Most of the indoor localization systems nowadays are based on received signal strength indication (RSSI), which has further increased the importance of precise localization of access points (AP) in a wireless local area network (WLAN). Since most existing AP localization algorithms suffer from a high error rate in practical scenarios due to multipath fading and temporal dynamics, we propose an AP localization algorithm based on the channel status information (CSI) sequence-based localization (SBL-CSI). The proposed algorithm SBL-CSI is an efficient localization method that consists of the following three major steps: Firstly, a 2D localization space is divided by special APs into distinct regions, and each region has a unique location sequence that represents the distance ranks of special APs to that region and constructs the location sequence table. Then, the relative distance of the ordinary AP, served in the location sequence, is obtained by using CSI between the ordinary AP and special AP. Finally, the “nearest” feasible sequence of the ordinary AP in the location sequence table is searched, and the centroid of the corresponding region is the ordinary AP’s localization. Compared with the traditional localization algorithm based on RSSI, the experiment results demonstrate that the positioning accuracy is improved approximately 24.31%. Wireless indoor positioning generates many applications based on geographical location in a wide range of life, production, business and public services. While the Global Positioning System (GPS) performs well in outdoor localization, it does not work effectively in indoor circumstances. A well-known bottleneck of the GPS indoor environment is that the transmission of the satellite signal  will be Due to the popularization of intelligent terminal equipment, indoor localization service  is one o(i)We exploit the CSI location sequence to stretch the limit towards RSSI value localization accuracy.(ii)We develop a sequence-based localization (SBL)-CSI localization framework, which leverages fine-gained PHY layer information to improve AP positioning performance.(iii)We conduct extensive experiments to show the feasibility of our design. The performance of the proposed design is evaluated by data collected in the experiment. The results show that SBL-CSI achieves better localization accuracy compared to SBL-RSSI.Despite the increasing sophistication of indoor localization systems, precise indoor localization is still a critical problem. In this paper, we research the localization of wireless access points, the significance of which is that with the development of high-density WLAN, the coordination and management of wireless networks has become a critical issue and determines the APs’ location by using their signals. For individual users, AP localization can help them access the AP’s location information and quickly connect to the network. For network administrators, AP localization makes a great contribution to network management, identifies additional APs and finds illegal APs . EspeciaThe remainder of this paper is structured as follows: the related works are briefly presented in Wireless localization in WLAN has attracted extensive research attention. Currently, there exist two types of wireless localization methods: range-based localization ,15,16,17Sequence-based localization (SBL)  is an inThe existing methods for positioning APs are mostly RSSI localization techniques. The work in  is basedIn order to improve the positioning accuracy, the state-of-the-art wireless localization schemes collect more data at many points and angles, which requires time and effort. This paper demonstrates that the sequence localization algorithm in  can indeIn this section, we introduce the application of the sequence location algorithm to position APs in WLAN. We first define the WLAN network model, followed by introducing the SBL localization algorithm.With the wide coverage of wireless APs in the indoor environment, users can access the Internet at anytime and anywhere via a portable wireless communication device. Sometimes, we need to know the location of APs, whose location is unknown. According to the ability to parse CSI, we divide APs into two categories: special AP and normal AP. Normal APs are commercially available wireless APs, but do not have the ability to parse CSI, and their location is unknown. Compared with normal APs, special APs are equipped with special configurations, such as having the configuration of the wireless network card and operating system to parse CSI, and their location can be known by GPS or other methods. Considered the cost of a special AP and the necessity of the location of all APs, there are only a few special APs’ locations that are known when deploying APs. To know the location information of some normal APs, we estimate the location of normal APs based on the special APs.N special APs are distributed in 2D localization space, where a perpendicular bisector is drawn between any two APs; there should be d between a centroid and special APs in the localization space, we can obtain the ordered sequence for that centroid with respect to the location of the special APs. We define the ordered sequence as the location sequence. Based on the above division, the location sequence of a given region is unique to that region . path propagates a shorter distance than the non-line-of-sight (NLOS) path and preferentially arrives at the receiver. Therefore, in the ideal case, the first bar in the CIR plot represents the energy of the LOS path. However, in fact, there is an uncertain time delay due to phase drift or other factors at the shortest time delay. This is effective data after the uncertain time delay. Therefore, there exists a situation where LOS path and NLOS path energy are superimposed on the same bar in the CIR graph, as shown in The noise signal has a significant impact on multipath elimination, which leads to the reduction of the positioning accuracy. However, since the interference signal consists of random noise and high frequency noise, it is unreasonable to simply consider the interference signal as random noise. If collected CSI values in complex environments are directly substituted into the ranging model, there will be a very large location error. Therefore, we eliminate the multipath fading effect before establishing the mapping relationship between CSI and distance. In order to calculate the effective CSI data, we first reduce the influence of random noise by linearly filtering the original frequency domain data and then use the Butterworth filter to filter out the environmental changes and other factors that lead to high frequency noise. • Linear filtering:i, then O is the noise, i-th subcarrier and N is the sample number of the fast Fourier transform (FFT).Due to the influence of random noise, the CSI phase information is rarely used for indoor positioning systems. In this paper, the obtained original CSI data are linearly transformed to mitigate the effect of random noise on the phase information. Assuming that p and q:The core idea of linear filtering is to eliminate the timing offset O, we can get a pure phase linear combination Ignoring the smaller measurement noise • Butterworth filtering:N-order Butterworth filter is generally expressed by Equation  method. An important aspect that needs to be identified before localization experiments is whether the CSI value can establish a relationship with the distance. d. LMS applied to the CSI versus distance data gives that n to evaluate the SBL-CSI technique.In this paper, we calibrate parameters S into three types. Secondly, we use the CSI measurement method to get the location sequence of ordinary AP and then calculate the Kendall’s Tau between the ordinary AP location sequence and the location sequences in table; according to the optimized correlation to obtain the maximum value of Algorithm 1Input: N special APs:   (1) The coordinates of S;(2) The boundary of localization space Output: Location sequence of all divided regions constitutes location sequence table;1:Use CSI measurement to get effective CSI value between ordinary AP and all special APs;2:for each do3:    Collect CSI data between ordinary AP and all special APs;4:    Denoise CSI data by using Butterworth filtering to filter out the high frequency noise;5:    Filter out time delay based on the time-domain LOS path identification method;6:end for7:Estimate the distance and calculate the location sequence of ordinary AP;8:Calculate the Kendall coefficient Equation ;9:for each do    10:end forreturn  11:Choose the centroid represented by the location sequence that has the This section combines the above two sections to give the algorithm of SBL-CSI, as shown in Algorithm 1. Firstly, the SBL algorithm is applied to get the location table of each region in 2D space. The perpendicular bisectors among special APs divide the boundary space In this section, we present the implementation and experimental evaluation of SBL-CSI. First, we describe the construction of the experimental scenario, and then, we compare and analyze the positioning results of SBL-RSSI and SBL-CSI in the experimental scene. Subsequently, by using the experimental results, we introduce the criterion to measure the positioning effect of different localization algorithms. Finally, we evaluate the influence of the number of special APs on the positioning error of the two localization algorithms.Based on the concrete working principle of the improved SBL algorithm described above, we deploy three or more special APs to collect CSI information for verifying the validity of the algorithm. As shown in The positioning results and positioning error are shown in In the case of the positioning effect evaluation, location error is a profound reference, and location error generally refers to the Euclidean distance between the estimated location and the physical location. The location error is described as:Since different numbers of APs have a great influence on the positioning results, we evaluate the performance of the algorithms fairly and effectively by using the average location error. To assess the effectiveness of the SBL-CSI localization approach, in the following, we compare the performance of our localization system with the counterpart SBL-RSSI method. The experiment is conducted in the laboratory where we place three or more special APs. In our experiment, there are many desks and chairs, even walking students. The set of experiment aims to study the effect of the number of special APs on the system performance. Indoor localization is one of the most promising technologies that can be widely applied to many fields, where RSSI-based schemes, for indoor localization, have drawn much attention. RSSI is easily affected by multipath fading. In this paper, we introduce SBL-CSI, a novel scheme based on fine-grained information, which uses channel state information for the accuracy of AP localization. We have conducted extensive experiments in the laboratory to prove the effectiveness of CSI in complex environments. The experimental results show that the accuracy of average location error can be significantly reduced by using CSI.


