After developed the formulation of a "general relativity" in C⁴ [2], we proceed with the formulation of a Hamilton-Jacobi equation in C⁴. We argue that in this consideration, the usual problems of the ADM formalism, do not exist, due to the complex time as it exists in our consideration. Speci cally, we can derive a suitable dispersion relation in order to work with and nd a generalised super Hamiltonian

We explore the possibility to nd the usual quantum theories, within the formulation of a classic theory of mechanics in C⁴. Speci cally, by releasing the end-point of the integral of the action derived in C⁴, we derive the dynamic path length of the geodesic equation in C⁴. In the at case, the derived Hamilton-Jacobi equations, were identi ed as the usual Klein-Gordon equation, where the complex functional action S(z_i), is identi ed as the usual complex scalar field φ. Afterwards, we study the energy-momentum 4-d complex vector, in order to re-establish the usual covariant derivative of gauge theories.

We explore the field equations in a 4-d complex space-time, in the same way, that general relativity does for our usual 4-d real space-time, forming this way, a new "general relativity" in C⁴ space-time, free of sources. Afterwards, by embedding our usual 4-d real space-time in C⁴ space-time, we describe geometrically the energy-momentum tensor T_μν as the lost geometric information of this embedding. We further give possible explanation of dark eld and dark energy.

The arrival of new developments in the field of power electronics circuit’s applications in power systems builds new control strategy to improve voltage quality for power grid by overcome interruptions. Wind energy resources are unconventional resources and get advanced problems to power grid when it is connected. Uncertainty of load sharing, peak energy management, climatic conditions, wind velocity and wind energy injected into power grid leads many of power quality problems on power grid based on the existing guidelines specified in IEC-61400 standard. This system plans efficient operation of DFIG to eliminate the voltage collapse and mismatch frequency to power grid. The DFIG connected diode rectifier and rotor side converter wind generator works as an Efficient Static Synchronous Compensator (E-SATCOM) for supplying the demand of reactive power for power grid to mitigate PQ problems. The benefit of using a combined controller was verified by simulink/Matlab and its simulated results used Doubly Fed Induction Generator (DFIG), wind Turbine. This simulation results gives good quality transient and stable state response to manage and support reactive power for both symmetrical and unsymmetrical faults in connection of grid codes to provide continuous quality of power supply, multiple wind generators are required for 140 bus power grid.

This research work deals hybrid control system based integrated Cuk converter fed brushless DC motor (BLDCM) for power factor correction. In this work, moth-flame optimization (MFO) and fuzzy logic controller (FLC) has been combined and moth –flame fuzzy logic controller (MFOFLC) has been proposed. Firstly, the BLDC motor modelling is composed with power factor correction (PFC) based integrated Cuk converter and BLDC speed is regulated using variable DC-Link inverter voltage which makes low switching operation with less switched losses. Here, with the use of switched inductor, the task and execution of proposed converter is redesigned. The DBR (diode bridge rectifier) trailed by proposed PFC based integrated Cuk converter operates in discontinuous inductor conduction mode(DICM) for achievement of better power factor.MFO is exhibited for gathering of dataset from the input voltage signal. At that point separated datasets is send to FLC to improve the updating function and minimization of torque ripple. However, our main objective is to assess adequacy of proposed method, the power factor is broke down. The execution of the proposed control methodology is executed in MATLAB/Simulink working platform and the display is assessed with the existing techniques.

The increased cultivation of high THC-containing Cannabis sativa L. (cannabis), particularly in greenhouses, has resulted in a greater incidence of diseases and molds that can negatively affect the growth and quality of the crop. Among them, the most important diseases are root rots (Fusarium and Pythium spp.), Botrytis bud rot (Botrytis cinerea), powdery mildew (Golovinomyces ambrosiae), cannabis stunt disease (caused by Hop latent viroid), and a range of microbes that reduce post-harvest quality. An integrated management approach to reduce the impact of these diseases/microbes requires combining different approaches that target the reproduction, spread and survival of the associated pathogens, many of which can occur on the same plant simultaneously. These approaches will be discussed in the context of developing an integrated plan to manage the important pathogens of greenhouse-grown cannabis at different stages of plant development. These stages include maintenance of stock plants, propagation through cuttings, vegetative growth of plants, and flowering. The cultivation of cannabis genotypes with tolerance or resistance to various pathogens is a very important approach, followed by the maintenance of pathogen-free stock plants. When combined with cultural approaches (sanitation, management of irrigation, and monitoring for diseases) and environmental approaches (greenhouse climate modification), a significant reduction in pathogen development and spread can be achieved. The use of preventive applications of microbial biological control agents and reduced risk biorational products can also reduce disease development at all stages of production in jurisdictions where they are registered for use. The combined use of promising strategies for integrated disease management on cannabis plants during greenhouse production will be reviewed. Future areas for research are identified.

