The global use of alcohol based hand sanitizers (ABHS) as a means of controlling the transmission of infectious disease increased dramatically in 2020 as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. The hand sanitizer tetrahedron, is a novel concept that considers both ABHS formulation factors and product performance factors from a multi-dimensional perspective. The four faces of the tetrahedron represent input/formulation factors: 1) the type and amount of alcohol, 2) inactive ingredients, 3) the type of formulation/delivery system and 4) manufacturing practices. The four corners of the tetrahedron represent output/product performance factors: 1) efficacy, 2) sensory characteristics, 3) usage, usability and compliance and 4) product safety/adverse effects. All factors are of importance to ensuring the effectiveness and utility of these products.

The endoplasmic reticulum (ER) comprises a network of tubules and vesicles that constitutes the largest organelle of the eukaryotic cell. Being the location where most proteins are synthesized and folded, it is crucial for the upkeep of cellular homeostasis. In addition, it is the largest ionic calcium reservoir in cells, tightly regulating the levels of this second messenger according to cellular necessities. Disturbed ER homeostasis triggers the activation of an intricate and conserved molecular machinery, termed the unfolded protein response (UPR). Given the impact of this signaling network upon an extensive list of cellular processes, ER stress is involved in the onset and progression of multiple diseases, including cancer and neurodegenerative disorders. There is, for this reason, an increasing number of publications focused on characterizing and/or modulating ER stress, which have resulted in a wide array of techniques employed to study ER-related molecular events. This review aims to sum up the tools available design a study of this nature.

This paper shows a method for pipeline leak detection using a transient-based method with MATLAB® functions. The simulation of a pipeline systems in the time domain are very complex. In the case of the dissipative model, transfer functions are hyperbolic Bessel functions. Simulating a pipeline system in the frequency domain using a dissipative model we could find an approximate transfer function with equal frequency domain response to in order get the pipeline system's time domain response. The method described in this paper can be used to detect, by comparison, to detect a leak in a pipeline system model.

Malnutrition and dental caries in early childhood remain persistent and intertwined global health challenges, particularly for indigenous and geographically-remote populations. To examine the prevalence and associations between early childhood dental caries, parent-reported mouth pain and malnutrition in the Amazonian region of Ecuador, we conducted a cross-sectional study of the oral health and nutrition status of 1,407 children from birth through age 6 in the “Alli Kiru” program (2011-2013). We used multivariate regression analysis to examine relationships between severe caries, parent-reported mouth pain measures, and nutritional status. The prevalence of dental caries was 65.4%, with 44.7% of children having deep or severe caries, and 33.8% reporting mouth pain. The number of decayed, missing and filled teeth dmft) increased dramatically with age. Malnutrition was prevalent, with 35.9% of children stunted, 1.1% wasted, 7.4% underweight, and 6.8% overweight. As mouth pain increased in frequency, odds for severe caries increased. For each unit increase in mouth pain frequency interfering with sleeping, children had increased odds for underweight (AOR: 1.27; 95% CI: 1.02 – 1.54) and decreased odds for overweight (AOR: 0.76; 95% CI: 0.58 – 0.97). This relationship was most pronounced among 3-6 year-olds. Early childhood caries, mouth pain and malnutrition were prevalent in this sample of young children. Parent-reported mouth pain was associated with severe caries, and mouth pain interfering with sleeping was predictive of poor nutritional status. We demonstrate the utility of a parsimonious parent-reported measure of mouth pain to predict young children’s risk for severe early childhood caries and malnutrition, which has implications for community health interventions.

Analysis of SARS-CoV-2 spike protein sequences of over 19 countries from biological databases submitted around the globe was carried out with help of bioinformatics tools and structure prediction databases. Initial data analysis showed entry of virus into different geographic regions started in the month of January 2020. Meanwhile, alignment of spike protein sequences of SARS-CoV-2 isolates from China and other countries revealed a critical mutation of D614G. Surprisingly, mutation D614G was not seen in early samples submitted in the month of January but gradually it started appearing globally from the month of March 2020. However, the mutations of amino acids in the spike protein other than D614G exhibiting similar pI and altered polarity were found to be specific to geographical regions. Besides, prediction of homology model for interaction of spike protein showed predominant role of chain C of trimeric spike protein in adhering receptor binding domain (RBD) of human ACE2 receptor. Furthermore, the prediction of glycosylation points has revealed that there are about 20 N-glycosylation potential sites on spike protein. We believe that the information present here would not only help in thorough understanding of infectivity but also enhance the knowledge of the scientific community in developing prophylactics and/or therapeutics for SARS-CoV19-2 virus.

The feedback collection and analysis has remained an important subject matter since long. The traditional techniques for student feedback analysis are based on questionnaire-based data collection and analysis. However, the student expresses their feedback opinions on online social media sites, which need to be analyzed. This study aims at the development of fuzzy-based sentiment analysis system for analyzing student feedback and satisfaction by assigning proper sentiment score to opinion words and polarity shifters present in the input reviews. Our technique computes the sentiment score of student feedback reviews and then applies fuzzy-logic module to analyze and quantify student’s satisfaction at the fine-grained level. The experimental results reveal that the proposed work has outperformed the baseline studies as well as state-of-the-art machine learning classifiers.

The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The fragments were selected from patients with invasive ductal carcinoma of the breast, the most common and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers, useful for diagnostic and prognostic categorization of patients, in assessing post-surgical therapeutic regimes. The proteomic screening, by 2D-IPG and mass spectrometry, allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients, and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is generally supported by two concurrent pathways: the inhibition of apoptosis and the stimulation of cellular proliferation. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. To our knowledge this report on large-scales proteomics of breast cancer is currently a unique approach in the literature that offers the opportunity to evaluate the presence and recurrence of proteins to be used as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast.

The severity of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), greatly varies from patient to patient. In the present study, we explored and compared mutation profiles of SARS-CoV-2 isolated from mildly affected and severely affected COVID-19 patients in order to explore any relationship between mutation profile and disease severity. Genomic sequences of SARS-CoV-2 were downloaded from GISAID database. With the help of Genome Detective Coronavirus Typing Tool, genomic sequences were aligned with the Wuhan seafood market pneumonia virus reference sequence and all the mutations were identified. Distribution of mutant variants was then compared between mildly and severely affected groups. Among the numerous mutations detected, 14,408C>T and 23,403A>G mutations resulting in RNA-dependent RNA polymerase (RdRp) P323L and spike protein D614G mutations, respectively, were found predominantly in severely affected group (>82%) compared with mildly affected group (<46%, p<0.001). The 241C>T mutation in the non-coding region of the genome was also found predominantly in severely affected group. The 3,037C>T, a silent mutation, also appeared in relatively high frequency in severely affected group. We concluded that RdRp P323L and spike protein D614G mutations predominate in severely affected COVID-19 patients. Further studies will be required to explore whether these mutations have any impact on the severity of COVID-19.

Background: There are no known medicines or vaccines to control the COVID-19 pandemic caused by SARS-CoV-2 (nCoV). Antiviral peptides are superior to conventional drugs and may also be effective against COVID-19. Hence, we investigated the SARS-CoV-2 Spike RBD (nCoV-RBD) that interacts with hACE2 for viral attachment and entry. Methods: Three strategies and bioinformatics approaches were employed to design potential nCoV-RBD - hACE2 interaction-blocking peptides that may restrict viral attachment and entry. Firstly, the key residues interacting with nCoV-RBD - hACE2 are identified and hACE2 sequence based peptides are designed. Second, peptides from five antibacterial peptide databases that block nCoV-RBD are identified; finally, a chimeric peptide design approach is used to design peptides that can bind to key nCoV-RBD residues. The final peptides are selected based on their physiochemical properties, numbers and positions of key residues binding, binding energy, and antiviral properties. Results: We found (i) three amino acid stretches in hACE2 interact with nCoV-RBD; (ii) effective peptides must bind to three key positions of nCoV-RBD: Gly485/Phe486/Asn487, Gln493, and Gln498/Thr500/Asn501; (iii) Phe486, Gln493, and Asn501 are critical residues; (iv) AC20 and AC23 derived from hACE2 may block two key critical positions; (iv) DBP6 identified from databases can block the three sites of the nCoV-RBD interacting with one critical position Gln498; (v) seven chimeric peptides were considered promising among which cnCoVP-3, cnCoVP-4, and cnCoVP-7 are the top three; and (vi) cnCoVP-4 meets all the criteria and is the best peptide. Conclusion: All the ten peptides need experimental validation for their therapeutic efficacy.

The COVID-19 pandemic situation, disease intensity, weak healthcare facilities, unawareness, and misinformation led people to fear and anxiety in Bangladesh. This study intended to get peoples’ perception on psychosocial, socio-economic and environmental crisis amidst the pandemi. An online questionnaire was surveyed nationwide (respondents no.1066). Datasets were analyzed through the Principal Component Analysis (PCA), hierarchical Cluster Analysis (CA), Pearson’s correlation matrix (PCM), Linear regression analysis (LRA), and psychometric characteristics were included in the Classical Test Theory (CTT) analysis. There were good associations among the psychosocial, socio-economic and environmental parameters. A significant association between fear of COVID-19 with struggling healthcare system (p<0.05) was found. Also, negative association between fragile health system and government’s ability to deal with the pandemic (p<0.05) revealing poor governance. Again, a positive association of shutdown and social distancing with fear of losing life, and due to lack of health treatment (p<0.05) reveals that shut down hampers normal activities which may lead to mental and economic stress. However, a positive association of socio-economic impact of the shutdown with poor people’s suffering, the price hike of basic need, hamper of formal education (p<0.05) may lead to severe socio-economic and health crisis. There is a possibility of climate-induced disaster during/after the pandemic, which will create severe food insecurity (p<0.01). Daily wage earners and poors will suffer most by food and nutritional deficiency, and the country may face huge economic burden. Proper risk assessment and communications is needed to alleviate fear and anxiety. Thus, financial support and mental boosting is required.

Hydrogen peroxide is an important chemical of increasing demand in today’s world. Currently, the anthraquinone autoxidation process dominates the industrial production of hydrogen peroxide. Herein, hydrogen and oxygen are reacted indirectly in the presence of quinones to yield hydrogen peroxide. Owing to the complexity and multi-step nature of the process, it is advantageous to replace the process with an easier and straightforward one. The direct synthesis of hydrogen peroxide from its constituent reagents is an effective and clean route to achieve this goal. Factors such as water formation due to thermodynamics, explosion risk, and the stability of the hydrogen peroxide produced hinder the applicability of this process at an industrial level. Currently, the catalysis for the direct synthesis reaction is palladium based and the research into finding an effective and active catalyst has been ongoing for more than a century now. Palladium in its pure form, or alloyed with certain metals are some of the new generation of catalysts that are extensively researched. Additionally, to prevent the decomposition of hydrogen peroxide to water, the process is stabilised by adding certain promoters such as mineral acids and halides. A major part of today’s research in this field focusses on the reactor and the mode of operation required for synthesising hydrogen peroxide. The emergence of microreactor technology has helped in setting up this synthesis in a continuous mode, which could possibly replace the anthraquinone process in the near future. This review will focus on the recent findings of the scientific community in terms of reaction engineering, catalyst and reactor design in the direct synthesis of hydrogen peroxide.

The experiment was conducted at livestock research and development station surezai Peshawar during March 2012 to study the effect of cotton seed cake, Lucerne hay supplementation on intake of maize stover and weight gain by male sahiwal bull. Twelve (12) young Sahiwal bull breed, 280 kg average liveweight and 2 years of age were randomly put into 4 groups of 3 animals under intensive feeding system to determine the effect of different protein supplements on growth, and intake of chopped, dried maize stover. A control group was fed stover adlibitum only, and the other groups were fed daily 750 g cottonseed cake/head, 1 kg lucerne hay or 900 g of lucerne/cottonseed cake (66:34; w/w). Significant differences were observed on average daily live weight gains. Animals on lucerne and its mixture registered higher daily gains (243 g) and (330 g) respectively, followed by cottonseed cake (156 g); the control group lost weight (-8.0 g/d). Contrary to the live weight gains, animals fed on lucerne and its mixture had lower maize stover intakes, 3.35 kg DM/animal/day and 3.70 kg DM respectively, while those on cottonseed cake and the control group ingested respectively 4.72 kg DM and 4.16 kg DM maize Stover. It is concluded that during the critical period in the suburb of Peshawar, small-scale farmers can prevent loss in live weight by utilizing simple available rations.

