The plasma membrane lipid rafts are cholesterol- and sphingolipid-enriched domains that allow regularly distributed, sub-micro-sized structures englobing proteins to compartmentalize cellular processes. These membrane domains can be highly heterogeneous and dynamic, functioning as signal transduction platforms that amplify the local concentrations and signaling of individual components. Moreover, they participate in cell signaling routes that are known to be important targets of environmental toxicants affecting cell redox status and calcium homeostasis, immune regulation, and hormonal functions. In this work, the evidence that plasma membrane raft-like domains operate as hubs for toxicants’ cellular actions is discussed, and suggestions for future research are provided. Several studies address the insertion of pesticides and other organic pollutants into membranes, their accumulation in lipid rafts, or lipid rafts’ disruption by polychlorinated biphenyls (PCBs), benzo[a]pyrene (B[a]P), and even metals/metalloids. In hepatocytes, macrophages, or neurons, B[a]P, airborne particulate matter, and other toxicants caused rafts’ protein and lipid remodeling, oxidative changes, or amyloidogenesis. Different studies investigated the role of the invaginated lipid rafts present in endothelial cells in mediating the vascular inflammatory effects of PCBs. Furthermore, in vitro and in vivo data strongly implicate raft-localized NADPH oxidases, the aryl hydrocarbon receptor, caveolin-1, and protein kinases in the toxic mechanisms of occupational and environmental chemicals. Lipid rafts and plasma membrane domains abundant in cholesterol and sphingolipids have been reported to participate in important cellular processes, namely, in terms of the space-time dimension of signal transduction and cell signaling ,2,3, andEnvironmental and occupational toxicants can bring about a great diversity of cellular and systemic alterations implicated in the short-term and long-term outcomes of toxic exposures ,6,7,8,9.Many environmental chemicals are lipophilic, which allows them to accumulate in the plasma membrane, but the potential role of membrane raft-like domains unleashing their cellular effects is debatable. As it will be discussed in the following sections, experimental evidence exists for the targeting of lipid rafts—on cells in vitro—by some toxicants, such as polychlorinated biphenyls (PCBs) and air pollutants ,16,17. ITherefore, it is plausible that raft-like domains at the plasma membrane play a role as hubs/platforms for environmental and occupational toxicants to trigger or amplify their toxic actions in cells. The present work aimed to collect and discuss the existing evidence supporting this hypothesis and to identify gaps to be addressed in future research.The lipid rafts concept marked a change in the understanding of the plasma membrane organization and function. Before it, the plasma membrane was understood by Singer and Nicholson’s classical membrane fluid mosaic model. Nevertheless, the new concept amplified the understanding related to the structure and function of the plasma membrane ,25 into The frontier between floating membrane domains and larger and more stable membrane subdomains is not clear. Lipid rafts can vary from highly transient domains to larger and more stable structures . In thisIn many mammalian cells, caveolae are the most abundant membrane subdomains . They weThe physical-chemical characteristics of caveolae facilitate their identification by electron microscopy, while the existence of lipid rafts in living cells remains to be clearly demonstrated . The dirDespite the doubts of the scientific community about the appropriate nomenclature of membrane raft-like domains and methodological limitations to proof the existence of lipid rafts, from the perspective of Sevcsik and Schütz 2015), the concept of lipid rafts is defended until methodological evidence is clarified . Having 5, the coThe lipid rafts, which originate from the interactions between sterols and saturated lipids, form a liquid-ordered phase that is tightly packed, distinct from the typical disordered lipid phase regarding flexibility and permeability . Regen  48]. Th. Th48]. In general, cholesterol is an essential player in the different types of lipid rafts. The deprivation of cholesterol reduced the number of caveolae in the cell, showing its essential role in the formation of these structures , but itsA well-described lipid specific to membrane rafts is the GM1 glycosphingolipids or ganglioside ,60, whicThe lipid rafts are also composed of membrane proteins that can be recruited by different molecular mechanisms, such as post-translational modifications like palmitoylation or protein-protein/lipid interactions, among others . MoreoveAt the experimental level, having proteins identified by different studies as characteristic of lipid rafts allows us to use them as lipid raft markers in DRMs. DRMs are considered representative of membrane lipid rafts  since thAs described in It is expected that the presence of proteins in lipid rafts in nanoscale dimensions favors the ability of lipid raft components to respond to diverse stimuli . For exaCell maintenance and proper functioning rely on the different intra and extra-cellular processes, their flux, equilibrium, and control. And lipid raft-like domains are described as contributing to different cellular processes as described previously ,82,83,84Different studies investigated the importance of lipid rafts in neurodegeneration, some pointing to neuroprotective effects while others pointed to neuropathological consequences. In this sense, different points of view are reflected in  and a reIn terms of understanding the disrupting effects of oxidative and nitrosative stress in lipid rafts, they are well described in neuroimmune disorders . In the Another example of lipid rafts’ relevance in cell signaling is their implication in TNFα-mediated signaling. A study showed that cholesterol sequestration from lipid rafts inhibits the activation of the nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) pathway and therefore induces the switch of TNFα-mediated responses toward apoptosis . Moreove2+ signaling and the endothelial nitric oxide synthase (eNOS or NOS3) are localized in caveolae of endothelial cells and play central roles in regulating blood pressure and flow, angiogenesis, and vascular inflammation P-induced expression of the intercellular adhesion molecule-1 (ICAM-1), again revealing a pro-inflammatory mechanism involving AhR signaling dependent on caveolae . Thus faAlteration of lipid raft properties and composition by environmental toxicants has been reported in different studies ,55,147.A concrete effect on lipid rafts was described for iron associated with silica exposure in macrophages, where disruption of lipid rafts was observed together with an increase in superoxide, lipid oxidation, and cytokine production . Iron chLipid oxidation and oxidative stress were also observed in lipid raft fractions from both the cerebral cortex of mice and neuronal cell models of AD exposed to airborne PM with pro-amyloidogenic activity . PointinThe effect of B[a]P in membrane remodeling was investigated by using rat liver F258 epithelial cells, revealing modification of lipid rafts . PreviouB[a]P was also suggested as a destabilizing agent of lipid raft structure . By usinTogether with disruption, changes in the membrane order and levels of raft-related lipids are also reported after exposures to other organic and inorganic pollutants. By incorporating into the bilayer, DTT decreased the phase transition temperature of model membranes ,135 and The membrane raft-associated AhR discussed before and their possible functions as signaling mediators, in addition to being transcription factors, might play important roles in fibroblasts, hepatocytes, and endothelial cells’ responses to dioxin-like pollutants, especially under conditions of membrane cholesterol deficit ,142. A dIn humans, it is well established that cadmium, lead, and mercury exposures increase serum cholesterol levels . CorrelaHowever, how these changes in lipid levels reflect in cell membrane lipid rafts has yet to be investigated. In one study, exposure to manganese induced apoptosis in PC12 cells together with an alteration of the lipidic profile of the DRMs regarding their composition on phosphatidylinositol, phosphatidylcholine, and sphingomyelin . ConcernFollowing the rationale of the previous section for the effects of environmental toxicants on the lipid composition of lipid rafts, in this section, the evidence for the effect of environmental toxicants on the protein composition of lipid rafts will be presented together with associated cellular effects.A recent study using red blood cells reported that mercury exposure leads to alterations in flotillin-2 levels, detected by electrophoresis of total membrane proteins . This isAnother example of alterations in rafts’ proteomes is the displacement of proteins from these membrane regions, as occurs for occluding in human brain endothelial cells exposed to the industrial chemical 2,2’,4,4’,5,5’-hexachlorobiphenyl, also known as PCB153 . The celExposure of CHO-K1 cells transfected with TSHR to the pesticide DDT abrogated the co-localization between the TSHR and lipid rafts, with consequences for receptor internalization . InteresRecently, exposure to vanadium (IV) compounds was revealed to promote aggregation and accumulation of the luteinizing hormone receptors in the plasma membrane of CHO cells, with the formation of clusters containing these receptors . One of The exposure to traffic-related PM revealed that it altered the processing of amyloid precursor protein in lipid raft fractions from in vivo and in vitro samples . On hepaLipid rafts were reported as a structural scenario for the PCB153-induced phosphorylation of JAK and Src kinases and upregulation of cell adhesion molecules (CAMs) that affect leukocyte infiltration in brain endothelial cells . In thisLipid rafts are also implicated in the signaling pathway associated with the TCR by favoring the co-localization of the TCR, of the linker for activation of T cells (LAT), and of the LCK . This laMore recently, a study reinforced the role of G protein-coupled receptor (GPCR) activation by toxicants through lipid raft regions. In CHO cells, an increase in intracellular cAMP was observed after exposure to vanadium compounds, which is complementary to the aggregation of luteinizing hormone receptors in clusters, as described previously . In addiWhen studying the effect of a toxicant in lipid rafts, several effects can be considered for research since they have already been reported to be common to different toxicant exposures. They include alteration of lipid raft composition (lipids and proteins), alteration of cholesterol content and membrane fluidity, recruitment or displacement of proteins from these membrane domains, and oxidative stress.The accumulation of toxicants in lipid rafts is not a clear point, with only PCB77 being reported to accumulate in these membrane domains . NeverthThe effect of environmental toxicants on inflammatory processes deserves to be further investigated, considering that inflammatory signaling is a common response to environmental pollutants , with soIn the case of exposure to B[a]P, alteration of GM1 and raft protein localization is reported. With this in mind, investigating the effect of other environmental toxicants on the distribution of GM1 can be highly interesting if we consider that the location of GM1 near membrane channels affects their activity ,68. MoreThe activation of a specific GPCR type via membrane clustering after exposure to vanadium , togetheAnother research dimension to be explored is how environmental toxicants can interfere with the interplay of different signals coming from proteins associated with lipid rafts. For example, the lipid rafts are near enzymatic systems producing ROS, like NADPH oxidases and nitric oxide synthases ,66,78. TAhR is a reported target of PCBs, PAHs, PM, and persistent organic pollutants ,141,146 Finally, to address the role of lipid rafts in triggering a specific cellular mechanism after any toxic exposure, it is important to employ different cell models expressing different membrane receptors and signaling components at lipid rafts since signaling differences were identified in this work. For example, in endothelial cells, the toxicant effects described to be associated with lipid rafts are changes in Nrf2 signaling, an increase in MCP-1 associated with AhR, p38, and JNK signaling pathways, and the displacement of occludin from lipid rafts is also described ,145,164.The evidence collected throughout this work points to the role of lipid rafts as targets of environmental toxicants—such as PM, PAHs, PCBs, pesticides, and metal ions, among others—unleashing cell signaling mechanisms consequent to toxic exposure. The identified triggering mechanisms may be toxicant-specific, while other mechanisms are common to different toxicants. Considering this, some suggestions for future research are given:Information on the effect of environmental toxicants in lipid rafts and associated cell signaling mechanisms is compiled in this article, and to the best of our knowledge, this is the first review approaching the effect of environmental toxicants on lipid raft signaling. The collected data endorse that membrane raft-like domains can function as hubs for the regulation of toxic cellular mechanisms triggered by these harmful chemical agents. Therefore, this concept can provide meaningful insights into the comprehension of environmental toxicants’ molecular effects at the cellular level.