Synthetic lethality has attracted a lot of attentions in cancer therapeutics due to its utility in identifying new anticancer drug targets. Identifying synthetic lethal (SL) interactions is the key step towards the exploration of synthetic lethality in cancer treatment. However, biological experiments are faced with many challenges when identifying synthetic lethal interactions. Thus, it is necessary to develop computational methods which could serve as useful complements to biological experiments.In this paper, we propose a novel graph regularized self-representative matrix factorization (GRSMF) algorithm for synthetic lethal interaction prediction. GRSMF first learns the self-representations from the known SL interactions and further integrates the functional similarities among genes derived from Gene Ontology (GO). It can then effectively predict potential SL interactions by leveraging the information provided by known SL interactions and functional annotations of genes. Extensive experiments on the synthetic lethal interaction data downloaded from SynLethDB database demonstrate the superiority of our GRSMF in predicting potential synthetic lethal interactions, compared with other competing methods. Moreover, case studies of novel interactions are conducted in this paper for further evaluating the effectiveness of GRSMF in synthetic lethal interaction prediction.In this paper, we demonstrate that by adaptively exploiting the self-representation of original SL interaction data, and utilizing functional similarities among genes to enhance the learning of self-representation matrix, our GRSMF could predict potential SL interactions more accurately than other state-of-the-art SL interaction prediction methods. Cancers are complex diseases that caused by the defects of multiple genes. Exploring the genetic interactions within cancer cells is important for understanding the mechanisms of cancers. Synthetic lethality, which is a kind of genetic interaction, has attracted a lot of attentions in cancer therapeutics due to its utility in identifying new anticancer drug targets , 2. SyntRecently, various computational algorithms have been proposed to predict SL interactions . AccordiTo address the above problems, in this paper, we introduce a novel graph regularized self-representative matrix factorization (GRSMF) model for SL interaction prediction. Based on known SL interactions, our method focuses on learning a representation matrix from the original input data, which could capture the similarities between genes based on their SL interaction partners. Moreover, GRSMF also draws support from the function similarities among genes that derived from Gene Ontology (GO) annotations to enhance the prediction accuracy. Experiment results on SynLethDB dataset demonstrate that compared with other competing interaction prediction methods, our GRSMF model could achieve more accurate prediction results. Furthermore, case studies of predicting novel SL interactions also demonstrate the effectiveness of GRSMF in predicting SL interactions in human cancer.In this section, we demonstrate the performance of GRSMF on SynLethDB database . We perfWe test the performance of GRSMF and compare it with existing methods on SynLethDB database. We also use the GO similarity matrix as graph regularization term in GRSMF.https://decipher.sanger.ac.uk/, GenomeRNAi http://www.genomernai.org/[https://thebiogrid.org/ [Currently, SynLethDB is the most comprehensive database for human SL pairs. It collects SL pairs of human and other four model species from four different sources: (1) biochemical experiments, (2) related databases , (3) terid.org/  and 4)  https://As demonstrated in , functio2MF [In our experiments, we compare our proposed GRSMF against two existing methods, namely SL2MF . We chooSL2MF predicts the SL pairs based on logistic matrix factorization and it trains the model by assigning higher importance weights for known SL pairs than unknown pairs. The parameters c, λ and α are set to 50, 0.01 and 1.0 respectively. In addition, the number of nearest neighbors in GO similarity graph k1 is set to 150.BLM-NII was originally designed for drug-target interaction prediction. It was applied for SL prediction in [ction in  and thusSMF is a variant of GRSMF without the graph regularization. The parameter λ in SMF is set to 2−7.λ and β and we adopt grid search to select the optimal values for them from the range { 2−8,2−7,…,24,25}. In particular, λ and β are set to 2−7 and 2−5 respectively.For GRSMF, it has two parameters In addition, we adopt 5-fold cross-validation in our experiments for performance evaluation and comparison. The known SL pairs are equally split into 5 non-overlapping subsets. We iteratively use 1 subset for testing and the remaining for training in 5-fold cross validation and use the AUC score  as our evaluation metric.2MF (0.847) and SMF (0.893). In particular, we can also have the following two observations based on the comparison in Fig. Figure 2MF significantly, showing that self-representative matrix factorization is very effective for SL prediction. Unlike SL2MF that projects genes into a latent space and predict the SL interaction probability between two genes based on the inner product of their latent vectors, SMF adaptively learns the intra-similarities among genes from the observed SL interactions, according to representation rule introduced in Eq.  outperforms SLd in Eq. . Thus, SWe analyze the running time of various methods. All the experiments are conducted on a laptop with 3.6 GHz CPU and 32G memory. The results are shown in Table λ and β to control the influence of l2 regularization and graph regularization respectively. In this section, we study the impact of these parameters on GRSMF’s prediction performance.Recall that GRSMF has two parameters, namely, β as 2 −5 and set λ to different values. We can observe that the AUC scores of GRSMF under different λ values are quite close, indicating that our GRSMF model is not very sensitive to the parameter λ.In Fig. λ as 2 −7 and then investigate the impact of graph regularization using GO similarity. As shown in Fig. β usually lead to poor performance while small values  result in very good performance of GRSMF. Based on the results in Fig. In Fig. X in descending order based on their interaction scores predicted by GRSMF. Thus, the top-ranked pairs are more likely to be potential SL pairs. In Table We further take all the known SL pairs in SynLethDB as training data and apply GRSMF to predict novel SL pairs. In particular, we rank the unknown pairs in th pair) have back-up functions like DNA repair [th pair) is predicted as a potential SL pair.The gene XRCC2 is involved in the repair of DNA double-strand breaks by homologous recombination. The gene IGHMBP2 also has the functions including DNA binding, DNA recombination, DNA repair and DNA replication. XRCC2 and IGHMBP2  form SL interactions with the two breast cancer genes BRCA1 and BRCA2 . As showSynthetic lethality is a new angle for cancer therapeutics. Computational methods have been proposed to predict potential SL interactions, which can greatly reduce the costs of biological experiments. In this paper, we present a novel model, named graph regularized self-representative matrix factorization (GRSMF) algorithm, to identify potential SL interactions among genes. Our model focuses on self-representative matrix factorization and also integrates GO similarity matrix as graph regularization. Compared with previous matrix factorization models, we do not need to determine the dimensionality of the latent space and directly learn the similarities among genes based on observed SL interactions. Experiment results on SynLethDB database demonstrate that our GRSMF achieves better performance than other competing methods. Case studies on our predicted novel SL pairs show that our model can effectively identify some candidate SL pairs for further verification.In conclusion, revealing the molecular mechanisms underlying cancers is essential to the treatment of cancers and development of new anticancer drugs. Predicting potential SL interactions via computational approaches not only helps to improve our understanding of the mechanisms underlying cancers, but also provides a effective way to aided anticancer therapies. In this study, we provide an efficient model to predict potential SL interactions. In contrast to most existing matrix factorization models, our model avoids the determination of some sensitive hyper-parameters, which makes it easy to implement. Our model provides a promising strategy to predict potential SL interactions for further experimental verification, and contributes to the treatment of cancers. In the future, we plan to integrate biological knowledge such as pathways, protein domains, TCGA data, etc., to further improve our GRSMF model.In this section, we first describe the notations and formulate the problem, then we propose a novel graph regularized self-representative matrix factorization model and introduce a relaxed Majorization-Minimization algorithm to solve the optimization problem.n is the number of genes. A binary association matrix G. If there exists a validated SL interaction between genes gi and gj, Xij is set to 1; otherwise, Xij is set to 0. Here, gene pair  with Xij=0 is referred to as “unknown pair”, since there is no clear evidence to demonstrate whether there is an SL interaction between genes gi and gj or not. Note that gene pairs  and  are treated as the same pair, and we set Xii=0 for i=1,…,n. Therefore, X is a symmetric matrix with Xij=Xji.In this paper, a set of genes is denoted by G. Furthermore, based on the functional similarities between genes, we also incorporate a neighborhood regularization in our model to enhance the accuracy of prediction.Given a set of observed SL interactions, the problem of SL interaction prediction is to identify a set of gene pairs that are most likely to have SL interaction from the “unknown pairs”. This task can be achieved by ranking the candidate gene pairs according to the predicted SL propensities in descending orders, and selecting the top-ranked gene pairs as potential SL interactions. In this study, we propose a regularized self-representative matrix factorization model to identify the SL interactions among genes in X in which the data itself is treated as a dictionary, i.e., the input data X is self-represented by a linear combination of its columns as X≈XU, where U∈Rn×n denotes the coefficient matrix which is a meaningful representation of the columns of X. In this study, since the input data X is a symmetric matrix, the representations of its rows should be same as the representations of its columns. Thus, we propose a new model in which X is self-represented by linear combinations of its rows and columns as X≈UTXU. For the i-th gene gi, Uli can be used to denote the probability of gene gi being represented by gene gl, which captures the similarity between genes gi and gl based on their SL interactions with other genes. To guarantee the probability property of Ui· (which denotes the i-th column of U), we introduce constraints 0≤Uli≤1 and i=1,…,n. To avoid the trivial solution that only one element in Ui· has value 1 while all the other elements being zeros, we also impose a constraint on Ui·. In particular, we choose the l2 norm The proposed model is developed based on self-representative matrix factorization, which has been successfully used in subspace clustering . In tradHence, by taking into account the above constraints, we have the following regularized self-representative matrix factorization modelF is the Frobenius norm and λ is a tuning parameter which controls the influence of the l2 regularization.where ∥·∥U is learned from the original data matrix X, which makes it sensitive to the input data X. If the input data only covers very few known SL interactions (which means most of the elements in X are zeros), it may be hard to learn a comprehensive representation matrix. Therefore, we would like to incorporate some prior information that can reflect the similarities among genes into our model. In particular, based on the assumption that genes with similar functions tend to have similar presentations, we take into account the Gene Ontology (GO) semantic similarities among genes to promote the determination of representation matrix and improve the prediction performance. Let S∈Rn×n denote the GO similarity matrix where Sij describes the functional similarity between genes gi and gj. The value of Sij is ranging from 0 to 1, where the larger the value of Sij, the more similar the corresponding two genes. In this study, we adopt the method presented in [S is defined as followsIn the above objective function , the repented in  to calcuTr(·) denotes the trace of a matrix, D is a diagonal matrix with L=D−S.where By incorporating the above graph regularization term  into Eq.β controls the effect of graph regularization.where the parameter U denotes the gradient of our objective function with respect to U.In this study, we solve the objective function  based onU respectively. Then we have Let Uli≤1, we obtain the following updating rule for Uli:Due to the constraint ai and bi can be obtained by Eqs. where U can be updated by Eq. (e−4, i.e., t-th iteration. Finally, the predicted label matrix The details of the optimization algorithm are described in Algorithm 1. d by Eq. . In this


Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. The different systemic treatment approaches attempted in the last 35 years have not improved overall survival in the advanced stage. Targeted therapies assessed in clinical trials have failed to show efficacy against SCLC. Within the potentially interesting targets, the hepatocyte growth factor (HGF)/mesenchymal-epithelial transition (MET) pathway activation is associated with worse survival and chemoresistance in SCLC. Preclinical data suggest that the inhibition of the MET pathway can revert chemoresistance and prevent tumor growth. Recently, immunotherapy has shown modest but relevant activity in SCLC. Interestingly, MET modulation seems to be involved in increasing the efficacy of standard checkpoint inhibitors. Here, we review the preclinical and clinical data of MET inhibition in SCLC, and the role of this pathway in the immune response. Lung cancer is the most common cancer worldwide . Its incSCLC is the most aggressive type of lung cancer and it is highly linked to tobacco smoking ,7. CombiThe emergence of immunotherapy has represented the first shift in decades in the treatment of advanced SCLC, and checkpoint inhibitors have been recently approved by the Food and Drug Administration (FDA) for the treatment of this disease. Based on the results of the phase I/II trial CheckMate 032, the combination of nivolumab and ipilimumab was added as a recommendation in the National Comprehensive Cancer Network (NCCN) guidelines, and afterwards, nivolumab, as single-agent, was approved by the FDA in the third-line setting . MoreoveSCLC is characterized as having one of the highest rates of mutational tumor burden . HoweverMET was originally described in 1984 [MET is located in chromosome 7q21-q31 [The human proto-oncogene  in 1984 . After t7q21-q31 , and cod7q21-q31 . The MET7q21-q31 . By the time the MET receptor was characterized, its ligand had not yet been identified . Later, After binding to HGF, the MET receptor suffers a dimerization , which cUnder physiological conditions, the HGF/MET pathway mediates several cellular responses, such as cell migration  and tissHowever, aberrant activation of the MET pathway leads to increased cell motility and cell cycle progression and many other protumorigenic signaling , and hasMET and the metastatic potential of the overexpression of HGF in murine and human cancer cell lines [During the last three decades, the dysregulation of the HGF/MET pathway has been identified as a common characteristic in different types of human cancer. In the early 1990s, Rong et al. proved the tumorigenic feature of the oncogene ll lines ,43. Thisll lines . Later oll lines ,48,49,50The MET downstream signaling can be aberrantly enhanced by gene mutation or amplification, by protein overexpression, or in a ligand-dependent fashion. In 1997, Schmidt et al.  reportedAmong the acquired functions due to the aberrant activation of MET, the epithelial-mesenchymal transition (EMT) is of pronounced significance. EMT is a phenomenon whereby cancer cells suffer a loss of epithelial features and acquire a mesenchymal phenotype, conferring the capability to go through the boundaries of the tumor and metastasize . The driThe HGF/MET axis also plays a crucial role in resistance to targeted drugs. It has been show that HGF can induce tyrosine-kinase inhibitors resistance in lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations, presumably through cross-talk activation of the PI3K/AKT pathway ,63.In addition to its role in tumor cells, MET activation can also be observed in endothelial cells, promoting angiogenesis ,65, thusActivation of the HGF/MET axis has not only been shown to be a marker of aggressiveness in preclinical research. Several groups reported a decreased survival rate in cancer patients with an aberrant tumor expression of either MET or its ligand HGF, including SCLC patients ,68,69,70The first study to show the expression of MET in SCLC was conducted by Rygaard et al. in 1993 . They exThe role of the MET/HGF axis in SCLC was later elucidated via stimulation of SCLC cell lines with HGF. Maulik et al. found an increased tyrosine phosphorylation of MET, and an increase in cell motility (observed by the formation of filopodia) in response to HGF . They alIn light of the relevance of the HGF/MET axis activation in SCLC, several novel MET inhibitors were tested. SU11274 is a small molecule inhibitor of MET and it has been proved to be 50 times more selective for MET relatively to other kinases . SU11274MET mutant SCLC [MET targeting drugs were later tested in vivo. PHA665752 is a specific, small-molecule MET ATP-competitive inhibitor that also synergizes with the downstream specific mTOR inhibitor rapamycin . SCLC xeant SCLC .Once specific MET inhibitors were shown to be active in SCLC, further new strategies were evaluated. Prof. Salgia’s group  aimed toShortly after, a multikinase inhibitor was tested by our group  in combiIn spite of all the preclinical research of the efficacy of anti-MET therapy in SCLC developed in the last two decades, few clinical trials have been conducted, of which none delivered positive results. Tivantinib (ARQ-197) is a small-molecule inhibitor of MET . HoweverEfficacy of rilotumumab (anti-HGF) or ganitumab (anti-insulin-like growth factor 1 receptor) in combination with platinum-etoposide was assessed in first-line treatment in advanced stage SCLC. A phase Ib/II clinical trial  failed tFinally, a phase II clinical trial  evaluatiThe data available to this day regarding the importance of aberrant activation of the HGF/MET axis in SCLC supports the evaluation of the inhibition of this pathway as a therapeutic strategy. Initially, Ma et al. reported a prevalence of 12.5% in a cohort of 32 SCLC tumor samples : only onThere is increasing evidence of the role of the HGF/MET signaling in immune responses, and its potential effects in the immune compartment of the tumor microenvironment . As mentioned before, MET is highly expressed in many cancer types, acting as an epitope. As such, it can be recognized by cytotoxic CD8+ T cells, eliciting an activation toward tumor cells expressing MET . On the other hand, MET is not only expressed by cancer cells, but also in stromal and immune cells ,101. It MET is also expressed in neutrophils. Finisguerra et al.  showed tEven though these findings call for caution, the scenario changes when immunotherapy (anti-programmed death(PD)-1 agents) is added into the treatment regime. In a tumoral context, interleukin (IL)-17 from γδ T cells induce neutrophils’ ability to suppress cytotoxic CD8+ T cells . Glodde There is recent evidence suggesting that patients with MET exon 14 mutant lung cancer respond worse to immunotherapy ,108, furSCLC is a highly lethal malignancy with a dismal prognosis and little improvements have been achieved to date. In the last few years, the advent of immunotherapy has allowed us to witness the emergence of a small percentage of patients presenting a longer survival than expected. However, targeted therapies failed to show any progress and none of them are available for the treatment of patients with SCLC.There are currently around 120 clinical trials in active recruitment worldwide involving targeted therapies and immunotherapy in SCLC, including those basket trials for solid tumors, allowing for the inclusion of SCLC patients. Of those, none of them includes drugs targeting MET to our knowledge. In the past, only two trials attempted to block MET with a selective target SCLC population, and both were negative. Diverse explanations can be hypothesized for this failure. First, the anti-MET agents used had scarce preclinical data on SCLC. Rilotumumab (AMG-102) is a monoclonal antibody that prevents the HGF binding to the MET receptor; to the best of our knowledge there are no reports on preclinical data of rilotumumab in SCLC. Furthermore, given the consecutive negative results in several clinical trials and its increased toxicity, its mechanism of action was further studied. Greenall et al.  reportedImmunotherapy has shifted how cancer patients are treated nowadays, and SCLC patients are no exception. A combination of immunotherapy and MET-inhibitors seems a potentially promising strategy to be assessed regarding SCLC, irrespective of patients harboring MET overexpression/mutation. Adequate selection of patients for clinical trial success will require biomarker studies including MET activation, HGF expression, immune infiltrate evaluation, and others.In conclusion, we believe there is rationale for the evaluation of MET inhibitors with immunotherapy in SCLC. It is now time to design proper clinical trials and take this knowledge from the bench to the bedside.


Novel fluorinated polyhedral oligomeric silsesquioxane (POSS) acrylic copolymers were synthesized by the radical solution polymerization. The superhydrophobic coating was prepared using a one-step breath figure method. Chemical constitution, morphology, hydrophobicity, and anticorrosion ability of as-prepared coatings were investigated by the corresponding equipment. The addition of proper fluorinated POSS can synchronously promote the formation of the micro-nano convex structure and the enrichment of fluorinated groups on the surface. Compared to commercial acrylic coating, the fluorinated POSS coating presented enhanced anticorrosion performance. The impedance was the highest and the corrosion current density was the lowest for superhydrophobic coating with 25 wt % fluorinated POSS. Researches on superhydrophobic surfaces with a water contact angle (WCA) of more than 150° ,3, self-4 plasmachemical fluorination on the polybutadiene honeycomb surfaces with the contact angle increasing to 170°. The porous PS/SiO2 films were furthermore modified by chemical vapour deposition (CVD) of chlorotrimethylsilane on the film surface under 100 °C for 2 h to achieve the superhydrophobic behaviour [The porous structure is a typical topological structure with greater roughness than the flat film. The breath figures (BF) method is a self-assembly template technology and has been widely employed to form porous polymer films because of a reduction in the production time and costs . The watehaviour . ReducinOver the past decades, inspired from nature self-cleaning surface, a lot of surface structures have been proposed to be superhydrophobic, such as hierarchical stripes , hemisphPolyhedral oligomeric silsesquioxane (POSS), the smallest hybrid particle of silica , is a cuHere, a fluorinated POSS with seven fluorine-containing groups connected with the Si atom was synthesized and used to tune the amphipathic property of POSS-based polymer. Then, we proposed a one-step BF process