This paper details the comprehensive activities conducted in a laboratory setting to assess the Structural Health Monitoring (SHM) of prefabricated building envelopes. Aimed at enhancing the structural evaluation of buildings, the focus of this research lies in employing nondestructive sensors for SHM with the objective to advance in the understanding and assessment of facade conditions. The paper outlines the methodologies employed, starting with a modal analysis to define the structural vibration's modal frequency. Subsequently, tests were defined and executed to validate building envelope compliance in case of stress typical of high-rise building. Throughout these tests, continuous monitoring of the façade was conducted using both conventional (accelerometers, extensimeter washers) and non-conventional sensors (Fiber Optic Sensing) The gathered data underwent thorough processing and analysis to provide an overall perspective on the structure's behavior during the stress test. The investigation aimed to identify whether specific physical phenomena correlate with distinct signals and to evaluate if continuous façade monitoring over the building's lifespan aids in preventing potential structural damage. Moreover, two modal analyses were conducted to compare final data and frequencies with earlier data, enabling the detection of any structural alterations. The results from compliance testing and structural analysis yielded noteworthy insights contributing to the evolving field of structural health monitoring, offering valuable findings that advance our ability to proactively manage and maintain the integrity of building structures.

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

Chinese texts often feature a substantial volume of normative content, and their analysis has increasingly become a focal point in recent semantic analysis endeavors. Enhancing the effectiveness of text classification and clustering is pivotal in unveiling the intricate semantics within extensive textual data. Empirical research within the realm of computational social science has underscored the need for improved explanatory power when it comes to general text clustering methods applied to normative texts. This study introduces an innovative hierarchical clustering method that incorporates part-of-speech (POS) features and pioneers a novel semantic network model. It achieves this by amalgamating a POS-based feature weight calculation method with hierarchical clustering techniques. To assess its efficacy, the method is rigorously evaluated across three diverse text datasets, encompassing normative reports, news articles, and social media content. The experimental results unequivocally demonstrate the superior performance of the POS-HC method, surpassing the traditional TF and TF-IDF feature extraction methods in terms of clustering accuracy, and surpassing some existing clustering methods. Furthermore, its classification effectiveness exhibits notable advantages, particularly in the semantic classification of normative texts.

This paper presents a study about the integration of Piezoelectric Energy Harvesting Systems (PE-EHS) in building envelopes for powering Fiber Bragg Grating (FBG) sensors, enabling efficient and low-consumption monitoring with the objective to leverage Structural Health Monitoring (SHM). The research includes preliminary tests conducted in a real environment to validate the PE-EHS when fully integrated into the façade, capturing mechanical vibrations generated mainly by wind loads. Based on these activities, the final configuration of PE-EHS is defined to provide a complete system for façade monitoring. This integrated system includes the Piezoelectric Generator (PEG), Supercapacitor (SC), Power Conditioner Circuit (PCC), Fibre Optic Sensing (FOS) Interrogator, and the IoT Gateway trans-mitting measurement data within an Internet of Things (IoT) monitoring platform. This configuration is tailored to address the challenges related to the structural integrity of building envelopes. Results demonstrate a potential for a stand-alone solution in the façade sector, but, raising issues for certain limitations, requiring further investigation. In particular, the study emphasizes constraints related to the energy production of PE-EHS for façade integration. It highlights the necessity to carefully consider these limitations within the broader context of their applicability, providing insights for the informed deployment of Piezoelectric Energy Harvesting technology in building envelope monitoring.

In this work, we explore the ability to dynamically group the Wind Turbine (WT) of a Wind Farm (WF) based on the behaviour of some of their Supervisory Control And Data Acquisition (SCADA) signals to detect the turbines that exhibit abnormal behaviour. We centre this study on a small WF of five WTs. We use the fact that the same signals from different turbines in the same WF coherently evolve temporally in a time domain, describing very similar waveforms. In this contribution, we use averaged signals from the SCADA system and omit maximums, minimums and standard deviations, focusing mainly on velocities and other slowly varying signals. For the temporal analysis, sliding windows of different temporal durations and overlapings are explored. The capability to automatically identify WTs whose signals differ from the group’s behaviour can alert and program preventive maintenance operations on such WTs before a major breakdown occurs.

With the significant annual increase in the market demand for biopesticides, the industrial production demand for predatory mites, which hold the largest market share among biopesticides, has also been rising.To achieve efficient and low energy consumption control of predatory mite breeding environmental parameters, accurate estimation of breeding environmental parameters is necessary. This paper collects and pre-processing hourly time-series data of temperature and humidity from industrial breeding environments. Time series prediction models such as SVR, LSTM, GRU, and LSTNet are applied to model and predict historical data of the breeding environment. Experiments validate that the LSTNet model is more suitable for such environmental modeling. To further improve prediction accuracy, the training data for the LSTNet model is enhanced using hierarchical clustering of time-series features. After augmentation, the root mean square error (RMSE) of temperature prediction decreased by 27.3%, and the RMSE of humidity prediction decreased by 32.8%, significantly improving the accuracy of multi-step predictions and providing substantial industrial application value.

In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 0.414\% of these 3617 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.

Ebolavirus has a membrane envelope decorated by trimers of a glycoprotein (GP), which is responsible for host cell attachment and membrane fusion. Therefore, GP is a primary target for antiviral drugs development. Here, this article reports the first, to my knowledge, set of structural analysis of all Ebolavirus GP structures as of March 10, 2020, and also a brief update of the structurally identified electrostatic features of the Ebolavirus GP structures in both apo (unliganded) state and also in bound states with a series of small compounds, including a variety of approved drugs. With this comprehensive set of structural analysis, this article puts forward a hypothesis of two Achilles' heels of Ebolavirus GP structure, where the formation of two interfacial salt bridges, instead of destabilizing the prefusion conformation of Ebolavirus GP, constitutes a positive contribution towards the structural rigidification of the prefusion conformation of the Ebolavirus GP structure, thereby acting against GP-mediated Ebolavirus cell entry and/or preventing fusion between the viral and endosome membranes.

Survivability is a critical concern in WSNs, heavily influenced by energy efficiency. Addressing severe energy constraints in WSNs requires solutions that meet application goals while prolonging network life. This paper presents an energy optimization approach (EOAMRCL) for WSNs, integrating the Grey Wolf Optimization (GWO) for enhanced performance. EOAMRCL aims to enhance energy efficiency by selecting the optimal duty-cycle schedule, transmission power, and routing paths. The proposed approach employs a centralized strategy using a hierarchical network architecture. During the cluster formation phase, an objective function, augmented with GWO, determines the ideal cluster heads (CHs). The routing protocol then selects routes with minimal energy consumption for data transmission to CHs, using transmission power as a metric. In the transmission phase, the MAC layer forms a duty-cycle schedule based on cross-layer routing information, enabling nodes to switch between active and sleep modes according to their network allocation vectors (NAV). This process is further optimized by an enhanced CSMA/CA mechanism, which incorporates sleep/activate modes and pairing nodes to alternate between active and sleep states. This integration reduces collisions, improves channel assessment accuracy, and lowers energy consumption, thereby enhancing overall network performance. EOAMRCL was evaluated in a MATLAB environment, demonstrating superior performance compared to EEUC, DWEHC, and CGA-GWO protocols, particularly in terms of network lifetime and energy consumption. This highlights the effectiveness of integrating GWO and the updated CSMA/CA mechanism in achieving optimal energy efficiency and network performance.

Building envelope can play a crucial role in building improvement efficiency and the adoption of Phase Change Materials (PCMs) coupled with transparent elements may (i) allow a better control of the heat flows from/to the outdoor environment, (ii) increase the exploitation of solar energy at building scale and (iii) modulate the light transmission to avoid glare effects. Starting from a literature review of experimental works, this research identifies the main possible integration of PCM in transparent/translucent building envelope components (in glazing, in shutters and in multilayer façade system) drawing a global picture potentials and limitations of these technologies. Transparent envelopes with PCMs have been classified from the simplest “zero” technology, which integrates the PCM into the double glass unit (DGU), to more complex solutions – with different numbers of cavities of the glass (TGU), different position of PCM layer (internal/external shutter), and in combination with other materials (TIM, aerogel, prismatic solar reflector, PCM curtain controlled by an electric pump). The results of the analysis are resumed in a SWOT (strengths, weakness, opportunities and threats) analysis table to underline strengths and weaknesses of transparent building envelope components with PCMs, and to indicate opportunities and threats for future research and building application.

Clustering is a data mining task used for the data extraction from the data bases or files. Clustering is used to find unknown groups present in the data sources like files or data bases. This paper focuses on clustering algorithms performance dependency on the parallel clustering platforms and the clustering algorithms along with their clustering criteria. The problems with the present Traditional clustering algorithms were throughput and data source size changes (scalability). So they can’t address the big data. So for handling the huge volumes of data, parallel clustering algorithms along with clustering criteria were used. For processing the big Data Parallel clustering algorithms are of two types based on computing platforms used. They were the horizontal scaling platforms and vertical scaling platforms.

The influence of the film thickness and the substrate’s refractive index on the surface mode at the superstrate is an important study step that may help clearing some of the misunderstandings surrounding their propagation mechanism. A single sub-wavelength slit perforating a thin metallic film is among the simplest nanostructure capable of launching Surface Plasmon Polaritons on its surrounding surface when excited by an incident field. Here, the impact of the substrate and the film thickness on surface waves is investigated. When the thickness of the film is comparable to its skin depth, SPP waves from the substrate penetrate the film and emerge from the superstrate, creating a superposition of two SPP waves, that leads to a beat interference envelope with well-defined loci which are the function of both the drive frequency and the dielectric constant of the substrate/superstrate. As the film thickness is reduced to the SPP’s penetration depth, surface waves from optically denser dielectric/metal interface would dominate, leading to volume plasmons that propagate inside the film at optical frequencies. Interference of periodic volume charge density with the incident field over the film creates charge bundles that are periodic in space and time.

Major (exo)planetary and satellite bodies seem to concentrate at intermediate areas of the radial 1 distributions of all the objects orbiting in each (sub)system. We show that angular-momentum transport during secular evolution of (exo)planets and satellites necessarily results in the observed intermediate accumulation of the massive objects. We quantify the ‘middle’ as the mean of mean motions (orbital angular velocities) when three or more massive objects are involved. Radial evolution of the orbits is expected to be halted when the survivors settle near mean-motion resonances and angular-momentum transfer between them ceases (gravitational Landau damping). This dynamical behavior is opposite in direction to what has been theorized for viscous and magnetized accretion disks, in which gas spreads out and away from either side of any conceivable intermediate area. We present angular momentum transfer simulations in few-body systems, and we calculate the tidal dissipation timescales and the physical properties of the mean tidal field in planetary and satellite (sub)systems.

Galectins are β-galactosyl-binding proteins that fulfill essential physiological functions. Recently, we introduced galectin-1 (Gal-1) and galectin-3 (Gal-3) as fusion proteins of a His6-tag, a SNAP-tag, and a fluorescent protein. We characterized their binding in ELISA-type assays and their application in cell-surface binding. In the present study, we have constructed further fusion proteins of galectins with fluorescent protein color code. The fusion proteins of Gal-1, Gal-3, and Gal-8 were purified by affinity chromatography. For this, we have prepared glycoprotein affinity resins based on asialofetuin (ASF) and fetuin and combined this in a two-step purification with Immobilized Metal Affinity chromatography (IMAC) to get pure and active galectins. Purified galectin fractions were analyzed by size-exclusion chromatography. The binding characteristics to ASF of solely His6-tagged galectins and galectin fusion proteins were compared. As an example, we demonstrate a 1.6-3-fold increase in binding efficiency for HSYGal-3 (His6-SNAP-yellow fluorescent protein-Gal-3) compared to the HGal-3 (His6-Gal-3). Our results reveal an apparent higher binding efficiency for galectin SNAP-tag fusion proteins compared to His6-tagged galectins which are independent of the purification mode. This is also demonstrated by the binding of galectin fusion proteins to extracellular glycoconjugates laminin, fibronectin, and collagen IV. Our results indicate the probable involvement of the SNAP-tag in apparently higher binding signals, which we discuss in this study.