Pulmonary tuberculosis is an inflammatory disease associated with an elevated cortisol/cortisone ratio at the site of infection and an array of cytokine changes. Tuberculous pericarditis is a less common but more lethal form of tuberculosis and has a similar inflammatory process in the pericardium. As the pericardium is largely inaccessible, the effect of tuberculous pericarditis on pericardial glucocorticoids is largely unknown. We wished to describe pericardial cortisolcortisone ratio in relation to plasma and saliva cortisol/cortisone ratios and the associated changes in cytokine concentrations. The median (interquartile range) of plasma, pericardial, and saliva cortisol concentration was 443 (379–532), 303 (257–384), and 20 (10–32) nmol/L, respectively, whereas the median (interquartile range) of plasma, pericardial, and saliva cortisone concentrations was 49 (35–57), 15.0 (0.0–21.7), and 37 (25–55) nmol/L, respectively. The cortisol/cortisone ratio was highest in pericardium with median (interquartile range) of 20 (13–445), followed by plasma of 9.1 (7.4–12.1) and saliva of 0.4 (0.3–0.8). The elevated cortisol/cortisone ratio was associated with elevated pericardial, interferon gamma, tumor necrosis factor–alpha, interleukin-6, interleukin-8, and induced protein 10. Administration of a single dose of 120 mg of prednisolone was associated with the suppression of pericardial cortisol and cortisone within 24 h of administration. The cortisol/cortisone ratio was highest at the site of infection, in this case, the pericardium. The elevated ratio was associated with a differential cytokine response. The observed pericardial cortisol suppression suggests that 120 mg of prednisolone was sufficient to evoke an immunomodulatory effect in the pericardium. Baker et al., for example, have demonstrated the elevated cortisol/cortisone ratios in patients with pulmonary TB, yet this ratio is decreased with recovery . MoreoveM. tuberculosis (TB pericarditis (TBP) is a chronic granulomatous inflammatory disease caused by infection of the pericardium by rculosis . The immrculosis , followerculosis . About 8rculosis . Immunomrculosis , emphasirculosis , samplinrculosis . A systeWe previously published data on cytokine concentrations in the pericardium, plasma, and saliva of patients with TBP, in which we found that adjunctive corticosteroid therapy reduced saliva IL-1β, plasma IL-6, and pericardial IL-8 concentrations . As chanWe hypothesized that there is a shift in the cortisol-cortisone shuttle enzyme activity, resulting in escalated cortisol concentrations, leading to a rise in the cortisol/cortisone ratio in patients infected with TBP, particularly of the pericardium. We further hypothesize that the rise in the cortisol/cortisone ratio is potentiated by a rise in pro-inflammatory cytokines at the site of infection, leading to the suppression of cortisone and relatively greater concentrations of cortisol.Our objectives were, therefore, to describe the pericardial cortisol/cortisone ratio, a site that has never been previously evaluated for excursions of cortisol and cortisone, given its relative inaccessibility in patients with TBP, and to compare it to the more accessible plasma and saliva compartments, respectively, and to evaluate whether this rise corresponds to a rise in pericardial pro-inflammatory cytokines in the pericardium.2in situ for 24 h to sample pericardial fluid continuously, and their endogenous glucocorticoids and prednisolone concentrations were assessed serially over a 24-h period. Patients were eligible for inclusion here if they were 18 years of age or older; had a pericardial effusion confirmed by echocardiography; had evidence of definite or probable TBP, according to the Tygerberg diagnostic score; and had less than 1 week of anti-tuberculous therapy  inactive placebo comprising sugar and starch. Either prednisolone or placebo was administered immediately after the baseline samples were taken for saliva, plasma, and pericardial fluid and subsequently administered after a period of 24 h and then daily for 28 days.2.1g for 10 min, and 1 ml of supernatant was pipetted into each cryotube and performed in duplicate. The cryotubes containing pericardial fluid and plasma were immediately stored at −80°CC in dedicated trays for subsequent analysis in a single batch. The salivettes were also stored at −80°CC to preserve stability, also using trays for vertical storage. On the day of analysis, they were thawed and centrifuged at 1,500g for 15 min. Time of day was recorded for each participant but differed in each case as patients presented at different times to the hospital, as were extremely unwell in each case. The time intervals were logged for subsequent sampling and administration of prednisolone or placebo. The continuous monitoring of the freezer revealed no accidental temperature fluctuations.Pericardial fluid, plasma, and saliva samples were then collected at baseline, before the administration of prednisolone, and then at the following time intervals after the administration of prednisolone or placebo: 0.5, 1, 2, 3, 5, 8, and 24 h, following insertion of the pigtail catheter. In view of the serial nature of the samples, a decision was made to collect single samples at each time point, rather than duplicate. Baseline venous blood, saliva, and pericardial fluid samples were collected simultaneously at bedside, following pericardiocentesis (as described above). Venous blood was extracted from a peripheral vein. Saliva was collected using Sarstedt salivettes . The swab remained inside the mouth for a period of 2 to 3 min while gentle chewing it and then was replaced in the salivette tube. Blood and pericardial fluid were collected in ethylenediamine tetraacetic acid (EDTA) tubes, each with a minimum of 4 ml, which were subsequently centrifuged at 2,0002.2Liquid chromatography–tandem mass spectrometry (LCMS/MS) was used to measure cortisol and cortisone concentrations in all our serial samples. Cortisol, cortisone, prednisolone, and prednisone concentrations were also determined by LCMS/MS assay, developed in the Division of Clinical Pharmacology, University of Cape Town, using the methodology described by the Food and Drug Administration (FDA) guidance for industry for bioanalytical method validation , 19. TheThe assays were validated according to the FDA guidelines . Samples2.3Milliplex™kits  and the Bioplex200 reader from Bio-Rad were used to measure the following cytokines: IFN-γ, IL-1α, IL-1β, IL-6, IL-10, IL-12p40, TNF-α, IL-8, and IP-10, in pericardium, plasma, and saliva. When performing the cytokine analyses, a minimum volume of 250 μl. Samples were batched and analyzed on a single occasion. We did not perform our own validation study for pericardial fluid and saliva but employed the same methodology outlined by the manufacturer for the plasma cytokines that we analyzed . We reported p-values of less than 5% to represent significance.Descriptive statistics were used to summarize patient data, namely, frequency and percentage for categorical data and median with interquartile range (IQR) for continuous data. The differences between participant allocated to placebo and those allocated to prednisolone were compared using the Mann–Whitney U-test and were performed using GraphPad Prism version 9.2.0  and StataCorp version 17.0 . Comparisons among the three sampled compartments  were performed using the Friedman test, with 3The participants screened and subsequently enrolled into this sub-study are shown in 3.1At baseline, the median (IQR) cortisol concentration in the pericardium was 303 (258–385) nmol/L, plasma cortisol was 443 (379–523) nmol/L, and salivary cortisol was 20 (10–32) nmol/L. The median (IQR) cortisone concentration was 15.0 (0.6–21.7) nmol/L, 49 (35–58) nmol/L, and 37 (25–55) nmol/L, in pericardium, plasma, and saliva, respectively. The relevant median (IQR) cortisol/cortisone ratios in the three compartments were significantly different from each other at 20 (13–445) in the pericardium, 9.1 (7.4–12.1) in plasma, and 0.4 (0.3–0.8) in saliva Figure 23.23.2.1The cytokine concentrations in the three compartments, pericardium, plasma, and saliva are shown in 3.2.23), TNF-α (10-fold), IL-6 (log3), IL-8 (log3), IL-10 (7-fold), and IP-10 (20-fold) are higher than their respective plasma reference ranges (3), IL-1β (30-fold), IL-6 (log3), IL-8 (log3), IL-10 (3-fold), IP-10 (20-fold), and IL-12P40 (20-fold) are lower than their reference ranges, respectively, whereas TNF-α was comparable to its respective reference range  20 (13–445), followed by plasma median (IQR) of 9.1 (7.4–12) and then lowest in saliva median (IQR) of 0.4 (0.3–0.8). In the placebo arm, the cortisol and cortisone concentrations were unchanged throughout the 24-h period in all three matrices, suggesting a high degree of reproducibility. In participants allocated to prednisolone, there was a rapid (from as early as 3 h) and sustained reduction of cortisol and cortisone concentration for all three compartments.The cortisol/cortisone ratios in the placebo arm did not change significantly in all the matrices over the 24-h period, as shown in 4This is the first examination of pericardial cortisol and cortisone levels and their relationship to cytokine concentrations in patients with TBP. We found that the pericardium has a high concentration of cortisol, close to that of the plasma compartment and, by contrast, much higher than in the salivary compartment, but a lower cortisone concentration. This resulted in an elevated pericardial cortisol/cortisone ratio when compared with plasma and saliva. In addition, most key cytokines measured were markedly elevated in the pericardium versus the plasma.Local cortisol-to-cortisone equilibriums are mostly dependent on the activity of local