The growing importance of sustainability in organizational success, particularly in the pharma-ceutical industry, underscores the need for leveraging technologies like blockchain to enhance sustainability indicators across environmental, social, and economic pillars. This study aims to identify and understand the challenges hindering the adoption of blockchain in the pharmaceuti-cal sector for improving sustainability performance, addressing two research questions: the spe-cific challenges faced by blockchain adoption in this context and the interdependencies among these challenges. Employing a two-step approach, the study compiles challenges through a litera-ture review, refines them via expert opinions, and establishes their interrelationships using methodologies like Fuzzy Interpretive Structural Modeling (FISM) and Cross-Impact Matrix Multiplication Applied to Classification (MICMAC). The research contributes to unraveling the complex relationships and dependencies within the system, providing a structured framework for improved decision-making and strategic planning. It fills a literature gap by being the first attempt to outline driving and dependent factors related to the challenges of adopting blockchain technology for sustainability enhancement in the pharmaceutical sector, offering insights that can significantly impact brand image, company perception, and consumer value.

In the dynamic landscape of drug discovery, Computer-rAided Drug Design (CADD) emerges as a transformative force, bridging the realms of biology and technology. This paper overviews CADD's historical evolution, categorization into structure-based and ligand-based approaches, and its crucial role in rationalizing and expediting drug discovery. As CADD advances, incorporating diverse biological data and ensuring data privacy become paramount. Challenges persist, demanding the optimization of algorithms and robust ethical frameworks. Integrating Machine Learning and Artificial Intelligence amplifies CADD's predictive capabilities, yet ethical considerations and scalability challenges linger. Collaborative efforts and global initiatives, exemplified by platforms like Open Source Malaria, underscore the democratization of drug discovery. The convergence of CADD with personalized medicine offers tailored therapeutic solutions, though ethical dilemmas and accessibility concerns must be navigated. Emerging technologies like quantum computing, immersive technologies, and green chemistry promise to redefine the future of CADD. The trajectory of CADD, marked by rapid advancements, anticipates challenges in ensuring accuracy, addressing biases in AI, and incorporating sustainability metrics. The paper concludes by highlighting the need for proactive measures in navigating the ethical, technological, and educational frontiers of CADD to shape a healthier, brighter future in drug discovery.

Microbial foodborne pathogens can cause major risks to public health and the food industry. Rapid and accurate detection of these pathogens is crucial to prevent outbreaks and ensure food safety. Traditional single-mode biosensing approaches have their limitations in terms of specificity, sensitivity, and speed. Over the years, there has been an increasing research interest in developing multimodal biosensing strategies that integrate multiple sensing techniques to achieve enhanced accuracy, efficacy, and precision in foodborne pathogen detection. This article review paper explores the current state of multimodal biosensing technologies and their promising applications in the food industry. We discuss various integrated biosensing platforms, including optical, electrochemical, and nanomaterial-based systems, among others. The advantages, challenges, and future prospects of multimodal biosensing for foodborne pathogens are thoroughly examined, highlighting the potential impact of these advanced technologies on food safety and public health.