Background: Staphylococcus aureus (S. aureus) is an opportunistic pathogen and a predominant cause of life-threatening nosocomial infections. Drug resistance in S. aureus is attributed to production of biofilm, which is controlled largely by bacterial quorum sensing (QS) systems. Methodology: In vitro analysis of biofilm inhibition assay was performed using crystal violet staining assay, swarming motility, light microscopy and growth curve analyses. Identification of the major constituents of I. verum fruit extract was performed by GC-MS. Ligand-protein interaction was analyzed by molecular docking investigations. Results: The methanol extract of I. verum inhibited the growth of MRSA at the concentration of 4.8 mg/ml. At the sub-inhibitory concentration (2.4mg/ml), the extract showed significant reduction in biofilmogenesis. Light microscopy analysis confirmed the antibiofilm activity as well as the efficacy in disturbing biofilm architecture. A reduced swarming motility was observed at the lowest concentration of 2.4mg/ml. GC-MS analysis revealed anethol (AL) as the major constituent. The molecular docking analysis attributes the antibiofilm activity to an active ligand AL, which strongly interacted with the active site residues of AgrA and SarA proteins of S. aureus. Conclusion: We report the activities of I. verum to be immensely interfering with QS system and biofilm formation in MRSA.

The future of machine tools will be dominated by highly flexible and interconnected systems, in order to achieve the required productivity, accuracy and reliability. Nowadays, distortion and vibration problems are easily solved in labs for the most common machining operations by using models based on equations describing the physical laws of the machining processes; however additional efforts are needed to overcome the gap between scientific research and the real manufacturing problems. In fact, there is an increasing interest in developing simulation packages based on “deep-knowledge and models” that aid machine designers, production engineers or machinists to get the best of the machine-tools. This article proposes a methodology to reduce problems in machining by means of a simulation utility, which uses the main variables of the system&process as input data, and generates results that help in the proper decision-making and machining planification. Direct benefits can be found in a) the fixture/clamping optimal design, b) the machine tool configuration, c) the definition of chatter-free optimum cutting conditions and d) the right programming of cutting toolpaths at the Computer Aided Manufacturing (CAM) stage. The information and knowledge-based approach showed successful results in several local manufacturing companies and are explained in the paper.

Many complex behaviours in biological systems emerge from large populations of interacting molecules or cells, generating functions that go beyond the capabilities of the individual parts. Such collective phenomena are of great interest to bioengineers due to their robustness and scalability. However, engineering emergent collective functions is difficult because they arise as a consequence of complex multi-level feedback, which often spans multiple length-scales. Here, we present a perspective on how some of these challenges could be overcome by using multi-agent modelling as a design framework within synthetic biology. Using case studies covering the construction of synthetic ecologies to biological computation and synthetic cellularity, we show how multi-agent modelling can capture the core features of complex multi-scale systems and provide novel insights into the underlying mechanisms which guide emergent functionalities across scales. The ability to unravel design rules underpinning these behaviours offers a means to take synthetic biology beyond single molecules or cells and towards the creation of systems with functions that can only emerge from collectives at multiple scales.

Virus-infected Flu is a common disease. To date, no specific drugs are available to manage the symptoms of cough, headache and sputum production. An alternative Chinese herb medicine is introduced for virus-infected Flu or similar infection. Before hospitalization, some of patients may scare for cross-infection with mild symptoms or hardly go to hospital if encountered a temporary lockdown or quarantine. Some Chinese practice self-treatment of cough, headache and sputum production by inhalation of volatile chemicals from onion and garlic. Author used to take the same alternative approach of inhalation of onion, garlic or scallions for self-treatment when suffered virus caused flu with cough, headache and sputum production at onset disease. In this article, the biomedical effects of onion and garlic are reviewed. To help patients with mild symptoms of virus infected Flu, a simple home-based treatment was suggested to self-treatment because of temporary isolation and hardly going to hospitalization. The alternative approach may also suggest for some mild virus infected respiratory diseases caused by virus at onset disease.

Background: Serious games are conceptualized as a broad topic and overlap segments of more modern forms of education: e-learning, edutainment, game-based learning, and digital game-based learning. Serious Games aligns with digitalization and the modern era and creates novel opportunities for learning and assessment in medical education. Escape rooms, a type of serious games, merge mental and physical aspects to reinforce critical skills useful in daily life. It challenges logic and reasoning and demands careful analysis of situations to correlate and solve different stages of the escape room under pressurized, timed conditions. Furthermore, it serves as an adequate environment to build problem-solving skills, communication skills, and leadership skills through the collaboration of people to achieve a common goal. The aim of this study was to investigate the applications of escape rooms in Medical Education. Method: This study investigated the applications of escape rooms in medical education. Serious games are expanding in education and have attained great relevance due to their intriguing and intrinsically motivating attributes. Within serious games, we focused on escape rooms in which participants are locked in a room, faced with puzzles that must be solved to ‘escape the room’. Compiling the data from the first 100 hits of medical application of escape rooms, we found 72 cases and categorized them by year, specialty, participants structure, simulation experience, and design. Results: We reported on escape rooms in medical education by the year in which they were reported, the medical specialty, the participant structure, grouped or individual, the experience design; real, hybrid, or digital, and the modality of the delivery. 72% of the escape rooms focused on four main areas: nursing education (25.0%), emergency medicine (22.2%), pharmacy (12.5%), and interprofessional education (12.5%). Most of the escape rooms had a group-based physical design and little attention was given to provide a detailed description of the design considerations, such as the pathway type (linear, semi-linear, open). Conclusion: Escape rooms are applied in a wide range of medical education areas. In Medical Education, group-based on-site escape rooms with a focus on nursing, emergency medicine, pharmacy and interprofessional education dominates the implementation landscape. To further advance the field, stronger emphasis on making explicit the design considerations will advance the research and inform implementations.

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high infectivity in humans, attributed to the strong affinity of its spike (S) protein to human angiotensin-converting enzyme 2 (ACE2). Here, we analyzed the structural similarity of the S protein between SARS-CoV-2 and other SARS-related coronaviruses (CoVs). Methods We performed multiple alignment analysis of nine amino acid sequences of CoV S proteins from NCBI with MAFFT web-based software, followed by phylogeny analysis. Three-dimensional structure modeling was performed by SWISS-MODEL. We calculated the template modeling score between the S protein of SARS-CoV-2 and that of other SARS-related CoVs. Results The S1 domain of the unclassified CoV RaTG13 (the host of which is the intermediate horseshoe bat) was structurally very similar to that of SARS-CoV-2, implying that RaTG13 could be the origin of SARS-CoV-2. In addition, the folding property of the entire S protein was nearly the same between SARS-CoV-2 and RaTG13 after the PRRA amino acid insertion was removed from SARS-CoV-2. Conclusions RaTG13 could have a high binding affinity to ACE2, similar to SARS-CoV-2, and it is therefore highly likely to infect other animals. Therefore, massive research and monitoring of CoVs in animals is necessary to prevent future COVID-19-like disasters.

Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.

The growth and dynamics of multicellular tissues involve tightly regulated and coordinated morphogenetic cell behaviours, such as shape changes, movement, and division, which are governed by subcellular machinery and involve coupling through short- and long-range signals. A key challenge in the fields of developmental biology, tissue engineering and regeneration is to understand how relationships between scales produce emergent tissue-scale behaviours. Recent advances in molecular biology, live-imaging and ex vivo techniques have revolutionised our ability to study these processes experimentally. To fully leverage these techniques and obtain a more comprehensive understanding of the causal relationships underlying tissue dynamics, computational modelling approaches are increasingly spanning multiple spatial and temporal scales, and are coupling cell shape, growth, mechanics and signalling. Yet such models remain technically challenging: modelling at each scale requires different areas of technical skills, while integration across scales necessitates the solution to novel mathematical and computational problems. This review aims to summarise recent progress in multiscale modelling of multicellular tissues and to highlight ongoing challenges associated with the construction, implementation, interrogation and validation of such models.

Recent years have witnessed a breakthrough in identification of a trimer-of-hairpins motif within viral envelopes that triggers a broad range of virus-host fusion. Identifying a domain capable of controlling virus-host fusion remains a challenge due to sequence diversity, heavy glycan shielding and multiple conformations. Here, we report that HR2, a prevalent heptad repeat sequence comprising an alpha-helical coil anchored in viral membranes, is an accessible site to triterpenes, a class of widely distributed natural products. Triterpenes and their derivatives inhibit the entry of Ebola, HIV, and influenza A viruses with distinct structure-activity relationships. Specifically, triterpenoid probes, upon activation by ultraviolet light, capture the viral envelope via crosslinking the HR2 coil. Profiling the Ebola HR2 sequence using amino acid substitution, surface plasmon resonance (SPR) and nuclear magnetic resonance (NMR) spectroscopy disclosed six constitutive residues that are accessible to triterpenoids, leading to wrapping of the hydrophobic helix by triterpenoids and blocking of the HR1-HR2 interaction, which is critical in the trimer-of-hairpins formation. This finding was also observed in the envelopes of HIV and influenza A viruses and might potentially extend to a broader variety of viruses. Our findings might translate into a shared mechanism that host utilize natural product triterpenoids to antagonize membrane fusion of respective viruses, complementing the current repertoire of antiviral agents.

The proposal that the genetic code was formed on the basis of protein synthesis directed by tRNA dimers is reviewed and updated. The tRNAs paired through the anticodon loops are an indication on the process. Dimers are considered mimics of the ribosomes – structures that hold tRNAs together and facilitate the transferase reaction, and of the translation process – anticodons are at the same time codons for each other. The primitive protein synthesis system gets stabilized when the product peptides are able to bind the producers therewith establishing a self-stimulating production cycle. The chronology of amino acid encoding starts with Glycine and Serine, indicating the metabolic support of the Glycine-Serine C1-assimilation pathway, which is also consistent with evidence on origins of bioenergetics mechanisms. Since it is not possible to reach for substrates simpler than C1 and compounds in the identified pathway are apt for generating the other central metabolic routes, it is considered that protein synthesis is the beginning and center of a succession of sink-effective mechanisms that drive the formation and evolution of the metabolic flow system. Plasticity and diversification of proteins construct the cellular system following the orientation given by the flow and implementing it. Nucleic acid monomers participate in bioenergetics and the polymers are conservative memory systems for the synthesis of proteins. Protoplasmic fission is the final sink-effective mechanism, part of cell reproduction, guaranteeing that proteins don’t accumulate to saturation, which would trigger inhibition.

the intermittency and variability of these permeated Distributed Generators (DGs) could critically cause many security and economy risks to distribution systems. This paper applied a certain mathematical distribution to imitate the output variability and uncertainty of DGs. And then, four risk indices EENS, PLC, EFLC and SI were established to reflect the system risk level of distribution system. For the certain mathematical distribution of the DGs' output power, a developed PEM (point estimate method)-based method was proposed to calculate these four system risk indices. In this developed PEM-based method, enumeration method was used to list the states of distribution systems, an improved PEM was presented to deal with the uncertainties of DGs and the value of load curtailment in distribution systems was calculated by an optimal power flow algorithm. Finally, the effectiveness and advantages of this proposed PEM-based method for distribution system assessment were verified by the tests of a modified IEEE 30-bus system. Simulation results have shown that this proposed PEM-based method has a high computational accuracy and highly reduced computational costs compared with other risk assessment methods and is very effective for risk assessments.

The COVID-19 pandemic has brought about unprecedented changes to human lifestyles across the world. The virus and associated social restriction measures have been linked to an increase in mental health conditions. A considerable body of evidence shows that spending time in and engaging with nature can improve human health and wellbeing. Our study explores nature’s role in supporting health during the COVID-19 pandemic. We created web-based questionnaires with validated health instruments and conducted spatial analyses in a geographic information system (GIS). We collected data on people’s patterns of nature exposure, associated health and wellbeing responses, and potential socioecological drivers such as relative deprivation, access to greenspaces, and land-cover greenness. We applied a range of statistical analyses including bootstrap resampled correlations and binomial regression models, adjusting for several potential confounding factors. We found that respondents significantly changed their patterns of visiting nature as a result of the COVID-19 pandemic. People spent more time in nature and visited nature more often during the pandemic. People generally visited nature for a health and wellbeing benefit and felt that nature helped them cope during the pandemic. Greater land-cover greenness within a 250 m radius around a respondent’s postcode was important in predicting higher levels of mental wellbeing. There were significantly more food-growing allotments within 100 m and 250 m of respondents with high mental wellbeing scores. The need for a mutually-advantageous relationship between humans and the wider biotic community has never been more important. We must conserve, restore and design nature-centric environments to maintain resilient societies and planetary health.

The origin of life has not been solved as yet, in spit of the time passage more than thirty years from publication of RNA world hypothesis by W. Gilbert (1986), which is based on the “gene/replicator--first” theory. On the contrary, I have proposed [GADV]-protein world hypothesis (GADV hypothesis), assuming that life emerged from [GADV]-protein world, which is grounded on the “protein/metabolism-first” theory. However, two weak points of protein world hypothesis, (i) protein cannot be produced without gene, and (ii) protein cannot be self-replicated, have been frequently pointed out by supporters of RNA world hypothesis. Then, I examined whether the two weak points could be overcome by GADV hypothesis or not. From the results, it was confirmed that (i) [GADV]-protein could be pseudo-replicated in the absence of gene owing to protein 0^th-order structure or [GADV]-amino acids, and (ii) the replication ability is not always required from the beginning but it is sufficient to acquire it at some time point until the emergence of life. Thus, it was concluded that life emerged as [GADV]-protein world hypothesis, which is grounded on the “protein/metabolism-first” theory, expects.