expression of the enzyme 11HSD-1 and 11HSD-2. In salivary glands, for example, there is a well-established high expression of 11HSD-2, resulting in local conversion of cortisol to cortisone and a low cortisol/cortisone ratio . In viewThese findings are consistent with the findings of Baker et al., who showed an elevated cortisol/cortisone ratio in bronchoalveolar lavage fluid in patients with pulmonary TB despite a normal central control of glucocorticoid production, in keeping with altered peripheral metabolism at the site of infection .We do not know whether the altered local glucocorticoid equilibrium is potentially beneficial, harmful, or not of pathogenic relevance at all. TB is an inflammatory disease, and much of the damage in PTB is due to an inflammatory response . The elePrevious work has shown that providing supraphysiological doses of prednisolone in a clinical study of TBP has conferred clinical benefit in HIV-negative patients, by reducing duration of hospitalisation and incidence of constrictive pericarditis, a lethal complication . Our stuIt is apparent that the vast majority of our participants were of black African ancestry. Black and white women did not differ in the study evaluating the HPA axis using the 24-h urinary excretion of cortisol and dexamethasone suppressibility matched for age, weight, body mass index, and body surface area . DespiteHowever, the study had a number of weaknesses, it is composed of a small sample size, and sampling was limited to the first 24-h time period. It is likely that additional physiological responses occurred beyond this period, for example, during recovery. This study did not undertake cortisol-cortisone shuttle enzyme expression studies, thus relying on indirect evidence that it conferred an immune modulatory response, which warrants confirmation in the future. The participants were mainly of black African ancestry; therefore, there is uncertainty whether these findings are generalizable to other populations. We did not perform our own validation study on the cytokines but used the prescribed reference values. This represents an additional weakness of our study. Moreover, the reference ranges in plasma may not be applicable to pericardial fluid, thus invoking another degree of uncertainty in the interpretation of these data.5This pilot study was able to show a greater inflammatory response in the pericardium of patients with TBP, as evidenced by the following elevated proinflammatory cytokines: INF-γ, TNF-α, IL-6, and IL-8. In the pericardium, there was also a raised cortisol/cortisone ratio, compared with plasma and saliva. In light of the previously documented evidence for the beneficial effect of adjunctive corticosteroids in patients with TBP, the elevated endogenous pericardial cortisol/cortisone ratio may have a partial immunomodulatory and, potentially, an immunostimulatory effect. The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by University of Cape Town Human Research Ethics Committee. The patients/participants provided their written informed consent to participate in this study.JS, PR, and IR contributed to conception and design of the study. JS organized the database. JS and PR performed the statistical analysis. JS wrote the first draft of the manuscript, whereas PR and IR contributed to manuscript revision. All authors contributed to the article and approved the submitted version.


We propose an early-detection scheme to reduce communications latency based on sequential tests under finite blocklength regime for a fixed-rate transmission without any feedback channel. The proposed scheme processes observations sequentially to decide in favor of one of the candidate symbols. Such a process stops as soon as a decision rule is satisfied or waits for more samples under a given accuracy. We first provide the optimal achievable latency in additive white Gaussian noise channels for every channel code given a probability of block error. For example, for a rate  In fifth-generation cellular network technology (5 G), a large set of autonomous devices will require quick and reliable radio access. 5 G will enable scenarios like Internet-of-Things (IoT), where one cell is expected to contain up to 10entclass1pt{minimaURLLC focuses on technologies that require special attention in the time needed to transmit a packet under predefined reliability. Among these low-latency emerging technologies are applications like autonomous vehicles, interactive multi-player gaming, health remote surgery, real-time teleoperation, and virtual/augmented reality , 4.The transition time of information in a communication system is the sum of all latencies inherent to the system. Some latency-source examples are the routing delay, the over-the-air transmission time, the network queuing, the number of active users, and many others. Latency sources are numerous and vary in nature.With the aim of reducing the system latency, several approaches have been explored. At the physical layer alone, for example, researchers investigated more efficient channel codes, faster signal processing, new frame structures, and improved radio-resource management , 6.Concerning channel coding, to achieve the latency and reliability goals in URLLC, the use of short blocklengths, also referred to as short blocklength regime, is mandatory . HoweverAlong with short packets, we can reduce latency through a quick signal processing stage, i.e., have the receiver achieve a reliable decision using only a fraction of the transmitted-symbol length. A sequential probability test can reach such a decision –11. HoweIn this paper, focusing on fixed-rate communication without any feedback channel, we aim to reduce the detection latency by using a scheme that decodes a short packet with high reliability from fractions of the received signal.In the proposed scheme, we define the detection latency as the interval between the beginning of the symbol transmission and the moment of its correct detection .We provide detailed results about the maximal code size achievable under normal approximation in terms of physical variables like latency, power, and symbol duration.We provide analyses of the normalized average latency for various rates, blocklength, and block error rate (BLER) of practical interest.We conjecture a threshold for the sequential test when the receiver uses a list decoder to reduce the number of candidate messages.We provide the upper bound of the block error rate as a function of any given threshold when the system uses the EDS.We discuss how the proposed EDS is effective with orthogonal frequencydivision multiplexing (OFDM) signals via random coding or pre-coding Hadamard random matrices.We show that, in multi-hop links, the proposed EDS can reliably detect symbols before the end of their transmission, significantly reducing the latency while maintaining the error probability.The remainder of this work is organized as follows. In Sect. This work contributes to the field of URLLC by combining sequential detection and short packet communication. The main contributions of this paper are summarized as follows:n. In other words, the maximum code rate is the largest rate at which an encoder-decoder pair operates with a finite blocklength n and whose BLER is not greater than a predefined value To guarantee reliable communication, Shannon established as a necessary condition the use of large blocklengths, a condition known as the infinite blocklength (IBL) regime . HoweverIn this paper, we leverage the Polyanskiy’s bounds to construct a sequential hypothesis test that will be used to make an early decision on the received symbol. A sequential test processes the received samples as they periodically arrive at the detector based on the statistical distribution of the data source. These types of tests are characterized by the average number of samples used to make a decision and the probability of error in making that decision . The firM multiple hypotheses, where the test stops as soon as a decision rule is satisfied or waits for more samples under a given accuracy 10], instThere is a trade-off to be found between low latency and high reliability . AchieviTherefore, unlike , 19, witAs mentioned above, the EDS tries to reduce the detection latency by using a technique that decodes a short message with high reliability from fractions of the received packet. In order to achieve it, the proposed scheme combines a sequential test guided by list decoding.The performance comparison will be provided in terms of the normalized average latency, which is a ratio between the average early-detection time and the symbol duration. We assume that the channel remains constant within the transmission time of a symbol, meaning that the symbol duration does not exceed the channel coherence time. This assumption means that if the coherence time of the channel is greater than the symbol duration, then the channel conditions will remain constant during the transmission of a single symbol. As a result, the transmission time of a symbol, which is determined by the symbol rate and the channel’s bandwidth, will be equal to the symbol duration.The transmission mode chosen is a multi-carrier system. The symbols of a message are BPSK modulated and transmitted in parallel through the channel and that detection is performed simultaneously on the receiver. We chose BPSK modulation since it is simple to implement, and it is the signaling scheme that maximizes the distance between symbols, providing the maximum immunity to noise . FurtherAlso, the EDS operates in a BLER range where the normal approximation is accurate . In addiIn this section, we use an extension of the classical equation of channel capacity to formulate the parameters involved in the minimal latency problem.k bits of information