Salmonella is the intracellular pathogen and etiological known for the cause of asymptomatic carriage, gastroenteritis, systemic disease (typhoid fever), in severe cases death may also occur. Altered function of mitochondria due to Salmonella infection impacts the immune response. Mitochondria which are recognized as the “powerhouse” of the cells are also know to play central role in the immune metabolism. Mitochondrial dynamics such as fusion, fission, signaling, transport and mitophagy influences the immune system and also maintains the cellular integrity. Mitochondrial DNA and Reactive oxygen species formation also elicits the inflammatory responses. This review discusses the immune metabolism and effect of altered mitochondrial dynamics in case of Salmonella infection.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

Current stock market forecasting methods encompass fundamental, technical, emotional, and bargaining factors. Predominantly, price prediction hinges on order volume and price, although correlating these two within existing models proves challenging. This study employs Cycle Generative Adversarial Network (Cycle GAN) to unravel the intricate price-volume relationship, combining it with Bollinger Bands for trading signal analysis, overcoming hurdles in short-term forecasting prevalent in numerical analysis and AI. Focusing on TSMC (2330.TW) stock price, the research leverages Cycle GAN in deep learning to master the price-volume nexus, juxtaposed with LSTM and RNN. Historical TSMC closing prices and transaction counts are model inputs, scrutinizing their interconnectedness for predictions. This innovative approach aligns stock price, volume, market value, taxes, and prior changes via system engineering. By intertwining Bollinger Bands with stock price forecasts, trading signals are distilled, factoring in extended index %b for a comprehensive market picture.

IQGAP1 is a multi-functional scaffold protein. However, its role in B cell development and function is not known. Here, we demonstrate Iqgap1mice contained significantly increased numbers of B220+ B, B220+IgM pro/pre-B, and B220+IgM+ immature-B cells in the bone marrow. Here, we show IQGAP1 as the essential scaffold that regulates early B cell development and function. Iqgap1mice contained significantly increased numbers of B220+ B, B220+IgM pro/pre-B, and B220+IgM+ immature-B cells in the bone marrow. New-forming and follicular B cell numbers were increased, while the marginal zone B cell numbers were significantly reduced in the spleen of the Iqgap1mice. Lack of IQGAP1 reduced T-dependent and T-independent humoral responses. Mechanistically, the lack of IQGAP1 considerably decreased the phosphorylation of Mek1/2, Erk1/2, and Jnk1/2. B cells from Iqgap1mice failed to suppress IL-7R-mediated activation of Stat5a/b, an essential step for cell-cycle exit and initiate light-chain recombination, leading to a reduction in RS rearrangement frequency. Lack of IQGAP1 resulted in a significant reduction of IRF4 and IRF8 in BM B cells. Our study provides the first evidence that IQGAP1-based signalosome is essential for the development and functions of B cells.

In the realm of modern drug discovery, the integration of chemoinformatics and quantitative structure-activity relationship (QSAR) modeling has emerged as a formidable alliance, enabling researchers to harness the vast potential of machine learning (ML) techniques for predictive molecular design and analysis. This review delves into the fundamental aspects of chemoinformatics, elucidating the intricate nature of chemical data and the crucial role of molecular descriptors in unveiling the underlying molecular properties. Molecular descriptors, including 2D fingerprints and topological indices, in conjunction with the structural-activity relationships (SARs), play a pivotal role in unlocking the pathway to small-molecule drug discovery. Technical intricacies of developing robust ML-QSAR models, including feature selection, model validation, and performance evaluation, are discussed herewith. Various ML algorithms, such as regression analysis and support vector machines, are showcased in the text for their ability to predict and comprehend the relationships between molecular structures and biological activities. This review serves as a comprehensive guide for researchers, providing an understanding of the synergy between chemoinformatics, QSAR, and ML. By embracing these cutting-edge technologies, predictive molecular analysis holds promise for expediting the discovery of novel therapeutic agents in the pharmaceutical sciences.

Reinventing approved therapeutic proteins for a new dose, a new formulation, a new route of administration, an improved safety profile, a new indication, or a new conjugate with a drug or a radioactive source is a creative approach to benefit from the billions spent on developing new therapeutic proteins. These new opportunities were created only recently with the arrival of AI/ML tools and high throughput screening technologies. Furthermore, the complex nature of proteins offers mining opportunities that are not possible with chemical drugs; bringing in newer therapies without spending billions makes this path highly lucrative financially while serving the dire needs of humanity. This paper analyses several practical reinventing approaches and suggests regulatory strategies to reduce development costs significantly. This should enable the entry of hundreds of new therapies at affordable costs.