Chronic kidney disease (CKD) affects >10% of the adult population. Each year approximately 120,000 Americans develop end-stage kideny disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6-0.8 g/kg/day comprised of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, can be promising. The scientific premise of the PLADO is based on the observations that high protein diets with high meat intake are not only associated with higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of hyperkalemia, given constipation from the typical low fiber intake. Plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk in CKD patients. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

The early-mid Paleocene Farewell Formation is stratigraphically distributed across the southern Taranaki Basin (STB) which is also encountered within the Maui Gas Field. Using available 3D seismic and well log data, a challenging task to delineate the spatial distribution and geobody patterns of the potential reservoir sands of the formation was performed. Object based modeling coupled with sequential indicator simulation were used to analyze the spatial distribution of facies configuration and a conceptual model was developed based on the outputs from the structurally- modeled grids. The facies modeling followed a hierarchical object-based mechanism which was set to perform with constraints like channel geometry and heterogeneity within the formation. The resultant 3D geobody model showed that the distributary channels, mainly braided geobodies flowed from northeast cutting through several regional normal-fault systems to the southwest. Overbank facies was adhered to the fringe of the channels whereas the floodplain facies was at the periphery of the model. Meandering channel-sand facies were mostly observed at the center of the model flowing in a more random manner, occupying major flow directions of northwest to southwest and southeast to northwest within the model.

Objective: The aim of the current study was to examine whether and to what extent mood disorders, comprising major depression and bipolar disorder, are accompanied by structural changes in the brain as measured using voxel-based morphometry (VBM). Methods: We have performed a VBM study using a 3Т MRI system (GE Discovery 750w) in patients with mood disorders (n=50), namely 39 with major depression and 11 with bipolar disorder, compared to 42 age, sex and education matched healthy controls. Results: Our results show that depression was associated with significant decreases in grey matter (GM) volume restricted to regions located in medial frontal and anterior cingulate cortex on the left side and middle frontal gyrus, medial orbital gyrus, inferior frontal gyrus (triangular and orbital parts), and middle temporal gyrus (extending to the superior temporal gyrus) on the right side. When the patient group was separated into bipolar disorder and major depression the reductions remained significant only for the patients with major depressive disorder. Conclusions: Using VBM the present study was able to replicate decreases in GM volume restricted to frontal and temporal regions in patients with mood disorders mainly major depression, as compared with healthy controls.

This paper outlines evidence-based practice in the context of professionalism, and highlights the contribution evidence-based practice can make to the professional practice of higher education course managers. Implications of the changing HE landscape for the status of academics as professionals are reviewed, and evidence-based practice is proposed as a solution for both enhanced course management and to remedy perceived deprofessionalisation. Finally, questions regarding researching professional practice within one’s own institution are addressed.

The next future using machine tools will be dominated by highly flexible and interconnected systems, in order to achieve the required productivity, accuracy and reliability. Nowadays, distortion and vibration problems are easily solved for the most common cases by sing models based on equations describing the physical laws dominating the machining process; however additional efforts are needed to overcome the gap between scientific research and the real manufacturing problems. In fact, there is an increasing interest in developing simulation packages based on “deep knowledge and models” that aid the machine designer, the production engineer, or machinists to get the best of their machines. This article proposes a systematic methodology to reduce problems in machining by means of a simulation utility, which recognizes, collects and uses the main variables of the system/process as input data, and generates objective results that help in the proper decision-making. Direct benefits by such an application are found in a) the fixture/clamping optimal design, b) the machine tool configuration, c) the definition of chatter free optimum cutting conditions and the right programming of cutting tool path at the Computer Aided Manufacturing (CAM) stage. The information and knowledge-based approach showed successful results in several local manufacturing companies.

Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic which has been a topic of major concern to global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7, B.1.351, P1 and, B.1.617., which show in-creased transmissibility and resistance towards vaccines and therapies. Importantly, the likelihood of susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response or comorbidities needs greater attention. Herein, we provide a comprehensive perspective regarding ongoing vaccine (mRNA, protein-based, viral vector based etc.) and therapeutic (mono-clonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

Over half of adult Americans now have diabetes or prediabetes and worse, this epidemic is now world-wide and shows no signs of slowing, with rates of both diabetes and diabetes-related health complications still rising. When advising patients with diabetes on food choices, many providers rely on nutrition guidelines provided by the American Diabetes Association (ADA), and these guidelines influence other recommendations across the globe. Given the alarming trends in diabetes, it is paramount to review the treatment guidelines to ensure they are based on rigorous and accepted scientific methods. Our review included the evidence cited by the ADA in support of its claims and recommendations for eating patterns to combat diabetes (see Description of Eating Patterns, Supplemental Appendix), as presented in the most current edition of the annual ADA’s Standards of Medical Care in Diabetes (2018 Standards). Our review also includes sources cited in the latest edition of the ADA’s Nutrition Therapy Recommendations for Adults with Diabetes (2014 Recommendations), which also informed the 2018 Standards. In October 2018 low carbohydrate was named as a recommended eating pattern by the ADA and European Association for the Study of Diabetes (EASD)⁵but only citations from the 2014 and early 2018 ADA documents were reviewed.

With the proliferation of locating devices, more and more raw spatial trajectories are formed, and many works enrich these raw trajectories with semantics, and mine patterns from both raw and semantic trajectories, but access control of spatial trajectories is not considered yet. We present a multi-policy secure model for semantic spatial trajectories. In our model, Mandatory Access Control, Role Based Access Control and Discretionary Access control are all enforced, separately and combined, and we represent the model semi-formally in Ontology Web Language.

Background: The aim of this study was to investigate the risk of obstructive sleep apnea (OSA) among ankylosing spondylitis (AS) patients in a nationwide population. Methods: We conducted a nationwide cohort study between 2003 and 2013 using the Taiwan National Health Insurance Research Database. The AS cohort included 2210 patients who were newly diagnosed between 2003 and 2013. Randomly selected non-AS controls were matched at a 1:4 ratio based on age, sex and index date. The endpoint of OSA was occurrence or the end of 2013. Cumulative incidences, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated after adjusting for age, gender, comorbidities and co-medications. Multivariate analyses were performed using Cox proportional hazards model. Due to violation of the proportionality assumption, landmark analysis was conducted to explore the risk of OSA during specific follow-up periods. Results: The adjusted HR (aHR) of OSA for the AS group was 2.826 (95% C.I. = 1.727–4.625) compared to the control group. On landmark analysis, aHR was 7.919 (95% C.I. = 3.169–19.792) for AS group 0–24 months from index date, and decreased to 1.816 (95% C.I. = 0.944–3.494) at ≥ 24 months from index date. On subgroup analyses increased risks of OSA in AS group compared to the control group were found for both males and females (aHRs were 4.533 (95% C.I. = 1.441–14.262) and 2.672 (95% C.I. = 1.522–4.692) for females and males, respectively). On age stratified analysis, there was significant risk only for the 40–59 age group with aHR of 3.913 (95% C.I. = 1.890–8.102). Conclusions: A higher risk of developing OSA was found among newly diagnosed AS cohort during the 12-year follow-up period, especially within 2 years after AS index date and in the 40–59 age group.

G protein-coupled receptors (GPCRs) are critical drug targets. GPCRs convey signals from the extracellular to the intracellular environment through G proteins. There is evidence that some ligands that bind to the GPCRs activate different downstream signaling pathways. G protein activation or -arrestin biased signaling involves ligands binding to receptors and stabilizing conformations that trigger a specific pathway. Molecular dynamics (MD) simulations are especially valuable for obtaining detailed mechanistic information, including identification of allosteric sites and understanding modulators' interactions between receptors and ligands. Here, we highlight recent simulation studies and methods used to study biased G protein-coupled receptor signaling and their conformational dynamics. We also highlight applications of MD simulations to drug discovery.

Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess the safety of current and future mRNA vaccines, further analysis on the risks due to the platform itself, and not specifically the expressed antigen. If harm can be exclusively and conclusively attributed to the spike protein, then it is possible that future mRNA vaccines expressing other antigens will be safe. If harms are attributable to the platform itself, then regardless of the toxicity, or lack thereof, of the chosen payload therein, the platform may be inherently unsafe, pending modification. In this work, we examine previous studies of RNA-based delivery by a lipid nanoparticle and break down the possible etiological elements of harm.

The adaptive immune system in vertebrates comes in two flavors. Historically, adaptive immunity focused on the study of immunoglobulins (also referred to as Ig-based antibodies herein); more recently, jawless vertebrates were found to use an entirely different class of proteins for their adaptive immunesystem. Specifically, these organisms express variable lymphocyte receptors (so called VLR antibodies) that create diversity based on the rearrangement of leucine-rich repeats. Meanwhile, various, naturally occurring repeat motifs have been used as building blocks for the design of artificial binding scaffolds which, among others, include designed ankyrin repeat proteins (DARPins). Such binding scaffolds are also referred to as non-Ig-based antibodies or non-Ig scaffolds herein). DARPins display several benefits such as a low molecular weight (~15 kDa), high thermal stability, high specificity and affinity, versatility (e.g., in terms of valency and multi-specificity), speedy preclinical development, low production costs and, thus, bear the potential to not only complement existing therapeutic Ig-based antibodies but also open up novel therapeutic strategies. The first generation DARPin therapeutic abicipar pegol has completed two Phase III studies in 2020 while several other DARPin drug candidates are currently undergoing clinical validation. Most recently, the rapid development of tri-specific SARSCoV-2 DARPin therapeutics showcases the immense potential of recombinant repeat proteins in adopting quickly e.g., new forms of target neutralization that a single Ig-based antibody cannot afford. Here, we highlight the design principles of repeat proteins in general and summarize in detail the continuous advancements of the DARPin scaffold that made it one of the most promising antibody mimetics to date. This review provides an overview of current and emerging applications of DARPins as both a research tool and therapeutic drug that can match or even surpass Ig-based antibody applications.

Dietary recommendations to decrease the risk of cardiovascular disease (CVD) have focused on reducing intake of saturated fatty acids (SFA) for more than 50 years. While the 2015-2020 Dietary Guidelines for Americans advise substituting both monounsaturated and polyunsaturated fatty acids for SFA, evidence supports other nutrient substitutions that will also reduce CVD risk. For example, replacing SFA with whole grains, but not refined carbohydrates, reduces CVD risk. Replacing SFA with protein, especially plant protein may also reduce CVD risk. While dairy fat (milk, cheese) is associated with a slightly lower CVD risk compared to meat, dairy fat results in a significantly greater CVD risk relative to unsaturated fatty acids. As research continues, we will refine our understanding of dietary patterns associated with lower CVD risk.

Spatio-temporal aspects of data lead to critical information. Sensors capture data at all scales continually so it is imperative that useful information be extracted ubiquitously and regularly. Location plays a vital part by helping understand relations between datasets. It is crucial to link developmental works with spatial attributes and current challenge is to create an open platform that manages real-time sensor data and provides critical spatial analytics atop expert domain knowledge provided in the system. That is a two-faced problem where the solution tackles not only data from multiple sources but also runs data management platform, a spatial data infrastructure(SDI) as backbone framework able to harness sensor web(SW). The paper proposes development of such a globally shared open spatial expert system(ES), SmaCiSENS, a first of a kind geo-enabled knowledge based(KB) ES for multiple fields, smarter cities to climate modeling. SmaCiSENS is integration of SW and SDI with domain KB on data and problems, ready to infer solutions. The paper describes an architecture for semantic enablement for SW, SDI; connect interfaces, functions of SDI and SW, and sensor data application program interfaces (APIs) to better manage climate modeling, geohazard, global changes, and other vital areas of attention and action.

Indoor positioning based on the received signal strength (RSS) of the WiFi signal has become the most popular solution for indoor localization. In order to realize the rapid deployment of indoor localization systems, solutions based on crowdsourcing have been proposed. However, compared to conventional methods, crowdsourced RSS values are more erroneous and can result in large localization errors. To mitigate the negative effect of the erroneous measurements, a graph-based semi-supervised learning (G-SSL) method is used to exploit the correlation between the RSS values at nearby locations to estimate an optimal RSS value at each location. Before using the G-SSL method, the Linear Regression (LR) algorithm is proposed to solve the device diversity problem in crowdsourcing system. Since the spatial distribution of the APs is sparse, the Compressed Sensing (CS) method is applied to precisely estimate the location of the APs. Based on the location of the APs and a simple signal propagation model, the RSS difference between different locations is calculated and used as an additional constraint to improve the performance of G-SSL. Furthermore, to exploit the sparsity of the weights used in the G-SSL, we use the CS method to reconstruct these weights more accurately and make a further improvement on the performance of the G-SSL. Experimental results show improved results in terms of the smoothness of the radio map and the localization accuracy.