and transmitted through a noisy channel in one of n denominated codeword, where n is referred to as blocklength. We denote the resulting code as an -code. Also, we define P is the received power and T is the duration of an entire codeword. Similar to the channel coding process, at the receiver, a decoding function R cannot be greater than the capacity C [T, the latency can be expressed as W, the minimal latency is then given by:A channel coding scheme adds redundancy to the user message to decrease the error probability to an arbitrarily small value. A user message is composed of pacity C . Since tm was transmitted. Thus, an n, and power constraint In specific modern applications , it is mandatory to use short packets to achieve the required latency and reliability constraints. In those cases, the error probability will no longer be arbitrarily low. Thus, a framework that relates packet error probability, communication rate, short packet size, and latency is essential. Toward this end, Polyanskiy et al.  establiscument}ρ , Th. 54.C, Q function, and e is Euler’s constant. In [ For the AWGN channel with SNR entclass1pt{minimatant. In , 23, it L, the power P, and the symbol duration T in  sh shPT is From here on, we define communication latency as the delay between the beginning of the transmission of a message and the instant at which the receiver makes a correct decision. Ignoring the propagation delay, the latency can be smaller than the symbol duration if an early detection mechanism is used .T. We take equidistant samples of this symbol and form a collection of i.i.d. random vectors f, where n indexed by T. Specifically, when We consider a transmitter that sends a message with a fixed symbol duration M transmitted messages are equiprobable, i.e., the a priori distribution is constant [m, and decide that m was transmitted. Otherwise, data reception continues. By using the proposed EDS, latency is reduced when the message is received without errors at a time T. It should be noted that if the posterior probability maximized for some m does not exceed the threshold T. In Sect. If we decide which message was sent using only a small proportion of the duration of the transmitted symbol, we can reduce latency. To do so, we leverage on one of the quick decision techniques called sequential test –11. Suchconstant , 24. ThuT, the decision will be made at T.An EDS is optimal if it minimizes the expectation of the proportion of the symbol duration used for detection for which the error rate does not exceed a predefined value. For such a scheme, we assume that a perfect error-detecting code checks whether or not there are errors in the transmitted message, i.e., the undetected error probability is zero. In that case, the decision rule is as follows: as soon as an error has not been detected, decode the message. Otherwise, wait for the next sample until no error occurs. If errors are detected up until the end of the transmitted symbol R, SNR n, the non-asymptotic error-correction performance of such codes can be determined solving (O(1) term is a small constant, and the term n is greater than 100 channel uses [Under such a condition, the average latency can be determined by the error rate as a function of the SNR nel uses , 26.C being expressed as   n,M,\docnt}ϵ∗ in  as shownnt}ϵ∗ in .This theorem can be proved by using the following lemma.For an AWGN channel with an arbitrary n,M,\docued as in , and by }τ as in . This coIn the following section, we design the EDS based upon a sequential test. The test employs a list decoder in which the MSPRT can make a decision based on a few hypotheses.k bits encoded by an arbitrary  Let From Theorem In the next section, we show through examples that the EDS can be designed via sequential tests based on list-decoding combined with MSPRT.Examples of the EDS for low-latency communication are provided in this section. Noteworthy results on both latency and error probabilities are discussed in Sect. n symbols that are transmitted simultaneously through a parallel AWGN channel with n branches. There are T and is modulated by a binary phase-shift keying (BPSK). The signal messages are denoted by Considering a message of entclass1pt{minimaatisfies . The varM, prior probabilities for For a large information block size, the receiver needs mentclasspt{minima renders  accurate renders . 30a\docSince the threshold MSPRT in , 15, 29,For AWGN channels, and under normal distribution, he noise . HoweverT, which guarantees orthogonality [M possible codewords, and its OFDM signal y(t) and As shown above, early detection via a sequential tests reduce latency if symbols are transmitted in parallel. A typical parallel transmission is OFDM signaling because data is transmitted in parallel by mapping each symbol to a carrier . OFDM isgonality . A critiThere are several noteworthy features on the distances of these OFDM signals.Assuming a random coding where M codewords that are mapped to quadrature phase-shift keying (QPSK) modulation, in which there are at most two different symbols among these n dimensions, i.e., the number of elements in However, codewords are generally non-i.i.d. random vectors. Consider a codeword T, the system is orthogonal at 0.25T, 0.5T, 0.75T and T. In other words, such an increase in subcarrier spacing would be convenient if the early detection could be guaranteed at We may use fewer subcarriers to increase the space between subcarriers; hence, the system remains orthogonal. However, for the band-limited OFDM system, the orthogonality holds for specific samples. For instance, with a subcarrier spacing of 4/Latency can be reduced through EDS if the squared distance lm′, Eq.  can be re obtain  where \dIt should be noted that there are orthogonal matrices that meet such a condition. A Hadamard matrix is a typical example in which h hops with synchronous detection (SD), i.e., detection at the end of the symbol duration. A transmitted codeword has latency T, the latency in  term in (O(1) is a small constant [For a fixed-duration transmission, the minimal latency analyzed in Sect. entclass1pt{minimaconstant , 26.Fig.n decreases for a given k as the SNR increases. Such a trend is congruent with what we stated in Sect. Thus, following , it can n and code rates n grows since the term n greater than 100, resulting in asymptotic error behavior [An analysis of the codes whose latency can be reduced using a sequential test for a given error rate behavior , 25, 26.n, Fig. k grows, the symbol time required to receive messages becomes larger. Nevertheless, it is interesting to note that for a blocklength of R of 0.5 and 0.95 bit per channel use, respectively. Figure n grows, the required SNR to reach the necessary error performance decreases. Furthermore, when The normalized average latency of these codes is computed using Theorem k. On the one hand, it can be seen that the average latency decreases when the code rate increases. In other words, for a fixed information block size, a large blocklength increases latency slightly. On the other hand, for a fixed R, a large information block size increases latency. Indeed, it can be seen in this figure that for a rate of Figure The initial increasing behavior of the curves in Fig. k for a fixed code rate k grows, the symbol time needed to reach such an error probability increases. For example, for an information block size of Figure Concerning the scheme described in Sect. fined in  quickly fined in  is reachM possible messages. However, such a selection of distances can be computationally prohibitive. Fortunately, many efficient decoding algorithms provide the As seen above, the proposed scheme uses the -Solomon  or polar-Solomon .Concerning EDS with OFDM as discussed in Sect. ind from  that \doBy taking results obtained in Fig. cated in  and 38)\documentFinally, we present the results for different SNRs and blocklengths of the EDS for the previously analyzed multi-hop system in Sect. Figure Figure In this work, we introduced new optimal low-latency communication strategies. Combined together, they form an early-detection scheme (EDS). By focusing on fixed-rate coding in the finite blocklength regime, the key ingredient of the proposed EDS is the use of sequential tests to make decisions before the end of the symbol duration. Furthermore, compared to conventional sequential detection techniques, our proposal does not necessitate feedback, thus avoiding additional latency.R of 0.5 and 0.95 bits per channel use, respectively.In that regard, we derived the minimal achievable latency over the additive white Gaussian noise (AWGN) channel for both synchronous detection and our EDS. We also demonstrated that the EDS attains the optimal achievable latency by minimizing the time needed to make decisions. For example, we showed that messages with a blocklength of 500 symbols could be correctly received using only Moreover, we developed a sequential test based on a multihypothesis sequential probability-ratio test (MSPRT). Results showed that, compared to synchronous detection, receivers could make decisions faster while maintaining the required reliability. Such scheme is effective if all symbols are simultaneously transmitted in parallel AWGN channels via orthogonal frequency-division multiplexing (OFDM)-like signals. However, it should be kept in mind that the proposed technique for OFDM signals is feasible if the message is pre-coded by random matrices, which guarantees no loss of orthogonality.As our proposed EDS would allow relay nodes to start their retransmission earlier, we think that they are promising solutions for ultra-reliable and low-latency communications (URLLC) transmissions in multi-hop communications. Finally, as future work, it would be interesting to extend the proposed schemes to fading channels.