The pressure exerted on the heart and blood vessels because of blood flow is considered as an important parameter for the cardiovascular function. It determines sufficient blood perfusion as well as transportation of nutrition, oxygen and other essential factors to every organ. Pressure in the primary arteries located near the heart and the brain, known as central blood pressure (CBP), while in peripheral arteries, known as peripheral blood pressure (PBP). Normally, CBP and PBP are correlated; however, cardiovascular disorders interfere their regulation and affect the blood flow in vital organs and accessory organs, differently. Therefore, understanding each of them in normal and disease conditions is essential for managing various cardiovascular disorders and increasing their treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic and cellular) of the blood pressure and its regulation in hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). Newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. Regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

The Severe acute respiratory syndrome-Corona virus-2 (SARS-CoV-2) which is responsible for recurring pandemics takes advantage of host-cell processes including the glycosylation pathway. The heavily glycosylated spike protein assists viruses in attachment and penetration. The N-glycans of N-terminal domain N165 and N234 play a significant role in conformational dynamics of the receptor-binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2). In addition, the deletion of N-glycan sites N331 and N334 have been associated with reduced infectivity. This signifies the importance of targeting the N-glycans making them unavailable for interacting with the ACE2 receptor, ultimately leading to reduced infectivity. These glycans can be specifically targeted and can be used for designing SARS specific drugs or neutralizing molecules. In the current study, lectins Griffithsin, Cyanovirin-N, Cyanovirin homolog, and BanLec H84T were used to target the spike protein's N-glycans. Molecular docking programs AutoDock Vina and HADDOCK were used to study lectin-glycan interactions. The interactions look convincible in accordance with the lowest interaction energies best-fit approach but the characteristic feature (scoring functions) of the docking programs are questionable concerning Lectin-Glycan interactions exist in nature. There is a high need of the hour for developing specific algorithms for docking glycans with a preferential selection of terminal residues.

Neurological / neurovascular disorders constitute the leading cause of disability and second leading cause of deaths in the world. Some of the major neurological / neurovascular disorders or diseases include stroke, Alzheimer’s disease, spinal cord injury, neonatal hypoxic-ischemic encephalopathy, etc. Their pathophysiology is considered as highly complex and has been blamed as the main obstacle in the development of any drugs for these diseases. In this review, we have described the endothelin system, their involvement in neurovascular disorders, importance of endothelin B receptors (ETBRs) as a novel potential drug target, and its agonism by IRL-1620 (INN - sovateltide), which we are developing as a drug candidate for treating the above-mentioned neurological disorders / diseases. We have highlighted the results of our pre-clinical and clinical studies related to these diseases. The phase I, safety and tolerability study of sovateltide has shown it as a highly safe and well tolerable compound at tested dosages, while pre-clinical and clinical phase II studies have demonstrated its efficacy in treating acute ischemic stroke, where it is currently being developed as a “First in Class” drug. Its testing in Alzheimer’s disease (AD), acute spinal cord injury and neonatal hypoxic-ischemic encephalopathy (HIE) is currently being carried out and are at different stages of drug development. Successful completion of these studies will prove the involvement of ETBRs signaling in neurological / neurovascular diseases and help in development of novel neurological drugs in future.

Visceral Leishmaniasis is a neglected tropical disease affecting 12 million people annually. Even in the second decade of the 21st century, it has remained without an effective vaccine for human use. In the current study, we have designed three multiepitope vaccine candidates by the selection of multiple IFN-γ inducing MHC-I and MHC-II binder T-cell specific epitopes from 3 previously identified antigen genes of Leishmania donovani from our lab, by immune-informatic approach using IFNepiotpe, NET-MHC-1 and NET MHC-2 webservers. We have tested the protective potential of these three multiepitope proteins as vaccine in a hamster model of visceral leishmaniasis. The immunization data revealed that the vaccine candidates induced a very high level of Th-1 biased protective immune response in-vivo in a hamster model of experimental visceral Leishmaniasis, with one of the candidates inducing a sterile immunity. The vaccinated animals displayed highly activated monocyte macrophages with the capability of clearing intracellular parasites due to increased respiratory burst. Additionally, these proteins induced activation of polyfunctional T cells secreting INF-γ, TNF-α, and IL-2 in ex-vivo stimulation of human peripheral blood mononuclear cells, further supporting the protective nature of designed candidates.