for the fabrication of a superhydrophobic surface with the fluorinated POSS-acrylate random copolymer solution. The hierarchical and discrete convex structure of the superhydrophobic surface was constructed by taking advantage of the self-assembly of the fluorinated POSS in the forming process of BF pattern. The variation of surface topographies and wettability as a function of fluorinated POSS content was investigated. The electrochemical behaviours of the fabricated superhydrophobic surface were discussed in detail. The resultant superhydrophobic surface exhibits a remarkable marine anticorrosion ability. We believe this one step BF process may supply great convenience for constructing the superhydrophobic surface and extending its potential functional applications.3,3,3-trifluoropropyl trimethoxysilane (TFP-TMS) and 2-Perfluorohexyl ethyl methacrylate (PFHEMA) were purchased from Qinba Chemical Co., Ltd., Shanghai, China. Methylacrylatepropyl trichlorosilane (MAPTS) was supplied by Gelest. Methyl methacrylate (MMA) and butyl acrylate (BA) were obtained from BASF Chemical Co., Ltd., Tianjin, China. Acrylic acid (AA) was purchased from Damao Chemical Reagent Factory, Tianjin, China. Azobisisobutyronitrile (AIBN) was supplied by Kemiou Chemical Reagent Co., Ltd., Tianjin, China. Triethylamine, tetrahydrofuran, butyl acetate, xylene, 1,1,2-trifluorotrichloroethane, chloroform and sodium hydroxide were obtained from China National Medicines Co., Ltd. Calcium hydride was purchased from Aladdin Reagent Co., Ltd., Shanghai, China.7-(ONa)3, was synthesized using the method reported by Fukuda et al. [7-(ONa)3 as a white powder (38 g) in a quantitative yield. Second, 7F-MAP-POSS was prepared by following the method reported by Ke Zeng et al. [7-(ONa)3  and triethylamine  were charged to a flask equipped with a magnetic stirrer, 200 mL dry THF were added with vigorous stirring. The system was immersed into an ice-water bath and purged using highly pure nitrogen for 1 h. Then, Methylacrylatepropyl trichlorosilane  dissolved in 20 mL dry THF was slowly dropped within 30 min. After immersed in the ice-water bath for 4 h, the reactive system was taken out and held at room temperature for 20 h with vigorous stirring. The resultant precipitate was removed by centrifugal separation, and the supernatant fluid was concentrated by a rotary evaporator to obtain a crude product. The obtained 7F-MAP-POSS was washed 3 times with 50 mL methanol and dried in vacuum at 40 °C for 24 h, and 7.6 g of product was obtained. 29Si NMR  δ −67.61 , −69.94 , −69.44 , and −68.95 . 1H NMR  δ 0.62 , 0.92 , 1.18 , 1.86 , 6.03 , 2.13 , 4.06 , 6.03 , 5.50 .Methylacrylatepropyl hepta POSS was prepared through a typically two-step reaction . First, a et al. . 3,3,3-tg et al. . 7F-T7-, was placed into a flask equipped with a reflux condenser and a magnetic stirrer at 85 °C. Then the system was purged using highly pure nitrogen for 30 min. A mixture of MMA (4.4 g), BA (1.45 g), AA (0.02 g), AIBN (0.06 g) and the reaction solvent (1 g) was slowly dropped within 1h. After about 1h, the amount of the solution (1 g), trifluorotrichloroethane (3 g), 2-Perfluorooctane ethyl methacrylate (1.5 g) and AIBN (0.02 g) was added into the flask. After about 1h, the mixture of 7F-MAP-POSS , the reaction solvent  and AIBN  was added into the flask. After about 1 h, AIBN  and the reaction solvent (2 g) were added into the flask. After being stirred for another 4 h, the reactants were concentrated by a rotary evaporator. The resulting production was precipitated in cool methanol and dried under vacuum at 40 °C for 24 h. The obtained samples 1–4  were named as FAC, FPOSS10-FAC, FPOSS20-FAC and FPOSS25-FAC with the 7F-MAP-POSS content of 0, 10, 20 and 25 wt %, respectively.The 7F-MAP-POSS-Acrylate copolymers were prepared by the radical solution polymerization . The reaFirstly, the Q235 steel sheets were cleaned by successively wiping the surface with absolute ethanol and chloroform and dried under atmosphere. Then, 7F-MAP-POSS-Acrylate copolymer solutions of fixed volume in chloroform were directly cast onto the Q235 steel substrates. The wet coatings were blown by the humid air (relative humidity ~85% at room temperature) containing micro ultrasonic atomized water droplets using the assembled equipment shown in −1. The samples were prepared by following the KBr pellet method. 29Si NMR and 1H NMR spectrum of 7F-MAP-POSS before and after copolymerization process were recorded on a 500MHz AVANCE III spectrometer  using CDCl3 as a solvent. A gel permeation chromatography (GPC) system  was calibrated with narrow molecular weight polystyrene standards. The resulting calibration curves were used to estimate the molecular weights and polydispersity (PD) of 7F-MAP-POSS-Acrylate copolymers. THF was introduced as the mobile phase at a flow rate of 1.0 mL/min. The concentrations of samples were 5.0 mg × mL−1, and the injection volume was 100 μL for each analysis. The columns and detector were maintained at 40 °C. Contact angles (CA) were measured using SL200KS contact angle analyzer  that had a CCD camera equipped for image capture.Fourier transform infrared (FT-IR) spectrum of F-POSS and F-POSS-Acrylate copolymer were measured by a TENSOR 27 FT-IR spectrometer  from 400 to 4000 cmScanning electron microscopy (SEM) images and energy dispersive spectrum (EDS) were taken using a JSM-6700F scanning electron microscope . The surface morphology of the films was observed after gold was sputtered onto the surfaces.5 Hz–10−2 Hz. Prior to electrochemical tests, the specimens with 1 cm2 area exposure were immersed in 3.5% NaCl aqueous solution for more than 30 min to stabilize the system. All of the EIS data were fitted and analysed through ZSimpWin software. The polarization curves were recorded at a scan rate of 0.5 mV/s in the applied potential range from −250 to 250 mV. Corrosion potential, Ecorr, current and icorr, were derived from the potentiodynamic polarization curves after Tafel extrapolation.All the electrochemical tests were performed with AMETEK PARSTAT 4000 by immersing the specimens into a 3.5% NaCl aqueous solution. In a typical process, a standard three-electrode system equipped with a saturated calomel reference electrode, Pt plate as a counter electrode and specimen as the working electrode were employed. The electrochemical impedance spectroscopy (EIS) was carried out at open circuit potential (OCP) in the frequency range of 1029Si NMR spectroscopy was used to demonstrate the formation of an octameric silsesquioxane cage. The resonance at −67.61 ppm is assignable to the corner silicon atom connected to methylacrylatepropyl group [The chemical composite and structure of 7F-MAP-POSS and 7F-MAP-POSS acrylate copolymers were characterized by NMR and FTIR. As shown in yl group , while tyl group , it is c2CH2CF3) and 2.13 (–CH2CF3) for 7F-MAP-POSS [3O– were found indicating the successful polymerization of MMA. The signal at 3.80–4.15 ppm from –CH2CH2O– and 2.26 ppm assigned to –CH2CH2–CF2– can confirm the successful polymerization of PFHEMA. The polymerization of BA can be proved by the signal at 3.80–4.15 ppm (–CH2CH2O–), 1.25–1.81 ppm (–CH2CH2–CH2–) and 0.84 ppm (–CH3). Unfortunately, the polymerization of AA cannot be confirmed from the 1H NMR spectrum because of the minimal addition. The FT-IR spectrum of MAP-TS, 7F-T7-(ONa)3, 7F-MAP-POSS and as-prepared copolymers were shown in −1 are attributed to Si-O-Si and C-F groups, respectively. The appearance of the MAP group in the structure of 7F-MAP-POSS can be proved by strong vibration bands at 1730 cm−1 (C=O) and 2960 cm−1 (CH3). Meanwhile, the peaks in the range of 3400–3600 cm−1 (OH) in spectra of MAP-TS and 7F-T7-(ONa)3 are disappeared in 7F-MAP-POSS due to the complete corner-capping reaction between MAP-TS and 7F-T7-(ONa)3. For the copolymers, the characteristic bands at 1737 cm−1 is assigned to the carbonyl group in MMA, PFHEMA, BA, AA and 7F-MAP-POSS units, while the bands at 1240 cm−1 are attributed to C-F group. The peak at 1141 cm−1 is due to the combination of stretching vibration of C-O-C and Si-O-Si. The NMR and FTIR analysis verified the successful synthesis of 7F-MAP-POSS and FPOSS-FACs.The chemical structure of 7F-MAP-POSS acrylate copolymer is confirmed by comparison of its 1H NMR spectrum in MAP-POSS , the app−1 for FAC to 31,378 g·mol−1 for FPOSS20-FAC with a little wide PDI of 1.9–2.0. However, the molecular weights were decrease to 29,415 g·mol−1 for FPOSS25-FAC when the 7F-MAP-POSS. Therefore, the obtained results indicate that 7F-MAP-POSS is successfully reacted with the other acrylate monomers to form a 7F-MAP-POSS-Acrylate copolymer.On the other hand, the molecular weights and their polydispersity (PDI) of FAC and 7F-MAP-POSS-Acrylate copolymers are calculated from GPC curves . With thThe 7F-MAP-POSS-Acrylate copolymer coatings cast from chloroform under a flow of humid air were investigated via SEM. As shown in EDS was performed to analyse the elemental chemistry of the as-prepared surfaces and the result was shown in To investigate the roughness of FPOSS-FAC film with different 7F-MAP-POSS contents, AFM was performed on the surfaces, and the results were shown in According to Cassie’s law :cosθ*=ØsAlthough the procedure is simple, the formation mechanism of BF arrays is very complicated. According to the above analysis, the formation mechanism of micro-nano structure with low surface energy using the one step BF method was deduced and illustrated by Tafel curves and EIS data are two main methods for the evaluation of material corrosion situation . For comcorr (−0.424 V) and the highest icorr (4.43 × 10−7 A cm−2), which indicated the fluorinated coating could obviously enhance the Ecorr and reduce the icorr values. Especially, for the FPOSS25-FAC specimen, the icorr value was 1–2 orders of magnitude lower than that of other coatings. This could be explained by the highest water repellency due to the formation of micro and nanostructures. Furthermore, the inhibition efficiency (IE) was consistent with the evolution of icorr value, the result of which were 96.44% (AC), 99.22% (FPOSS10-FAC), 99.83% (FPOSS20-FAC) and 99.98% (FPOSS25-FAC), suggesting the addition of 25 wt % 7F-MAP-POSS produced the best shielding effect for Q235 substrate.Obviously, the Tafel curves of these coating systems shifted to the positive direction compared with Q235 steel, suggesting that the coatings as a shield could effectively restrain the corrosion of Q235 steel . In the 0.01 Hz was broadly used to evaluate the barrier ability of coating [0.01 Hz is, the more outstanding the anticorrosion ability is [0.01 Hz decreased with the increased of immersion time for all coatings, which was because of the permeation of corrosion medium. The |Z|0.01 Hz of the commercial acrylic coating was about 4.51 × 104 Ω cm2 during the initial stage of immersion (24 h) and then decreased to 1.43 × 104 Ω cm2 after 7 d immersion , the highest Ecorr (−0.320 V), the highest |Z|0.01 Hz (2.16 × 107 Ω cm2), the highest Rc 1.62 × 106 Ω cm2 and the highest Rct (1.26 × 107 Ω cm2) after immersion of 7 d in 3.5% NaCl solution. In summary, this experimental study proposed a facile one-step breath method to prepare the superhydrophobic coating using a fluorinated POSS acrylic copolymer, which has a potential application in the anticorrosion area.A superhydrophobic coating was successfully fabricated by BF method using an acrylic copolymer containing fluorinated POSS (P(MMA-BA-AA-PFHEMA-7F-MAP-POSS)). The enhanced hydrophobicity of the copolymer synchronously promoted the coalescence of the droplet to form the micro-nano convex structure and the enrichment of fluorinated groups on the surface to reduce the surface energy. The as-prepared superhydrophobic coating owned the lowest the lowest i