Mesoporous silica engineered nanomaterials are of interest to the industry due to their drug-carrier ability. Advances in coating technology include using mesoporous silica nanocontainers (SiNC) loaded with organic molecules as additives in protective coatings. The SiNC loaded with the biocide 4,5-dichloro-2-octyl-4-isothiazolin-3-one (DCOIT), i.e., SiNC-DCOIT, is proposed as an additive for antifouling marine paints. As the instability of nanomaterials in ionic-rich media has been reported and related to shifting key properties and its environmental fate, this study aims at understanding the behaviour of SiNC and SiNC-DCOIT in aqueous media with distinct ionic strengths. Both nanomaterials were dispersed in (i) low- (ultrapure water—UP) and (ii) high- ionic strength media—artificial seawater (ASW) and f/2 medium enriched in ASW (f/2 medium). The morphology, size and zeta potential (ζP) of both engineering nanomaterials were evaluated at different timepoints and concentrations. Results showed that both nanomaterials were unstable in aqueous suspensions, with the initial ζP values in UP below −30 mV and the particle size varying from 148 to 235 nm and 153 to 173 nm for SiNC and SiNC-DCOIT, respectively. In UP, aggregation occurs over time, regardless of the concentration. Additionally, the formation of larger complexes was associated with modifications in the ζP values towards the threshold of stable nanoparticles. In ASW, SiNC and SiNC-DCOIT formed aggregates (<300 nm) independently of the time or concentration, while larger and heterogeneous nanostructures (>300 nm) were detected in the f/2 medium. The pattern of aggregation detected may increase engineering nanomaterial sedimentation rates and enhance the risks towards dwelling organisms. In Europe, more than one million tons of silica engineering nanomaterials (ENMs) were traded in 2022 . Thus, iSeveral types of silica ENMs  can be used in different industrial applications ,4. In paGiven their high surface area, ENMs may experience homo- and hetero-aggregation in natural environments and undergo other physicochemical processes, such as sedimentation, adsorption or coating. Those processes are known to modulate the fate and bioavailability of ENM ,21 and aDespite the progress in understanding the interactions of ENMs in environmental matrices , the beh50 > 100 mg/L) in all models except for freshwater microalgae (EC50 = 83.6 mg/L). In parallel, the hydrodynamic size of the ENM was estimated in different test media. The silica nanoparticles detected in freshwater (575 ± 65 nm) were smaller than what was found in the saline medium (1101 ± 76 nm), which suggests that particle size may have implications for the toxicological effects of this ENM. On the other hand, Figueredo et al. [The characterization of silicon nanoparticles, structurally distinct from SiNC, in seawater, confirmed the formation of aggregates of different sizes with implications for ENM ecotoxicity ,36,37,38o et al. , who tesIn the present study, the ENMs (1) hollow silica nanocapsules (SiNC) and (2) SiNC loaded with the antifouling biocide 4,5-dichloro-2-octyl-4-isothiazolin-3-one (SiNC-DCOIT), two forms of mesoporous silica nanomaterials, were characterized in terms of stability in media of different ionic strengths and concentrations, through time. The results gather data on the sizing and electric charge of these ENMs in standardized test media used in ecotoxicological surveys: artificial seawater and f/2-enriched artificial seawater medium, plus ultrapure water. The dataset will help unveil the transformations experienced by these ENMs when reaching the ocean.® . Analytical grade xylene was provided by Labscan . All other chemicals were obtained from Riedel-de-Haën .Acetonitrile and methanol (HPLC grade) were purchased from Fisher Scientific . The SEA-NINE™ 211N (30% of DCOIT in xylene) was obtained from Rohm and Haas . Tetraethoxysilane , cetyltrimethylammonium bromide  was supplied by Sigma-Aldrich . Pro-Reef salt was purchased from Tropic MarinMesoporous silica nanocontainers (SiNCs) were synthesized according to Chen and collaborators  and the Both ENMs were characterized previously regarding textural properties , biocideSEA-NINE™ 211N (hereinafter referred as DCOIT) was first dried for 30 min under 140 °C in a dry oven to evaporate xylene. The same drying step was performed in SiNC and SiNC-DCOIT. The test dispersions were prepared  in the following: (i) low ionic strength medium, ultrapure water ; and (ii) two high ionic strength media, 0.45 μm filtered artificial seawater with 35 salinity   coupled with energy dispersive spectroscopy using an electron beam energy of 15 kV. Both nanomaterial suspensions were prepared in UP water (1 mg/L), and the corresponding external particle diameter was determined using ImageJ .Intensity-based dynamic light scattering , default high sensitivity settings of 173° backscatter detection, and the hydrodynamic diameter calculated using the Strokes-Einstein equation. As previously described, the ζP was determined in suspensions of ENMs in UP water using a capillary cuvette  and the Smoluchowski’s equation was used to derive the ζP. Except for SEM analysis, all the measurements were performed at 25 °C in triplicate.p = 0.05). Statistical differences in the ζP and DLS of each ENM, regarding different concentrations and time points, were established using a two-way ANOVA followed by a Holm-Šidák multiple comparison test whenever significant differences were attained (p < 0.05). The same approach was adopted to assess the effects of ionic strength on the DLS of each ENM. The statistical analyses were performed using SigmaPlot v.12.5 , and the results were expressed as average values (mean ± standard deviation). The variation within each parameter measured over time was assessed to estimate the stability of the colloidal suspensions [Shapiro-Wilk and Levene’s tests were performed to analyse the dataset normality and homoscedasticity, respectively , reaching the −30 mV threshold after 48 h, but remained approximately −15 mV for SiNC-DCOIT until the end of the essay.Previous studies testing hollow SiNC and SiNC loaded with organic molecules reported similar ζP values under this pH range, corroborating our results ,12,26,48Based on the stability criteria defined by the OECD GD317 (2021) which set ±20% as the maximum deviation from the initial value, the dispersion of SiNC-DCOIT is considered stable, but not the SiNC. Ambrosone and co-authors (2014)  justify There is evidence showing that SiNC colloidal stability could be improved by adjusting the synthesis conditions, such as the catalyst concentration  or the bUnderstanding the ENM stability is important while studying their effects in biota. The presence of organisms, leading to the release of excretion material, organic matter or other potential ligands, is a key factor affecting stability measurements ,52,53. THerein, NOM was absent from the test media. However, studies demonstrated that NOM present in seawater has a minor effect on the stabilization of some ENMs, delaying but not preventing nanoparticle sedimentation ,57,58. AThus, we speculate that the low NOM present in seawater  will notColloidal stability determines the state of aggregation of ENMs  and is m medium) .The DLS analysis recorded values of the polydispersity index above 0.7, reinforcing the heterogeneous nature of the dispersions formed. Consequently, Z-average estimations do not fulfil the set quality criteria. Thus, the ENM’s hydrodynamic size was based on the average value of peaks obtained in size distribution histograms (intensity-based) on the instrument software .p < 0.05). Similar results were detected at 0.01 mg/L SiNC-DCOIT  and divalent ions  in the ASW , the increase in the ionic strength (UP < ASW < f/2) promoted the agglomeration of SiNC, with the largest complexes being detected in f/2 medium at concentrations 0.01 mg/L ( the ASW  might adFor the highest tested concentration (1.0 mg/L), differences in the media ionic strength and composition had no significant effect on the ENMs’ hydrodynamic size. However, particle enlargement and bimodal size distribution were evident, suggesting the presence of agglomerates. When the concentration increases, the frequency of collisions between particles is enhanced, which facilitates the agglomeration of ENMs ,64. Our Time promoted the formation of agglomerates of larger dimensions for both ENMs in the conditions tested, but the effects were more evident with low ionic strength media. In UP water, particle complexes with average dimensions of 451, 318 and 264 nm were reported at 48 h for 0.01, 0.5 and 1.0 mg/L SiNC, respectively. Meanwhile, in ionic-rich media, the minimum and maximum hydrodynamic sizes detected were 235–287 nm for ASW and 276–363 nm for f/2 medium. In SiNC-DCOIT, unimodal dispersions and particle enlargement were evident in UP water by the end of the assay , but differences between time points were only significant at 1.0 mg/L in f/2 medium.Because particle enlargement occurred along with variations on the ζP value for SiNC, as described in 2 NPs, which can last for months in the water column [A decrease in the particle size was registered in 1.0 mg/L SiNC suspended in UP water after 48 h, suggesting the removal of SiNC from the water column by settling, while in the f/2 medium, the same was recorded after 24 h in 1.0 mg/L SiNC. These results indicate faster deposition of ENM aggregates in seawater and differ from what was reported for SiOr column . In SiNCThe agglomeration pattern observed in SiNC (widely used in nanotechnology) and SiNC-DCOIT  indicates a lack of colloidal stability of manufactured nanomaterials in both low- and high-ionic-strength media, as confirmed by the zeta potential and hydrodynamic size estimations. The encapsulation of DCOIT biocide in SiNC contributed to stabilizing the nanomaterial when dispersed. However, the extent of electrostatic repulsive forces was insufficient to prevent particle agglomeration.Saline media, either a natural matrix or presenting as a defined composition, are characterized by high ionic content and complexity. Given the lack of specific nanosafety guidelines for marine water quality, this dataset is paramount to interpreting ecotoxicological results more reliably, as confirmed by the agglomeration or aggregation of nanoparticles and, eventually, sedimentation occurring in high-ionic media.The present results highlight the aggregation of these novel ENMs and the increased bioavailability of these nanomaterials to sessile and sediment-dwelling marine organisms. Despite the benefits of reduced toxicity described for SiNC-DCOIT compared to free DCOIT, the risks associated with the release of coating pain particles containing ENMs should not be neglected.