The comprehensibility of good predictive models learned from high-dimensional gene expression data is attractive because it can lead to biomarker discovery. Several good classifiers provide comparable predictive performance but differ in their abilities to summarize the observed data. We extend a Bayesian Rule Learning (BRL-GSS) algorithm, previously shown to be a significantly better predictor than other classical approaches in this domain. It searches a space of Bayesian networks using a decision tree representation of its parameters with global constraints, and infers a set of IF-THEN rules. The number of parameters and therefore the number of rules are combinatorial to the number of predictor variables in the model. We relax these global constraints to a more generalizable local structure (BRL-LSS). BRL-LSS entails more parsimonious set of rules because it does not have to generate all combinatorial rules. The search space of local structures is much richer than the space of global structures. We design the BRL-LSS with the same worst-case time-complexity as BRL-GSS while exploring a richer and more complex model space. We measure predictive performance using Area Under the ROC curve (AUC) and Accuracy. We measure model parsimony performance by noting the average number of rules and variables needed to describe the observed data. We evaluate the predictive and parsimony performance of BRL-GSS, BRL-LSS and the state-of-the-art C4.5 decision tree algorithm, across 10-fold cross-validation using ten microarray gene-expression diagnostic datasets. In these experiments, we observe that BRL-LSS is similar to BRL-GSS in terms of predictive performance, while generating a much more parsimonious set of rules to explain the same observed data. BRL-LSS also needs fewer variables than C4.5 to explain the data with similar predictive performance. We also conduct a feasibility study to demonstrate the general applicability of our BRL methods on the newer RNA sequencing gene-expression data.

Summary: Studying biological systems generally relies on computational modeling and simulation, e.g., for model-driven discovery and hypothesis testing. Progress in standardization efforts led to the development of interrelated file formats to exchange and reuse models in systems biology, such as SBML, the Simulation Experiment Description Markup Language (SED-ML), or the Open Modeling EXchange format (OMEX). Conducting simulation experiments based on these formats requires efficient and reusable implementations to make them accessible to the broader scientific community and to ensure the reproducibility of the results. The Systems Biology Simulation Core Library (SBSCL) provides interpreters and solvers for these standards as a versatile open-source API in Java™. The library simulates even complex bio-models and supports deterministic Ordinary Differential Equations (ODEs); Stochastic Differential Equations (SDEs); constraint-based analyses; recent SBML and SED-ML versions; exchange of results, and visualization of in silico experiments; open modeling exchange formats (COMBINE archives); hierarchically structured models; and compatibility with standard testing systems, including the Systems Biology Test Suite and published models from the BioModels and BiGG databases. Availability and implementation: SBSCL is freely available at https://draeger-lab.github.io/SBSCL/.

As the coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2, continues to spread rapidly around the world, there is a need for well validated serological assays that allow the detection of viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used multiple indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological assays to study the antibody response in COVID-19 patients. In order to validate the assays we determined the cut off values, sensitivity and specificity of the assays using sera collected from pre-pandemic healthy controls, COVID-19 patients at different time points after disease-onset, and seropositive sera to other human coronaviruses. The developed SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N)-based ELISAs not only showed high specificity and sensitivity but also did not show any cross-reactivity with other CoVs. We also show that all RT-PCR confirmed COVID-19 patients tested in our study developed both virus specific IgM and IgG antibodies as early as week one after disease onset. Our data also suggest that the inclusion of both S1 and N in serological testing would capture as many potential SARS-CoV-2 positive cases as possible than using any of them alone. This is specifically important for tracing contacts and cases and conducting large-scale epidemiological studies to understand the true extent of virus spread in populations.

Proteolysis Targeting Chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase. More generally referred to as bifunctional degraders, PROTACs have led the way in the field of targeted protein degradation (TPD) with several compounds currently undergoing clinical testing. Alongside bifunctional degraders, single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered as a viable approach for development of therapeutics, driven by advances in rational discovery approaches. This review focusses on drug discovery with respect to bifunctional and molecular glue degraders within the ubiquitin proteasome system, including analysis of mechanistic concepts and discovery approaches, with an overview of current clinical and pre-clinical degrader status in oncology, neurodegenerative and inflammatory disease.

The ubiquity of mobile sensors (such as GPS, accelerometer and gyroscope) together with increasing computational power have enabled an easier access to contextual information, which proved its value in next generation of the recommender applications. The importance of contextual information has been recognized by researchers in many disciplines, such as ubiquitous and mobile computing, to filter the query results and provide recommendations based on different user status. A context-aware recommendation system (CoARS) provides a personalized service to each individual user, driven by his or her particular needs and interests at any location and anytime. Therefore, a contextual recommendation system changes in real time as a user’s circumstances changes. CoARS is one of the major applications that has been refined over the years due to the evolving geospatial techniques and big data management practices. In this paper, a CoARS is designed and implemented to combine the context information from smartphones’ sensors and user preferences to improve efficiency and usability of the recommendation. The proposed approach combines user’s context information (such as location, time, and transportation mode), personalized preferences (using individuals past behavior), and item-based recommendations (such as item’s ranking and type) to personally filter the item list. The context-aware methodology is based on preprocessing and filtering of raw data, context extraction and context reasoning. This study examined the application of such a system in recommending a suitable restaurant using both web-based and android platforms. The implemented system uses CoARS techniques to provide beneficial and accurate recommendations to the users. The capabilities of the system is evaluated successfully with recommendation experiment and usability test.

Real-time energy management of a converter-based microgrid is difficult to determine optimal operating points of a storage system in order to save costs and minimise energy waste. This complexity arises due to time-varying electricity prices, stochastic energy sources and power demand. Many countries have imposed real-time electricity pricing to efficiently control demand side management. This paper presents a particle swarm optimisation (PSO) for the application of real-time energy management to find optimal battery controls of a community microgrid. The modification of the PSO consists in altering the cost function to better model the battery charging/discharging operations. As optimal control is performed by formulating a cost function, it is suitably analysed and then a dynamic penalty function in order to obtain the best cost function is proposed. Several case studies with different scenarios are conducted to determine the effectiveness of the proposed cost function. The proposed cost function can reduce operational cost by 12% as compared to the original cost function over a time horizon of 96 hours. Simulation results reveal the suitability of applying the regularised PSO algorithm with the proposed cost function, which can be adjusted according to the need of the community, for real-time energy management.

Artificial intelligence (AI) applications in different fields are developing rapidly, among which AI painting technology, as an emerging technology, has received wide attention from users for its creativity and efficiency. This study aimed to investigate the factors that influence user acceptance of the use of AIBPS by proposing an extended model that combines the Extended Technology Acceptance Model (ETAM) with the AI-based Painting System (AIBPS).A questionnaire was administered to 528 Chinese participants, using validated factor analysis data and Structural Equation Modeling (SEM) was used to test the hypotheses. The findings showed that hedonic motivation (HM) and perceived trust (PE) had a positive effect (+) on users' perceived usefulness (PU) and perceived ease of use (PEOU), while previous experience (PE) and technical features (TF) had no effect (-) on users' perceived usefulness (PU). This study provides an important contribution to the literature on AIBPS and the evaluation of systems of the same type, which helps to promote the sustainable development of AI in different domains and provides a possible space for further extension of TAM, thus helping to improve the user experience of AIBPS. The results of the study provide insights for system developers and enterprises to better motivate users to use AIBPS.

Background: Research continues to search for blood-based biomarkers sensitive to Alzheimer’s disease (AD) pathology during the initial stages when symptoms of cognitive decline are not yet apparent. A blood-based biomarker candidate is metalloprotein p53, the conformation of which was previously found to be altered in peripheral cells from individuals with mild cognitive impairment (MCI) and AD, presenting as an unfolded p53 (U-p53) conformational variant. Methods: Plasma samples from the well-characterized Australian Imaging, Biomarkers, and Lifestyle (AIBL) cohort were used to identify the clinically relevant AZ 284^® peptide, specifically present in samples from individuals with symptomatic AD. The AZ 284^® peptide, which is a marker of the U-p53 conformational variant (U-p53^AZ), was identified by immunoprecipitation (IP) with a novel U-p53 conformational variant-specific antibody followed by liquid chromatography (LC) tandem mass spectrometry (MS/MS) and protein sequencing. Using IP-LC surface-activated chemical ionization (SACI) MS/MS analysis, the prognostic and diagnostic performance of U-p53^AZ were examined in the longitudinal AIBL cohort, including 252 plasma samples derived from 214 elderly individuals. For the prognostic analyses, U-p53^AZ levels were assessed at 36, 72, and 90 months after baseline assessment. Results: The prognostic performance of U-p53^AZ to predict the progression to AD from preclinical or prodromal AD was high, with area under the receiver operating characteristic curve (AUC) values close to or above 0.90. Furthermore, U-p53^AZ predicted the progression to AD more than 6 years prior to symptom onset with positive and negative predictive values of about 90%. Additionally, the estimated prognostic performance of U-p53^AZ was superior to other main risk factors (i.e., age, sex, and either alone or in combination with amyloid status. Furthermore, U-p53^AZ had high diagnostic performance to differentiate cognitively normal individuals from those with AD (AUC values >0.88). Conclusion: These findings support the use of U-p53^AZ as a prognostic blood-based biomarker accurately predicting the progression to AD dementia during the preclinical and prodromal stages at least 6 years before receiving the clinical diagnosis of AD dementia.

As SARS-CoV-2 continues to spread among human populations, genetic changes occur and accumulate in the circulating virus. Some of these genetic changes have caused amino acid mutations, including deletions, which may have potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics. Considerable efforts have been made to categorize the amino acid mutations of the angiotensin-converting enzyme 2 (ACE2) receptor binding domain (RBD) of the spike (S) protein along with certain mutations in other regions within the S protein as specific variants in an attempt to study the relationship between these mutations and the biological behavior of the virus. However, the currently used whole genome sequencing surveillance technologies can test only a small fraction of the positive specimens with high viral loads and often generate uncertainties in nucleic acid sequencing that needs additional verification for precision determination of mutations. This article introduces a generic protocol to routinely sequence a 437-bp nested RT-PCR cDNA amplicon of the ACE2 RBD and a 490-bp nested RT-PCR cDNA amplicon of the N-terminal domain (NTD) of the S gene for detection of the amino acid mutations needed for accurate determination of all variants of concern and variants of interest according to the definitions published by the U.S. Centers for Disease Control and Prevention. This protocol was able to amplify both nucleic acid targets into cDNA amplicons to be used as templates for Sanger sequencing on all 16 clinical specimens that were positive for SARS-CoV-2.

At least six small alternate-frame open reading frames (ORFs) overlapping well-characterized SARS-CoV-2 genes have been hypothesized to encode accessory proteins. Researchers have used different names for the same ORF or the same name for different ORFs, resulting in erroneous homological and functional inferences. We propose standard names for these ORFs and their shorter isoforms, developed in consultation with the Coronaviridae Study Group of the ICTV. We recommend calling the 39 codon Spike-overlapping ORF ORF2b; the 41, 57, and 22 codon ORF3a-overlapping ORFs ORF3c, ORF3d, and ORF3b; the 33 codon ORF3d isoform ORF3d-2; and the 97 and 73 codon Nucleocapsid-overlapping ORFs ORF9b and ORF9c. Finally, we document conflicting usage of the name ORF3b in 32 studies, and consequent erroneous inferences, stressing the importance of reserving identical names for homologs. We recommend that authors referring to these ORFs provide lengths and coordinates to minimize ambiguity due to prior usage of alternative names.

Results-Based Funding (RBF) for Reducing Emissions from Deforestation and Forest Degradation (REDD+) has become an important instrument for channeling financial resources to forest conservation activities. At the same time, much literature on conservation funding is ambiguous about the effectiveness of existing RBF schemes. Many effectiveness evaluations follow a simplified version of the principal-agent model, although in practice the relation between aid providers and funding recipients is much more complex. As a consequence, intermediary steps of conservation funding are often not accounted for effectiveness studies. This research paper aims to provide a nuanced understanding of conservation funding by analyzing the allocation of financial resources for one of the largest RBF schemes for REDD+ in the world: the Brazilian Amazon Fund. As part of this analysis, this study has built a dataset of information on Amazon Fund projects at unprecedented detail in order to accurately reconstruct the allocation of financial resources across different stakeholders (i.e. governments, NGOs, research institutions), geographies and activities. The results show that stakeholders seem to hold preferences with respect to the type of activities that they support, thereby suggesting that project owners exert much influence on how deforestation reduction is to be attained. There are evidences that governmental organizations lack financial additionality of their projects, which renders the growing share of funding to this type of stakeholder particularly worrisome. By contrast, the geographical distribution of financial resources seemed to follow a more focused rationale as financial support tends to concentrate in areas where deforestation threats are highest. Overall, the allocation of the financial resources from the Amazon Fund reflects an arbitrary support of different projects that adopt very diverging theories of change that are not primarily concerned with attaining further deforestation reductions. As projects owners exert influence on funding effectiveness to some extent, the Amazon Fund may either seek to regulate the allocation of financial resources more actively or adopt funding effectiveness evaluations that account for this influence more comprehensively.