Nuclear vacuoles are specific structures present on the head of the human sperm of fertile and non-fertile men. Human sperm head vacuoles have been previously studied using motile sperm organelle morphology examination (MSOME) and their origin related to ab-normal morphology, abnormal chromatin condensation and DNA fragmentation. How-ever, other evidences argued that human sperm vacuoles are physiological structures and consequently, to date, the nature and origin of the nuclear vacuoles remains to be elucidat-ed. Here, we aim to define the incidence, position, morphology, and molecular content of the human sperm vacuoles using transmission electron microscopy (TEM) and immuno-cytochemistry techniques. Results showed that ~50% of the analyzed human sperm cells (n = 1908; 17 normozoospermic human donors) contained vacuoles mainly located (80%) in the anterior head region. A significant positive correlation was also found between the sperm vacuole and nucleus areas. Furthermore, it was confirmed that nuclear vacuoles were invaginations of nuclear envelope containing cytoskeletal proteins and a cytoplas-mic enzyme, discarding a nuclear or acrosomal origin. According to our findings, these human sperm head vacuoles are cellular structures which take the origin from nuclear invaginations and contain perinuclear theca (PT) components, allowing to define a new term of ‘nuclear invaginations’ rather than ‘nuclear vacuoles.

Zika virus (ZIKV) is a mosquito-borne flavivirus, and its infection may cause severe neurodegenerative diseases. The outbreak of ZIKV in 2015 in South American has caused severe human congenital and neurologic disorders. Thus, it is vitally important to figure out inner mechanism of ZIKV infection. Here, our data suggested that the ubiquitin-specific peptidase 38 (USP38) played an important role in host resistance to ZIKV infection, during which ZIKV infection did not affect USP38 expression. Mechanistically, USP38 bound to ZIKV envelope (E) protein through its C-terminal domain and attenuated its K48-linked and K63-linked polyubiquitination, thereby repressed the infection of ZIKV. In addition, we found that the deubiquitinase activity of USP38 was essential to inhibit ZIKV infection, and the mutant that lacked the deubiquitinase activity of USP38 lost ability to inhibit the infection. In conclusion, we found a novel host protein USP38 against ZIKV infection, and this may represent a potential therapeutic target for the treatment and prevention of ZIKV infection.

The ongoing mutations in the structural proteins of SARS-CoV-2 is the major impediment for prevention and control of the COVID-19 disease. The envelope (E) protein of SARS-CoV-2 is a structural protein existing in both monomeric and homopentameric forms, associated with a multitude of functions including virus assembly, replication, dissemination, release of virions, infection, pathogenesis, and immune response stimulation. In the present study, 81,818 high quality E protein sequences retrieving from the GISAID were subjected to mutational analyses. Our analysis revealed that only 0.012 % (982/81818) stains possessed amino acid (aa) substitutions in 63 sites of the genome while 58.77% mutations in the primary structure of nucleotides in 134 sites. We found the V25A mutation in the transmembrane domain which is a key factor for the homopentameric conformation of E protein. We also observed a triple cysteine motif harboring mutations (L39M, A41S, A41V, C43F, C43R, C43S, C44Y, N45R) which may hinder the binding of E protein with spike glycoprotein. These results therefore suggest the continuous monitoring of each structural protein of SARS-CoV-2 since the number of genome sequences from across the world are continuously increasing.

Since the severe acute respiratory syndrome (SARS) outbreak in 2003, human coronaviruses (hCoVs) have been identified as causative agents of severe acute respiratory tract infections. Two more hCoV outbreaks have since occurred, the most recent being SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The clinical presentation of SARS and MERS is remarkably similar to COVID-19, with hyperinflammation causing a severe form of the disease in some patients. Previous studies show that the expression of the SARS-CoV E protein is associated with the hyperinflammatory response that could culminate in acute respiratory distress syndrome (ARDS), a potentially fatal complication. This immune-mediated damage is largely caused by a cytokine storm, which is induced by significantly elevated levels of inflammatory cytokines interleukin (IL)-1beta and IL-6, which are partly mediated by the expression of the SARS-CoV E protein. The interaction between the SARS-CoV E protein and the host protein, syntenin, as well as the viroporin function of SARS-CoV E, are linked to this cytokine dysregulation. This review aims to compare the clinical presentation of virulent hCoVs with a specific focus on the cause of the immunopathology. The review also proposes that inhibition of IL-1beta and IL-6 in severe cases can improve patient outcome.

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

Nonlinear nonparametric statistics (NNS) algorithm offers new tools for curve fitting. A relationship between k-means clustering and NNS regression points is explored with graphics showing a perfect fit in the limit. The goal of this paper is to demonstrate NNS as a form of unsupervised learning, and supply a proof of its limit condition. The procedural similarity NNS shares with vector quantization is also documented, along with identical outputs for NNS and a k nearest neighbours classification algorithm under a specific NNS setting. Fisher's iris data and artificial data are used. Even though a perfect fit should obviously be reserved for instances of high signal to noise ratios, NNS permits greater flexibility by offering a large spectrum of possible fits from linear to perfect.

This study measures the technical and scale efficiency of Micro and Small Enterprises (MSEs) and input slacks using Data Envelop Analysis (DEA) model and identifies the determinants of efficiencies of MSEs by employing ordinary least square (OLS) econometrics model. A sample of 375 randomly selected MESs are included in the study. The study found that the average technical and scale efficiency of MSEs are relatively low; technical efficiency averaged at 30 percent and 38.4 percent under constant returns to scale (CRS) and variable returns to scale (VRS) assumptions, respectively. Besides, the overall average scale efficiency score of MSEs was estimated at 77.8 percent. The highest mean technical and scale efficiencies were registered in the construction (71.8 percent) and manufacturing (85.7 percent) sectors, respectively. Whereas, the lowest technical and scale efficiency goes to urban agriculture sector and service sector, with 38.9 percent and 67.2 percent, respectively. The level of inputs, enterprise age and sector, human capital, labor productivity variables significantly affect relative technical efficiency level of MSEs with different directions while variables such as start-up capital, gender of the enterprise manager and availability of support from the government identified statistically not significant in determining the MSEs’ technical efficiency.

Recently Candida auris has emerged as a multi-resistant fungal pathogen, with a significant clinical impact, and has become a critical issue in WHO fungal priority list, due to its unique ability to persist for long time on human skin and hospital environments. It is therefore fundamental to reinforce hospital surveillance protocols to limit nosocomial outbreaks. The study purpose was the Fourier-Transform Infrared Spectroscopy (FT-IR) application to investigate the phylogenetic relationships between isolated strains within the C. auris outbreak at the university Intensive Care Unit of a Tertiary University hospital in Turin (Italy). In order to calculate a clustering cut-off, intra- and inter-isolates distance values were analysed. Data showed the presence of a major cluster Alfa and a minor cluster Beta with a defined C. auris clustering cut-off. The results were validated by an external C. auris strain and Principal Component and Linear Discriminant Analysis. The application of FT-IR technology had allowed to obtain important information about the phylogenetic relationships between the analysed strains, defining for the first time a “not WGS-based” clustering cut-off with a statistical-mathematical approach. FT-IR could represent a valid alternative to molecular methods for rapid and cost saving typing of C. auris strains with important clinical implications.

Clustering coefficient measures are key complex network analysis tools. We examine local and global clustering coefficient measures with respect to the lexicographic graph product. As a preliminary condition, we analyze the $K_3$ subgraph structure focused on vertex inclusion with respect to the product graph. From this structure, we determine both the clustering coefficient for the product graph vertices and the average clustering coefficient for the product graph.

The $k$-means problem is to compute a set of $k$ centers (points) that minimizes the sum of squared distances to a given set of $n$ points in a metric space. Arguably, the most common algorithm to solve it is $k$-means++ which is easy to implement, and provides a provably small approximation factor in time that is linear in $n$. We generalize $k$-means++ to support: (i) non-metric spaces and any pseudo-distance function. In particular, it supports M-estimators functions that handle outliers, e.g. where the distance $\mathrm{dist}(p,x)$ between a pair of points is replaced by $\min {\mathrm{dist}(p,x),1}$. (ii) $k$-means clustering with $m\geq 1$ outliers, i.e., where the $m$ farthest points from the $k$ centers are excluded from the total sum of distances. This is the first algorithm whose running time is linear in $n$ and polynomial in $k$ and $m$.

Survival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression after infection in vivo is IFN-induced HERC5. Using a transcription- and replication-competent VLP system, we showed that HERC5 inhibits EBOV virus-like particle (VLP) replication by depleting EBOV mRNAs. The HERC5 RCC1-like domain was necessary and sufficient for this inhibition and did not require zinc finger antiviral protein (ZAP). Moreover, we showed that EBOV (Zaire) glycoprotein (GP) but not Marburg virus GP antagonized HERC5 early during infection. Our data identifies a novel ‘protagonist-antagonistic’ relationship between HERC5 and GP in the early stages of EBOV infection that could be exploited for the development of novel antiviral therapeutics.

Bovine herpesvirus (BoHV)-5 is a worldwide distributed pathogen usually associated with a lethal neurological disease (meningoencephalitis) in dairy and beef cattle resulting in important economic losses due to the cattle industry. Using recombinant glycoprotein D of BoHV-5 (rgD5), we evaluated the long-duration humoral immunity of the recombinant vaccines in a cattle model. Here we report that two doses of intramuscular immunization, particularly with the rgD5ISA vaccine, are superior to iBoHV-5ISA immunization in the induction of long-lasting antibody responses. Recombinant gD5 antigen elicited tightly mRNA transcription of the Bcl6 and the chemokine receptor CXCR5 which mediate memory B cells and long-lived plasma cells in germinal centers (GCs). In addition, using an in-house Enzyme-Linked Immunosorbent Assay (ELISA) we observed higher and earlier responses of rgD5-specific IgG antibody and the upregulation of mRNA transcription of IL2, IL4, IL10, IL15 and IFN-γ cytokines in rgD5 vaccinated cattle, indicating a mixed immune response. We further show that rgD5 immunization provides protection against both BoHV -1 and -5. Our findings indicate that the rgD5-based vaccine represents an effective vaccine strategy to induce an efficient control of alpha-herpesviruses.

Climate change and rapid urbanization are adversely affecting the urban environment by exacerbating the widely reported Urban Heat Island effect in Dhaka, Bangladesh. Two wetland areas with variable riparian shadings in the warm-humid conditions of urban Dhaka had been investigated through field campaigns on microclimatic parameters for their cooling potential on the surrounding urban fabric. It was observed that an inversion layer of fully saturated air develops over the water surface of wetland, suppressing evaporation from the wetland water surface layer, which was effectively reducing the heat exchange between the water surface and the air layer above it through its action as an insulating vapor blanket. Because of this effect, the wetland was unable to render as a source of coolth for the surrounding overheated urban area. This effect of the inversion layer was more pronounced in the urban wetland without riparian shading either by urban form or tree canopy. A Multiphysics simulation study conducted on the selected urban wetlands indicates the effect of differential shading pattern on the relation between fetch and inversion layer thickness. This research hypothesizes that the wetland can act as an urban adaption measure against the urban heat island effect by potentially transforming them into Urban Cooling Island (UCI) towards a favorable urban bioclimate.