In this study, the effects of interlayer interaction and biaxial strain on the electronic structure, phonon dispersion and optical properties of monolayer and bilayer BAs are studied, using first-principles calculations within the framework of density functional theory. The interlayer coupling in bilayer BAs causes the splitting of out-of-plane acoustic (ZA) and optical (ZO) mode. For both structures, positive phonon modes across the Brillouin zone have been observed under biaxial tensile strain from 0 to 8%, which indicate their dynamical stability under tensile strain. Also, the phonon band gap between longitudinal acoustic (LA) and longitudinal optical (LO)/transverse optical (TO) modes for monolayer and bilayer BAs decreases under tensile strain. An appreciable degree of optical anisotropy is noticeable in the materials for parallel and perpendicular polarizations, accompanied by significant absorption in the ultraviolet and visible regions. The absorption edge of bilayer BAs is at a lower energy with respect to the monolayer BAs. The results demonstrate that the phonon dispersion and optoelectronic properties of BAs sheet could as well be tuned with both interlayer interaction and biaxial strain that are promising for optoelectronic and thermoelectric applications. However, these 2D materials have inherent weakness in certain aspects. Graphene shows high electron mobility, which makes it particularly attractive for applications in sensors6 and photovoltaic cells7. However, the absence of a notable band gap in graphene restricts its potential application in digital electronics8. The BN monolayer is a semiconductor that possesses high chemical and thermal stability, but it has an excessively large band gap of about 6 eV and behaves nearly as insulator which cannot function as switch in transistor devices11.The distinctive physical properties and potential applications of two-dimensional (2D) materials, including graphene, hexagonal BN, MoS2 and phosphorene have suitable band gaps of about 1.8 eV and 1.5 eV, respectively13. Nevertheless, the carrier mobility of MoS2 is only 200–500 cm2/(V s), which is lower the carrier mobility of graphene, thereby limiting its application in nanoelectronic devices15. The phosphorene-based field effect transistor (FET) devices have larger hole mobility of order 104 cm2 V−1 s−1 have been given, but the devices are chemically instable and easy to degrade18. Therefore, it is significant and necessary to develop novel 2D materials with moderate band bap, high carrier mobility, and high thermal and chemical stability.Monolayer MoS20. These systems are found to be dynamically stable as predicted by the calculated phonon dispersion spectrum9. Density functional theory calculations have shown that the BP, BAs, and BSb monolayers possess direct band gaps around 1.0 eV22. Xie et al. showed that monolayer BP, BAs, and BSb also show high carrier mobilities exceeding 104 cm2 V−1 s−1, which is comparable to the high carrier mobility of graphene23. Therefore, BP, BAs, and BSb monolayers with high carrier mobility, which exceeds than that of phosphorene, and suitable direct band gap are promising channel materials for the production of next-generation 2D FET.Recently, other 2D honeycomb structure of III–V binary compounds, BX  monolayers have attracted intensive research interests26. At room temperature, it has been discovered that zinc-blende BAs exhibits a high thermal conductivity of approximately 1300 W m-1 K-127, semiconducting band structure with a suitable bandgap between 1.5 and 2.0 eV29, and good mechanical performance30. Moreover, among all the III–V compounds, BAs is the most covalent III–V compound31 and it is stable against chemical decomposition32. These intriguing properties motivated researchers to investigate electro-optical, thermal, and transport characteristics of BAs sheets in greater depth36. The studies have shown that BAs monolayer exhibits semiconducting properties with a direct band gap, which can be modulated by applying the strain and it is dynamically stable, as evidenced by the phonon mode behavior38. The h-BAs monolayer has a smaller bandgap than other III-V group materials such as BN, AlN, and BP monolayer. This suggests that the BAs monolayer has a higher electrical conductivity than these other materials, which could make it a promising material for applications in alkali metals-ion batteries39. The BAs monolayer is a promising material for ideal alloy systems due to its greatest covalent character, stability against chemical decomposition and dissolution, and well-aligned valence bands43. In addition, BAs monolayer possess high carrier mobility, high thermal conductivity comparable to graphene, and exhibits photoactivity under illumination by visible and UV light45. Research on the electrical transport properties of hexagonal BAs has revealed behaviors suitable for short-wavelength optoelectronic devices38. Theoretical studies have shown that BAs sheet has the potential to be used as gas sensor with high sensitivity and selectivity46. The combination of these useful properties makes BAs monolayer a promising 2D material for next-generation photonic and electronic applications.Researchers have synthesized bulk zinc-blende BAs and confirmed its properties through both theoretical predictions and experimental verifications50. By deforming the lattice parameters of a 2D material, strain can alter the electronic, optical and phononic properties of the material in various ways. For instance, strain can induce changes in the bandgap, carrier mobility, and thermal conductivity of a 2D material, leading to enhanced or new functionalities. The impact of strain on the phonon dispersion can affect the thermal conductivity of the material.Applying the strain on 2D materials is a highly effective method for modifying their properties53. In this paper, we investigate the phonon dispersion, electronic, and optical properties of bilayer BAs under strain, which has not been done before. By comparing the results with the corresponding monolayer cases, we provide a comprehensive description of the physical outcomes.Bilayer systems are of great interest as they offer additional control over properties compared to monolayers, through the interlayer interactions which can be tuned via stacking orientation, interlayer spacing, external electric fields, etc.54 code to study the electronic and optical properties. For exchange–correlation functional, the Perdew-Burke-Ernzerhof (PBE) type of the generalized gradient approximation (GGA) was implemented55. In order to determine band gaps with higher accurately, we have used the Heyd–Scuseria–Ernzerhof (HSE06) hybrid functional with the HONPAS package57. The selection of the double zeta polarized (DZP) basis set was accompanied by setting the orbital confining cut-off at 0.01 Ry. The value of the mesh cutoff for real space projection is 500 Ry. The threshold value for the total energy and forces during structural optimization is set to 10-6 eV and 0.01 eV/Å, respectively. The first Brillouin zone is sampled with a 10 × 10 × 1 Monkhorst–Pack grid of k-points. For optical properties, a sufficiently dense k-point grid of 150 × 150 × 1, within the Monkhorst–Pack scheme is used. Optical broadening of 0.15 eV was used for optical spectra.We have used density functional theory (DFT) as implemented in SIESTA58. The DFT calculations with a plane-wave basis set with a 50-hartree kinetic energy cutoff and, throughout, Coulomb truncation is included. During the process of structural optimizations, the relaxation of atoms was carried out until the force acting on each atom reached a convergence value of 0.1 mHa bohr−1. To capture the phonon properties, a 4 × 4 × 1 supercell is used. To prevent interlayer interactions, a vacant space of 20 Å separates the sheets.To structural optimizations and phonon dispersion calculations were performed using the JDFTx package. Incorporation of the van der Waals (vdW) interaction was achieved by implementing the dispersion correction through the use of the DFT-D2 method0)/a0 is used, where a0 represents the unstrained lattice constant and a represents the strained lattice constant.To simulate the in-plane tensile strain, the formula ε = (a − a59:The absorption coefficient α(ω) and reflectance R(ω) can be calculated by the following formula61.The optimized geometric structure of BAs monolayer is similar to graphene where alternating B and As atoms replace carbon atoms in the hexagonal lattice with a space group of P-6m2. The relaxed lattice parameters of BAs are a = b = 3.39 Å with B–As bond length of 1.95 Å and bond angle of 120° which coincide with previous results1, AB, AB1 and AB2 were considered  stacking pattern, the B atoms of top layer are located above the B (As) atoms of bottom layer. For AB stacking pattern, the B atoms on top layer are located above the As atoms on bottom layer, while As atoms on top layer centered above the hexagon of the bottom layer. In the AB1 (AB2) stacking pattern, the B (As) atoms on top layer are located above the B (As) atoms on bottom layer, while As (B) atoms on top layer centered above the hexagon of the bottom layer. After geometry optimizations, the interlayer distances of bilayer BAs for the AA, AA1, AB, AB1 and AB2 stacking patterns are 4.12, 3.78, 3.37, 3.57 and 3.85 Å, respectively. The binding energy (Eb) was obtained as the difference between the total energy of the BAs bilayers (Etot) and the isolated BAs monolayers (Em), as follows62:In order to find the most stable stacking mode of the BAs bilayer, five stacking patterns, namely AA, AA1, AB, AB1 and AB2 stacking patterns are − 40.55, − 63.86, − 95.51, − 84.48 and − 56.19 meV, respectively. The shortest interlayer distance and the smallest binding energy of the AB stacking pattern confirm that the AB stacking pattern is the most energetically favorable. After the structural optimizations, the planer bilayer structure is converted into buckled one, due to the interlayer interactions. For bilayer BAs, the optimized value of buckling height and B-As bond length is 0.96 Å and 1.96 Å, respectively.The calculated binding energy for the AA, AAThe calculated electronic band structures along with the corresponding partial density of states (PDOS) of monolayer and bilayer BAs is presented in Fig. The bilayer BAs is an indirect gap semiconductor. The CBM is situated at the K point while the VBM is slightly far from the K point. The calculated band gap is 0.63 eV using PBE method and 0.96 eV using HSE06 method. The calculated PDOSs show the contributions of individual orbitals of monolayer and bilayer BAs. The VBM is mainly contributed by p orbitals of As, and CBM mainly comes from the p orbitals of B.The calculated band structures of monolayer and bilayer BAs subjected to different biaxial strains is demonstrated in Fig. Figure 1, TA and TO1, LO2 and LO3, TO2 and TO3) implying that the main effect of the interlayer interactions is due to the ZA modes. The weak interlayer coupling causes the splitting of out-of-plane ZA and ZO modes to ZA and ZO1 and ZO2 and ZO3. The splitting of ZA and ZO1 and ZO2 and ZO3 has an appreciable magnitude near the Γ point.Figure Next, we study the effect of in-plane biaxial strain on the phonon dispersion of monolayer and bilayer BAs. The structural optimizations show that the value of buckling is decreased under tensile strain. Figures For monolayer BAs, by increasing the tensile strain the LO/TO, LA and TA phonon modes become soften which can be attributed to the weakness of atomic bond strength by increasing the