Hang-ju was one of five officinal varieties of Flos chrysanthemum for its edible and potable usage. Besides Flos Chrysanthemum (FL), there were also Bud Chrysanthemum (BC) and Fetal Chrysanthemum (FC) at the early and late stage of buds, respectively, in the consumption market of Hang-ju with higher prices. Whether the quality and efficiency of BC and FC was superior to FL or merely consumption misunderstandings? Three commercial products of Hongxinju, a representive cultivar of Hang-ju were studied with a GC-MS based metabolomics approach, complemented with morphology, contents of moisture and protein and the anti-oxidant activity, to reveal the metabolic alterations of violate components in Hongxinju in different flowering stage and at different processing periods. It revealed that most of the violate components were increased from fresh FC to FL, and the low-boiling fractions, inflammatory methyl arachidonate and air-polluting component of ethylbenzene were declined while the representative components with pungent flavor and cool nature of a-curcumene and (Z,Z,Z)-9,12,15-octadecatrienoic acid, vision improving carotenol of rhodopin and high-boiling fractions were elevated after processed in final FL compared with that in BC and/or FC. Though the content of protein and anti-oxidative capacity of final BC and FC were nearly equal to those of FL, in comprehensive consideration of the representative components related with the efficiency in heat cooling and vision improving, as well as the representative components related with inflammation and air-pollution, final FL was recommended other than BC and FC in the practice of medicine with the yield and quality integrated into account.

Interfaces between layers in 3D-printed elements produced by extrusion-based material deposition were investigated on both macro- and micro-scales. On the macro-scale, compression and bend tests were performed on two 3D-printable cement-based compositions (3PCs), namely C1 and C2. The influences of binder composition and time interval between layers on layer-interface strength were critically analyzed. In the context of additive manufacturing, the optimized composition C2, containing pozzolanic additives, exhibited mechanical performance superior to that of the mixture with Portland cement as the sole binder. In particular, Mixture C2 showed a less pronounced decrease in interface tensile strength. Even for time intervals between depositions of two layers as long as 1 day the loss in corresponding flexural strength was below 25%, as compared with C2 specimens tested in the perpendicular direction. In contrast, the decrease in flexural strength measured for C1 specimens amounted to over 90% for the same set of parameters. Higher porosity at the interfaces of the printed concrete layers was identified as the cause for the lower interface strengths of C1. Microscopic observations supported the findings of the macroscopic investigations. While a pronounced recovery (“self-healing”) of the porous, discontinuous interlayers was observed with increasing age for Mixture C2, in case of C1 the filling products grown in the porous interlayer were found to be non-strengthening.

Background: Metabolic flux analysis (MFA) is an indispensable tool in metabolic engineering. The simplest variant of MFA relies on an overdetermined stoichiometric model of the cell’s metabolism under the pseudo-steady state assumption, to evaluate the intracellular flux distribution. Despite its long history, the issue of model error in the overdetermined MFA, particularly misspecifications of the stoichiometric matrix, has not received much attention. Method: We evaluated the performance of statistical tests from linear least square regressions, namely Ramsey RESET test, F-test and Lagrange multiplier test, in detecting model misspecifications in the overdetermined MFA, particularly missing reactions. We further proposed an iterative procedure using the F-test to correct such an issue. Result: Using Chinese hamster ovary and random metabolic networks, we demonstrated that: (1) a statistically significant regression does not guarantee high accuracy of the flux estimates, (2) the removal of a reaction with a low flux magnitude can cause disproportionately large biases in the flux estimates, (3) the F-test could efficiently detect missing reactions, and (4) the proposed iterative procedure could robustly resolve the omission of reactions. Conclusion: Our work demonstrated that statistical analysis and tests could be used to systematically assess, detect and resolve model misspecifications in the overdetermined MFA.

With the rapid development of satellite remote sensing technology, the volume of image datasets in many application areas is growing exponentially and the demand for Land-Cover and Land-Use change remote sensing data is growing rapidly. It is thus becoming hard to efficiently and intelligently retrieve the change information that users need from massive image databases. In this paper, content-based image retrieval is successfully applied to change detection and a content-based remote sensing image change information retrieval model is introduced. First, the construction of a new model framework for change information retrieval in a remote sensing database is described. Then, as the target content cannot be expressed by one kind of feature alone, a multiple-feature integrated retrieval model is proposed. Thirdly, an experimental prototype system that was set up to demonstrate the validity and practicability of the model is described. The proposed model is a new method of acquiring change detection information from remote sensing imagery and so can reduce the need for image pre-processing, deal with problems related toseasonal changes as well as other problems encountered in the field of change detection. Meanwhile, the new model has important implications for improving remote sensing image management and autonomous information retrieval.

Cryptography has been used from time immemorial for preserving the confidentiality of data/information in storage or in transit. Thus, cryptography research has also been evolving from the classical Caesar cipher to the modern cryptosystems based on modular arithmetic to the contemporary cryptosystems based on quantum computing. The emergence of quantum computing imposes a major threat on the modern cryptosystems based on modular arithmetic whereby, even the computationally hard problems which constitute for the strength of the modular arithmetic ciphers could be solved in deterministic time. This threat triggered post-quantum cryptography research in order to design and develop post-quantum algorithms that can withstand quantum computing attacks. This paper provides a review of the various post-quantum cryptography and, in specific, code-based cryptography research dimensions. The research directions that are yet to be explored in code-based cryptography research is another key contribution of this paper.

More than a decade ago, a new mitochondrial Open Reading Frame (mtORF) was discovered in corals of the family Pocilloporidae, which turn out to be an effective barcode gene for these corals. However, its function remains unknown. Recently, this gene revealed the existence of a hybrid Stylophora lineage (RS_LinA) inhabiting in sympatry along the environmental gradient of the Red Sea (18.5°C to 33.9°C) with its parental species (RS_LinB). Furthermore, in RS_LinB, the mtORF uncovered phylogeographic patterns that were strongly correlated with environmental variations. This was similar to the patterns unraveled by hsp70, suggesting that mtORF too might be involved in thermal adaptation. Here we used computational approaches to characterize the mtORF and to identify its potential role. Results showed that this gene encodes a transmembrane protein (0.97<P< 1.00) involved in transport (0.80<P< 0.87), regulation of metabolic processes (0.70<P<0.85), and likely in the cell-surface receptor signaling pathway (0.56<P<0.80). Predicted protein functions differed among Stylophora lineages and interestingly, in RS_LinB only, the protein was intrinsically disordered and displayed domains involved in cellular complexes and stress response (0.0001< P <0.001). These characteristics, exclusive of an endemic lineage adapted to extreme environmental fluctuations, support a role of the mtORF in stress response, speciation and adaptation.

The thymus hosts the development of a specific type of adaptive immune cells called T cells. T cells orchestrate the adaptive immune response through recognition of antigen by the highly variable T-cell receptor (TCR). T-cell development is a tightly coordinated process comprising lineage commitment, somatic recombination of Tcr gene loci and selection for functional, but non-self-reactive TCRs, all interspersed with massive proliferation and cell death. Thus, the thymus produces a pool of T cells throughout life capable of responding to virtually any exogenous attack while preserving the body through self-tolerance. The thymus has been of considerable interest to both immunologists and theoretical biologists due to its multiscale quantitative properties, bridging molecular binding, population dynamics and polyclonal repertoire specificity. Here, we review mathematical modelling strategies that were reported to help understand the flexible dynamics of the highly dividing and dying thymic cell populations. Furthermore, we summarize the current challenges to estimating in vivo cellular dynamics and to reaching a next-generation multiscale picture of T-cell development.

Wetlands are among the most bio-diverse and highest productivity ecosystems on earth, making their monitoring a high priority to conservation, protection and management interests. Although visual interpretation of satellite images is generally precise for monitoring wetlands, recent works have emphasized computerized classification methods because of the reduction in analyst time. However, it is difficult to automatically identify wetland solely based on spectral characteristics due to the complexity of wetland ecosystems. The ability to extract wetland information rapidly and accurately is the basis and the key to wetland mapping at a large scale. Here we propose an operational method to map China wetlands based on Landsat TM data and ancillary data. On the basis of theoretical analysis of wetland automatic classification, we developed a revised multi-layer wetland classification scheme and a rule-based classification model. In the latter, supervised classification (SVM and decision tree) and unsupervised classification (ISODATA) methods were tested. Four Landsat TM images, representing various wetland eco-regions in China (i.e. the Sanjiang Plain in the northeast China, the North China Plain, the Zoige Plateau in the southwest China and the Pearl River Estuary in southeast China), were automatically classified. The overall classification accuracies were 86.57%, 96.00%, 84.51% and 88.30%, respectively, which we considered to be satisfactory accuracy. Our results indicate that issues such as the resolution of geographic data and the understanding of wetland samples should be carefully addressed in the future.

The importance of predicting the exposure to environmental hazards is highlighted by issues like global climate change, public health problems caused by environment stresses, and property damages and depreciations. Several approaches have been used to assess potential exposure and achieve optimal results under various conditions, for example, for different scales, groups of people, or certain points in time. Micro-simulation tools are becoming increasingly important in human exposure assessment, where each person is simulated individually and continuously. This paper describes an agent-based model (ABM) framework that can dynamically simulate human exposure levels, along with their daily activities, in urban areas that are characterized by environmental stresses such as air pollution and heat stress. Within the framework, decision making processes can be included for each individual based on rule-based behavior to achieve goals under changing environmental conditions. The ideas described in this paper are implemented in a free and open source NetLogo platform. A simplified modeling scenario of the ABM framework in Hamburg, Germany, further demonstrates its utility in various urban environments and individual activity patterns, and portability to other models, programs and frameworks. The prototype model can potentially be extended to support environmental incidence management by exploring the daily routines of different groups of citizens and compare the effectiveness of different strategies. Further research is needed to fully develop an operational version of the model.

In the current study, the failure behavior of retrofitted steel structures was studied experimentally and theoretically with steel/CFRP double strap joints (DSJs) under quasi-static tensile loading. A series of DSJs with different bonding lengths are also considered and examined to experimentally assess the effective bond length. To predict the failure load values of the tested specimens, a new stress-based criterion, namely the point stress (PS) criterion is proposed. Although some theoretical predictive modelling for the strength between steel/CFRP joints under various loading conditions has been presented, in this work by using the new proposed approach, one can calculate rapidly and conveniently the failure loads of the steel/CFRP specimens. Furthermore, to assess the validity of the new proposed criterion, further experimental data on steel/CFRP DSJs available in the open literature are predicted using the PS criterion. Finally, it was found that a good agreement exists between the experimental results and the theoretical predictions based on the PS criterion.

Of the roughly 20,000 canonical human protein sequences, as of September 15, 2020, 6,937 proteins have had their full or partial, medium- to high-resolution structures determined by x-ray crystallography or other methods. Which of these proteins dominate the Protein Data Bank (the PDB) and why? In this paper, we list the 273 top human protein structures based on the number of their PDB entries. This set of proteins accounts for more than 40% of all available human PDB entries and represent past trends as well as current status for protein structural biology. We briefly discuss the relationship which some of the prominent protein structures have with protein research as a whole and mention their relevance to human diseases. The top-10 soluble and membrane proteins are all well-known (most of their first structures being deposited more than 30 years ago). Overall, there is no dramatic change in recent trends in the PDB. Remarkably, the number of structure depositions has grown nearly exponentially over the last 10 or more years (with a doubling time of 7 yrs for proteins from all organisms). Growth in human protein structures is slightly faster (at 5.9 yrs, while E.Coli and Mouse+Rat protein structures accumulate more slowly, Zebrafish protein structures are growing most, at a doubling every 3.7 years, albeit starting from only approx. 100 structure entries in 2010). The information may be informative to senior scientists but also inspire researchers who are new to protein science, providing the year 2020 snap-shot for the state of protein structural biology.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). The replication rate generates a high polyprotein integration that can contribute to ER stress. Therefore, the host cell can develop an Unfolded Protein Response (UPR) to this protein accumulation which will stimulate appropriate cellular responses in the infectious context (Adaptation, autophagy or cell death). These different stress responses can help to overcome the virus and usually support antiviral strategies initiated by infected cells. In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in epithelial A549 cells with a special focus on the causal factors behind it. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway but surprisingly without activation of the ATF6 branch. When we examined the effects of modulating the ER stress response we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV can altered the UPR in order to escape to the host cell defense system.