Hox gene clusters are crucial in Embryogenesis. It was observed that some Hox genes are located in order along the telomeric to centromeric direction of the DNA sequence: Hox1, Hox2, Hox3…. These genes are expressed in the same order in the ontogenetic units of the Drosophila embryo along the Anterior-Posterior axis. The two entities (genome and embryo) differ significantly in linear size and in-between distance. This strange phenomenon was named Spatial Collinearity (SP). Later, it was observed that, particularly in the Vertebrates, a Temporal Collinearity (TC) coexists: first is Hox1 expressed, later Hox2 and even later Hox3,…,. According to a Biophysical Model (BM), pulling forces act at the anterior end of the cluster while a cluster fastening applies at the posterior end. Hox clusters are irreversibly elongated along the force direction. During Evolution, the elongated Hox clusters are broken at variable lengths thus split clusters may be created. An Empirical Rule was formulated distinguishing development due to a complete Hox cluster from development due to split Hox clusters. BM can ‘explain’ this Empirical Rule. In a spontaneous mutation where the cluster fastening is dismantled, a weak pulling force automatically shifts the cluster inside the Hox activation domain. This cluster translocation can probably explain the absence of Temporal Collinearity in Drosophila.

Nearest-neighbour clustering is a simple yet powerful machine learning algorithm that finds natural application in the decoding of signals in classical optical-fibre communication systems. Quantum k-means clustering promises a speed-up over the classical k-means algorithm; however, it has been shown to currently not provide this speed-up for decoding optical-fibre signals due to the embedding of classical data, which introduces inaccuracies and slowdowns. Although still not achieving an exponential speed-up for NISQ implementations, this work proposes the generalised inverse stereographic projection as an improved embedding into the Bloch sphere for quantum distance estimation in k-nearest-neighbour clustering, which allows us to get closer to the classical performance. We also use the generalised inverse stereographic projection to develop an analogous classical clustering algorithm and benchmark its accuracy, runtime and convergence for decoding real-world experimental optical-fibre communication data. This proposed `quantum-inspired' algorithm provides an improvement in both the accuracy and convergence rate with respect to the k-means algorithm. Hence, this work presents two main contributions. Firstly, we propose the general inverse stereographic projection into the Bloch sphere as a better embedding for quantum machine learning algorithms; here, we use the problem of clustering quadrature amplitude modulated optical-fibre signals as an example. Secondly, as a purely classical contribution inspired by the first contribution, we propose and benchmark the use of the general inverse stereographic projection and spherical centroid for clustering optical-fibre signals, showing that optimizing the radius yields a consistent improvement in accuracy and convergence rate.

Data Extraction is a technique is called as clustering which is used to retrieve data either from the files or data bases or both. This paper focuses on the performance evaluation parameters of the clustering algorithms based on different parameters or conditions or constraints and parameters which are used to perform the clustering process to get the clusters on the data sets. Therefore best clusters are retrieved when best parameters or conditions or constraints or preferences which are applied on the data sources for the clustering process. These parameters or conditions or constraints are opted by the user called as user preferences.

Currently, maritime traffic is increasing with economic growth in several regions worldwide. However, this growth in maritime traffic has led to increased risk of marine accidents. These accidents have a higher probability of occurring in regions where geographical features, such as islands, are present. Further, the positioning of rescue ships in a particular ocean region with a high level of maritime activity is critical for rescue operations. This paper proposes a method for determining an optimal set of locations for stationing rescue ships in an ocean region with numerous accident sites in the Wando islands of South Korea. The computational challenge in this problem is identified as the positioning of numerous islands of varying sizes located in the region. Thus, the proposed method combines a clustering-based optimization method and an image processing approach that incorporates flood filling to calculate the shortest distance between two points in the ocean that detours around the islands. Experimental results indicate that the proposed method reduces the distance from rescue ships and each accident site by 5.0 km compared to the original rescue ship locations. Thus, rescue time is reduced.

This paper describes a stochastic clustering architecture that is used in the paper for making predictions over energy data. The design is discrete, localised optimisations based on similarity, followed by a global aggregating layer, which can be compared with the recent random neural network designs, for example. The topic relates to the IDEAS Smart Home Energy Project, where a client-side Artificial Intelligence component can predict energy consumption for appliances. The proposed data model is essentially a look-up table of the key energy bands that each appliance would use. Each band represents a level of consumption by the appliance. This table can replace disaggregation from more complicated methods, usually constructed from probability theory, for example. Results show that the table can accurately disaggregate a single source to a set of appliances, because each appliance has quite a unique energy footprint. As part of predicting energy consumption, the model could possibly reduce costs by 50% and more than that if the proposed schedules are also included. The hyper-grid has been changed to consider rows as single units, making it more tractable. A second case study considers wind power patterns, where the grid optimises over the dataset columns in a self-similar way to the rows, allowing for some level of feature analysis.

Dengue virus (DENV), being one of the lethal pathogens in the hot climatic regions of the world, have been extensively studied to decipher its mechanism of pathogenesis and missing links of its life cycle. With respect to the entry of DENV, multiple receptors have been recognised in different cells of the human body. However, scientists still argue whether these identified receptors are the exclusive entry mediators for the virus. Adding to the complexity, DENV has been reported to be infecting multiple organ types in its human host. Also, more than one receptor in a particular cell has been discerned to take part in mediating the ingress of DENV. In this review, we aim to discuss about the different cells of the human immune system that support DENV infection and their corresponding receptors that DENV deploy to gain access to the cells.

The inter-individual variability of CYP450s enzyme activity may be reduced by comparing the effects of bariatric surgery on CYP-mediated drug elimination in comparable patients before and after surgery. The current research will use a low-dose phenotyping cocktail to simultaneously evaluate the activities of six CYP isoforms and P-gp.The results showed that following weight reduction after surgery, the activity of all enzymes increased compared to the obese period, which was statistically significant in the case of CYP3A, CYP2B6, CYP2C9, and CYP1A2. Furthermore, the activity of P-gp after surgery decreased without reaching a statistical significance (p-value>0.05). Obese individuals had decreased CYP3A and CYP2D6 activity than the control group, albeit only CYP3A was statistically important. In addition, there was a trend to increase activity for CYP1A2, CYP2B6, CYP2C9, and CYP2C19 in obese patients compared to the control group, without reaching statistical insignificance (p-value≥0.05). After six months (at least), all enzymes and the P-gp pump activity were significantly higher than the control group except for CYP2D6.Ultimately, a greater comprehension of phenoconversion can aid in altering the patient's treatment. Further studies are required to confirm the changes in the metabolic ratios of probes after bariatric surgery to demonstrate the findings' clinical application. As a result, the effects of inflammation-induced phenoconversion on medication metabolism may differ greatly across persons and drug CYP pathways. It is essential to apply these results to the clinic to recommend dose adjustments.

The notion of luck clustering has gained traction in recent years due to its potential influence on performance and decision-making across a range of domains. This study concentrates on the application of luck clustering in sports, with an emphasis on its consequences for performance metrics and strategic decision-making. We employ time series analysis to investigate the presence of luck clustering in sports data, such as win-loss records, scoring, and player rankings, while considering the role of the Principle of Luck Conservation in the observed clustering patterns. Our findings provide evidence of luck clustering in sports, implying that periods of high luck tend to be followed by more high luck events, and vice versa for low luck events. These insights carry significant implications for coaches, players, and teams, who can utilize the understanding of luck clustering to develop more effective strategies, manage resources efficiently, and ultimately enhance their performance. By enriching our comprehension of luck's nature and its effects on sports outcomes, this study contributes valuable knowledge for practitioners and researchers in sports analytics and performance management.

A systematic investigation of the dynamic clustering behavior of active particles under confinement, including the effects of both particle density and active driving force is presented based on a hybrid coarse-grained molecular dynamics simulation. First, a series of scaling laws were derived with power relationships for the dynamic clustering time as a function of both particle density and active driving force. Notably, the average number of clusters N ̅ assembled from active particles in the simulation system exhibits a scaling relationship with clustering time t described by N ̅∝t^(-m). Simultaneously, the scaling behavior of the average cluster size S ̅ is characterized by S ̅∝t^m. Our findings reveals the presence of up to four distinct dynamic regions concerning clustering over time, with transitions contingent upon the particle density within the system. Furthermore, as the active driving force increases, the aggregation behavior also accelerates, while an increase in density of active particles induce alterations in the dynamic procession of the system.

Here we present a fast and highly scalable community structure preserving network module detection that recursively integrates graph sparsification and clustering. Our algorithm, called SparseClust, participated in the most recent DREAM community challenge on disease module identification, an open competition to comprehensively assess module identification methods across a wide range of biological networks.

Corona viruses hijack human enzymes to assembly sugar coat on Spike glycoproteins. The mechanism that human antibodies may uncover the antigenic viral peptide epitopes hidden by sugar coat are unknown. In this study, we analyzed recombinant SARS-CoV-2 Spike protein secreted from BTI-Tn-5B1-4 cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired MS/MS spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of Spike proteins according to Cryo-EM and homolog-modeled structures, and available antibodies that bind to SARS-CoV-1. The results showed that all 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose type of N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the Spike receptor binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains included those located on Central Helix, between amino acids 967 and 1016 of SARS-CoV-1, and 985 to 1034 of SARS-CoV-2 Spike protein. As the majority of antibody paratopes bind to peptide portion with or without sugar modification, we propose a snake-catcher model that a minimal length of peptide is first clamped by a paratope, and the binding is either strengthened by sugars close to peptide, or not interfered by sugar modification.

Both in lung adenocarcinoma (LUAD) and severe acute respiratory syndromes (SARS) uncontrolled inflammation could be detected in lung tissue. Whether the similarity mechanism exists is still unknown. PDZ-binding motif (PBM) in SARS-CoV E protein has been demonstrated as virulence factor induce inflammation storm. Study function of PBM in LUAD is significant for mechanism exploration of carcinogenesis mediated by SARS-CoV. To identify gene expression fluctuation induced by PBM, a microarray sequencing data of lung tissue infected by wild type (SARS-CoV-E-wt) and recombinant virus (SARS-CoV-E-mutPBM) was analysis followed by functional enrichment analysis. To understand the role of screened specific genes in LUAD, overall survival and immune correlation were calculated. A total of 12 genes (MAPK1, PRKCA, FGFR4, KDR, PTPRD, BCL2L15, UBD, MAMDC2, LTBP4, PTPRB, LGI3 and ITGA8) might participate in initial and development stage of LUAD through expression variation and mutation. Meanwhile, a total of 12 genes (CARHSP1, EIF4E2, HMGA1, IL1R2, MAGOHB, PVR, ADCY9, ELF5, ESYT3, SCML4, SECL14L4 and THRA) could lead to poorer prognosis via dysregulation. In addition, MAMDC2 and ITGA8 down-regulated by PBM could also alter prognosis. Though the conservative PBM (-D-L-L-V-) could be found at the end of carboxyl terminal in multi E proteins of coronaviruses, the specific function of each one depend on the whole amino acid sequence simultaneously. In conclusion, PBM of SARS-CoV E protein could promote carcinogenesis of LUAD by dysregulating important gene expression profiles followed by influence immune response and overall prognosis. The results in present study also provided reference for the therapy of SARS-CoV-2 in LUAD patients.