The Fermi energy lies in the range of 1.1 eV to 1.4 eV for NaxSi136 and increases as stoichiometry (x) is tuned from 8 to 12 to 16. The determined isotropic “Mexican-hat” shape of the guest-host potential describing Na motion in the Si28 cage indicates the “off-center” position when the temperature is elevated beyond zero. Accordingly, the calculated Na “off-center” displacements correlate well with the X-Ray Diffraction (XRD) data (0.4 Å–0.5 Å) for a similar composition range (0 < x < 24). The lack of first-principles analysis on quartic anharmonicity motivates us to initiate a self-consistent model to examine the temperature-dependent rattling frequency Ω(T) of the guest . The predicted values of Ω(T) for Na24Si136 at 300 K are significantly higher (approximately six times larger) than the value at absolute zero, which contrasts with the case of Rb8Si136. Moreover, underestimation of the isotropic atomic displacement parameter Uiso is caused by the temperature-dependent quartic anharmonicity of Na, and this discrepancy might be offset by the square of the “off-center” displacement.Electronic, vibrational, and anharmonic studies on some binary clathrate A Each cage can trap an impurity (“guest”) atom, which is usually from column I or column II of the periodic table. Several type-II clathrates have been synthesized with Si, Ge, or Sn on the framework lattice. The encapsulated guests are weakly bound to the host lattice, which means that their vibrational modes are expected to occur at very low frequencies. Several different type-II Si-based binary clathrates have been synthesized, including NaxSi136 , KxSi136 , and Na168Si136, and many of their properties have been measured . On the other hand, D(q) can still be calculated for nonzero q if it is assumed that the matrix elements of D(q) vanish for atoms separated by a distance greater than the third nearest neighbor distance [k-point grid utilizing the k-points along certain high-symmetry directions is adopted to compute D(q). Second, it is clear that the diagonalization of D(q) allows us to find the vibrational eigenvalues (squared frequencies) and eigenvectors.In the following, we apply our approach to analyze the vibrational features of A16Rb8Si136 and K16Rb8Si136 is presented in [E) at an energy scale of several kBT, which is indicative of the temperature-dependent Knight shift effect observed experimentally for the NMR-active nuclei in Na16Rb8Si136 [xSi136 , which shows an analogous quasi-activation energy ΔE when taking the T-dependent Knight shift into consideration. 8Si136 and Na16Si136, where the corresponding Fermi energies are denoted by EF,2 and EF,4. Here, quasi-activation energy ΔE2,4 is predicted to lie in the range of approximately 0.4 eV to 0.46 eV. Moreover, the predicted ΔE2 of Na8Si136 and ΔE4 of Na16Si136 are similar to that of K16Rb8Si136 (ΔE ~ 0.41 eV) from a previous work [For the purpose of revealing how guest-framework interactions affect the electronic and vibrational properties of clathrate lattices, we initiate our beginning step to provide an EDOS study for the optimized geometries. A previous comprehensive description of the electronic structure associated with Naented in , where KRb8Si136 . Therefoous work .12Si136, we found the existence of a direct “pseudogap,” which is defined as the energy difference between the top of the valence band and the bottom of the conduction band at the same L point from the band structure (BS) perspective. Specifically, our DFT computation shows that the pseudogap is approximately equal to 0.48 eV. In view of the filled intermetallic clathrate NaxSi136 system is understood through the variation of the Fermi energy level, whose position is shifted into a deep portion of the conduction band as x ranges from 8 to 12 and 16 in x. In particular, the energy states occupying the valence band in three materials seem to be populated in a significantly consistent manner.One of the electronic characteristics of the NaxSi136  can reveal very interesting basic physics, such as lattice dynamics and guest-host coupling. The main idea of the “rattler” concept originates from the fact that loosely bound guest atoms encapsulated in the “oversized” (28-atom) cages in the type-II clathrates vibrate and produce “localized” modes that are capable of efficiently scattering heat-carrying acoustic phonons [Calculations of the “rattling” vibrational modes of the alkali metal atom guests in A phonons ,27. Thusersized” -atom cagxSi136 is divided into two parts, as follows. First, the VASP code is used to calculate the phonon dispersion curves, along with the effective potential energy diagrams, which may contain apparent anharmonicity at zero temperature, depending on the guest (A) type. Second, the significant anharmonicity of the motion of the Na rattling guests in the Si28 cages in NaxSi136 is investigated in detail with the aid of a self-consistent phonon model to reveal its temperature dependence. The results predict that these anharmonic effects can strongly affect the force constants for the guest vibrational modes.Our study of the vibrational properties of the filled clathrate A4Si136 agrees fairly well with the data obtained from inelastic neutron scattering (INS) experiments [−1, which are approximately 4% lower than that of the experimentally observed mode (52 cm−1). In addition, an effective force constant K for the rattling frequency ω in the harmonic approximation (HA) may be obtained by assuming ω = (K/M)1/2, where M is the atomic mass of the guest. For Na4Si136, this gives K = 0.44 eV/Å2 from the first-principles viewpoint for the Na vibrations in the Si28 cages.The LDA-calculated result correlating to the guest vibrational mode from the phonon dispersion relations in Naeriments . Specifi28 cages, we carried out a method that can be summarized as follows. Using the LDA to generate the effective guest-host potential energy for an Na guest in an Si28 cage acts as the first step. Then, to approximately treat the lowest order anharmonic effects present in the guest-host interaction, we expand this effective potential in a power series in the guest atom displacements, keeping only the second and fourth order terms. That is, we assume that the guest-host potential energy Veff can be approximately written as Veff = ½ Kisor2 + ¼ Ɛisor4, where r is the displacement from equilibrium and Kiso and Ɛiso represents empirical constants determined by fitting to the effective potential energy. Only even order terms are kept in this polynomial expansion because of the symmetry of the energy function.To gain insight into the anharmonic effects associated with the Na guest vibrations in the Si28 cage while keeping all remaining atoms in the unit cell fixed. More concretely, each Na is displaced a distance from the center of the Si28 cage. In all cases, this displacement distance is strictly restricted to the range of 0 to Δr, where the upper limit Δr describes the “excess” radius of that cage. Our previous work [28 cage is Δr = 1.83 Å for Na vibrations. Therefore, our calculation is performed in the NaxSi136 system for Na guests moving in the X direction, but limited to the range of 0 to approximately 1.2 Å and repeated for guest compositions x = 4, 8, and 24. In the coordinate system considered here, the X and Y axes are chosen to be aligned in a plane that is parallel to the plane of the hexagon, while the Z axis is perpendicular to the hexagon in the 28-atom cage. The resulting effective potential energy curves for the compositions x = 4, 8, and 24 are shown in In this paper, the procedure used to determine the guest-host framework effective potential energy curves displaces one Na guest atom inside an Sious work ,26 showe4Si136 and Na8Si136, the results of this procedure predict that the effective potential energy has an obvious “bump” at the cage center (zero Na displacement in Si28). Additionally, each of these energy curves in NaxSi136  has a “Mexican-hat”  shape. This form of the potential energy shape shows that Na guests in the Si28 cages are dynamically unstable at the cage center. Thus, these calculations predict that, at elevated temperatures, thermal excitation can induce Na guests to move off the cage center to a site with a lower potential energy. In other words, these calculations find that the “localized” off-center minimum valley of the effective potential curve is approximately 0.017 eV and 0.01 eV below zero for Na4Si136 and Na8Si136, respectively. That is, the effective potential energy valley depth is predicted to be approximately 0.66 kBT and 0.39 kBT at room temperature for Na4Si136 and Na8Si136, respectively. It is likely that the minimum energy valley causes the “off-center” position of Na guest to form due to increased temperature. This kind of anharmonic effect might be correlated with the measured strong temperature dependence of the isotropic atomic displacement parameter Uiso, as reported in References [Here, for Naferences ,30.28 cages in NaxSi136 can, in principle, be correlated with the experimentally measured guest equilibrium location at various temperatures. However, the disorder of the guest position makes the understanding of such “off-center” sites complex. Similar effects have been observed in some type-I clathrates, including Sr8Ga16Ge30, Ba8Ga16Ge30, and Eu8Ga16Ge30 [24Si136 compared to others.This predicted “off-center” position for Na in the SiGa16Ge30 ,25,27,31xSi136 by Beekman and collaborators focused on detecting the isotropic, “off-center” displacement of Na in Si136 and studying the system in significant detail [28 showed a nearly x-independent “off-center” displacement measured to be approximately 0.4–0.5 Å [28 are shown as a function of guest stoichiometry amount x. For cases x = 12 and x = 16, these calculations predict an isotropic displacement that ranges from 0.50 Å for Na12Si136 to 0.42 Å for Na16Si136. Another report [28) in the presence of the above discussed anharmonic guest-host potential energy, which causes the “off-center” displacement of the guests to appear.Considerable experimental work on Nat detail ,33,34,35.4–0.5 Å . Our fir136, we show the isotropic guest-framework effective potentials for K8Si136, Rb8Si136, and Cs8Si136 ) at 300 K appearing in ΩT = 300 K) can be quantitatively understood by correlating the thermal displacement Uiso to the spring constant and quartic anharmonic coefficient arising from potential energy Veff: MΩ2(T) = Kiso + Ɛiso<u2>. Here, the average mean square amplitude of the phonon atomic displacement <u2> (= Uiso) relating to the wavevector (k) and phonon branch (j) is defined via the Debye model [M denotes the atomic mass of the guest rattler.To examine the anharmonic effects in the guest-host interaction, the self-consistent phonon (SCP) model  is used ye model , and M d28 polyhedron cage, a very slight variation in temperature-dependent Ω(T) is observed for the localized Rb impurity in u2>. Our numerical results describing Ω(T) in −1 (≈5.27 meV) for the Rb vibration frequency at T = 0, which is approximately 4.2% smaller than that obtained at T = 300 K. However, the predicted values of Ω(T) at 300 K are significantly higher than that at absolute zero for sodium filled clathrate. This strong temperature dependence of Ω(T) in Na24Si136 indicates that static disorder effects might impact the isotropic atomic displacement parameters (ADPs). In other words, the average mean square isotropic atomic displacement for Na that resides in the “off-center” system has a boosted value, compared to <u2> for the “on-center” vibration at the same temperature. Our work predicts that this difference in thermal average <u2> is nearly close to the square of the “off-center” displacement investigated above > for Na@Si28 in NaxSi136 might be attributable to thermal excitation, which causes the guest to explore the minimum of the “Mexican-hat” shape potential (see Ω(T) at room temperature instead of the DFT-calculated rattling mode ωph when considering the harmonic oscillator model [ΩT = 300 K) obtained at 300 K. This difference in frequency can lead to differences with respect to the corresponding atomic displacement parameters Uiso. To account for this discrepancy, this effect is interpreted in the picture of the thermal displacement parameter while taking “off-center” displacement due to static disorder into account. Mathematically, we