Location-Based Services (LBS) have been widely deployed for the connected vehicle (CV) applications such as vehicle navigation,vehicle tracking and location-based augmented reality. The current LBS deployments have limitations in supporting time-critical CV use cases, including vehicle to vehicle (V2V), vehicle to infrastructure (V2I) and vehicle-to-people (V2P) safety applications. The paper presents the new LBS framework based on the publish-subscribe communication paradigm, to enable device-to-device (D2D) connections through use of selected application protocols in the application layer of the TCP/IP layered protocol model. Two publish-subscribe application protocols, Distributed Data Service (DDS) real-time publish and subscribe (DDS-RTPS) and Message Queue Telemetry Transport (MQTT), are introduced to support the LBS D2D applications. A number of test scenarios with Mosquitto MQTT and OpenDDS under 4G-mobile broadband (MBB) services are designed to assess the transmit/receive round-trip time (RTT) and packet-loss rate (PLR) with settings of a publisher to multiple subscribers, to simulate the connections to multiple vehicles. The transmission frequency is set for 10 Hz and the message sizes vary from 100 to 2000 Bytes. The PLRs are defined as the percentages of the delayed messages beyond a delay limit. Static test results with OpenDDS show that for the RTT delay beyond the limit of 100 ms, the total PLRs range between 5.25% and 8.76% for the message size of 50 to 2000 Bytes. Vehicle testing results with Mosquitto show that PLRs for the RTT delays between 200 ms and 1000 ms are 0.63%, 3.58% and 5.77%, for connections with 1, 4 and 10 vehicles, respectively. The results demonstrate the potential of the D2D LBS framework for medium-demanding CV safety applications such as V2P and V2I use cases, taking advantages of the 4G-MBB services and 5G extreme mobile broadband (eMBB) services and mobile devices generally available with all road users.

Renal artery thrombosis is a sporadic serious clinical condition which potentially cause renal infarction. Diagnosis of renal infarction can be delayed or missed due to non specific clinical presentation and overlapping appearance of medical and surgical phenomena. Early diagnosis supported by biochemical and radiological findings while appropriate management potentially improve morbidity and mortality. Persistent abdominal or flank pain with raised LDH and proteinuria on background of thromboembolism risk factors supports the diagnosis. Despite the rarity of the disease rapid identification with prompt medical or endovascular intervention could prevent irreversible renal parenchymal damage.

In this work, a hybrid component Fault Detection and Diagnosis (FDD) approach for industrial sensor systems is established and analyzed, to provide a hybrid schema that combines the advantages and eliminates the drawbacks of both model-based and data-driven methods of diagnosis. Moreover, it shines the light on a new utilization of Random Forest (RF) together with model-based diagnosis, beyond its ordinary data-driven application. RF is trained and hyperparameter tuned using three-fold cross validation over a random grid of parameters using random search, to finally generate diagnostic graphs as the dynamic, data-driven part of this system. This is followed by translating those graphs into model-based rules in the form of if-else statements, SQL queries or semantic queries such as SPARQL, in order to feed the dynamic rules into a structured model essential for further diagnosis. The RF hyperparameters are consistently updated online using the newly generated sensor data to maintain the dynamicity and accuracy of the generated graphs and rules thereafter. The architecture of the proposed method is demonstrated in a comprehensive manner, and the dynamic rules extraction phase is applied using a case study on condition monitoring of a hydraulic test rig using time-series multivariate sensor readings.

Non-invasive, electroencephalography (EEG)-based brain-computer interfaces (BCIs) on motor imagery movements translate the subject’s motor intention into control signals through classifying the EEG patterns caused by different imagination tasks, e.g. hand movements. This type of BCI has been widely studied and used as an alternative mode of communication and environmental control for disabled patients, such as those suffering from a brainstem stroke or a spinal cord injury (SCI). Notwithstanding the success of traditional machine learning methods in classifying EEG signals, these methods still rely on hand-crafted features. The extraction of such features is a difficult task due to the high non-stationarity of EEG signals, which is a major cause for the stagnating progress in classification performance. Remarkable advances in deep learning methods allow end-to-end learning without any feature engineering, which could benefit BCI motor imagery applications. We developed three deep learning models: 1) a long short-term memory (LSTM); 2) a proposed spectrogram-based convolutional neural network model (pCNN); and 3) a recurrent convolutional neural network (RCNN), for decoding motor imagery movements directly from raw EEG signals without (manual) feature engineering. Results were evaluated on our own, publicly available, EEG data collected from 20 subjects and on an existing dataset known as 2b EEG dataset from "BCI Competition IV". Overall, better classification performance was achieved with deep learning models compared to state-of-the art machine learning techniques, which could chart a route ahead for developing new robust techniques for EEG signal decoding. We underpin this point by demonstrating the successful real-time control of a robotic arm using our CNN based BCI.

Some of the most promising small molecule toxins used to generate antibody drug conjugates (ADCs) include anti-mitotic agents (e.g auristatin and its derivatives) which are designed to attack cancerous cells at their most vulnerable state during mitosis. We were interested to identify a human cystostatic protein eventually showing comparable activities and allowing the generation of corresponding targeted fully human cytolytic fusion proteins. Recently, we identified the human microtubule associated protein tau (MAP tau) which binds specifically to tubulin and modulates the stability of microtubules thereby blocking mitosis and presumably vesicular transport. By binding and stabilizing polymerized microtubule filaments, MAP tau-based fusion proteins skew microtubule dynamics towards cell cycle arrest and apoptosis. This biological activity makes rapidly proliferating cells (e.g cancer and inflammatory cells) an excellent target for MAP tau-based targeted treatments. Their superior selectivity for proliferating cells confers additional selectivity towards upregulated tumor-associated antigens at their surface, thereby preventing off-target related toxicity against normal cells bearing tumor-associated antigens at physiologically normal to low levels. In this review, we highlight recent findings on MAP tau-based targeted cytolytic fusion proteins reported in preclinical immunotherapeutic studies.

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.

The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme activities and inhibition as well as some of the methods that are in current use for such studies with these two enzymes. Their applicability and potential pitfalls arising from their inappropriate use are discussed. Since inhibitor potency is frequently assessed in terms of the quantity necessary to give 50% inhibition (the IC50 value), the relationships between this and the mode of inhibition is also considered, in terms of the misleading information that it may provide. Incorporation of more than one functionality into the same molecule to give a multi-target-directed ligands (MTDLs) requires careful assessment to ensure that the specific target effects are not significantly altered and that the kinetic behaviour remains as favourable with the MTDL as it does with the individual components. Such factors will be considered in terms of recently developed MTDLs that combine MAO and ChE inhibitory functions.

Respiratory transmission is the primary route of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Angiotensin I converting enzyme 2 (ACE2) is the known receptor of SARS-CoV-2 surface spike glycoprotein for entry into human cells. A recent study reported absent to low expression of ACE2 in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 (a homolog of ACE2 and also known as ACE) in human lungs compared to very low expression of ACE2. In fact, ACE1 has a wider and more abundant tissue distribution compared to ACE2. Although it is not obvious from the primary sequence alignment of ACE1 and ACE2, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Critical amino acids in ACE2 that mediate interaction with the viral spike protein are present and organized in the same order in the PD of ACE1. In silico analysis predicts comparable interaction of SARS-CoV-2 spike protein with ACE1 and ACE2. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 and/or ACE1, potentially interfere with the entry of SARS-CoV-2 inside the host cells and alleviate the symptoms of Coronavirus disease (COVID-19).

New hybrid nanostructured electrodes for supercapacitors made by combination of electrical double layer and faradaic supercapacitors based-nanomaterials within a single hybrid composite has a great potential on expanding the range of use of these devices and increase their electrochemical performance. In this work, we developed several hybrid nanostructured composites with combinations of such types of materials with potential applicability as electrodes in supercapacitors. In particular, these composites were obtained by easy, cost-effective and scalable procedures, and were composed by NiCo2O4 nanocores as the main faradaic-based nanomaterial and either the conductive polymer polyaniline (PANI), multiwall carbon nanotubes (MWCNTs), or reduced graphene oxide (r-GO) as the electrical double layer-based carbonaceous-based nanomaterials in order to enable the combination of both type of energy storage processes within a single nanostructured device. These constructions allowed us to obtain specific capacitance as large as 1760 F/g, 900 F/g and 734 F/g at a current density of 1 A/g for NiCo2O4/PANI, NiCo2O4/MWCNT, and NiCo2O4/r-GO hybrid nanocomposite electrodes, respectively. Besides, the stability of NiCo2O4/MWCNTs and NiCo2O4/r-GO-based electrodes was outstanding, with capacity losses below 10% after long periods of operation (> 500 cycles).

Background. Increasing evidence demonstrate that concentration of protein in infant formula >1.9g/100Kcal with high levels of insulinogenic aminoacids is associated with accelerated weight gain, increased fat mass accumulation and risk of adiposity. Purpose of this study was to conduct a systematic review to determine the metabolic effects in infants feed with infant formula optimized in protein. Methods. Systematic review was conducted according PRISMA Statement. RCTs with one intervention group (infant formula with 1.6-1.9gr of protein/100Kcal) and at least one comparative control group (infant formula with >1.9gr of protein/100Kcal) were included. Standardized mean differences (SMD), through random model were calculated. Results. 15 RCT were included. Optimized protein in infant formula was associated with less gain of BMI at 24 months of follow-up (SMD -0.25, IC95% -0.36 to -0.13, p 0.01) and less fat mass accumulation (SMD -0.68, IC95% -0.98 to -0.37, p 0.01). Optimized protein was also associated to less gain of weight, weight/age Z-score, weight/length Z-score, BUN (mmol/dL) and IGF1 (ng/ml). No effect on length/age Z-score was observed. Conclusions. Robust evidence showed optimized protein (1.6gr/100Kcal to 1.9gr/100Kcal) in infant formula is associated with metabolic benefits in infants with less weight gain, BMI and fat mass accumulation.

Infiltration based stormwater best management practices bring considerable economic, social and ecological benefits. Controlling stormwater quantity and quality are primarily important to prevent urban flooding and minimizing loads of pollutants to the receiving waters. However, there have been growing concerns about how the traditional design approach contributes to the failure of infiltration based BMP’s that have caused flooding, ponding, prolonged movement of surface water, and frequent clogging, etc. Many of these problems were due to the fact that the current design approaches of stormwater BMP’s only focus on surface hydrology and give little or no attention to the underline subsoil permeability rate and other constraints during the design and sizing process. As a result, we are exhibiting many newly constructed infiltration based BMP’s are failing to function well. This paper presents and demonstrates a new paradigm shift in designing infiltration-based stormwater BMP’s by combining subsurface hydrology and undelaying native soil constraints to establish acceptable criteria for sizing infiltration based BMPs.

Wireless communication has proliferated due to the colossal augmentation of smart phones, mobile phones, tablets and laptops etc. Multimedia applications such as live videos, audios, still images, animated graphics and live communications all requires accompaniments of quality of service (QoS) as well as reliable end-to-end transfer of data. Information about the availability of resources in channel is must in order to improve the QoS. QoS can be determined in terms of capacity of channel, available bandwidth (ABW), and bulk transfer capacity (BTC). Bandwidth availability is a key check for improving the QoS in a network. The performance of a multimedia application is directly affected by the bandwidth availability. One of the most important QoS characteristic is ABW at a wireless route and it can be demarcated as least unused capacity of links instituting a network route. Since now there have been many bandwidth estimation techniques are available in the literature to increase the network performance. Bandwidth estimation techniques have been arranged into three leading classifications: i) Active probing bandwidth estimation techniques, ii) Passive bandwidth estimation technique and iii) Model based bandwidth estimation techniques. Each of these techniques are briefly discussed in this paper.

Meshfree particle method, which is always regarded as a pure Lagrangian approach, is easily represented complicated domain topologies, moving boundaries, and multiphase media. Solving acoustic problems with the mesfree particle method forms a branch of the acoustic wave modeling field, namely, particle-based computational acoustics (PCA). The aim of this paper is to improve the accuracy of using the PCA method to solve two-dimensional acoustic problems, and realize the particle representation with a hybrid meshfree and finite-difference time-domain (FDTD) method for acoustic boundary conditions at both the plane and curved surface. As a widely used Lagrangian meshfree method, the smoothed particle hydrodynamics (SPH) based on the support domain and the kernel function has developed rapidly in recent years. The traditional SPH method is easily implements parallel processing and has been applied in sound wave simulation. As a corrective method with higher accuracy than SPH, the acoustic propagation and scattering in the time domain is simulated with the corrective smoothed particle method (CSPM). Moreover, a hybrid meshfree-FDTD boundary treatment technique is utilized to represent different acoustic boundaries in the Lagrangian approach. In this boundary treatment technique, the parameter value of virtual particles is obtained with the FDTD method, which concerns truncation errors based on the Tayler series expansion. Soft, rigid, and Mur’s absorbing boundary conditions are developed to simulate sound waves in finite and infinite domain. Results of modeling acoustic propagation and scattering show that CSPM is accurate and convergence with exact solutions, and different acoustic boundaries are validated to be effective in the computation.