Dirofilaria immitis infection is one of the most severe parasitic diseases of dogs. Prevention is achieved by the administration of drugs containing macrocyclic lactones (MLs). These products are very safe and highly effective, targeting the third and fourth larval stages (L3, L4) of the parasite. Until 2011, claims of ineffectiveness of MLs, reported as “Lack of Efficacy” (LOE), were generally attributed to owners’ non-compliance, or other reason for inadequate preventative coverage. There was solid argumentation that a resistance problem is not likely to occur because of i) the great extent of refugia, ii) the complexity of resistance development to MLs, and iii) the possible big number of genes involved in resistance selection. Nevertheless, today it is unequivocally proven that ML resistant D. immitis strains exist, at least in the Lower Mississippi region, USA. Accordingly, tools have been developed, to evaluate and confirm the susceptibility status of D. immitis strains. A simple, in-clinic, microfilariae suppression test, 14-28 days after ML administration, and a “decision tree” (algorithm), including compliance and preventatives’ purchase history, and testing gaps, may be applied for assessing any resistant nature of the parasite. On the molecular level, specific SNPs may be used as markers of ML resistance, offering a basis for validation of clinically suspected resistant strains. In Europe, no LOE/resistance claims have been reported so far, and the existing conditions (stray dogs, rich wildlife, majority of owned dogs not on preventive MLs treatment) do not favor selection pressure on the parasites. Considering the genetic basis of resistance and the epizootiological characteristics of D. immitis, ML resistance neither establishes easily nor spreads quickly, a fact confirmed by the current known dispersion of the problem, which is limited. Nevertheless, ML resistance may propagate from an initial geographical point, via animal and vector mobility, to other regions, while it can also emerge as an independent evolutionary process in a new area. For these reasons and considering the current chemoprophylaxis recommendations and increasing use of ML endectoparasiticides as a potential selection pressure, it is important to remain vigilant for timely detection of any ML LOE/resistance, in all continents where D. immitis is enzootic.

Many corporations and governments aspire to become Net Zero Carbon Dioxide by 2030-2050. Achieving this goal requires understanding where energy is produced and consumed, the magnitude of CO₂ generation, and the Carbon Cycle. Many prior proposed solutions focus on reducing future CO₂ emissions from continued use of fossil fuels. Examination of these technologies exposes their limitations and shows that none offer a complete solution. For example, bioethanol is shown to be both carbon and energy inefficient. Direct Air Capture technologies are needed to reduce CO₂ already in the air. The most natural form of Direct Air Capture involves letting nature do the work of creating biomass via photosynthesis. However, it is necessary to break the Carbon Cycle by permanently sequestering that biomass carbon in “landfills” modified to discourage decomposition to CO₂ and methane. Tree leaves and biomass grown on-purpose, such as high yield switchgrass, are proposed as good biomass sources for this purpose. Left unsequestered, leaves decompose with a short Carbon Cycle time constant releasing CO₂ back to the atmosphere. While in any given year, leaves represent a small fraction of a tree’s above ground biomass, leaves can represent a substantial fraction of the total biomass generated by a tree when integrated over a tree’s lifetime. Understanding the chemistry of the distinct phases landfills undergo is the key to minimizing or eliminating decomposition. First, the compact cross-linked structure of cellulose and keeping water out will make it difficult for initial depolymerization to release sugars. Air ingress should be minimized to minimize Phase I aerobic decomposition. pH manipulation can discourage acid formation during Phase II. Lignocellulose is low in nutrients needed for anaerobic decomposition. Inhibitors can be added if needed. The goal is to move quickly to the dormant phase where decomposition stops. The cost for Carbon Capture and Storage (CCS) for growing and sequestering high yield switchgrass is estimated to be lower than CCS for steam reforming of methane hydrogen plants (SRM) and supercritical or combined cycle coal power plants. Thus, sequestration of biomass is a natural, carbon efficient, and low-cost method of Direct Capture. Biomass sequestration can provide CO₂ removal on giga tonnes per year scale and can be implemented in the needed timeframe (2030-2050).

