to transmit healthy parameters from nano-nodes inside human body to outside devices are not specified. Some groups specified the communication paradigm with corresponding interface either using EM paradigm or MC paradigm. The authors of proposed a network deployment tailored for coronary heart disease monitoring, which is shown in Fig 12a. The network consists of two major components: Nanodevice-embedded Drug Eluting Stents (nanoDESs) and Nano-macro Interface (NM). The nanoDESs are deployed to occluded regions of coronary arteries and responsible for measuring the arterial constriction, communicating relevant information, and controlling the release of any required drugs. NanoDESs use THz band to communicate with an interface which is inserted in the intercostal space of the rib cage of a Coronary Heart Disease (CHD) patient and acts as a gateway between the nanonetworks and the macroworld. Another example that chooses THz communication is presented in BIB006 . It proposed a nanoscale communication network consisting of nanonodes circulating in bloodstream and a nanorouter implanted between epidermis and dermis in hand skin, illustrated in Fig. 12b . The nanonodes in blood vessels collect healthy parameters and exchange data with the nanorouter using THz band only when they approach the nanorouter. In this way, the relatively short distance between nanonodes and the nanorouter minimizes the negative impact of path loss. Subsequently, the nanorouter transmits the received information also in THz band to a gateway wristband that relays the healthy data to external devices or the Internet via traditional communication methods. As for MC paradigm, authors in BIB004 implemented artificially synthesized materials (ARTs) as an interface. In their wet laboratory experiments, the ART contains pHrodo molecules which are a kind of fluorescent dyes that are almost non-fluorescent under neutral solutions while fluorescent in acidic solutions. Therefore, conducting fluorescence microscopy observations and measuring fluorescent intensity can tell us the information inside our body. Apparently, all the above schemes can enable the connection between the In-Body Network and the Body-Area Network using electromagnetic paradigm or molecular paradigm, but there are some factors making them less practical. First, the nanonodes in BIB006 and nanoDESs in are nonbiological and may intervene other physiological activities, as the nanonodes need to be injected into blood vessels or enter the human body through drinking a solution containing them, and the nanoDESs are even required to be surgically placed into body. Moreover, the injection or insertion of numerous nanonodes into the human body may not be accepted by the public, and some countries have published national laws to strictly regulate the production and marketing of such devices BIB005 . Meanwhile, how to recycle these nanonodes is also a problem. Second, with regard to the method in BIB004 , the need of externally devices, fluorescent microscope, makes the method too complicated to implement for ordinary being. Furthermore, the fluorescent intensity information has to be transformed to electromagnetic form for the following transmission to the Internet. The nanoscale is the natural domain of molecules, proteins, DNA, organelles, and major components of cells BIB002 , . investigated three kinds of possible signaling particles and discussed their corresponding biological building blocks to serve as transmitters and receivers for MC. A physiological process that happens naturally is the neurotransmitters transmission between presynaptic part and postsynaptic terminal, which is depicted in Fig. 13 . In response to an excitation of a nerve fiber, the generated action potential moves along the presynaptic part and triggers the release of neurotransmitters (signaling particles) contained in vesicles. The released information molecules diffuse in the environment, and they can bind to the ion channel located at the membrane of postsynaptic terminal. Then, the binded ion channel becomes permeable to some ions, which the ion influx finally leads to a depolarization of the cell membrane that propagates subsequently as a new action potential along the cell , . Undoubtedly, the neurotransmitter delivery establishes a MC link and is much more biological, biocompatible, and less invasive than nanonetworks systems consisting of nanonodes and using electromagnetic paradigm, since spontaneously existed molecular paradigms eliminate the risk of injection or The red molecules are signaling neurotransmitters enclosed by roundshaped vesicles, and the green molecules are ion molecules who can result in a depolarization of the cell membrane . intake of nano devices. In other words, the molecular paradigm makes up for the drawback of , BIB006 . Moreover, the implementation in BIB007 further demonstrates the feasibility of that some physiological processes can be interpreted as MC systems. In MC, the information is generally modulated by molecules' concentration, while the information is usually transmitted outside the human body via electromagnetic waves, so a chemical concentration/electromagnetic wave convertor or interface is needed. Fortunately, some nanonodes with chemical nanosensors being embedded on the CNTs or GNRs are able to take this responsibility BIB001 - BIB003 . The mechanism is that some specific type of molecules can be absorbed on the top of CNTs and GNRs, thus resulting in a locally change in the number of electrons moving through the carbon lattice and generating an electrical signal BIB002 . So far, the discussed advantages brougth by MC and electromagnetic communication provide the opportunity and open a door to propose a hybrid communication for nanonetworks systems.