Mapping vegetation species is critical to facilitate related quantitative assessment, and for invasive plants mapping their distribution is important to enhance monitoring and controlling activities. Integrating high resolution multispectral remote sensing (RS) image and lidar (light detection and ranging) point clouds can provide robust features for vegetation mapping. However, using multiple source of high-resolution RS data for vegetation mapping at large spatial scale can be both computationally and sampling intensive. Here we designed a two-step classification workflow to decrease computational cost and sampling effort, and to increase classification accuracy by integrating multispectral and lidar data to derive spectral, textural, and structural features for mapping target vegetation species. We used this workflow to classify kudzu, an aggressive invasive vine, in the entire Knox County (1,362 km2) of Tennessee, the United States. Object-based image analysis was conducted in the workflow. The first-step classification used 320 kudzu samples and extensive coarsely labeled samples (based on national land cover) to generate an overprediction map of kudzu using random forest (RF). For the second step, 350 samples were randomly extracted from the overpredicted kudzu and labeled manually for the final prediction using RF and support vector machine (SVM). Computationally intensive features were only used for the second-step classification. SVM had constantly better accuracy than RF, and the Producer’s Accuracy, User’s Accuracy, and Kappa for the SVM model on kudzu was 0.94, 0.96, and 0.90, respectively. SVM predicted 1010 kudzu patches covering 1.29 km2 in Knox County. We found the sample size of kudzu used for algorithm training impacted the accuracy and number of kudzu predicted. The proposed workflow could also improve sampling efficiency and specificity. Our workflow had much higher accuracy than the traditional method conducted in this research, and could be easily implemented to map kudzu in other regions or other vegetation species.

SARS-CoV-2 has been the talk of the town ever since the beginning of 2020. The pandemic has brought the complete world on a halt. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to repurposing of drugs and vaccine development. The rapid data analysis and widespread tools, software and databases have made bioinformatics capable of giving new insights to the researchers to deal with the current scenario more efficiently. Vaccinomics, the new emerging field of bioinformatics uses concepts of immunogenetics and immunogenomics with in silico tools to give promising results for wet lab experiments. This approach is highly validated for the designing and development of potent vaccines. The present in-silico study was attempted to identify peptide fragments from spike surface glycoprotein that can be efficiently used for the designing and development of epitope-based vaccine designing approach. Both B-cell and T-cell epitopes are predicted using integrated computational tools. VaxiJen server was used for prediction of protective antigenicity of the protein. NetCTL was studied for analyzing most potent T cell epitopes and its subsequent MHC-I interaction through tools provided by IEDB. 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further done to carry out docking studies using AutoDock4.0. Various tools from IEDB were used to predict B-cell epitopes on the basis of different essential parameters like surface accessibility, beta turns and many more. Based on results interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as a potential B-cell epitope and T-cell epitope respectively. This in-silico study will help us to identify novel epitope-based peptide vaccine target in spike protein of SARS-CoV-2. Further, in-vitro and in-vivo study needed to validate the findings.

The transition from the Peptide/RNA world to the Protein/RNA world in the hydrothermal vent environment was a major event in the history of life. The advent of proteins utterly changed the conditions of emerging life, representing a watershed in its development. During subsequent translation various protein enzymes emerged driving protocells into a more complex and interconnected system. With their astonishing versatility, the protein enzymes catalyzed crucial biochemical reactions within protocells into more complex biomolecules in diverse metabolic pathways, whereas structural proteins provided strength and permeability in the cell membrane. Four major events followed after availability of various kinds of protein molecules during prebiotic synthesis. These are: (1) the modification of the phospholipid membrane into the plasma membrane; (2) the origin of primitive cytoplasm; (3) the beginnings of the virus world; and (4) the advent of DNA. The first innovation mediated by proteins was the improvement of the cell membrane. The phospholipid membrane was initially evolved in a vent environment from the gradual modification of a fatty acid membrane via an intermediate phosphatidate acid by non-enzymatic reactions. The phospholipid is then synthesized from phosphatidate acid by a series of enzymes. To make the phospholipid membrane more permeable, various protein molecules interacted with the cell membrane. Proteins not only stabilized the wall membrane, but also acted as pumps, preventing some molecules from the protocells from crossing the membrane barriers, while permitting other selected molecules and ions to enter and leave the protocell. The second modification led by proteins is the gradual conversion of the interior of the protocell from a water-like medium into a gel-like cytoplasm, which became the storehouse of a wide range of biomolecules including amino acids, proteins, nucleic acids, ribosomes, as well as salt and water. The third innovation utilizing the newly synthesized proteins was the emergence of the ancient virus world. In the milieu of different kinds of mRNAs in the prebiotic soup, jelly-roll capsid genes originated de novo within genomes of nonviral mRNAs by overprinting. These fragile capsid genes were possibly coated by proteins on the mineral substrate for stability and durability, transforming them into ancient viral particles. These protein coats were random and were not encoded by encased genes. Some protocells might have engulfed these viral particles, when the capsid genes utilized the ribosomes of the host to translate into the appropriate capsid proteins. These capsid proteins then coated the viral genes to make new copies of primordial viruses inside the protocell. Since then, viruses became capsid-encoding organisms. These primordial mRNA viruses parasitized RNA-based protocells, manipulating them to make new copies of themselves. This was the beginning of a relentless war between viruses and their protocellular hosts. The next stage in viral evolution was the emergence of a primitive retrovirus (pre-retrovirus) with a new kind of replicative strategy in a sense that it could turn its RNA into DNA using its own reverse transcriptase enzyme. This is the beginning of the Retro world that facilitated the transition from RNA to DNA genomes. The infection of RNA protocells with pre-retroviruses progressively transferred the RNA genome to a viral DNA genome by retro-transcription. The advent of DNA by the pre-retrovirus marks the fourth innovation, when a number of enzymes had already developed and were utilized by pre-retroviruses. With continued infection, DNA viruses slowly transferred not only their core replication enzymes, such as helicase, primase, and DNA polymerase, to RNA protocells, but also to their DNAs as well. Thus, began the DNA world, when DNA replaced RNA as the major genome of the protocells. With the advent of DNA, replication of information was entirely dissociated from its expression. Because DNA is much more stable than mRNA with more storage capacity, it is a superb archive for information systems in the form of base sequences. DNA progressively took over the replicative storage function of mRNA, leaving the latter for protein synthesis. The new protocell with the DNA genome will diversify into large populations of DNA protocells that will outcompete populations of RNA protocells. Genetic information began to flow from DNA to mRNA to protein in a two-step process involving transcription and translation. In the biological stage, DNA replication was central to the binary fission of the first cell, orchestrated by the duplication of genomes and then the division of the parent cell into two identical daughter cells. It was carried out by a set of enzymes that formed a Z-ring at the site of replication. With the onset of binary fission, the population of primitive cells grew rapidly in the hydrothermal vent environment, undergoing Darwinian evolution and diversification. These primordial hyperthermophiles, presumably the first life, obtained food and energy directly from the vent environment. However, such a situation was self-limiting, so the early cells evolved their own mechanisms for generating metabolic energy and synthesizing the molecules necessary for their reproduction. The earliest fossil record (≥ 3.5 Ga) of biotic activity is preserved in the Archean hydrothermal and sedimentary rocks of the Nuvvuagittuq Craton of Canada, the Isua Craton of Greenland, the Pilbara Craton of Australia, the Kaapvaal Craton of South Africa, and the Singhbhum Craton of India in the form of the carbonaceous remains of microbial cells, cellular microfossils, and stromatolites. These microscopic fossils provide crucial evidence of the origin and early evolution of prokaryotic cells, beginning with hyperthermophiles. Molecular phylogenetic analysis suggests that both domains of life ¬– Bacteria and Archaea probably split from the last universal common ancestor (LUCA), a hyperthermophilic organism. In the younger sequences of these Archean cratons, two kinds of photosynthetic bacteria, anoxygenic green sulfur bacteria, and oxygenic cyanobacteria, appeared in quick succession from the thermophilic ancestor, indicating a shift of niche from a benthic to a planktonic, with reduced thermotolerance. The development of anoxygenic and oxygenic photosynthesis would have allowed life to escape the hydrothermal setting and invade a newly evolved habitat—broad continental shelves to tap solar energy. Cyanobacteria invaded the global ocean, turned it into blue and green, produced oxygen for the first time, and left their signatures in the carbonates and stromatolites.

Nuclear export of viral mRNAs, is an essential step in the HIV replication cycle. This role is played by a small regulatory protein of HIV-1 called Rev.The N-terminal region of Rev contains an arginine-rich sequence. The arginine-rich motif (ARM) is located between amino acids 38-50 and forms an alpha-helical secondary structure. Expression of the structural proteins of human immunodeficiency virus type 1 requires the direct interaction of multiple copies of the viral Rev protein with its highly structured RNA target sequence, the Rev Response element (RRE). The major viral proteins are not produced if this transport of RNA is stopped. Therefore, knowledge of Rev structure is essential for understanding of its cooperative binding to the RRE, for understanding the mechanism of HIV infection and for the development of antiviral drugs that interfere with Rev’s essential functions and for acknowledgment of good candidate drugs for treatment of AIDS. To understand how REV interact with RRE element of HIV-RNA and its formation of oligomeric complex it is better to characterize the domain wise structure of REV with regard in function of each domain. Due to lack of structural data on Rev no single compound is reported as inhibitor of REV expect antiviral drugs. Identification of a high-affinity RNA-binding site for the human immunodeficiency virus type 1 Rev Protein is much more important. The ARM is a highly specific sequence which allows for the multimerization of Rev and also binding of REV with RNA. Here we are first time exploring the structural characteristics of REV protein both in free form and in complex with RNA at domain function level especially explore the role of ARM motif in REV HIV-1 protein as RNA binding sites by molecular dynamics (MD) simulation and homology modeling studies. Results indicate that the arginine-rich motif (ARM) is crucial in stability of this complex. The residues ARG38, 39, 41, 43, 44, 48, 50, and ASN40 are most interacting with nucleobases of RRE in Crystal structure of Rev and Rev-response-element RNA complex. Our study plays a major role in elaboration of binding of RNA with REV and pave the way for further investigation for therapeutically agent for HIV.

Latin binomials, popularised in the eighteenth century by the Swedish naturalist Linnaeus, have stood the test of time in providing a stable, clear and memorable system of nomenclature across biology. However, relentless and ever-deeper exploration and analysis of the microbial world has created an urgent unmet need for huge numbers of new names for Archaea and Bacteria. Manual creation of such names remains difficult and slow and typically relies on expert-driven nomenclatural quality control. Keen to ensure the legacy of Linnaeus lives on in the age of microbial genomics and metagenomics, we propose an automated approach, employing combinatorial concatenation of roots from Latin and Greek to create linguistically correct names for genera and species that can be used off the shelf as needed. As proof of principle, we document over a million new names for Bacteria and Archaea. We are confident that our approach provides a road map for how to create new names for decades to come.

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

The interest on the use of renewable energy resources is increasing, especially towards wind and hydro powers, which should be efficiently converted into electric energy via suitable technology tools. To this aim, data--driven control techniques represent viable strategies that can be employed for this purpose, due to the features of these nonlinear dynamic processes working over a wide range of operating conditions, driven by stochastic inputs, excitations and disturbances. Some of the considered methods, such as fuzzy and adaptive self--tuning controllers, were already verified on wind turbine systems, and similar advantages may thus derive from their appropriate implementation and application to hydroelectric plants. These issues represent the key features of the work, which provides some guidelines on the design and the application of these control strategies to these energy conversion systems. The working conditions of these systems will be also taken into account in order to highlight the reliability and robustness characteristics of the developed control strategies, especially interesting for remote and relatively inaccessible location of many installations.

While the Internet of Things (IoT) technology has been widely recognized as the essential part of Smart Cities, it also brings new challenges in terms of privacy and security. Access control (AC) is among the top security concerns, which is critical in resource and information protection over IoT devices. Traditional access control approaches, like Access Control Lists (ACL), Role-based Access Control (RBAC) and Attribute-based Access Control (ABAC), are not able to provide a scalable, manageable and efficient mechanism to meet the requirements of IoT systems. Another weakness in today's AC is the centralized authorization server, which can be the performance bottleneck or the single point of failure. Inspired by the smart contract on top of a blockchain protocol, this paper proposes BlendCAC, which is a decentralized, federated capability-based AC mechanism to enable an effective protection for devices, services and information in large scale IoT systems. A federated capability-based delegation model (FCDM) is introduced to support hierarchical and multi-hop delegation. The mechanism for delegate authorization and revocation is explored. A robust identity-based capability token management strategy is proposed, which takes advantage of the smart contract for registering, propagating and revocating of the access authorization. A proof-of-concept prototype has been implemented on both resources-constrained devices (i.e., Raspberry PI node) and more powerful computing devices (i.e., laptops), and tested on a local private blockchain network. The experimental results demonstrate the feasibility of the BlendCAC to offer a decentralized, scalable, lightweight and fine-grained AC solution for IoT systems.