This work is developed over the question ”How to automatically create a good clustering on spatial dataset with high different local densities?” opened by previus work of Berzi [5]. To answer the main question, this work describe a approach of recursive clustering process based on a technique of finding ”vague-solution”, where the output is an hierarchical clustering of initial dataset. In particularly the the approach is developed and tested on DBSCAN algorithm [11] with large dataset gathered by Google Place in Metropolitan Area of Milan. The core solutions developed in this algorithm are condensed in the capacity of generation a Hierarchical Clustering with a recursive select the best solutions in according tothe our goals, previously dfined by some sets of rules. The algorithm described here, and developed in my Master Thesis, rosolve two problem: - When we use an algorithm of clustering that can create a set of differents clustering, but equally valid and don’t know exctly what we must have as good solution, we areled to ask ourselves: ”What are the better?” This obviously depends by our goals, sonow the question is: ”What are our goals?”; - The second problem is condensed in the sentence ”Not all clusters can be found in one-shot clustering process, more often we must reapply the process to some part of datataset”, so there we have a second question that this paper answering: ”How to create clustering of data with ad-hoc processing for each different part of input dataset?”; These questions are resolved by the approaches named in this work as: Space of Solutions, Vague-Solution, Vague-Solution finding Method and finaly Recursive Clustering. All of these approaches was drafted and tested in mine Master Thesis titled ”Geospatial data analysis for Urban informatics applications: the case of the Google Place of the City of Milan” [25].

The disease of COVID-19 comprises the most serious against human health worldwide with a high rate of virulence and mortality. The disease is caused by the 2019-nCoV virus from the beta coronavirus family. The virus makes use of its surface glycoprotein named S protein or spike to enter the human cells. The virus attached to its receptor named angiotensin-converting enzyme 2 on host cells surface via its receptor-binding domain and its fusion is mediated by cleavage at S2' site that is carried out by surface protease. Vaccines or drugs interfering with S protein binding or cleavage sites could be considered as drugs to get rid of the infection. In the current work and though docking and molecular dynamic experiments we have checked more than 100 drugs with high enough molecular weights for their shielding potency toward S protein binding sites and processing S2' sites. Our results indicate the shielding potency of: fidaxomicin > ivermectin > heparin > azithromycin > clarithromycin > eryhthromycin > niclosamide > ritonavir. Considering affluent reports regarding the complex disturbance in the immune system and multi-organ involvement in the disease there is no single or binary drug regime for cure expectedly and instead, we claim the multi-drug regime should be the choice in this context. Accordingly, we suggest our extracted drugs as an adjuvant for clinical trials.

Lactic acid bacteria (LAB) have an extracellular proteolytic system that includes a multi-domain, cell envelope protease (CEP) with a subtilisin homologous protease domain. These CEPs have different proteolytic activities despite having similar protein sequences. Structural characterization has previously been limited to CEP homologs of dairy and human derived LAB strains, excluding CEPs of plant derived LAB strains. CEP structures are a challenge to determine experimentally due to their large size and attachment to the cell envelope. This study aims to clarify the prevalence and structural diversity of CEPs by using the structure prediction software AlphaFold 2. Domain boundaries are clarified based on a comparative analysis of 21 three-dimensional structures, revealing novel domain architectures of CEP homologs that are not necessarily restricted to specific LAB species or ecological niches. The C-terminal flanking region of the protease domain is divided into fibronectin type-III-like domains with various structural traits. The analysis also emphasizes the existence of two distinct domains for cell envelope attachment that are preceded by an intrinsically disordered cell wall spanning domain. The domain variants and their combinations provide CEPs with different stability, proteolytic activity and potentially adhesive properties, making CEPs targets for steering proteolytic activity with relevance for both food development and human health.

The monkeypox virus (MPXV) has become a major threat due to the increasing global caseload and the ongoing multi-country outbreak in non-endemic territories. Due to limited research in this avenue and the lack of intervention strategies, the present study was aimed to virtually screen bioactive phytochemicals against envelope proteins of MPXV via rigorous computational approaches. Molecular docking and molecular dynamic (MD) simulations were used to investigate the binding affinity of 12 phytochemicals against three envelope proteins of MPXV, viz., D13, A26, and H3. Silibinin, oleanolic acid, and ursolic acid were computationally identified as potential phytochemicals that showed strong binding affinity towards all the tested structural proteins of MPXV through molecular docking. The stability of the docked complexes was also confirmed by MD simulations. ADME analysis also computationally confirmed the drug-like properties of the phytochemicals, thereby asserting their suitability for consumption. Hence, this study envisions the candidature of bioactive phytochemicals as promising inhibitors against the MPXV, serving as template molecules that could further be experimentally evaluated for their efficacy against monkeypox.

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

As a model for economic and ecological systems, replicator dynamics represents a basic form of agent competition for finite resources. Here, we investigate the effects of stochastic resetting in this kind of processes. Random reset events abruptly lead individual resources to a small value from which dynamics must start anew. Numerical results show that resource distribution over the population of competing agents develops highly nonuniform profiles, exhibiting clustering and fluctuations with anomalous dependence on the population size. This non-standard statistical behavior jeopardizes an analytical treatment based on mean-field assumptions. We propose alternative simplified analytical approaches which provide a stylized description of entropy evolution for the clustered distribution of resources and explain the unusually slow decrease of fluctuations.

Assessment of drugs toxicity and associated biomarker genes is one of the most important tasks in the pre-clinical phase of drug development pipeline as well as in the toxicogenomic studies. There are few statistical methods for the assessment of doses of drugs (DDs) toxicity and their associated biomarker genes. However, these methods consume more time for computation of the model parameters using the EM (Expectation-Maximization) based iterative approaches. To overcome this problem, in this paper, an attempt is made to propose an alternative approach based on hierarchical clustering (HC) for the same purpose. There are several types of HC approaches whose performance depends on different similarity/distance measures. Therefore, we explored suitable combinations of distance measures and HC methods based on Japanese Toxicogenomics Project (TGP) datasets for better clustering/co-clustering between DDs and genes as well as to detect toxic DDs and their associated biomarker genes. We observed that Word’s HC method with each of Euclidean, Manhattan and Minkowski distance measures produces better clustering/co-clustering results. For an example, in case of glutathione metabolism pathway (GMP) dataset LOC100359539/Rrm2, Gpx6, RGD1562107, Gstm4, Gstm3, G6pd, Gsta5, Gclc, Mgst2, Gsr, Gpx2, Gclm, Gstp1, LOC100912604/Srm, Gstm4, Odc1, Gsr, Gss are the biomarker genes and Acetaminophen_Middle, Acetaminophen_High, Methapyrilene_High, Nitrofurazone_High, Nitrofurazone_Middle, Isoniazid_Middle, Isoniazid_High are their regulatory (associated) DDs explored by our proposed co-clustering algorithm based on the distance and HC method combination Euclidean: Word. Similarly, for the PPAR signaling pathway (PPAR-SP) dataset Cpt1a, Cyp8b1, Cyp4a3, Ehhadh, Plin5, Plin2, Fabp3, Me1, Fabp5, LOC100910385, Cpt2, Acaa1a, Cyp4a1, LOC100365047, Cpt1a, LOC100365047, Angptl4, Aqp7, Cpt1c, Cpt1b, Me1 are the biomarker genes and Aspirin_Low, Aspirin_Middle, Aspirin_High, Benzbromarone_Middle, Benzbromarone_High, Clofibrate_Middle, Clofibrate_High, WY14643_Low, WY14643_High, WY14643_Middle, Gemfibrozil_Middle, Gemfibrozil_High are their regulatory DDs. These results are validated by the available literature and functional annotation.

The world population increased from 1 billion in 1800 to around 8 billion today. The Population Division of the United Nations predicts a global population of approximately 10.4 billion people by the end of the century. That represents over 2 billion more people. Moreover, the global community is currently experiencing a precarious state due to the enduring repercussions of the COVID-19 pandemic across all sectors, including energy. Given the rising global population and the limited availability of primary energy resources, we must reach a balance between the demands of a growing human population and the planet’s carrying capacity. The dreadful conflict in Ukraine has precipitated an enormous energy crisis. This crisis served as a warning to the world population of how much they depend on this resource to survive. In France, building sectors (i.e., residential and tertiary) alone consume 45% of the final energy disposable. It is the first energy consumer of the country and one of the most polluting (i.e.; about 34% of CO2 emitted by France). Consequently, we must consider alternative energy resource forms (i.e.; substitution energy forms). Harvesting energy from the building envelope may be a viable technique for partially satisfying the electricity demands of building users. In this context, scientific research offers considerable potential for developing more innovative and efficient systems. This article aims to review the state of the art of advances on the subject to orient and further optimize energy production systems, particularly electricity. This work will address several points of view: Discusses the overall backdrop of the present study and introduces the subject ; details the research strategy and procedures used to produce this paper ; develops state of the art on the potential for generating or recovering power from the building envelope ; presents the SWOT analysis of the earlier-described systems. And finally, it concludes by offering findings and viewpoints.

While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine for other potential interactions between the virus and other cell receptors. Based on the clinical observation of low smoking prevalence among hospitalized COVID-19 patients, we recently identified a “toxin-like” amino acid (aa) sequence on the receptor binding domain of the spike glycoprotein of SARS-CoV-2 (aa 375-390) with homology to a sequence of a snake venom toxin, which could interact with nicotinic acetylcholine receptors (nAChRs). We now present computational molecular modelling and docking experiments using 3D structures of the SARS-CoV-2 spike glycoprotein and the extracellular domain of the nAChR alpha9 subunit. We identified an interaction between the aa381-386 of the SARS-CoV-2 spike glycoprotein and the aa189-192 of the extracellular domain of the nAChR alpha9 subunit, a region which forms the core of the “toxin-binding site” of the nAChRs. The mode of interaction is very similar to the interaction between the alpha9 nAChR and alpha-bungarotoxin. A similar interaction was observed between the pentameric alpha7 AChR and the SARS-CoV-2 spike glycoprotein. Our findings support the hypothesis that severe COVID-19 may be associated with disruption of the nicotinic cholinergic system which could be caused by an interaction between SARS-CoV-2 and nAChRs.

There are many applications of anomaly detection in IoT domain. IoT technology consists of large number of interconnecting digital devices not only generating huge data continuously but also making real-time computations. Since IoT devices are highly exposed due to Internet, they frequently meet with the challenges of illegitimate accesses in the form of intrusions, anomaly, fraud, etc. Identifying these illegitimate accesses in IoT domain can be an exciting research problem. In numerous applications fuzzy clustering and rough set theory have been successfully employed. As the data generated in IoT domains are high-dimensional, the clustering methods used for lower dimensional data cannot be applied efficiently. In this article, mixed approaches consisting of nano topology and fuzzy clustering techniques are proposed for anomaly detection. First of all, the nano topology is generated to find lower dimensional apace and then a couple of well-known fuzzy clustering techniques are employed on it for the efficient anomaly detection. The effectiveness of the proposed approaches is evaluated using time-complexity analysis, experimental studies with a synthetic dataset and a real-life dataset along with comparative studies with traditional fuzzy clustering approaches namely fuzzy c-means clustering (FCM) algorithm, Gustafson-Kessel (GK) Algorithm, Gath-Geva (GG) Algorithm, Mahalanobis Distance based Fuzzy C-Means algorithm (M-FCM), and Common Mahalanobis Distance based Fuzzy C-Means algorithm (CM-FCM). Experimentally, it has been found that the proposed approaches outperform the aforesaid algorithms in terms of detection rates, accuracy rates, false alarm rates and computational times.