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 14. <s> The ability of engineered biological nanomachines to communicate with biological systems at the molecular level is anticipated to enable future applications such as monitoring the condition of a human body, regenerating biological tissues and organs, and interfacing artificial devices with neural systems. From the viewpoint of communication theory and engineering, molecular communication is proposed as a new paradigm for engineered biological nanomachines to communicate with the natural biological nanomachines which form a biological system. Distinct from the current telecommunication paradigm, molecular communication uses molecules as the carriers of information; sender biological nanomachines encode information on molecules and release the molecules in the environment, the molecules then propagate in the environment to receiver biological nanomachines, and the receiver biological nanomachines biochemically react with the molecules to decode information. Current molecular communication research is limited to small-scale networks of several biological nanomachines. Key challenges to bridge the gap between current research and practical applications include developing robust and scalable techniques to create a functional network from a large number of biological nanomachines. Developing networking mechanisms and communication protocols is anticipated to introduce new avenues into integrating engineered and natural biological nanomachines into a single networked system. In this paper, we present the state-of-the-art in the area of molecular communication by discussing its architecture, features, applications, design, engineering, and physical modeling. We then discuss challenges and opportunities in developing networking mechanisms and communication protocols to create a network from a large number of bio-nanomachines for future applications. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 14. <s> In this paper, we consider a multi-hop molecular communication network consisting of one nanotransmitter, one nanoreceiver, and multiple nanotransceivers acting as relays. We consider three different relaying schemes to improve the range of diffusion-based molecular communication. In the first scheme, different types of messenger molecules are utilized in each hop of the multi-hop network. In the second and third schemes, we assume that two types of molecules and one type of molecule are utilized in the network, respectively. We identify self-interference, backward intersymbol interference (backward-ISI), and forward-ISI as the performance-limiting effects for the second and third relaying schemes. Furthermore, we consider two relaying modes analogous to those used in wireless communication systems, namely full-duplex and half-duplex relaying. We propose the adaptation of the decision threshold as an effective mechanism to mitigate self-interference and backward-ISI at the relay for full-duplex and half-duplex transmission. We derive closed-form expressions for the expected end-to-end error probability of the network for the three considered relaying schemes. Furthermore, we derive closed-form expressions for the optimal number of molecules released by the nanotransmitter and the optimal detection threshold of the nanoreceiver for minimization of the expected error probability of each hop. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 14. <s> This paper studies a three-node network in which an intermediate nano-transceiver, acting as a relay, is placed between a nano-transmitter and a nano-receiver to improve the range of diffusion-based molecular communication. Motivated by the relaying protocols used in traditional wireless communication systems, we study amplify-and-forward (AF) relaying with fixed and variable amplification factor for use in molecular communication systems. To this end, we derive a closed-form expression for the expected end-to-end error probability. Furthermore, we derive a closed-form expression for the optimal amplification factor at the relay node for minimization of an approximation of the expected error probability of the network. Our analytical and simulation results show the potential of AF relaying to improve the overall performance of nano-networks. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 14. <s> Molecular communications (MC) is a promising paradigm which enables nano-machines to communicate with each other. Due to the severe attenuation of molecule concentrations, there tends to be more errors when the receiver becomes farther from the transmitter. To solve this problem, relaying schemes need to be implemented to achieve reliable communications. In this letter, time-dependent molecular concentrations are utilised as the information carrier, which will be influenced by the noise and channel memory. The emission process is also considered. The relay node (RN) can decode messages, and forward them by sending either the same or a different kind of molecules as the transmitter. The performance is evaluated by deriving theoretical expressions as well as through simulations. Results show that the relaying scheme will bring significant benefits to the communication reliability. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 14. <s> This paper focuses on the development of a novel radio channel model inside the human skin at the terahertz range, which will enable the interaction among potential nano-machines operating in the inter cellular areas of the human skin. Thorough studies are performed on the attenuation of electromagnetic waves inside the human skin, while taking into account the frequency of operation, distance between the nano-machines and number of sweat ducts. A novel channel model is presented for communication of nano-machines inside the human skin and its validation is performed by varying the aforementioned parameters with a reasonable accuracy. The statistics of error prediction between simulated and modeled data are: mean (μ)= 0.6 dB and standard deviation (σ)= 0.4 dB, which indicates the high accuracy of the prediction model as compared with measurement data from simulation. In addition, the results of proposed channel model are compared with terhaertz time-domain spectroscopy based measurement of skin sample and the statistics of error prediction in this case are: μ = 2.10 dB and σ = 6.23 dB, which also validates the accuracy of proposed model. Results in this paper highlight the issues and related challenges while characterizing the communication in such a medium, thus paving the way towards novel research activities devoted to the design and the optimization of advanced applications in the healthcare domain. <s> BIB005 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 14. <s> The envisioned dense nano-network inside the human body at terahertz (THz) frequency suffers a communication performance degradation among nano-devices. The reason for this performance limitation is not only the path loss and molecular absorption noise, but also the presence of multi-user interference and the interference caused by utilising any communication scheme, such as time spread ON—OFF keying (TS-OOK). In this paper, an interference model utilising TS-OOK as a communication scheme of the THz communication channel inside the human body has been developed and the probability distribution of signal-to-interference-plus-noise ratio (SINR) for THz communication within different human tissues, such as blood, skin, and fat, has been analyzed and presented. In addition, this paper evaluates the performance degradation by investigating the mean values of SINR under different node densities in the area and the probabilities of transmitting pulses. It results in the conclusion that the interference restrains the achievable communication distance to approximate 1 mm, and more specific range depends on the particular transmission circumstance. Results presented in this paper also show that by controlling the pulse transmission probability and node density, the system performance can be ameliorated. In particular, SINR of in vivo THz communication between the deterministic targeted transmitter and the receiver with random interfering nodes in the medium improves about 10 dB, when the node density decreases one order. The SINR increases approximate 5 and 2 dB, when the pulse transmitting probability drops from 0.5 to 0.1 and 0.9 to 0.5. <s> BIB006 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> 14. <s> A preliminary investigation is carried out on the artificial human skin tissues with and without metastatic melanomas using Terahertz Time Domain Spectroscopy (THz-TDS). Both the refractive indexes and absorption coefficients of artificial skin with melanomas are higher than the normal artificial skin samples over the entire frequency range between 0.2 THz to 1.6 THz. The reason is that tumour cells degrade the contraction of fibroblasts causing more water content in malignant tissues. This study quantifies the impact of melanomas on the optical parameters of artificial skin tissue and can help in techniques that will diagnose and prevent tumours at the early stage. <s> BIB007

In the proposed hybrid communication network, the MC is utilized in the human body because it shows a superiority over other communication schemes in terms of biocompatibility and noninvasiveness. The blue nano-node in Fig. 14 refers to a MC system, and MC systems are grouped to constitute a molecular nanonetwork who is only responsible for a certain area. The molecular nanonetworks are either made up of multiple MC transmitters and receivers or a MC transmitter, MC receiver, and multiple transceivers that play the role of relaying. A biological transmitter first collects health parameters, and then modulates and transmits the collected information among the molecular nanonetworks. In order to successfully delivery the information to the outside of the human body, a graphene based nano-device is implanted into the human body. This device is mainly made up of a chemical nanosensor, a transceiver, and the battery. The embedded chemical nanosensor is capable of detecting the concentration information coming from the molecular nanonetworks, and converts it to an electrical signal. The THz electromagnetic signal is further transmitted to a nano-micro interface. This interface can either be a dermal display device [229] or a gateway to connect with the Internet. The nano-micro interface is usually equipped with two kinds of antennas: THz antenna and micro/macro antenna. The proposed hybrid communication architecture not only tries its best to avoid using non-biological nanonodes inside the body but also makes in-body healthy parameters easily be detected outside. There are several enabling technologies to enhance the feasibility of the proposed hybrid communication. First, the molecular nanonetworks have been well studied (see Sec. III-B2) BIB002 , BIB003 , BIB004 , BIB001 . Different relaying or multihop schemes have been proposed and their performance are theoretically and numerically analysed, which demonstrate the effectiveness of communication distance extension and communication reliability improvement. Then, the in-vivo THz communication including the channel modelling, modulation methods, and channel capacity has been studied (see Sec. VI-A1) BIB005 , BIB006 , BIB007 . The conducted research not only helps us understand the impact of human tissue on signal propagation but also assists researchers to estimate the received signal level which is a key indicator for the further information transmission.