In this changing world, we all are surrounded by the surmountable risk of getting injured. Amongst various risk factors, major burns are the most distressing and catastrophic. Burn wounds are not easy to heal via natural healing process and ultimately ended up with scar formation. If the degree of burn is high then the loss of tissue and its function is very common. To fasten-up the natural burn wound healing; zinc, an essential trace element is found to be very much effective. But due to its’ particle size limitation, less contact with wounded cells and tissues, and high inherent toxicity restrict its use. Needlessly, zinc is an element with dual action i.e. both antimicrobial and wound healing it is a prime choice to apply its aptitude in burn wound healing. To overcome the documented limitations zinc has converted to nanoparticle form. Zinc oxide nanoparticles, in particular, have attained ample of interest due to their unique properties and potential antimicrobial activity along with wound healing activity which makes it promising for the healing of topical burn wounds. Plant mediated green synthesis of nano-metal oxide particles is gaining a lot of significance due to its simplicity, eco-friendliness and extensive antimicrobial activity and recommended as an appealing substitute to not only physical methods but also chemical methods avoiding the use of the high rate of toxic chemicals and extreme surroundings. This study includes ZnO NPs role in burn wound healing with Phyto-mediated synthesis methods to provide evidence of their potential applications. Additionally, it provides an overview of traditional methods used for the synthesis of ZnO nanoparticles and characterization techniques to obtain information concerning the size, shape and optical properties along with toxicity and safety concern of ZnO NPs and its biomedical applications.

Nature-based solutions (NbS) - working with and enhancing nature to address societal challenges - are increasingly being featured in climate change adaptation policy and plans. While there is growing evidence that NbS can reduce vulnerability to climate change impacts in general, there is a lack of understanding on the mechanisms through which this can be achieved, particularly in the Global South. To address this, we analyse 85 nature-based interventions in rural areas across the Global South, and factors mediating their effectiveness, based on a systematic map of peer-reviewed studies encompassing a wide diversity of ecosystems, climate impacts, and intervention types. We develop and apply an analytical framework of people’s social-ecological vulnerability to climate change, in terms of six pathways of vulnerability reduction: social and ecological exposure, sensitivity, and adaptive capacity. Most cases (95%) report a reduction in vulnerability, primarily by lowering ecosystem sensitivity to climate impacts (73% of interventions), followed by reducing social sensitivity (52%), reducing ecological exposure (36%), increasing social adaptive capacity (31%), increasing ecological adaptive capacity (19%) and/or reducing social exposure (14%). An analysis of mediating factors shows that social dimensions are equally important as technical factors in NbS to achieving equitable and effective outcomes. Attention to the distinct social and ecological pathways through which vulnerability is reduced helps to harness the multiple benefits of working with nature in a warming world.

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcome. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but also might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies, as well as preliminary clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

The present Feature Paper highlights the application of bacterial surface (S-) layer proteins as versatile components for the fabrication of biosensors. One technologically relevant feature of S‑layer proteins is their ability to self-assemble on many surfaces and interfaces to form a crystalline 2D protein lattice. The S-layer lattice on the surface of a biosensor becomes part of the interface architecture, linking the bioreceptor to the transducer interface, which may cause signal amplification. The S-layer lattice as ultrathin, highly porous structure with functional groups in a well-defined special distribution and orientation and an overall anti-fouling characteristics can significantly raise the limit in terms of variety and ease of bioreceptor immobilization, compactness of bioreceptor molecule arrangement, sensitivity, specificity, and detection limit for many types of biosensors. The present paper discusses and summarizes examples for the successful implementation of S-layer lattices on biosensor surfaces in order to give a comprehensive overview on the application potential of these bioinspired S-layer protein-based biosensors.

G-protein-coupled receptors (GPCR) belong to a large family of molecules eliciting different responses to a variety of signaling molecules. These receptors participate in various physiologic pathways such as metabolism, growth, immune responses, inflammation, vision, taste, olfaction, neurotransmission and even and pathologic responses including chronic inflammatory and vascular diseases. Receptors contributing to the biological responses of renin-angiotensin system (RAS) are members of GPCR family. COVID-19-induced inflammatory cascade has been attributed to acute ACE2 downregulation and imbalance of proinflammatory ACE/AngII/AT1R and anti-inflammatory ACE2/angiotensin (1-7)/Mas axes in favor of the former. Some of the receptors contributing to activities of proteins in RAS including AT1R, AT2R and Mas receptors are members of GPCR family. It is notable that these receptors induce their effects both through G protein and β-arrestin pathway; the former exerts temporary and the latter more sustained effects. In addition to the imbalance of GPCR responses contributing to RAS activities, it has been suggested that SARS-CoV2 pathogenesis might be attributed to the activation of GPCRs or modulating G-proteins involved in adenosine-CFTR regulation system and epithelial Na channel function.This article includes a minireview about the physiological functions of GPCRs and their contribution to COVID-19.

Purpose: Pandemic Novel Coronavirus (SARS-CoV-2) has emerger centered from wuhan, China. Structurally homologous spike protein of SARS-CoV-2 receptor is taxonomically homologous with SARS-Cov and SARS associated bat coronavirus. Still now scientists are trying to find out proper vaccine and treatments for this disease. Methods: Systematically we modeled and compared the structure of SARS-CoV-2 spike protein along with Bat Cov, Bat SARS Cov and SARS Cov Urbani. S1 and S2 unit of the coronavirus (SARS-CoV-2) are attached with ACE2 and furin, here we docked 5 Ca+ chelating drugs with these two proteins. Results: Structural comparison with all these spike proteins revealed that less significant but not negligible difference exists among them. Inserted stable nucleotide sequences and corresponding surface exposed peptidal region may be considered as epitope. Docking result with Toxicokinetics and half life of Penicillamine can effectly inhibit the attachment site of spike protein of coronavirus (SARS-CoV-2). Conclusions: Docking summery and the pharmacokinetics with toxicokinetics index recommend that Penicillamine can able to inhibit the infection of SARS-CoV-2.

This paper presents a brief account and rationale for implementation of competency-based learning in any form of management and leadership development programmes in South Africa. The fact that competency-based learning (CBL), also known as outcomes-based learning has been scrapped from the schooling system in South Africa is unfortunate as this method enhances critical thinking skills and practical problem-solving skills. This paper presents CBL as a model of meta-cognitive approach to learning that integrates both theory and practice into experiential learning through six dimensions, namely, active learning, constructive learning, cumulative learning, goal-oriented learning, learner-centred and curriculum design strategies. In the advent of the fast-paced global economy, managers and leaders need to seek those business schools that value real-time practical approach to curriculum for relevance and to maximize shareholder value through human resource development. This brief presentation ends by recommending an approach through CBL that fosters three critical pillars of leadership development, namely: intellectual, behavioural and emotional agenda.

This paper attempts at applying adaptive network-based fuzzy inference system (ANFIS) for analysis of the resonant frequency of a microstrip rectangular patch antenna with two equal size slots which are placed on the patch vertically. The resonant frequency is calculated as the position of slots is shifted to the right and left sides on the patch. As a result , the antenna resonates at more than one frequency . Commonly, machine algorithms based on artificial neural networks are employed to recognize the whole resonant frequencies. However ,they fail to estimate the resonant frequencies correctly as in some cases variations are not very sensible and the resonant frequencies overlap each other . It can be concluded that artificial neural networks could be replaced in such designs by the adaptive network-based fuzzy Inference system due to its high approximation capability and much faster convergence rate.

A novel coronavirus (2019-nCoV) that is initially found to trigger human severe respiratory illness in Wuhan City of China, 2019, has been recognized as a public health emergency of international concern. In the past two months, this deadly agent has caused 77,785 cases with 2,666 deaths via rapid person-to-person transmission and reached at least 25 countries. However, its evolutionary origin is poorly understood. Here we show integrative evidence that 2019-nCoV is a possible progenitor for SARS-CoV with bat origin. Our finding underscores the importance of tracing origin in the efficient monitoring, and effectively preventing the interspecies transmission of such emerging/re-emerging coronaviruses.

Bangladeshi construction industry suffers a lot of safety and accidental issues than other developing countries in the world. Among many of these, accident of construction project goes far beyond and shape a horrific figure of death for every year. The aims of this study is that analysis and discussion of causes of accident at construction project in Bangladesh. A widespread statistical data collection and data analysis take place to identify the causes and design the questionnaire. The questionnaire-based survey was used to elicit the attitude of four stakeholders as workers, owners, consultants, and contractors towards passive causes of fatal accident at construction site. These study also identify 77 passive causes under 14 major groups and ranked them based on Relative Importance Index (RII). The top 5 major group of causes are (1) Management related, (2) Consultant related, (3) Technology related, (4) Labour related and (5) Contractor related. The top 5 passive causes are: (1) Unaware of safety-related issue, (2) Lack of personal protective equipment, (3) Lack of safety eliminating/ avoiding design, (4) Unfit equipment, (5) Lack of knowledge and training on equipment.

The spike protein of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2), which is mediated by the receptor binding domain (RBD) of the spike protein. Recently, an analysis based on decade-long structural studies of SARS was reported to illustrate with atomic-level details receptor recognition by the novel coronavirus from Wuhan, i.e., 2019-nCoV. Here, this article reports a comprehensive set of structural electrostatic analysis of all SARS-CoV spike protein RBD-related structures as of February 13, 2020, aiming at identifying the electrostatic hot spots for SARS-CoV spike protein to be complexed with ACE2 and its neutralizing antibodies. First, this article identified a structural action mechanism of the F26G19 antibody (of SARS-CoV spike protein), where its Asp56 residue binds to the Arg426 of the SARS-CoV spike protein RBD against the formation of the interfacial Arg426-Glu329 salt bridges between ACE2 and the SARS-CoV spike protein RBD. Second, a hypothesis is reported that a pair of electrostatic clips exist at the interface between ACE2 and the SARS-CoV spike protein RBD, including both Arg426-Glu329 and His445-Glu23-Lys447 salt bridges. Last, this article reports a structurally identified interfacial Glu35-Arg479 salt bridge which helps stabilize the complex structure of ACE2 and the SARS-CoV spike protein RBD. Overall, the structurally identified electrostatic hot spots reported here may be useful for the design of SARS-CoV-neutralizing antibodies in future.

There is increasing evidence that the impact of climate change on the productivity of grasslands will at least partly depend on their biodiversity. A high level of biodiversity may confer stability to grassland ecosystems against environmental change, but there are also direct effects of biodiversity on the quantity and quality of grassland productivity. To explain the manifold interactions, and to predict future climatic responses, models may be used. However, models designed for studying the interaction between biodiversity and productivity tend to be structurally different from models for studying the effects of climatic impacts. Here we review the literature on the impacts of climate change on biodiversity and productivity of grasslands. We first discuss the availability of data for model development. Then we analyse strengths and weaknesses of three types of model: ecological, process-based and integrated. We discuss the merits of this model diversity and the scope for merging different model types.

Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges in size from one to one hundred nanometers. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism that it is tested on, all have a large determining factor on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signaling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress, as well as the effects of nanosilver on the responses to such stresses, are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis, as well as other pathway alterations are examined in this review.

The potential advantages of plant-based interventions in decreasing the incidence and lessening the morbidity and mortality of COVID-19 are yet to be widely acknowledged. Nevertheless, recent publications propose that these interventions could be effective. Our cardiology center conducted an interventional study in which we incorporated plant-based foods and provided supplementation to 3470 elderly COVID-19 patients with multiple comorbidities. We pay close attention to the precise selection of food items, the application of appropriate processing methods, and the provision of nourishing meals to our patients. Our outcome was highly successful as we achieved a zero mortality rate, and none of our patients experienced worsening conditions or required hospitalization. In this review article we present the mechanisms how plant-based and supplement interventions can mitigate COVID-19 disease severity and mortality. And experts have validated our hypotheses very recently. The measures and methods used to address the ongoing SARS-CoV-2 pandemic through plant-based interventions and supplements are effective and may help prevent or manage future pandemics.

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses concerning SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear IgG B-cell epitopes in its Spike glycoprotein with a SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. Bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA assay for anti-SARS-CoV-2 antibodies. Higher reactivity indices were often measured in individuals with a pre-pandemic dengue infection than those with COVID-19. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infection of monocytes was observed with pre-pandemic dengue-positive sera. A significant increase in viral load was measured compared to controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. This study highlights the importance of identifying the epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future conditions on disease. Vaccine development and optimization strategies should be mindful of the potential for A.D.E. that could differ geographically due to endemic biological risks.