While there are several ways to identify customer behaviors, few extract this value from information already in a database, much less extract relevant characteristics. This paper presents the development of a prototype using the recency, frequency, and monetary attributes for customer segmentation of a retail database. For this purpose, the standard K-means, K-medoids, and MiniBatch K-means were evaluated. The standard K-means clustering algorithm was more appropriate for data clustering than other algorithms as it remained stable until solutions with 6 clusters. The evaluation of the clusters’ quality was obtained through the internal validation indexes: Silhouette, Calinski Harabasz, and Davies Bouldin. Once consensus was not obtained, three external validation indexes were applied: global stability, stability per cluster, and segment-level stability across solutions. Six customer segments were obtained, identified by their unique behavior: Lost customers, disinterested customers, recent customers, less recent customers, loyal customers, and best customers. Their behavior was evidenced and analyzed, indicating trends and preferences.

Collective spread of aggregated viral particles may have beneficial effects on viral capability to survive in the external environment, to counteract immune responses, and to successfully colonize host cells. Here we ask whether SARS-Cov-2 particles, responsible for COVID-19, display collective clustering behavior. Looking at microphotographs and movies of SARS-Cov-2 particles emerging from the surface of cultured cells, we describe single virions that tend to aggregate in progressively larger globular assemblies, until a network-like appearance is achieved. When SARS-Cov-2 particles stick into each other, the squeezing of single virions leads to improved viral package in host’s fluids. We discuss how these findings might explain both the ability to spread of SARS-Cov-2 and the clinical severity of COVID-19 in humans, paving the way to novel therapeutic strategies to mechanically disrupt collective clustering.

Clustering is an important task in data mining that has become more challenging due to the ever-increasing size of available datasets. To cope with these big data scenarios, a high-performance clustering approach is required. Sparse grid clustering is a density-based clustering method that uses a sparse grid density estimation as its central building block. The underlying density estimation approach enables the detection of clusters with non-convex shapes and without a predetermined number of clusters. In this work, we introduce a new distributed and performance-portable variant of the sparse grid clustering algorithm that is suited for big data settings. Our compute kernels were implemented in OpenCL to enable portability across a wide range of architectures. For distributed environments, we added a manager-worker scheme that was implemented using MPI. In experiments on two supercomputers, Piz Daint and Hazel Hen, with up to 100 million data points in a 10-dimensional dataset, we show the performance and scalability of our approach. The dataset with 100 million data points was clustered in 1198s using 128 nodes of Piz Daint. This translates to an overall performance of 352TFLOPS. On the node-level, we provide results for two GPUs, Nvidia's Tesla P100 and the AMD FirePro W8100, and one processor-based platform that uses Intel Xeon E5-2680v3 processors. In these experiments, we achieved between 43% and 66% of the peak performance across all compute kernels and devices, demonstrating the performance portability of our approach.

The lipid composition of biomembranes influence the properties of the lipid bilayer as well as that of the proteins. In this study, the lipidome and the lipid/protein ratio of membranes from High FiveTM insect cells overexpressing mouse P-glycoprotein was characterized. This provides a better understanding of the lipid environment in which P-glycoprotein is embedded, and thus of its functional and structural properties. The relative abundance of the distinct phospholipid classes and their acyl chain composition was characterized. A mass ratio of 0.57 +/- 0.11 phospholipids to protein was obtained. Phosphatidylethanolamines are the most abundant phospholipids, followed by phosphatidylcholines. Membranes are also enriched in negatively charged lipids (phosphatidylserines, phosphatidylinositols and phosphatidylglycerols), and contain small amounts of sphingomyelins, ceramides and monoglycosilatedceramides. The most abundant acyl chains are monounsaturated, with significant amounts of saturated chains. The characterization of the phospholipids by HPLC-MS allowed identification of the combination of acyl chains, with palmitoyl-oleoyl being the most representative for all major phospholipid classes except for phosphatidylserines, which are mostly saturated. A mixture of POPE:POPC:POPS in the ratio 45:35:20 is proposed for the preparation of simple representative model membranes. The adequacy of the model membranes was further evaluated by characterizing their surface potential and fluidity.

Autism spectrum disorder (ASD) is characterized by diverse patterns of social interaction, communication, and behavior. This study explores the application of clustering and stochastic migration models to visualize and understand the social and neural connectivity patterns associated with autism. The clustering model, with its strong internal connections and limited external connections, mirrors the tight-knit social groups and communication barriers often observed in individuals with autism. In contrast, the stochastic model, characterized by more dispersed connections and greater adaptability, represents the variability and flexibility seen in social interactions across typical individuals. By comparing these models, we can gain deeper insights into the unique challenges and strengths of individuals with autism, highlighting the importance of personalized interventions. Additionally, these models provide a visual framework for understanding the differences in brain connectivity patterns observed in autism, with implications for both behavioral and neural correlates. This study underscores the value of computational models in advancing our understanding of autism and guiding effective support strategies.

The aerospace industry develops prognosis and health management algorithms to ensure better safety on board. Particularly for in-flight controls where jamming is dreaded. For that, vibration signals are monitored to predict future defect occurrences. However, time series are not labeled according to severity level, and the user can only assess the system health from the data mining procedure. To that extent, we developed a clustering algorithm using a deep neural network core. We encoded the time series into pictures to be feed into an artificially trained neural network: U-NET. From the segmented output, one-dimensional information on cluster frontiers is extracted and filtered without any parameter selection. Then, a kernel density estimation finally transforms the signal into an empirical density. Ultimately, a Gaussian mixture model extracts the latter independent components. The method empowered us to reveal different degrees of severity faults in the studied data, with their respective likelihood without prior knowledge. We compared it to state-of-the-art machine learning algorithms. However, internal clustering results evaluation for time series is an open question. As state-of-the-art indexes were not producing relevant results, we built a new indicator to fulfill this task. We applied the whole method to an actuator consisting of an induction machine linked to a ball screw. This study lays the groundwork for future training of diagnosis and prognosis structures in the health management framework.

The goal of clustering is to identify common structures in a data set by forming groups of homogeneous objects. The observed characteristics of many economic time series motivated the development of classes of distributions that can accommodate properties such as heavy tails and skewness. Thanks to its flexibility, the Skewed Exponential Power Distribution (also called Skewed Generalized Error Distribution) ensures a unified and general framework for clustering possibly skewed and heavy tailed time series. This paper develops a clustering procedure of model-based type, assuming that the time series are generated by the same underlying probability distribution but with different parameters. Moreover, we propose to optimally combine the estimated parameters to form the clusters with an entropy weighing $k$-means approach. The usefulness of the proposal is showed by means of application to financial time series, demonstrating also how the obtained clusters can be used to form portfolio of stocks.

Smart grids require flexible data driven forecasting methods. We propose clustering tools for bottom-up short-term load forecasting. We focus on individual consumption data analysis which plays a major role for energy management and electricity load forecasting. The two first sections are dedicated to the industrial context and a review of individual electrical data analysis. We are interested in hierarchical time-series for bottom-up forecasting. The idea is to disaggregate the signal in such a way that the sum of disaggregated forecasts improves the direct prediction. The 3-steps strategy defines numerous super-consumers by curve clustering, builds a hierarchy of partitions and selects the best one minimizing a forecast criterion. Using a nonparametric model to handle forecasting, and wavelets to define various notions of similarity between load curves, this disaggregation strategy applied to French individual consumers leads to a gain of 16\% in forecast accuracy. We then explore the upscaling capacity of this strategy facing massive data and implement proposals using R, the free software environment for statistical computing. The proposed solutions to make the algorithm scalable combines data storage, parallel computing and double clustering step to define the super-consumers.

In recent years, governments applied intelligent transportation system (ITS) technique to provide several convenience services (e.g., garbage truck app) for residents. This study proposes a garbage truck fleet management system (GTFMS) and data feature selection and data clustering methods for travel time prediction. A GTFMS includes mobile devices (MD), on-board units, fleet management server, and data analysis server (DAS). When user uses MD to request the arrival time of garbage truck, DAS can perform the procedure of data feature selection and data clustering methods to analyses travel time of garbage truck. The proposed methods can cluster the records of travel time and reduce variation for the improvement of travel time prediction. After predicting travel time and arrival time, the predicted information can be sent to user’s MD. In experimental environment, the results showed that the accuracies of previous method and proposed method are 16.73% and 85.97%, respectively. Therefore, the proposed data feature selection and data clustering methods can be used to predict stop-to-stop travel time of garbage truck.

Flaviviruses replicate in membrane factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus viral protein accumulation contribute to ER stress. As a consequence, the host cell exhibits an Unfolded Protein Response (UPR), subsequently stimulating appropriate cellular responses such as adaptation, autophagy or apoptosis. The correct redox conditions of this compartment are essential to form native disulfide bonds in proteins. ZIKA virus (ZIKV) has ability to induce persistent ER stress leading to activation of UPR pathways. In this study, we wondered whether ZIKV affects the redox balance and consequently the oxidative protein folding in the ER. We found that ZIKV replication influences redox state leading to aggregation of viral envelope protein as amyloid-like structures in the infected cells.

The novel coronavirus (SARS-CoV-2) is a human pathogen recently emerged in China, causing a global pandemic of severe respiratory illness (COVID19). SARS-CoV-2 makes entry into human cells through its spike (S) protein that binds to cell surface receptors. Widespread of SARS-CoV-2 has been attributed to high affinity of S protein to its receptor. A homology model of the receptor binding domain of SARS-CoV-2 S protein (RBD) was built. RBD- receptor docking and published molecular dynamics data were used to map the key RBD-receptor interaction hotspot (RBDhp) on the RBD. Primary virtual screening was carried out against RBDhp using more than 3300 compounds approved by U.S Food and Drug Administration (FDA) and other authorities for human use. Compounds that bind to hpRBD with a binding energy ≤ - 6.5 kcal/mol were subjected to secondary screening using a recently published cryo EM (2.9 Å) structure of RBD. A cardiac glycoside (dgitoxin), two anthracyclines (zorubicin and aclarubicin), a tetracycline derivative (rolitetracycline), a cephalosporin (cefoperazone) and a food dye (E-155) were predicted to be most potent inhibitors of RBD – receptor interaction. An anti-asthmatic drug (zafirlukast) and several other drugs (itrazol, fazadinium, troglitazone, gliquidone, Idarubicin, Oxacillin) were found to be high affinity binders that may have a potential to inhibit RBD – receptor interaction.

Keywords: Requirements prioritization, Next release plan, Software product planning, Decision support, MoSCoW, AHP, K-Menas, GMM, BIRCH, PAM, Hierarchical, Clustering, Clusters Evaluation

Anomaly Detection in real time data is accepted as a vital research area. Clustering has effectively been tried for this purpose. As the datasets are real time, the time of generating of the data is also important. In this article, we introduce a mixture of partitioning and agglomerative hierarchical approach to detect anomalies from such datasets. It is a two-phase method which follows partitioning approach first and then agglomerative hierarchical approach. The dataset can have mixed attributes. In phase-1, a unified metric defined on mixed attributes is used. The same is also used for merging of similar clusters in phase-2. Also, we have kept the track of time attribute of each data instance which produces the clusters with their lifetimes in phase-1. Then in phase-2, we merge the similar clusters. While merging, the similar clusters, the lifetimes of the corresponding clusters with overlapping cores are to be superimposed producing fuzzy time intervals. This way, each cluster will have an associated fuzzy lifetime. The data instances either belonging sparse clusters or not belonging to any of the clusters can be treated as anomalies. The efficacy of the algorithms can be established using both complexity analysis as well as experimental studies.