A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Security in traditional wireless networks <s> Over the past 5 years, there has been a significant interest in employing terahertz (THz) technology, spectroscopy and imaging for security applications. There are three prime motivations for this interest: (a) THz radiation can detect concealed weapons since many non-metallic, non-polar materials are transparent to THz radiation; (b) target compounds such as explosives and illicit drugs have characteristic THz spectra that can be used to identify these compounds and (c) THz radiation poses no health risk for scanning of people. In this paper, stand-off interferometric imaging and sensing for the detection of explosives, weapons and drugs is emphasized. Future prospects of THz technology are discussed. <s> BIB001 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Security in traditional wireless networks <s> Nano communication is one of the fastest growing emerging research fields. In recent years, much progress has been achieved in developing nano machines supporting our needs in health care and other scenarios. However, experts agree that only the interaction among nano machines allows to address the very complex requirements in the field. Drug delivery and environmental control are only two of the many interesting application domains, which, at the same time, pose many new challenging problems. Very relevant communication concepts have been investigated such as RF radio communication in the terra hertz band or molecular communication based on transmitter molecules. Yet, one question has not been considered so far and that is nano communication security, i.e., will it be possible to protect such systems from manipulation by malicious parties? Our objective is to provide some first insights into the security challenges and to highlight some of the open research challenges in this field. The main observation is that especially for molecular communication existing security and cryptographic solutions might not be applicable. In this context, we coin the term biochemical cryptography that might lead to significant improvements in the field of molecular communication. We also point to relevant problems that have similarities with typical network architectures but also completely new challenges. <s> BIB002 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Security in traditional wireless networks <s> Incredible improvements in the field of nano-technologies have enabled nano-scale machines that promise new solutions for several applications in biomedical, industry and military fields. Some of these applications require or might exploit the potential advantages of communication and hence cooperative behavior of these nano-scale machines to achieve a common and challenging objective that exceeds the capabilities of a single device. Extensions to known wireless communication mechanisms as well as completely novel approaches have been investigated. Examples include RF radio communication in the terahertz band or molecular communication based on transmitter molecules. Yet, one question has not been considered so far and that is nano-communication security, i.e., how we can protect such systems from manipulation by malicious parties? Our objective in this paper is to provide some first insights into this new field and to highlight some of the open research challenges. We start from a discussion of classical security objectives and their relevance in nano-networking. Looking at the well-understood field of sensor networks, we derive requirements and investigate if and how available solutions can be applied to nano-communication. Our main observation is that, especially for molecular communication, existing security and cryptographic solutions might not be applicable. In this context, we coin the new term biochemical cryptography that might open a completely new research direction and lead to significant improvements in the field of molecular communication. We point out similarities with typical network architectures where they exist but also highlight completely new challenges where existing solutions do not apply. <s> BIB003 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Security in traditional wireless networks <s> In wireless body area network (BAN), node authentication is essential for trustworthy and reliable gathering of patient's critical health information. Traditional authentication solutions depend on prior trust among nodes whose establishment would require either key pre-distribution or non-intuitive participation by inexperienced users. Most existing non-cryptographic authentication schemes require advanced hardware or