lattice constant. The phonon band gap between LO/TO and LA modes decreases by increasing the tensile strain. A hardening of the ZO and ZA modes is also found for monolayer BAs under biaxial tensile strain and the hybridization between LA/TA and ZO mode is removed. For all applied tensile strains, the acoustic TA/LA/ZA phonons remain degenerate at Γ-point.2, LO3/TO2, TO3) phonon modes shift to lower mode frequencies leading to phonon softening and the phonon band gap between  and LA and LO1 decreases. The ZA mode becomes harden, similar to the monolayer structure.For bilayer BAs, by applying the tensile strain the )LO1(ω) + iε2(ω) where ε1(ω) and ε2(ω) are the real and imaginary terms, respectively. By counting the matrix elements of interband optical transitions between occupied and unoccupied states using the random phase approximation (RPA), it is possible to identify the imaginary part. The Kramers–Kronig relations can then be applied to compute the real part. With both the real and imaginary components, it becomes feasible to calculate other optical parameters of a material, including its absorption and reflectivity spectra.In order to examine how interlayer interaction and strain affect the BAs sheet, we calculated the most important optical parameter, namely, the complex dielectric function which is represented by: ε(ω) = ε1(ω) and imaginary part ε2(ω) of dielectric function, and reflectance R(ω) for monolayer and bilayer BAs without and with strain are investigated and demonstrated in Figs. The frequency dependent absorption coefficient α(ω), real εFigures When light is polarized along the z direction, the unstrained monolayer BAs sheet exhibits an almost negligible absorption in the visible region. However, it demonstrates a robust absorption feature in the UV region with significant absorption peaks at 6.92, 9.80, 11.11, 12.45, 13.10, 14.76, and 16.42 eV. The absorption spectrum of the unstrained bilayer BAs has a small peak at visible region and several absorption peaks at UV region. The unstrained bilayer BP has main absorption peaks at 3.22, 6.67, 10.19, 13.62, 16.15 and 17.32 eV. It can be observed that the number of peaks in the bilayer structure is more than the monolayer structure and the peaks become broader, due to the interaction between the layers along the z direction.The absorption spectra of monolayer and bilayer BAs show an effective absorption of light in both the visible and UV regions. This property makes them promising candidates for the development of optoelectronic devices that operate at short wavelengths, where high absorption efficiency is critical. Additionally, their ability to absorb UV light could make them useful in applications where protection against UV radiation is important, such as in sunscreen or protective coatings. Overall, the demonstrated ability of BAs to absorb light in multiple regions of the electromagnetic spectrum highlights their potential for a range of applications in the field of materials science and optoelectronics.2(ω) of dielectric function for monolayer and bilayer BAs under biaxial tensile strain is demonstrated in Figs. 2(ω) peak up to 6 eV when subjected to z-direction polarization, which suggests that the material has no optical absorption within this spectral range. For bilayer BAs, a multiple peak is observed in the visible region from 1.9 to 3.4 eV.The calculated imaginary part ε1(ω), provides insight into both the electronic polarizability and dispersion effects of the material. Figures 1(ω) for light polarized along the x and z directions for monolayer and bilayer BAs, respectively. The key parameter of interest in this part is the static dielectric constant, which is determined by the magnitude of ε1(ω) at ω = 0. The static dielectric constant of the unstrained monolayer BAs has been calculated to be 4.45 and 1.31 along the x and z directions, respectively. The calculated ε1(0) for bilayer BAs, is found to be 8.26 and 2.23, along the x and z directions.The real part of the dielectric function, ε2(ω) values.The calculated reflectance spectra R(ω) for monolayer and bilayer BAs under biaxial tensile strain is demonstrated in Figs. 1(ω) and ε2(ω) for monolayer and bilayer BAs using HSE06 method are shown in Figs. For light polarized along the x direction, the main absorption peaks of monolayer and bilayer BAs become red-shifted and their intensities decreases as the applied strain changes from ε = 0% to ε =  + 8%. Also, for monolayer and bilayer BAs the first peak of ε2(ω) becomes blue-shifted, while the second and third peaks become red-shifted as the strain changes from ε = 0 to ε =  + 10%. Similar behavior is observed in the reflectance spectrum. The absorption edge for monolayer and bilayer structures remains almost unchanged under application of tensile strain. Therefore, application of compressive strain decreases the absorption of monolayer BAs by decreasing the intensity and width of absorption. The calculated εUsing the first-principles calculations based on DFT, the impact of interlayer interaction and biaxial strain on the band structure, phonon dispersion and optical characteristics of BAs sheet was systematically studied. Based on the phonon dispersion curve calculations, both the monolayer and bilayer BAs are dynamically stable under zero strain. The phonon dispersion of bilayer BAs is very similar to the one of monolayer BAs. Almost no change is observed in the in-plane doubly degenerated bands while, the interlayer coupling causes the splitting of out-of-plane modes. When the tensile strains is applied, both the monolayer and bilayer structures are dynamically stable. For light polarized along the x direction, the main absorption peaks of monolayer and bilayer BAs become red-shifted and their intensities decreases by increasing the tensile strain. This study implies the potential applications of BAs sheet for optoelectronic and thermoelectric devices in nanoscale.Supplementary Figures.


Community-based organizations (CBOs) are important equity-promoting delivery channels for evidence-based interventions (EBIs). However, CBO practitioners often cannot access needed support to build EBI skills. Additionally, the capacity-building literature is hindered by inconsistent definitions, limited use of validated measures, and an emphasis on the perspectives of EBI developers versus implementers. To address these gaps, we explored commonalities and differences between CBO practitioners and academics in conceptualizing and prioritizing core EBI skills.We utilized Group Concept Mapping, a mixed-methods approach connecting qualitative data  and quantitative data  to create conceptual maps integrating perspectives from diverse participants. A total of 34 practitioners and 30 academics working with cancer inequities participated in the study.Participants nominated 581 core skills for EBI use, and our team (including practitioners and academics) identified 98 unique skills from this list. Participants sorted them into conceptual groups, yielding five clusters: (1) using data and evaluation, (2) selecting and adapting EBIs, (3) connecting with community members, (4) building diverse and equitable partnerships, and (5) managing EBI implementation. The ordering of importance and presence of skill clusters were similar across groups. Overall, importance was rated higher than presence, suggesting capacity gaps.There are helpful commonalities between practitioners’ and academics’ views of core EBI skills in CBOs and apparent capacity gaps. However, underlying patterns suggest that differences between the groups’ perceptions warrant further exploration. Many implementation strategies (the tactics used to support the integration of research evidence into routine practice) include efforts to train implementers . HoweverFirst, the bulk of the capacity-building literature focuses on skills held by staff of agencies with vastly different organizational contexts, resources, and professional development opportunities compared to CBOs  –7. SeconWe furthered our exploration of these issues using US cervical cancer inequities as an exemplar. This was a suitable choice for two reasons. First, despite the rich evidence base related to prevention , in 2018 there were about 12,000 new cases of cervical cancer, with disproportionate disease burden among racial and ethnic minorities, populations of low socioeconomic status, and those living in rural areas –17. SecoWe used group concept mapping to identify a parsimonious, prioritized list of skills for potential capacity-building interventions that draw on practitioner and academic expertise. Group concept mapping is a mixed-method approach that supports the development of a shared conceptualization among diverse participants . This meTM web-based platform .” Given that it is an unstructured sort, there was no pre-determined number of groups or piles that participants were expected to make. The only restrictions in the sorting task were that there could not be: (a) as many piles as there were statements, i.e., each pile having only one item in it; (b) one pile consisting of all statements; or (c) a “miscellaneous” pile that included statements that could not otherwise be grouped. Participants also named each pile with a title that captured the general theme of the statements contained.For the rating activity, participants rated each of the 98 statements on a five-point Likert-like scale for two variables: importance and presence. The importance variable supports prioritization of skills. The presence variable supports identifying what is available in CBO settings. Together, they point to gaps to be addressed in future interventions . For impTM, we created a similarity matrix for each participant in the form of a 98 × 98 matrix (one column and one row for each statement). For each cell, a “1” was placed at the intersection of two items if the participant grouped them and a “0” if the participant did not group the items together. The individual participant matrices were aggregated into a combined matrix, which was analyzed using non-metric multidimensional scaling analysis with a two-dimensional solution [Analysis (sorting): Utilizing groupwisdomsolution . This anThe x, y coordinates for each point were then used as the input for the hierarchical cluster analysis utilizing Ward’s algorithm  as the bx-axis) and average presence rating (y-axis) and is then divided into quadrants. The ladder graph also compares average ratings; however, unlike the go-zone map, it compares the average rating of each cluster instead of each statement. Analysis in groupwisdomTM displays the ladder graph using two side-by-side vertical axes, comparing clusters across participant groups.Analysis (rating): In addition to the cluster map solution, we created graphical representations of the statement and cluster rating data through ‘go-zone’ maps and ‘ladder’ graphs. The go-zone map is a bivariate x,y graph that plots each statement using its average importance rating . We solicited feedback from these advisors to define the project’s scope, evaluate the pared-down list of statements after the idea generation phase, review and interpret the cluster solution, and determine how best to share results with participants and other stakeholders. They also participated in the development of this manuscript and are co-authors. One advisor joined later than the others and contributed to the final two feedback activities. We also shared preliminary results with all participants in a brief that included an invitation to comment and share interpretations. We received feedback