In the field of machine learning, cluster analysis has always been a very important technology for determining useful or implicit characteristics in the data. However, the current mainstream cluster analysis algorithms require comprehensive analysis of the overall data to obtain the best parameters in the algorithm. As a result, handling large-scale datasets would be difficult. This research proposes a distributed related clustering mechanism for Unsupervised Learning, which assumes that if adjacent data are similar, a group can be formed by relating to more data points. Therefore, when processing data, large-scale datasets can be distributed to multiple computers, and the correlation of any two datasets in each computer can be calculated simultaneously. Later, results are processed through aggregation and filtering before assembled into groups. This method would greatly reduce the pre-processing and execution time of the dataset; in practical application, it only needs to focus on how the relevance of the data is designed. In addition, the experimental results show the accuracy, applicability, and ease of use of this method.

In document forensic, Ink mismatch relays very important information about forgeries in this way we can find out the authenticity of documents. Finding out and distinguishing these unique inks from the multispectral document is very challenging task. In this paper we proposed the method to identify the inks using clustering. We used K-Mean clustering instead of widely known Fuzzy C-Means Clustering (FCM) and successfully identity the number of inks. For the purpose of optimizing and improving our results we used two optimization techniques such as Elbow and silhouette optimization techniques.

Cardiovascular disease (CVD) and obesity are prevalent public health concerns with grave implications for morbidity and mortality, necessitating tailored interventions. This research explores the utility of fuzzy c-means clustering paired with principal component analysis (PCA) in detecting at-risk groups and personalizing health strategies for these conditions. Fuzzy c-means clustering allows for the dynamic classification of individuals into groups based on unique risk factors and intervention outcomes, while PCA aids in distilling complex data sets to uncover underlying patterns. The conjoined use of these methods has shown promise in identifying diverse risk profiles and in forecasting intervention success rates. The study acknowledges limitations, including possible biases stemming from data set composition and analytical parameter selection. Future research aims to refine these tools for clinical application. The results support implementing fuzzy c-means clustering and PCA for delineating specific target populations for health interventions, emphasizing careful use of these analytical approaches. Subsequent studies should focus on correlating these techniques with concrete clinical results to enhance public health measures.

(1) Background: The typical transporter protein, P-glycoprotein (P-gp), has been proven to be associated with multidrug resistance (MDR). Pyxinol and 24S-Pyxinol amino acid ester derivatives had been demonstrated to be promising P-gp inhibitors for reversal of tumor MDR in KBV cells, however, their roles in MDR reversal in other tumor-resistant cells are still unclear. (2) Methods: In the present study, we synthesized 40 amino acid ester derivatives of Pyxinol and 24S-Pyxinol. The MDR reversal effects of these derivatives were evaluated in A549/Tax, MCF-7/ADR, and HCT-8/VCR cells using the CCK-8 assay. Subsequently, western blot assay, intracellular Rhodamine123 (Rh123) accumulation assay and P-gp ATPase activity assay were utilized to investigate the effects of active compound on P-gp. Molecular docking was used to predict the possible binding patterns of active compound to P-gp. Moreover, based on UPLC-Q/TOF-MS cellular metabolomics technology to identify endogenous differential metabolites and metabolic pathways associated with tumor MDR effects of the active compound. (3) Results: The results of the CCK-8 assay showed that compounds 8, 14, 16, 17, 18, 23, 25, 34, 36, 37 exhibited strong MDR reversal effect in A549/Tax, MCF-7/ADR and HCT-8/VCR cells, which were screened by reversal fold (RF) greater than 5. Among them, 10 μM of derivative 37 (new compound) showed the outstanding activity (RF: 15.31) in reversing MDR in A549/Tax cells. Compound 37 could act as a substrate for P-gp and inhibit the efflux function of P-gp by competitively binding to the binding site of antitumor drugs. Meanwhile, the molecular docking results confirmed that compound 37 was identified to under-go high-affinity binding to the drug binding site of P-gp. In addition, 14 endogenous differential metabolites and 6 metabolic pathways involved closely associated with the reversal of tumor MDR effects of compound 37 were identified. (4) Conclusions: Overall, a new candidate compound 37 (24S-3-L-threonyl-Pyxinol) could be provided for reversing tumor MDR by this study.

With increasing constraints on energy and resource markets and the non-decreasing trend in energy demand, the need for relevant clean energy generation and storage solutions is growing and is gradually reaching the individual home. But small-scale energy storage is still an expensive investment in 2022 and the risk/reward ratio is not yet attractive enough for individual homeowners. One solution is for homeowners not to store excess clean energy individually but to produce hydrogen for mutual use. In this paper a collective production of hydrogen for a daily filling of a bus is considered. Following our previous work on the subject, the investigation consists of finding an optimal buy/sell rule to the grid, and the use of the energy with an additional objective: mobility. The dominant technique in the energy community is reinforcement learning, which is however difficult to use when the learning data is limited as in our study. We chose a less data-intensive and yet technically well-documented approach. Our results show that rulebooks, different but more interesting than the usual robust rule, exist and can be cost-effective. But they require fine-tuning as to not deteriorate system performance. In some cases, it is worth missing the H2 production requirement in exchange for higher economic performance.

The sensor nodes have limited computation, sensing, communication capabilities and generally operated by batteries in a harsh atmosphere with non-replenish able power sources. These limitations force the sensor network subject to failure because most of the energy is spent on sensing, computing and data transmission. This paper introduces an Energy Efficient Clustering and Shortest-Path Routing Protocol (EECSRP) to assist Wireless Sensor Networks (WSNs) by (a) extending the lifespan of the network (b) effectively using the battery power (c) decreasing the network overhead and (d) ensuring a high packet transmission ratio with minimal delay. The delay time-based Cluster Head (CH) is elected based on the node degree, residual energy and Received Signal Strength (RSS) to accomplish the goal. Additionally, the RSS-based network partitioning is implemented to evaluate the gradient based on demand routing between source (sensing node) and destination (BS). Whenever the current CH residual energy goes under the threshold level, the proposed protocol performs the clustering process, reducing the exchange of control packets. However, the BS periodically gathers the data from every single CH which helps to reduce the collision and Medium Access Control (MAC) layer conflict. From the simulation results, it is the evident that the proposed protocol performance in terms of average end-to-end latency, packet delivery ratio, average energy consumption and control overhead is better than the well-known current protocols.

A lightweight composite bridge deck system composed of steel orthotropic deck stiffened with thin Ultra-High Performance Concrete (UHPC) layer is developed to eliminate fatigue cracks in orthotropic steel decks. During the construction and operation period of the bridge, the debonding between the steel deck and the UHPC layer may introduce the several issues, such as crack-induced water invasion and distinct reduction of the shear resistance. In the study, an effective and novel non-destructive interface condition monitoring approach using piezoelectric lead zirconate titanate (PZT)-based technologies is proposed to detect interfacial delamination between steel deck and UHPC layer. Experimental tests are performed on several steel-UHPC composite slabs and a conventional steel-concrete composite slab. The thin styrofoam sheets with different sizes and thicknesses are set on different locations of the steel deck as the artificial debondings. The PZT ceramic patches are bonded on the surfaces of the steel deck and UHPC layer as the actuators/sensors. An improved PSO (Particle Swarm Optimization)-K-means clustering algorithms is proposed to obtain the debonding patterns based on the feature data set. The laboratory tests demonstrate that the proposed approach provides an effective and accurate way to detect interfacial debonding of steel-UHPC composite slab.

The energy crisis is currently a major topic in scientific and managerial discussions in the building and construction industry. While employing low-cost strategies for reducing energy usage is beneficial for principals and decision-makers, the primary purpose of this study is to recommend the use of phase change materials (PCM) to improve cooling and heating load management in buildings. In order to accomplish this, the study applies design-builder simulations to a developing country case study. The results indicate that integrating PCM in buildings can reduce energy usage by around 6 percent. Although this value may be lower than other techniques, it is nevertheless important for reaching green building goals in both developed and developing nations. The case study, which takes place in a four-season region, demonstrates the significant potential of the PCM system for both cooling and heating energy management. In addition, the reciprocal performance improvement of PCMs is a remarkable characteristic, especially when contrasted to some conventional systems that focus on a single energy management objective in buildings. Lastly, it should be underlined that the suggested platform is consistent with Sustainable Development Goal 7 (Affordable and Clean Energy Targets).

An important stage in SARS-CoV-2 life cycle is the fusion of spike(S) protein with the ACE2 host-cell receptor. Therefore, to explore conserved features in S protein dynamics and to identify potentially novel regions for drugging, we measured variability derived from 791 viral genomes and studied its properties by MD simulation. The findings indicated that S2 subunit (HR1, CH, and CD domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the RBD domain, which is typically targeted in drug discovery programmes, exhibits more sequence variability and flexibility. Interpretations from MD suggest that the monomer is in constant motion showing transitions up-to-down state, and the trimer cavity may function as a 'bouncing spring' that may facilitates S protein interactions with ACE2. Feasibility of trimer cavity for potential drug target was examined by SBVS screening. Several hits that have already been validated or suggested to inhibit the SARS-CoV-2 virus in cell systems were identified; in particular, the data suggest an action mechanism for such molecules including Chitosan and macrolide types. These findings identify a novel binding-site formed by the S protein, that might assist in future drug discovery programmes aimed at targeting the CoV family of viruses.

Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from Selaginella moellendorffii v1.0's genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein's receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex N-glycan and RBD residues, respectively, with binding free energies of -17.5, -13.0, and -26.5 Kcal/mol. The normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein’s receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein-protein manner. The precursors for the Hevein-like homologs underwent additional characterization and their expressional profile in different tissues was studied. These in-silico findings offered potential lectin candidates targeting key N-glycan sites crucial to the virus's virulence and infection.

In this paper we compare the effects of forecasting demand using individual (disaggregated) components versus first aggregating the components either fully or into several clusters. Demand streams are assumed to follow autoregressive moving average (ARMA) processes. Using individual demand streams will always lead to a superior forecast compared to any aggregates, however we show that if several aggregated clusters are formed in a structured manner then these subaggregated clusters will lead to a forecast with minimal increase in mean-squared forecast error. We show this result based on theoretical MSFE obtained directly from the models generating the clusters as well as estimated MSFE obtained directly from simulated demand observations. We suggest a pivot-algorithm, that we call Pivot Clustering, to create these clusters. We also provide theoretical results to investigate sub-aggregation, including for special cases such as, aggregating MA(1) streams and ARMA streams with similar or same parameters.

Semi-supervised consensus clustering is a promising strategy to compensate for the subjectivity of clustering and its sensitivity to design factors, with various techniques being recently proposed to integrate domain knowledge and multiple clustering partitions. In this article we present a new approach that makes double use of domain knowledge, namely to build the initial partitions as well as to combine them. In particular, we show how to model and integrate must-link and cannot-link constraints into the objective function of a generic consensus clustering (??) framework that maximizes the similarity between the consensus partition and the input partitions, which have, in turn, been enriched with the same constraints. In addition, borrowing from the theory of functional dependencies, the integrated framework exploits the notions of deductive closure and minimal cover to take full advantage of the logical implication between constraints. Using standard UCI benchmarks, we found that the resulting algorithm, termed ??? (double-Constrained Consensus Clustering), was more effective than plain ?? at combining base constrained partitions. We then argue that ??? is especially well-suited to profiling counterfeit e-commerce websites, because constraints can be acquired by leveraging specific domain features, and demonstrate its potential for detecting affiliate marketing programs. Taken together, our experiments suggest that ??? makes the process of clustering more robust and able to withstand changes in clustering algorithms, datasets, and features, with a remarkable improvement of average performance.