significant modifications to the system software, which are impractical for BANs. In this paper, for the first time, we propose a lightweight body area network authentication scheme BANA. Different from previous work, BANA does not depend on prior-trust among nodes and can be efficiently realized on commercial off-the-shelf low-end sensors. We achieve this by exploiting a unique physical layer characteristic naturally arising from the multi-path environment surrounding a BAN, i.e., the distinct received signal strength (RSS) variation behaviors among on-body channels and between on-body and off-body communication channels. Based on distinct RSS variations, BANA adopts clustering analysis to differentiate the signals from an attacker and a legitimate node. We also make use of multi-hop on-body channel characteristics to enhance the robustness of our authentication mechanism. The effectiveness of BANA is validated through extensive real-world experiments under various scenarios. It is shown that BANA can accurately identify multiple attackers with minimal amount of overhead. <s> BIB004 </s> A Comprehensive Survey on Hybrid Communication for Internet of Nano-Things in Context of Body-Centric Communications <s> A. Security in traditional wireless networks <s> This paper presents a study on physical layer authentication problem for in vivo nano networks at terahertz (THz) frequencies. A system model based on envisioned nano network for in vivo body-centric nano communication is considered and distance-dependent pathloss based authentication is performed. Experimental data collected from THz time-domain spectroscopy setup shows that pathloss can indeed be used as a device fingerprint. Furthermore, simulation results clearly show that given a maximum tolerable false alarm rate, detection rate up to any desired level can be achieved within the feasible region of the proposed method. It is anticipated that this paper will pave a new paradigm for secured, authenticated nano network for future applications, e.g., drug delivery and Internet of nano-things-based intelligent office. <s> BIB005

In traditional wireless networks, communication between legitimate nodes is prone to active and passive attacks by adversaries, due to the broadcast nature of the wireless medium. The literature have considered various kinds of attacks, e.g., impersonation attack, Sybil attack, Replay attack, Sinkhole attack, jamming, man-in-the-middle attack, denial of service attack, eavesdropping attacks, selfish/malicious relays in cooperative communication systems etc., and their potential (cryptography based) solutions. More recently, researchers have started to develop various security solutions at physical layer by exploiting the unique characteristics of the physical/wireless medium. Some of the most significant problems in physical layer security include intrusion detection/authentication, shared secret key generation, secrecy capacity maximization (for a wiretap channel), artificial noise generation, design of friendly jammers (in a cooperative communication system) etc. Keeping this context in mind, we evaluate the answer to the following question: do the aforementioned security solutions hold for the nano-scale communication? The answer is in negation for MC based nano networks because information exchange by using molecules instead of EM waves as carriers is a different regime altogether. On the other hand, we find that for EM based nano networks, operating at THz frequencies, some of the aforementioned concepts (if not the solutions) are still meaningful. BIB001 . However, THz based imaging systems are not the focus of this survey article. The survey articles BIB002 , BIB003 review some of the fundamental security mechanisms for THz systems and conclude that the traditional crypto based mechanisms could be ported to THz systems, but they need to be light weighted due to limited processing capabilities of the THz devices. The so-called BANA protocol proposed by Shi et. al. in BIB004 addresses the security needs of the micro-macro link of a body area network. In BIB005 , the authors consider a scenario where an onbody nano device communicates with inside-body nano device, while a malicious node attempts to send malicious/harmful data to the inside-body node. To this end, the authors utilize the measured pathloss as the fingerprint of transmit nano device to do the authentication at the physical layer. presents the device layout which consists of a micro-ring transceiver and a graphene based panda ring-resonator. The molecules are trapped in a whispering gallery mode, the polarized light is transceived and this device which could be used as a molecular RFID system.