from 7 of the 64 participants identifying points of interest and ideas for the next steps in the research.The Harvard University IRB reviewed all study procedures and materials, and the study was deemed exempt from review. At each stage, participants gave their consent for participation. All participants were offered gift cards of $50 for interviews, $75 for idea generation, and $100 for the sorting/rating activity.The group concept mapping activities included 64 participants, described in Table A total of 372 responses were offered through the web-based brainstorming activities and 142 from the interviews. Following the steps outlined by Kane & Rosas , the teaParticipants sorted statements into groups that seemed meaningful to them. After a systematic review of multiple solutions, a five-cluster solution was identified as the most parsimonious depiction of the point arrangement, as shown in Fig. 1 and we offer a brief description and an exemplar here. The “Using data and evaluation” cluster included skills to evaluate adaptations and process and impact outcomes. An exemplar skill was “how to develop and use ongoing monitoring, audit and feedback systems to collect data throughout the implementation.” The “Selecting and adapting EBIs” cluster emphasized the need to choose an appropriate EBI and then adapt it to balance local and organizational needs while attending to the fidelity of program delivery. An exemplar skill was “how to adapt the intervention to their specific population/situation without losing the fidelity of the intervention.” The “Connecting with community members” cluster emphasized skills related to centering the community receiving services and ensuring community voice impacts EBI delivery. An exemplar skill was “how to create bi-directional channels of communication with communities being served to get insight, feedback, and buy-in.” The “Building diverse and equitable partnerships” cluster emphasized skills relating to collaboration and Partnership with a wide range of stakeholders, including those in healthcare, public health, and academic institutions. The cluster also included skills related to relationship development and management. An exemplar skill was “how to demonstrate dependability & trustworthiness to partners.” The “Managing EBI implementation” cluster included a range of skills related to understanding how the EBI works and seeking and utilizing the necessary resources to support it. An exemplar skill was “how to access appropriate technical assistance and implementation guidance as needed.”The list of items in each cluster is included in Supplementary File In addition to understanding the clusters of items, we also examined the map to understand the broader patterns present in the configuration. Two dimensions were interpreted along separate axes based on the arrangement of points and clusters see Fig. . One potAnother potential axis of interest connected “Managing EBI implementation” and “Connecting with community members.” This can be described as attending to the requirements of the EBI as developed on one end and the requirements shared by community members and stakeholders on the other. Items on the EBI-related side of the axis suggest a gradual transition from a focus on understanding EBI elements (closer to the center of the map) to administrative skills (farther from the center of the map). Items on the stakeholder-driven side of the axis related to connecting with community members emphasize a gradual transition from centering and relating to community (closer to the center of the map) to communication-related adaptations made to the EBI (farther from the center of the map).r = 0.60) indicates a moderately strong, positive relationship between item-level ratings of importance and presence. Encouragingly, there were 40 skills in the green zone (the quadrant representing above-average importance and presence). The yellow quadrant is of greatest interest from a capacity-building standpoint, which includes skills that participants ranked as higher in importance but lower in presence. Of the 15 statements in this quadrant, five addressed equity considerations, e.g., how to evaluate the implementation process with an equity lens and how to use evaluation to ensure equity in program reach. Three focused on community engagement, emphasizing ongoing engagement and participation of community members in EBI processes. Another three addressed evaluation, two addressed adaptation for local context, one addressed ongoing stakeholder engagement, and one addressed EBI selection. The statements are labeled with numbers in Fig. 1 for further exploration.We utilized a “go-zone” map to compare the importance and presence among all the rated statements. As seen in Fig. We also examined how presence and importance were rated differently by cluster. As seen in Table M = 4.18, SD = 0.75, Range = 1.35) tended to rate items on the scale of importance higher than academics , the distribution of average ratings were comparable between the two groups. Thus, we observed consistency between the two groups in the average rating scores across all items. Moreover, the ordering of clusters between the two groups was quite similar, except for the “Using Data and Evaluation” and “Managing EBI Implementation” clusters. The pattern match correlation, which describes the pattern of average cluster ratings across groups, was 0.91, indicating a high magnitude of agreement between groups.As seen in Fig. M = 3.32, SD = 0.87, Range = 1.53) and within a narrower range than academics . Although the level and range of the ratings were observed to be different, the distributions of average ratings were not. This suggests that CBO practitioners perceive a fairly similar level of presence for all five skills, compared to a broader gap for academics, e.g., between skills for connecting with community members compared to using data and evaluation. The ordering of the clusters (in terms of presence) was markedly different between the two groups. However, the pattern match correlation, which describes the pattern of average cluster ratings across groups, was 0.83, indicating a high magnitude of agreement between groups.A similar examination of ratings for the presence of skills is presented in Fig. This study examined how academics and practitioners conceptualize the core skills CBO staff need to implement cervical cancer EBIs, with a focus on health equity. The model of core skills echoed many of the skills common to general models of EBI use but grouped them in different ways and also emphasized differences in skills for community member engagement versus partnership development and sustainment. The data also highlighted potential opportunities to support capacity-building through an extended focus on health equity in EBI use. Practitioner capacity to use EBIs is an important driver of implementation outcomes and, ultimately, health impact and is thus a critical area of focus ,29,30.We identified five distinct clusters based on how participants sorted the skills. Overall, the skills emphasized by participants were consistent with common models of EBI use: engaging stakeholders, using data and evaluation, adapting EBIs, and selecting an EBI ,7. In thInterestingly, we found statistically significant differences between the ratings of skills in each cluster in importance (higher) compared to presence (lower). This suggests a strong need for capacity-building interventions so that the presence of these skills in CBOs can match the level of importance. Both groups ranked “Managing EBI implementation” the lowest or second-lowest in terms of presence. One explanation may be the range of complex skills in this grouping, from finding funding for EBIs to understanding the mechanisms by which EBIs create behavior change. This complexity is echoed by models describing the multi-level determinants of implementation, from EBI characteristics to contextual barriers .There are several skills in the high-importance, high presence quadrant, which suggests a strong foundation for skill-building. The roughly 15% of skills in the high-importance, low-presence quadrant are prime areas to focus on in capacity-building work. One-third of these skills were related to integrating equity considerations into EBI utilization. This reflects a broader trend in the field of implementation science to address equity considerations more explicitly and in a manner integrated into EBI utilization and research . We alsoFinally, we found that CBO practitioners’ ratings for the presence of skills had a smaller range across clusters than the academics’ ratings. This is worth further investigation as it may be an important source of disconnect if CBO practitioners perceive the core skills to be available at about the same level, but academics perceive a subset of skills as lacking in practice settings. Similarly, if the source of disconnect reflects distance of the practitioner or academic from actual implementation efforts, that will be important to understand. At the same time, the general overlap in rating order offers a useful point of agreement to build on. This point is worth exploring further, given that the participants all focused on cancer inequities.As with any study, the findings must be placed in the context of strengths and limitations. One limitation of the study is that we used our networks and public listings to identify participants. Thus, we would not have been able to reach CBOs that are less visible and under-resourced. On a related note, the bulk of participants were from the Southern or Eastern US and there may be geographic variations that are unexplored in this study. However, the diversity of populations served by the CBOs in the sample (across a range of characteristics) suggests that we successfully recruited a diverse sample. The rigor of the analysis supports transferability to other settings in the US. We suggest this geographic boundary given the unique landscape for CBO activity in the USA, that may or may not be relevant in other countries. Another limitation is that important distinctions associated with each group might be difficult to see with the aggregation of multiple perspectives. For this reason, we will conduct subgroup analyses in the project’s next phase. Finally, the conceptual model presented here is bounded by the content generation process. We used standard models of EBI use as a starting point for our examination, and although many ideas were generated – presumably leading to some level of content saturation – it is still limited by those providing the input. At the same time, the study has several strengths. We were able to apply a group-based process to generate a constellation of ideas that are represented in the conceptual map presented here. By taking advantage of the positioning and relationships between nominated ideas, we could fully exploit the data set . We recrIn conclusion, the findings from this study highlight the need to look beyond the traditional skills of evidence-based public health and evidence-based programming and identify ways to incorporate principles of health equity and community engagement to align goals. The work also points to a need to understand in greater detail how differences between practitioners and academics may be masked by a common mental model and where the greatest needs for capacity-building lie. In this way, capacity-building efforts will be more effectively aligned with equity-focused CBOs, setting the stage for greater impact of EBIs in communities that can benefit greatly from them.