Life in the modern century is heavily reliant on an enormous amount of electricity consumption as technology has become the most integral part of daily life. In this context, smart grid systems play a pivotal role to maintain the uninterrupted power supply which needs to be monitored in a timely fashion to keep track of the electric consumers’ usage pattern. The smart meter is the one of smart applications of the smart grid that collects huge amounts of consumer load data on a daily basis which has become a focus for various researchers and analyzers to study load characterization. In this paper, an approach has been proposed to recognize the energy consumption patterns among diverse types of consumers ranging from residential to industrial levels. This approach is worth considering not only for load pattern recognition but also for involving customers in different events such as demand response or peak shaving. In such a way, this analytical mechanism certainly assists in reducing power wastage and saving costs. The proposed methodology is based on a two-fold clustering algorithm with the use of state-of-the-art technology, machine learning. The primary goal is to classify electric customers' data collected from smart meters. Then, analyzing the classified results with an aim to predict power consumption patterns for the customers in the future and making the right energy policy that will benefit both the grid operator and consumers as well.

Finding anomalies in the real-time system is recognized as one of most challenging study in information security. It has so many applications like IoT, and Stock-Market. In any IoT system the data generated are real-time, and temporal in nature. Since due to the extreme exposure to Internet and interconnectivity of devices, the IoT systems often face issues like fraud, anomalies, intrusions etc. Discovering anomaly in such domain can be interesting. Clustering and rough set theory have been tried in many cases. Considering the time-stamp associated with IoT data, time-dependent patterns like periodic clusters can be generated which could be helpful for the efficient detection of anomalies by providing more in-depth analysis of the system. In this paper, a mixed method comprising of nano topology, a modified k-means clustering and an interval superimposition technique is used for finding fuzzy periodic clusters in the subspace generated by the nano topology. For every clusters there will be an associated sequence of time-intervals where it exists. The sequence time-intervals accompanying with each clusters may exhibit some remarkable patterns. For example, there may exist different types of periodicity namely yearly, monthly, daily, and hourly etc. For finding such fuzzy periodicity, an operation called interval-superimposition has been used. The time-intervals associated with each cluster are superimposed if they have reasonable overlapping. Each superimposed time-interval generates a fuzzy time-interval. The data instances are thought to be anomalous if they either belong to sparse clusters or don't belong to any clusters. The efficacy of the method can be assessed by means of both time-complexity analysis and comparative studies with existing clustering-based anomaly detection algorithms with a real-life and a synthetic dataset. It can been found experimentally that our method can extract anomaly with 98% of accuracy and it runs cubic time approximately.

Brain tissue segmentation is an important component of clinical diagnosis of brain diseases by means of multi-modal magnetic resonance imaging (MR). Brain tissue segmentation is developed by many unsupervised methods in literature. The most commonly used unsupervised methods are: K-Means, Expectation Maximization and Fuzzy Clustering. Fuzzy clustering methods offer considerable benefits compared with the aforementioned methods as they are capable of handling brain images which are complex, largely uncertain and imprecise in nature. However, this approach suffers from the intrinsic noise and intensity inhomogeneity (IIH) in the data resulted from the acquisition process. To resolve these issues, we propose a fuzzy consensus clustering algorithm that defines a membership function resulted from a voting schema to cluster the pixels. In particular, we first pre-process the MRI data and employ several segmentation techniques based on traditional fuzzy sets and intuitionistic sets. Then, we adopted a voting schema to fuse the results of the applied clustering methods. Finally, to evaluate the proposed method, we used the well-known performance measures (boundary measure, overlap measure and volume measure) on two publicly available datasets (OASIS and IBSR18). The experimental results show the superior performance of the proposed method in comparison with the recent state of the arts.

Clustering algorithms for multi-database mining (MDM) rely on computing $(n^2-n)/2$ pairwise similarities between $n$ multiple databases to generate and evaluate $m\in[1, (n^2-n)/2]$ candidate clusterings in order to select the ideal partitioning which optimizes a predefined goodness measure. However, when these pairwise similarities are distributed around the mean value, the clustering algorithm becomes indecisive when choosing what database pairs are considered eligible to be grouped together. Consequently, a trivial result is produced by putting all the $n$ databases in one cluster or by returning $n$ singleton clusters. To tackle the latter problem, we propose a learning algorithm to reduce the fuzziness in the similarity matrix by minimizing a weighted binary entropy loss function via gradient descent and back-propagation. As a result, the learned model will improve the certainty of the clustering algorithm by correctly identifying the optimal database clusters. Additionally, in contrast to gradient-based clustering algorithms which are sensitive to the choice of the learning rate and require more iterations to converge, we propose a learning-rate-free algorithm to assess the candidate clusterings generated on the fly in a fewer upper-bounded iterations. Through a series of experiments on multiple database samples, we show that our algorithm outperforms the existing clustering algorithms for MDM.

In this paper, we provide a study on the effects of applying classical clustering algorithms, such as k-Means to free text recommender systems. A typical recommender system may face problems when the number of items from a database goes from a few items to hundreds of items. Currently, one of the most prominent techniques to scale the database is applying clustering, however clustering may have a negative impact on the accuracy of the system when applied without taking into consideration the underlying items. In this work, we build a conceptual text recommender system and use k-Means to partition its search space into different groups. We study how the variation of the number of clusters affects its performance in the light of two performance measurements: recommendation time and precision. We also analyze if this clustering is affected by the representation of text we use. All the techniques used in this study uses word-embeddings to represent the document. One of the main findings of this work is that using clustering we can improve the recommendation time in up to almost 30 times without affecting much off its initial accuracy. Another interesting finding is that the increment of the number of clusters is not directly translated into linear performance.

In this paper, we propose a simple tool to help the energy management of a large buildings stock defining clusters of buildings with the same function, setting alert thresholds for each cluster, and easily recognizing outliers. The objective is to enable a building management system to be used for detection of abnormal energy use. First, we framed the issue of energy performance indicators, and how they feed into data visualization (Data Viz) tools for a large building stock, especially for university campuses. Both for Data Viz and clustering algorithm processes, we discussed two possible approaches to choose the right number of clusters and the identification of alert thresholds and outliers, after a brief presentation of the University of Turin's building stock case study. Different Data Viz tools have been studied to apply a specific clustering algorithm, the k-means one. An explorative analysis based on the general Multidimensional detective approach by Inselberg has been performed. Two multidimensional analysis tools, the Scatter Plot Matrix and the Parallel coordinates method have been used. Secondly, the k-means clustering algorithm has been applied on the same dataset in order to test the hypothesis made during the explorative analysis. Data Viz techniques developed in this study revealed to be very useful to explore quickly and simply a large buildings' stock, identifying the worst efficient buildings and clustering them according to their distinct functions.

An adaptive spatial clustering (ASC) algorithm is proposed in this present study, which employs sweep-circle techniques and a dynamic threshold setting based on the Gestalt theory to detect spatial clusters. The proposed algorithm can automatically discover clusters in one pass, rather than through the modification of the initial model (for example, a minimal spanning tree, Delaunay triangulation or Voronoi diagram). It can quickly identify arbitrarily-shaped clusters while adapting efficiently to non-homogeneous density characteristics of spatial data, without the need of prior knowledge or parameters. The proposed algorithm is also ideal for use in data streaming technology with dynamic characteristics flowing in the form of spatial clustering in large data sets.

Dengue is a pan-tropical arthropod-borne disease, endemic in over 100 countries. The dengue virus comprises four antigenic serotypes (DENV 1-4). The envelope (E) and non-structural 1 (NS1) proteins are highly immunogenic, and the E protein carries epitopes eliciting neutralizing antibodies. In previous studies, mice immunizations with two DNA vaccines encoding the E ectodomain (pE1D2) and NS1 proteins (pcTPANS1) from DENV2 induced high protection. Based on these findings, we constructed new plasmids containing the codon-optimized genes from these proteins for expression in mouse and human cells, named pEotmD2 and pNS1otmD2. Compared to the pE1D2, the pEotmD2 mediated lower expression of the recombinant protein in human and mouse cell lines, while the pNS1otmD2 plasmid was slightly more efficient than the pcTPANS1 in these cells. Immunogenicity and protection were evaluated in BALB/c mice immunized with the original and codon-optimized plasmids followed by challenged with DENV2. In accordance with the in vitro experiments, the antibody response and protection elicited by the pE1otmD2 plasmid was lower than those observed with the pE1D2. In contrast, the pNS1otmD2 vaccine enabled slightly higher levels of the humoral and protective responses than the pcTPANS1. Overall, our study revealed different effects of codon optimization on these two dengue DNA vaccines.

Existing studies provide evidence that buildings and the construction sector are the largest consumers of natural resources and carry the greatest responsibility for greenhouse gas emissions. In order to reverse this situation, future challenges involve utilising the least resources possible. To this end, building refurbishment becomes a crucial strategy given its potential to improve operational energy efficiency and to extend the life span of existing building stock, thereby reducing the environmental impact while also providing social and economic benefits to our cities. Life Cycle Sustainability Assessment (LCSA) has become one of the scientific community’s most widely recognised methodologies for the evaluation of the social, economic, and environmental dimensions (Triple Bottom Line), since it assesses sustainability using quantitative metrics. However, the implementation of this methodology to support the refurbishment process at the project stage in building design tools, such as BIM, remains scarce. One of the main obstacles lies in the difficulties of accessing the building information, given that the system boundaries only cover new materials and products. Hence, this study proposes a BIM plug-in development to support the multi-dimensional building material selection in the early design steps based on the LCSA of a building during the refurbishment stage and validates its application in a case study. The results show the viability of using this tool during the early design stages and demonstrate the consistency of the results to evaluate various material and product alternatives for the refurbishment of the envelope system of a multi-family residential building. This study contributes towards the integration of decision-making by providing real-time assessment of the building envelope.

The present article is dealing with the state of question about building-energy monitoring systems used for data collection to estimate the Heat Lost Coefficient (HLC) with existing methods and so determinate buildings’ Envelope Energy Performance (EEP). In addition, the data requirements of HLC estimation methods are related with commonly used methods for fault detection, calibration and supervision of energy monitoring systems in buildings. Based on an extended review of experimental tests since 1978, a qualitative and quantitative analysis of Monitoring and Controlling System (MCS) specifications has been carried out. Although most actual Buildings Automation Systems (BAS) may measure the required parameters, further research is still needed to ensure that these data are accurate enough to rigorously apply the HLC estimation methods.

Currently, with a large number of fatality rates, coronavirus disease-2019 (COVID-19) has emerged as a potential threat to human health worldwide. It has been well-known that severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 and World Health Organization (WHO) proclaimed the contagious disease as a global pandemic. Researchers from different parts of the world amalgamate together inquest of remedies for this deadly virus. Recently, it has been demonstrated that the spike glycoprotein (SGP) of SARS-CoV-2 is the mediator behind the entrance into the host cells. Our group has comprehensibly analyzed the SGP of SARS-CoV-2 through multiple sequence analysis along with the phylogenetic analysis. Further, this research work predicted the most immunogenic epitopes for both B-cell and T-cell. Notably, we focused mainly on major histocompatibility complex (MHC) class I potential peptides and predicted two epitopes; WTAGAAAYY and GAAAYYVGY, that bind with the MHC class I alleles which are further validated by molecular docking analysis. Furthermore, this study also proposed that the selected epitopes were shown availability in a greater range of the population. Hence, our study comes up with a strong base for the implementation of designing novel vaccine candidates against SARS-CoV-2, however adequate laboratory works will need to be conducted for the appropriate application.