postulate that the relation Uiso(ΩT = 300 K) ≈ Uiso(ωph) + d2 can be used to account for the existence of the strong ADPs observed by means of XRD, INS, or temperature-dependent heat capacity (Cp) measurements [ΩT = 300 K) = kBT/Mω2 within a high-temperature approximation [4Si136, the calculation leads to the corresponding ADPs, which give approximately 0.497 Å2 and 0.122 Å2 for Uiso(ΩT = 300K) and Uiso(ωph) in Na4Si136, respectively. Therefore, the calculated Na “off-center” displacement d in Na4Si136 is approximately equal to 0.61 Å, which is reasonably comparable to the experimental counterpart (~0.52 Å) found in d value by virtue of the suggested model for Na24Si136 is 0.28 Å, which is in good agreement with the results estimated by Rietveld analysis in Ref. [24Si136 , while a similar effect characterized by a “double-peak” along with a dip near the Fermi energy in the EDOS calculation is observed in Na8Si136 and Na16Si136, in analogy to the 16Rb8Si136 case reported previously. Using an effective potential-energy curve to explore the Na vibration in the Si28 cage, we point out the existence of a dynamically unstable state in the “double-well” structure. This is also indicative of an “off-center” displacement for guests subjected to elevated temperatures. In addition, the guest vibrations are nearly isotropic in the same stoichiometry NaxSi136 (0 < x ≤ 24), independent of the composition x. Furthermore, the DFT-determined “off-center” displacement for the Na vibration in the Si28 cages is nearly independent of guest content, in fair agreement with the XRD data. It is noted that the quartic anharmonicity effect induced by the guest-framework interaction becomes comparably weakened when the ratio of the lowest even anharmonic coefficient to the spring constant decreases in the A8Si136 system. Making use of the SCP model, the determined temperature-dependent rattling frequency Ω(T) of Na in Na24Si136 implies strong static disorder effects associated with the average mean square isotropic atomic displacement Uiso. This is manifested by the fact that the values of Ω(T) for Na at 300 K are approximately six times larger than the value at absolute zero. To account for the experimental overestimation of Uiso at room temperature, we suggest that the existence of strong ADPs observed by means of XRD, INS, or temperature-dependent heat capacity (Cp) measurements in apparently anharmonic clathrate Na24Si136 is offset by the square of the Na “off-center” displacement in the Si28 cage. Considering the ability of tuning the alkaline guest (A) species and its composition x in such a “cage-structured” configuration of AxSi136, theoretical investigation on the corresponding rattling behavior, as well as guest “off-center” displacement, may contribute to boosting the search for novel thermoelectric materials. A good performance of TE material is manifested and parameterized by high electric conductivity and low thermal conductivity, according to “Phonon Glass Electron Crystal” criteria [We have employed criteria  presents


Improper use of antibiotics leads to the emergence of resistant microorganisms as well as drug toxicity, increased healthcare costs, morbidity and mortality. Globally, an estimated 25–68% of hospitalized patients receive suboptimal antibiotic regimes. Information on the extent of this problem in Ghana is currently limited, particularly in surgical units. To strategize for interventions, we estimated the antibiotic use prevalence in surgical departments in a country-wide point prevalence survey (PPS) in Ghana.Between October 2016 and December 2016, we conducted a cross-sectional multi-center country-wide PPS. This involved an audit of in-patients’ records from all units/departments of ten systematically selected hospitals in Ghana. Data were collected with a standardized questionnaire, adopted from the European Centre for Disease Prevention and Control. In this report, we present data on antibiotic use from the surgical units.Of 2107 eligible patients included in the PPS, 540 patients were identified in surgical units, of which 70.7% (382/540) received antibiotic therapy. A total of 636 antibiotic prescriptions were issued to these surgical patients; 224 (58.6%) for treatment, including 50 for treatment of hospital-acquired infections, and 144 (37.7%) for prophylaxis . Median duration of antibiotic therapy prior to the survey was 5 days (interquartile range (IQR): 3-8 days). Surgical prophylaxis was administered for longer than the recommended one day in 107 of 144 (88.4%) patients. The choice of antibiotics was largely similar for community- and hospital-acquired infections as well as for prophylaxis. Only 3.7% of patients had microbiological analysis done on clinical samples.We found a high prevalence of antibiotic use, with the choice of antibiotics, in some cases, inconsistent with the country’s treatment guidelines. Antibiotics were administered for long duration including antibiotics for prophylactic purposes and the majority was started without supporting microbiological analysis. Prescription practices that encourage rational use of antibiotics guided by microbiology and enforcement of antibiotic policy guidelines should be the target for future interventions.The online version of this article (10.1186/s12889-019-7162-x) contains supplementary material, which is available to authorized users. Correct use of antimicrobials, including antibiotics, can be defined as “the cost-effective use of antimicrobials which maximizes clinical therapeutic effect, while minimizing both drug-related toxicity and the development of antimicrobial resistance” . A recenIt is generally thought that inappropriate use of antimicrobials in healthcare facilities is widespread in LMIC but there are relatively few studies in limited geographical areas to document this. Generally, antimicrobial prescribing in hospitals, is said to be suboptimal in 25–68% of cases , 5, 6, aThe present study aims to estimate the prevalence of antibiotic use in surgical departments at all levels of the healthcare system in Ghana and examine its variation according to patient-related and care-related characteristics. The prevalence of multidrug resistant bacteria is widespread in Ghana, higher in the regional hospitals than in the teaching hospitals , and a rWe analyzed a recent cross-sectional multi-center country-wide point prevalence study (PPS) of hospital acquired infections conducted at selected hospitals under the Ghana Health Service/Ministry of Health between September and December 2016 . The PPSOverall in Ghana, there are 3 teaching hospitals, 10 regional hospitals and 162 district hospitals in the public health sector, with a total bed capacity of 12,806 and a 60.4% occupancy rate. District hospitals form the first referral point from health centers, with a 50–60 bed capacity and facilities for primary clinical care. Regional hospitals form the secondary level for healthcare, providing specialized care and with a 150–200 bed capacity. Tertiary hospitals provide complex tertiary care with availability of varied surgical specialties, a bed capacity ranging from 1000 to 2000 .Ten representative hospitals , one from each region, were selected across Ghana using a systematic sampling design adopted from the European Centre for Disease Prevention and Control (ECDC) methodology , 15. TheWe included all patients on admission for a surgical specialty, irrespective of the ward they were admitted on, in the selected hospitals before 8 a.m. on the day of the survey and who had not been discharged from the ward at the time of the survey. We excluded patients admitted after 8 a.m., patients undergoing same day treatment or surgery; out-patients including dialysis patients; and patients in the accident and emergency departments, except for wards attached to these departments where patients are monitored for more than 24 h.The survey was conducted in a single day over a 12-h period for all hospitals, except for hospitals with large bed capacity (> 1000), where two or three days were used. In these large hospitals however, the survey in a designated department or unit was conducted within a 12-h period, that is 8 a.m. to 8 p.m. on a specified date.Five personnel at each survey site, usually members of the hospital’s quality assurance team or infection control team, were recruited and trained on the data collection tool, to join the HAI Ghana research team in data collection.Data were collected from available medical and nursing records using a modified version of the ECDC data collection tool . From thP-values< 0.05 were considered statistically significant.Data was extracted from the multi-center country-wide study  and enteIn total, 540 patients were admitted to surgical units in the ten selected hospitals surveyed with the following distribution by hospital category: tertiary 47% (254), regional 18.5% (100) and district 34.4% (186). The median age was 39 years (range 3 days- 89 years [Interquartile range (IQR): 20-56 years]) and the male: female ratio was 1.7:1 Admissions to the general surgical units accounted for 71.5% (386) of patients, followed by 11.3% to the orthopedics and trauma units . For patients on antibiotic for treatment, the median duration of stay prior to the survey was 9 days  and for patients on antibiotic prophylaxis, it was 6 days ) received antibiotics, with an average of 1.66 prescriptions per patient. Among the 382 patients receiving antibiotics, 44.2% (169) were on one antibiotic, 46.6% (178) on two antibiotics, 7.6% (29) on three and 1.6% (6) were on four antibiotics  and (2) Presence of a healthcare associated infection (HAI) . Patients admitted for a urological specialty also had a significantly increased prevalence of antibiotic use . In contrast, the hospital type, patient age, sex and disease severity were not associated with antibiotic use  Surgical procedure done or not : Penicillins, cephalosporins and carbapenems (meropenem) were used more in tertiary level facilities , whereas β-lactam/ β-lactamase inhibitors were used more in district hospitals . The use of nitroimidazoles, fluoroquinolones, lincosamides and penicillins did not differ between hospital levels  ), 2nd and 3rd generations cephalosporins (cefuroxime and ceftriaxone respectively) (20.0% (127)), β-lactam/βlactamase inhibitors (amoxicillin/clavulanic acid) (16.7% (106)), fluoroquinolones (ciprofloxacin and levofloxacin) (12.3% (78)) and lincosamides (clindamycin) (10.2% (65)). The different antibiotic combinations use by groups is shown in Additional file The most commonly used antibiotics for treatment of both community- and hospital-acquired infections were cephalosporins, amoxicillin-clavulanic acid, clindamycin, ciprofloxacin and metronidazole Table . The samp = 0.7).Patients were prescribed antibiotics for treatment of infections (58.6% (224/382)) or for prophylaxis (37.7% (144/382)), and for 14 patients there were no recorded reason for antibiotic therapy. Of patients prescribed antibiotics for treatment, 77.7% (174/224) were given for community acquired infections – including cellulitis, osteomyelitis, septicemia, urinary tract infections, pyelonephritis, intracerebral abscesses and peritonitis due to typhoid ileitis with perforation, appendix abscesses and perforated duodenal ulcers; and 22.3% (50/224) for hospital acquired infections. Of the antibiotics used for prophylaxis, 16% (23/144) were given for medical prophylaxis and 84% (121/144) for surgical prophylaxis. The contribution of surgical prophylaxis to the total antibiotic usage was 32% (121 of 382 patients given antibiotics). For surgical prophylaxis, 88.4% (107/121) of the patients received antibiotics for more than one day, 9.9% (12/121) for one day and 1.6% (2/121) as a single dose. The distribution between antibiotic use for community- and hospital-acquired infections and prophylactic use was similar at district, regional and tertiary facilities  than orally (46%). For individual antibiotic agents, nitroimidazoles (metronidazole) were mainly given by the parenteral route (67%), whereas β-lactam/β-lactamase inhibitors (amoxicillin/clavulanic acid) were mainly given orally 53%). All 3rd generation cephalosporins (ceftriaxone) were given parenterally and 2nd generation cephalosporins (cefuroxime) were given both orally and parenterally  (62.5% (140/224)) and gastrointestinal tract (GIT) (9.8% (22/224)). For prophylaxis, 51.4% (74/144) and 25% (36/144) were given to prevent infections of SSTBJ and GIT infections, respectively. This picture was similar across hospital levels. Of note, cephalosporins (cefuroxime), β-lactam/βlactamase inhibitors, clindamycin and metronidazole use dominated treatment of skin, soft tissue, bone and joint infections whereas fluoroquinolone and metronidazole dominated treatment of gastro-intestinal tract infections . It was 4 days  in district hospitals, with a wider range of 1–89 days  in tertiary level hospitals.The median duration of antibiotic therapy prior to the survey was five days (IQR 3–8 days) with differences across different hospital levels (p = 0.001).Depending on the indication, median duration of therapy varied from 6 days (IQR 3–9 days) for hospital acquired infections to 1 day for surgical prophylaxis given for one day, . Of these, 56% (35/62) were surgical site infections (35/62) and 95.2% (59/62) were on antibiotics.About 4 % (14/382) of patients on antibiotics had microbiological analysis done on at least one clinical sample: eight of these in three district hospitals, none of which had microbiological services, but in such cases sent samples to private laboratories, and six from one teaching hospital.This study shows a high prevalence of antibiotic use (70.7%) among patients admitted to surgical wards across selected hospitals in Ghana. The study population represents almost a 1/3 of the hospital capacity in Ghana and is a fair representation of the surgical population across the country. Although teaching hospitals have a larger proportion of surgical patients due to their specialized personnel/ services and their overall bed size capacity, the results are likely to be representative of the country as a whole.Antibiotic use was highest in patients admitted with urological conditions, and amongst patients who had undergone a surgical procedure or had developed a HAI. All the patients admitted with a urologic condition in this study were from a single tertiary hospital where there is a long waiting time for patients to see urologists and a longer time still for those requiring surgeries to have them done. Such patients may develop recurrent urinary tract infections requiring antibiotics or if surgery is performed on the urinary system, have an increased risk of developing SSIs. This may explain the higher use of antibiotics. There are low numbers of urologist in the country and lack of a urology center dedicated to managing such large numbers of patients.Interestingly, the primary indication for antibiotic use was treatment of community-acquired infections, whereas only 1/3 was used for surgical prophylaxis. This calls into question the usefulness of previous studies in surgical wards in LMIC that have mostly focused on surgical prophylaxis –19.The rate of antibiotic use in this study is similar to the 70.8% recorded over a decade ago in a teaching hospital in Ethiopia  and highThere was a high use of 2nd and 3rd generation cephalosporins in community- and hospital-acquired infections as well as for medical and surgical prophylaxis. This goes against the recommendations in the standard treatment guideline of the Ministry of Health of Ghana to avoid cephalosporins to help reduce development of antibiotic resistance in the country . In contIn this study, the most commonly used antimicrobials were metronidazole, cephalosporins, amoxicillin/clavulanic acid, fluoroquinolones and clindamycin, and similar agents were used for antibiotic therapy for community- and hospital-acquired infections as well as for surgical prophylaxis. Carbapenems were used at a low rate and only in tertiary hospitals. Our study design did not allow for us to directly judge the appropriateness of the choice of antibiotics. We did, however, notice that half of the antibiotics given for surgical prophylaxis were nitroimidazole and cefuroxime as recommended in the Ghana standard treatment guideline for use as surgical antibiotic prophylaxis, especially in the instances of colorectal or appendix surgery .Most patients, having spent a median of nine days in hospital prior to the survey, would have had ample time for microbiological analysis to be carried out. The low rate of routine microbiological testing has been attributed to lack of diagnostic facilities , 29. RegPrevious antimicrobial treatment and excessive duration of treatment are the two most important factors in the selection of resistant microorganisms . Though Our study shows a widespread need for antibiotic stewardship programs, and for qualitative and quantitative monitoring and evaluation of healthcare professionals’ attitudes toward antibiotic use and microbiological testing. It also suggests the need for improving microbiological services, to forestall the problem of inadequate antibiotic use –38, withThe data were collected based on a review of the health records, i.e., paper records of patients who were on admission on the survey day. The district and regional hospitals used similar booklets for everyday recording of patient management and teaching hospitals used similar folders. Because there was limited variation in the format of the records, both types of paper records were easy to review and deemed reliable for obtaining standard information on patient management.The data on antibiotic use were limited, however, by the fact that this report only looks at the antibiotic use on the day of the survey and not all the antibiotics used by patients during the current admission, prior to the survey date. In addition, all indications were based on the judgement of the attending clinicians and were not scrutinized by the research team.The timing of administration of surgical antibiotic prophylaxis was not assessed in the study.The microbiological analysis may be underreported since only available microbiological reports were reviewed without respect to those which had been requested or those done and awaiting results, and this represents another limitation.There is a high prevalence of antibiotic use in surgical practice at all levels of hospital care throughout Ghana. Our study elucidated problems on the appropriate use of antibiotics, which included long duration of antibiotic use and limited microbiological testing. For hospitalized patients there is strong evidence from high income countries of an effect of antibiotic stewardship programs on reduction of antibiotic use and resulting benefits at individual and societal levels. Our findings form the basis of and strongly call for studies in Ghana aiming at testing the effects of tailored antibiotic stewardship programs in LMIC. Policy guidelines on antibiotic use should be re-emphasized for all stake holders in Ghana.Additional file 1:Table S1: Combination of antibiotics prescribed in patients. This shows antibiotic combinations prescribed in patients. Each column is the antibiotic group added on to the initial column for the 382 patients. A row gives an indication of antibiotics combination for patients (number of patients on that antibiotic). NB. 169 patients were on 1 antibiotic, 178 patients on 2 antibiotics, 29 patients on 3 antibiotics and 6 patients on 4 antibiotics. (DOCX 18 kb)


The results indicate that the moisture content, compressive strength, and splitting tensile strength of concrete are affected by the water environment; the splitting tensile strength varies almost linearly with the compressive strength of concrete; and the descent portion of the bond–slip curve dropped slowly owing to the confinement of stirrups. On the basis of the test data, the formulas for the prediction of bond strength, residual strength, and the corresponding slips with different soaking time are proposed. Finally, the constitutive relation of bond–slip with two portions in the water environment is established with good agreement with the experimental bond–slip curves.The present study concerns the bond behavior of steel bar in concrete under a water environment. This topic was put forward because of the changes of concrete under a water environment and the importance of reliable anchorage of steel bar for reinforced concrete structures. Thirty bond specimens with deformed steel bars were immersed in water and experimentally studied by pull-out tests. The soaking time from 28 day to 360 day and the cubic compressive strength of concrete with 20 N/mm Concrete is a kind of multiphase composite with microscopic pores and cracks. Owing to the wide application of concrete in civil and infrastructures, the typical working environment for concrete structures is chronically wet or exposed to water ,2. For eFor the reliable application of reinforced concrete structures, the bond property of steel bar in concrete is a fundamental issue to be considered ,24,25,262 and 40 N/mm2, and the soaking time of specimens immersed in water varied from 28 day to 360 day. The moisture content, compressive strength, and splitting tensile strength of concrete, as well as the bond–slip curves, were measured. On the basis of the test data, the prediction formulas for the bond strength and residual strength and the corresponding slips with different soaking time are proposed, and the bond–slip constitutive model of steel bar in concrete under the water environment is suggested.On the basis of the above review, the issue of the bond of steel bar in concrete under a water environment was put forward to address structural reliability concerns. Thirty concrete specimens with deformed steel bar were experimented using the pull-out test. The cubic compressive strength of concrete was 20 N/mm2, and tensile strength was 724 N/mm2.Thirty bond specimens were designed and fabricated considering the effects of concrete strength (identified as groups A and B) and soaking time under water. According to China code GB 50152 , the spe2. Accompanied with each group of specimens, six concrete cubes with a dimension of 150 mm were cast and cured in the same condition for the testing of compressive strength and splitting tensile strength of concrete, as per China code GB50081 [Two rectangular closed stirrups with a spacing of 100 mm were arranged in each specimen. In order to locate the stirrups, four constructional steel bars were tied at corners to form a frame, as shown in  GB50081 .2 and 40 N/mm2 [3, and the bulk density was 1440 kg/m3. The crushed limestone was continuous grading with a maximum particle size of 20 mm, the apparent density was 2718 kg/m3, and the bulk density was 1460 kg/m3. Naphthalene superplasticizer was used as reducer with the measured water reduction rate of 20.4%. The dosage of raw materials was computed by the mass method for a mix proportion design of concrete [The concrete was designed in two strength grades with cubic compressive strengths of 20 N/mm40 N/mm2 . The pro40 N/mm2 . Naturalconcrete , as presAs displayed in m1 of the concrete sample was weighed; then, the sample was put into a drying oven to be at a constant weight at a temperature of 105 °C to evaporate the free and absorbed water in the pores of the concrete, and the mass m2 of concrete sample was weighed. The moisture content ρ can be calculated as follows:As per China Codes GB50081 and JGJ 51 ,37, the As presented in Two failure modes including the pull-out of steel bar and the splitting of concrete were observed in the pull-out tests. Owing to the restraint effect of stirrups on concrete, the steel bar was pulled out slowly from most of the specimens. A few specimens failed with the splitting of concrete; the splitting cracks appeared on the surface of the concrete, as exhibited in According to previous studies ,31,32,33ρ in groups A and B, which varies with soaking time. The moisture content of concrete tends to increase with the soaking time, but the increase rate slows down in the later period. The concrete with higher strength has lower moisture content than that with lower strength.n days, n is the days of soaking time (n ≥ 28).The statistical uniform formula of moisture contents can be expressed as follows:n days can be predicted as follows:fcu,n and fst,n are the compressive and tensile strengths at n days under the water environment, and kc and kt are the statistical coefficients.On the basis of previous studies ,14,15, tkc = 0.219, kt = 0.030 for the concrete of group A and kc = 0.329, kt = 0.113 for the concrete of group B were obtained. Compared with the coefficient kc = 0.55 and 0.298 for the concrete made of cements of 32.5 and 42.5 at the normal curing condition with standard temperature and humidity [By the regression of test data, the values a and b are the statistical coefficients.The relationship between the compressive strength and the splitting tensile strength can be built with an exponential function . At the a = 0.0684 and b = 1.04. Different from the coefficient b = 0.716 for concrete at the normal curing condition with standard temperature and humidity [By the regression of the test data of this study, humidity , this inτ is the average bond stress, P is the pull-out force, d is the diameter of steel bar, and la is the bond length of steel bar.The bond–slip curves of all specimens were obtained through the central pull-out test, and the average bond stress was expressed by the following formula:τu is taken as the average. If one of the maximum or minimum values of bond strength exceeds 15% of the average, these data are discarded and the average of the remaining two is taken as the bond strength of this trail. The test would be invalid if two values exceed 15% of the average [su corresponding to τu is the average slip of the valid specimens. The residual slip sr is taken as being equal to the spacing of the adjacent cross ribs (measured for 10 mm) [τr corresponds to the residual slip sr. Typical tested bond–slip curves and the representative curve are presented in The curves of three specimens in each trail were normalized to obtain the representative curve. The bond strength  average . The slir 10 mm) ,32. The τu, residual strength τr, and slip su are presented in ks is 6.72 and 3.05 for groups A and B, respectively; and c is the thickness of concrete cover. Asv is the cross sectional area of stirrups, ssv is the spacing of stirrups, and sft is the splitting tensile strength of concrete.The tested values of the bond strength  formula :(8)τu,2By substitution of the test data, Formula (8) can be transformed as follows:With Formulas (7) and (9), the bond strength su is a necessary parameter to determine the bond–slip constitutive model. As displayed in su,n tends to increase with the The slip τr,n can be predicted by the bond strength with the following formula:The residual strength ascent stage :(12)ττudescent stage :(13)ττuwhere α is the coefficient of the ascent stage and β is the coefficient of the descent stage.The constitutive model of bond–slip of the steel bar in concrete under a water environment is built by the fitting regression of the test data. The shape of the bond–slip curve is similar to that of steel bar in concrete under normal conditions, and is expressed by the following formulas:α = 0.4 for the deformed steel bar. After the statistical analyses in several ways, a better correlation with R2 = 0.946, as displayed in β and the ratio of τu,n to su,n is achieved:On the basis of the test data, In order to verify the adaptability of the constitutive model proposed above, the experiment bond–slip curves were compared with the predictions, as presented in It can be seen that the proposed model can well evaluate the experiment curve in the ascent stage. Owing to the dispersion in the descent stage of some group specimens, the proposed curve is not so close to the tested representative curve; however, most proposed curves give a certain safety margin with lower residual bond strength.(1)The moisture content increased with the soaking time owing to the penetration of environmental water into macroscope pores and cracks of concrete. A higher moisture content was reached in concrete with lower compressive strength. This induced the different changes of concrete with soaking time. Different from the exponential relationship between tensile strength and compressive strength of concrete under normal environmental conditions, the tensile strength of concrete under a water environment was linear with the compressive strength. On the basis of the test data of this study, the predictive formulas for the compressive and splitting tensile strengths of concrete under a water environment are proposed with the influencing factor of soaking time.(2)Except for a few specimens that failed with the splitting of concrete, most specimens failed with the pulling out of steel bar owing to the confining of stirrups. The bond–slip curve has a complete descending stage. As the key points of the research objectives, the bond strength, residual bond strength, and corresponding slip are provided, and the predictive formulas are built considering the soaking time.(3)The constitutive model of bond–slip with ascent and descent portions for the steel bar in concrete under a water environment is proposed, and the relevant parameters considering the soaking time are provided. The comparison with experimental bond–slip curves is exhibited to indicate the applicability of the proposed model.On the basis of the experimental study of this paper, the following conclusions can be drawn:


Continuous improvement practices are increasingly common among all kinds of companies as a means to achieve business excellence. However, the reasons why companies implement continuous improvement might vary a lot. This article presents data on the motivations that induce companies to develop continuous improvement initiatives. The data were collected through a survey. Of the 209 companies surveyed, 109 answered it. The dataset includes information about the main characteristics of the company  together with information about the main reasons to set up continuous improvement management practices. The dataset is available in excel format. The authors consider that these data are useful not only for researchers but also for consultants and for those practitioners interested in decision sciences. This was aimed at those people responsible for the implementation of continuous improvement. In order to develop this study, the first step consisted in the design of the survey, which, as already mentioned in the previous section, consisted of several identifying questions  and a question about the motivations for implementing the continuous improvement.The first step involved carrying out a bibliographic review of the literature that would allow the authors to identify the motivations that had been previously stated in the literature and that, therefore, had to be included in the survey.The literature review was carried out in the Web of Science and Scopus databases, using the keywords "continuous improvement" and "kaizen" Since there was a large number of motivations, and with the aim of making a rigorous design of the survey, it was validated by consulting experts. These were professionals from academia (including Full Professors of Business Organization), business managers (both manufacturing and services), consultants and quality managers. After completing this process, the survey was finally composed of 10 items .In order to evaluate the representativeness of the obtained sample and taking into consideration that, as above-mentioned, the size of the population is unknown, three scenarios are analysed :•ScenariOn the basis of the 808 companies, the minimum number of answers needed so that the sample is representative is calculated for each of the scenarios making the formula shown below .n=,p = percentage = 50%It might be seen that the sample size obtained (109) is higher than the minimum sample needed in any of the three scenarios , even in


Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of cyclodextrins, cyclosophoraoses, and some linear oligosaccharides, are generally used as host complexation agents in drug delivery systems. Many antibiotics with low bioavailability have some limitations to their clinical use due to their intrinsically poor aqueous solubility. Bioavailability enhancement is therefore an important step to achieve the desired concentration of antibiotics in the treatment of bacterial infections. Antibiotics encapsulated in a complexation-based drug delivery system will display improved antibacterial activity making it possible to reduce dosages and overcome the serious global problem of antibiotic resistance. Here, we review the present research trends in carbohydrate-based host-guest complexation of various hydrophobic antibiotics as an efficient delivery system to improve solubility, permeability, stability, and controlled release. Staphylococcus aureus (S. aureus) could be treated with first-generation penicillin, but penicillin-resistant S. aureus appeared within a year. Subsequently, new methicillin-based antibiotics were developed to treat penicillin-resistant S. aureus, but methicillin-resistant S. aureus (MRSA) emerged in 1986. The newly developed vancomycin played a major role in the treatment of MRSA. However, the use of vancomycin caused the emergence of vancomycin-resistant S. aureus (VRSA) complex represents the concentration of guest molecules in the complex form, and [Guest]free and [Host]free represent the free guest and free host molecule concentration, respectively. The K1:1 can be obtained through phase solubility analysis. If the drug forms a 1:1 complex with host molecules, the drug solubility increases linearly as the concentration of host molecule increases. In this case, the slopes of the linear curve is always less than unity 0 represents the intrinsic solubility of the drug in water. Most values of K1:1 fall within the range 1000–20,000 . In. In76]. Butylparaben and triclosan can inhibit the growth of a broad range of microorganisms. Butylparaben inhibits cellular ATPase and phosphotransferase  and theyE. coli ATCC 11299 slightly decreased compared with previous reports [E. coli ATCC 11299 is not an antibiotic-resistant bacterium. Nevertheless, this result suggests that delivery of non-ionic antibiotics can be improved by forming complexes with C-βCDP.Cyclodextrin polymers have high solubility in water and the capability to complex with hydrophobic compounds of relatively large molecular size. This is due to the cooperation of two adjacent CD structures on the polymer chain . In part reports ,86. Howe reports ,88. Sincd-mannose (pMAN-βCD) and d-glucose-grafted β-cyclodextrin (pGLU-βCD) via a click reaction  dimers can complex with pyrimethamine to form an antibacterial drug . PyrimetP. aeruginosa and gentamicin-resistant strains [P. syringae can be demonstrated using NMR spectroscopy [P. syringae, antibiotic resistance due to the periplasmic glucans might be expected. On the one hand, other linear β-glucans have the potential to enhance the antibacterial activity and solubility of antibiotics.Tobramycin is an aminoglycoside antibiotic and has pharmacokinetic properties similar to those of gentamicin, but the antibacterial activity of tobramycin was more active than gentamicin for  strains . Tobramytroscopy . Tobramy®, Janssen Pharmaceuticals, Beerse, Belgium), chloramphenicol , and voriconazole  are commercial CD-antimicrobial medicines. Since these products increase the bioavailability of the drugs using several CD derivatives, the development of an effective antibiotic delivery system using carbohydrate-based host molecules might have potential in terms of antibiotic therapy.The emergence of antibiotic-resistant bacterial strains is a serious problem worldwide. The major cause of this emergence is the misuse and overdosing of antibiotics, practices that are monitored and regulated in many countries . Various