Background: Respiratory transmission is the primary route of SARS-CoV-2 infection. Angiotensin I converting enzyme 2 (ACE2) is the known receptor of SARS-CoV-2 spike glycoprotein for entry into human cells. A recent study reported absent to low ACE2 promoter activity in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE in human lungs compared to very low expression of ACE2. Methods: In silico tools were applied to assess potential interaction of SARS-CoV-2 surface spike protein with human ACE as well as predict the drugs that may block SARS-CoV-2 interaction with host receptor. Results: Although it is not obvious from the primary sequence alignment of ACE2 and its homolog ACE (also known as ACE1), comparison of X-ray crystallographic structures show striking similarity in the regions of these proteins which is known (for ACE2) to interact with the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Critical amino acids that mediate interaction with the viral spike protein in ACE2 are organized in the same order in ACE. In silico analyses predicts comparable interaction of SARS-CoV-2 spike protein with ACE2 and ACE. In addition, this study predicts and selects already approved drugs from a list of 1263, which may interfere with the binding of SARS-CoV-2 spike glycoprotein to ACE2 and/or ACE.

The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its spread to the whole world is currently posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARS-CoV based on the genome sequence comparison. Despite the genomic similarity between SARS-CoV and SARS-CoV-2, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows considerable difference compared to SARS-CoV, due to the presence of several point mutations. We analyzed the receptor binding domain (RBD) from recently published 3D structure of spike glycoprotein of SARS-CoV-2 and compared with RBD of SARS-CoV. The observations highlight few important features of RBD in the light of the recently published findings from the 3D structures of spike glycoprotein and its complex with human angiotensin-converting enzyme 2 (ACE2) (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)).

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (M^pro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as M^pro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

We analyze the humoral and B-cell mediated immunogenic response induced by GP5 lineal epitopes from porcine reproductive and respiratory syndrome virus (PRRSV) to explore the role of this protein in the protective response. For inoculation, pigs aged twenty-one days were allocated into six groups (seven pigs per group): control (PBS), vehicle (carrier), vaccinated (Ingelvac-PRRSV, MLV®), non-vaccinated and naturally infected, GP5-B and GP5-B3. Subsequently blood samples were collected and analyzed. Cytokine were measured by ProcartaPlex kit. Peptide-specific IgGs and cross-reactivity against peptides were analyzed by ELISA and B-cell subpopulations were analyzed by flow cytometry. At 2 days post-immunization (dpi), the GP5-B3 peptide increased the serum concentrations of cytokines associated to activate adaptive cellular immunity (IL-1β and IL-12). The concentration of IgGs anti-GP5-B increased in both cases at 21 and 42 dpi, while IgGs anti-GP5-B3 increased at 21 dpi and remained at the same level until 42 dpi. Also, antibody-forming/Plasma B cells (CD2+/CD21-) and primed B cells (CD2-/CD21+) from immunized pigs showed an increase at 42 dpi. Conversely the naïve B cells from immunized pigs decreased compared with the controls. Importantly, Both GP5-B and GP5-B3 peptides exhibited immunoreactivity against serum antibodies from vaccinated group, as well as non-vaccinated and naturally infected group. In conclusion, GP5-B and GP5-B3 peptides elicited immunogenicity mediated by antigen specific IgG´s and B-cell activation.

The large quantity of information retrieved from communities, public data repositories, web pages, or data mining can be sparsed and poorly classified. This work shows how to employ unsupervised classification algorithms such as K-means proper to classify user reviews into their closest category, forming a balanced data set. Moreover, we found that the text vectorization technique significantly impacts the clustering formation, comparing TF-IDF and Word2Vec. The value for mapping a cluster with movie genre was 81.34% ± 20.48 of the cases when the TF-IDF was applied, whereas Word2Vec only yielded a 53.51% ± 24.1. In addition, we highlight the impact of the removal of stop-words. Thus, we detected that pre-compiled lists are not the best method to remove stop-words before clustering because there is much ambiguity, centroids are poorly separated, and only 57% of clusters could match a movie genre. Thus, our proposed approach achieved a 94% of accuracy. After analyzing the classifiers’ results, we appreciated a similar effect when divided by the stop-words method removal. Statistically significant changes were observed, especially in precision metric and Jaccard scores in both classifiers, using custom-generated stop lists rather than pre-compiled ones. Reclassifying sparse data is strongly recommended as using custom-generated stop lists.

Cryptocurrencies have now become an emerging blockchain-based payment technology. Users’ identities on such networks are pseudo-anonymous in that all transactions made from an address are transparent and searchable by anyone; to preserve their privacy, users often use many different addresses. In recent years, some studies have been conducted regarding analyzing clusters of Bitcoin addresses that, according to certain heuristics, belong to the same entity. Such action allows law enforcement to have relevant information in cases where cryptocurrencies are used for illegal trafficking. Clustering methods based on a single heuristic do not allow the clustering of many addresses in a complete and accurate manner. This paper proposes Bitcoin Address Clustering based on multiple Heuristics (BACH), a tool that uses three different clustering heuristics to identify clusters of Bitcoin addresses, which are displayed through a three-dimensional graph. Based on the results, several analyses were conducted, including a comparison with Wallet Explorer, an address clustering tool similar to BACH. BACH, in addition to introducing the innovative feature of graphical visualization of the internal structure of clusters, is shown to improve address aggregation through the joint use of three heuristics for clustering.

Addressing sustainable mobility in urban areas has become a priority in today’s society, given the growing population and increasing vehicular flow in these areas. Intelligent Transportation Systems have emerged as innovative and effective technological solutions to address these challenges. Research in this area has become crucial, as it contributes not only to improve mobility in urban areas, but also to positively impact the quality of life of its inhabitants. To address this, a dynamic clustering methodology for vehicular trajectory data is proposed which can provide an accurate representation of the traffic state. Data was collected for the city of San Francisco, a dynamic clustering algorithm was applied and then an indicator was applied to identify areas with traffic congestion. Several experiments were also conducted with different parameterizations of the forgetting factor of the clustering algorithm. The results showed in terms of precision that the dynamic clustering methodology achieved high match rates compared to the congestion indicator applied to static cells.

The goal of this study is to categorize stakeholders in Internet of Things (IoT) security based on their roles in order to address the challenges associated with managing the large amount of data generated by IoT devices. With the increasing number of connected devices, the security risks also escalate, necessitating skilled stakeholders to mitigate these risks and prevent potential attacks. This study proposes a two-part approach that involves clustering stakeholders according to their responsibilities and determining relevant features to enhance decision-making. By grouping stakeholders into shared categories, the study aims to provide a more efficient and effective method for managing IoT security. The insights gained from this research will not only benefit stakeholders involved in IoT security but also assist policymakers and regulators in developing effective strategies.

In today's world, news events are emerging incessantly. Classifying the same event reported by different countries is of significant importance for public opinion control and intelligence gathering. Due to the diverse types of news, relying solely on translators would be costly and inefficient, while depending solely on translation systems would incur considerable performance overheads in invoking translation interfaces and storing translated texts. To address this issue, we mainly focus on the clustering problem of cross-lingual news. To be specific, we use a combination of sentence vector representations of news headlines in a mixed semantic space and the topic probability distributions of news content to represent a news article. In the training of cross-lingual models, we employ knowledge distillation techniques to fit two semantic spaces into a mixed semantic space. We abandon traditional static clustering methods like K-Means and AGNES in favor of the incremental clustering algorithm Single-Pass, which we further modify to better suit cross-lingual news clustering scenarios. Our main contributions are as follows: (1) We adopt the English standard BERT as the teacher model and XLM-Roberta as the student model, training a cross-lingual model through knowledge distillation that can represent sentence-level bilingual texts in both Chinese and English. (2) We use the LDA topic model to represent news as a combination of cross-lingual vectors for headlines and topic probability distributions for content, introducing concepts such as topic similarity to address the cross-lingual issue in news content representation. (3) We adapt the Single-Pass clustering algorithm for the news context to make it more applicable. Our optimizations of Single-Pass include adjusting the distance algorithm between samples and clusters, adding cluster merging operations, and incorporating a news time parameter.

In this work, we propose a self-supervised multi-agent system that meets the online learning of clustering tasks for video behavior recognition spatio-temporal tasks. Encoding visual behavioral actions as discrete temporal sequence(DTS). Real-time clustering recognition task in a multi-agent system for continuous model building, training, and correction. Finally, we implemented a fully decentralized multi-agent system and completed its feasibility verification in a surveillance video application scenario on vehicle path clustering.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus polyprotein integration contribute to ER stress and the host cell may exhibit an Unfolded Protein Response (UPR) to this protein accumulation, stimulating appropriate cellular responses such as adaptation, autophagy or cell death. These different stress responses support other antiviral strategies initiated by infected cells and can help to overcome viral infection. In epithelial A549 cells, a model currently used to study the flavivirus infection cycle and the host cell responses, all three pathways leading to UPR are activated during infection by Dengue virus (DENV), Yellow Fever virus (YFV) or West Nile virus (WNV). In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in A549 cells. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway without activation of the ATF6 branch. By modulating the ER stress response, we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV could manipulate the UPR to escape this host cell defence system. Since incomplete UPR could lead to unresolved and persistent ER stress, we found that ZIKV infection was associated with an abnormal accumulation of viral envelope proteins, which were aggregated with non-native disulfide bridges. As the presence of these “amyloid like” protein polymers may be cytopathic, our observations provide new insights into specific neuropathologies associated with ZIKA virus infections.

Previous studies showed that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, we synthesized and evaluated for their antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and ability of inhibiting P-gp-mediated MDR some ten diversely substituted 1-Ph-DHPIQ derivatives bearing at position 2 carboxylate groups (COOH, COOEt), nitriles (CN) and Mannich bases (e.g., morpholinomethyl derivatives). Lipophilicity parametrization and molecular docking calculations improved the understanding of the structure-activity relationships in cytotoxicity and P-gp inhibition of the investigated 1-Ph-DHPIQs, which led us to disclose a novel Mannich base HCl salt (8b’), which proved to be cytotoxic to all the tested tumor cell lines in the low micromolar range (IC50 < 20 M) and to inhibit in-vitro the efflux pumps P-gp and MRP1 responsible for MDR, with IC50s of 0.45 and 12.1 M, respectively.

P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or blood-brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structure-activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r² = 0.96, q²_CV = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q² = 0.80–0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

We describe a new approach for integrating multiple views of data into a common latent space using non-negative tensor factorization (NTF). This approach, which we refer to as the "Integrated Sources Model" (ISM), consists of two main steps: embedding and analysis. In the embedding step, each view is transformed into a matrix with common non-negative components. In the analysis step, the transformed views are combined into a tensor and decomposed using NTF. Noteworthy, ISM can be extended to process multi-view data sets with missing views. We illustrate the new approach using two examples: the UCI digit dataset and a public cell type gene signatures dataset, to show that multi-view clustering of digits or marker genes by their respective cell type is better achieved with ISM than with other latent space approaches. We also show how the non-negativity and sparsity of the ISM model components enable straightforward interpretations, in contrast to latent factors of mixed signs. Finally, we present potential applications to single-cell multi-omics and spatial mapping, including spatial imaging and spatial transcriptomics, and computational biology, which are currently under evaluation. ISM relies on state-of-the-art algorithms invoked via a simple workflow implemented in a Jupyter Python notebook.