A The present investigation was undertaken in foothill regions of Uttarakhand from July-2016 up to December-2018. A total of thirty four different sites ranging from the roadside areas, grasslands to forests were studied and Mushroom fruiting bodies were collected. A total of One Hundred sixty six fruiting counts were obtained and 68 mushroom genera belonging to 15 orders and 43 families were identified. During collection visits mushroom were apparent from organic debris of diversified habitats ranging from humid soil; grassland; leaf litter; living tree trunk; dead wood log of forest zone. Maximum fruiting bodies (75%) were obtained between July to September and minimum i.e. 6% between November – February. Among the collected mushroom Stereum rugosum, Crepidotus variabilis, Laccaria laccata, Schizophyllum commune, Ganoderma applantum, Cantharellus cibarius were more prevalent. Out of all collected mushroom sample the frequency of Mushroom belonging to order Agaricales was 45.18% followed by Polyporales i.e., 27.7%. The collected mushroom were cultured on PDA medium and their mycelial forms were preserved for further studies.

Background: General Practitioners (GP) have an important role in the prevention of suicidal behavior. The purpose of this study was to explore their views and experiences of identifying and assessing suicidal ideation. Methods: Ten GPs were recruited through convenience sampling, based on accessibility, interest and willingness to participate. In-depth interviews were carried out and results transcribed ver-batim. Aspects of experiences with suicidal patients emerged through the thematic analyses process. Results: The GPs described the varied clinical picture when patients presented in their office. How they identified depressive symptoms apart from originally somatic complaints, formed a trusting relationship and addressed suicide ideation. They described customized interventions as well as obstacles and factors that facilitated communication: time, own personal traits, pa-tient’s disclosure and organizational barriers. Conclusions: The levels of the suicidal process among patients in general practice vary greatly. GPs adjust their appraisals to profundity understand and intervene in order to prevent a crisis to escalate into subsequent suicidal behavior.

There is a crucial need for advancement in the online educational system due to the unexpected, forced migration of classroom activities to a fully remote format, due to the coronavirus pandemic. Not only this, but online education is the future, and its infrastructure needs to be improved for an effective teaching-learning process. One of the major concerns with the current video call-based online classroom system is student engagement analysis. Teachers are often concerned about whether the students can perceive the teachings in a novel format. Such analysis was involuntarily done in the offline mode, however, is difficult in an online environment. This research presents an autonomous system for analyzing the students' engagement in the class by detecting the emotions exhibited by the students. This is done by capturing the video feed of the students and passing the detected faces to an emotion detection mode. The emotion detection model in the proposed architecture was designed by finetuning VGG16 pre-trained image classifier model. Lastly, the average student engagement index is calculated. We received considerable performance setting reliability of the use of the proposed system in real-time giving a future scope to this research.

Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds, are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis.

Amorphous chalcogenide (ChGs) glasses are intrinsically metastable, highly photosensitive, and therefore exhibit numerous lightinduced effects upon bandgap and sub-bandgap illumination. Depending on the pulse duration of the excitation laser, ChGs exhibit a series of lightinduced effects spanning over femtosecond to seconds time domain. For continuous wave illumination, the effects are dominantly metastable in terms of photodarkening (PD) and photobleaching (PB) that takes place via homopolar to heteropolar bond conversion. On the other hand, under nanosecond and ultrafast pulsed illumination, ChGs exhibit transient absorption (TA) that is instigated from the transient bonding rearrangements through self-trapped exciton recombination. In the first part of the review, we pay special attention to continuous wave lightinduced PD and PB, while in the second part we will focus on the TA and controlling such effects via internal and external parameters e.g., chemical composition, temperature, sample history etc.

Emerging paradigms in interferon (IFN) biology suggest a dynamic INF induced interactome that extends through broader Interferon Stimulated Gene (ISG)- induction, which implicates interferon- ISG coordinated cross-talk with mRNA processing, post-translational modification and metabolic processes that underlie pathological (viral, autoimmune and tumor biology) and physiological (stem cell regenerative pathways) processes. INF immune responses can also be triggered by endogenous host-derived molecules that are generated in response to cellular stress or hemostasis imbalance to establish tissue repair and regeneration in first place, however, overactivation or lack of countermeasures can result in host tissue damage. The proteases are integral to viral and tumor pathology, and importantly serine proteases TMPRSS2 and trypsin have been identified as important molecular determinants underlying COVID-19 pathology, and emergence of coronaviruses cultured in vitro, respectively. We propose that pathogen associated proteases can act as novel stress-inducers to facilitate viral- competent immunomodulation. We term it as Protease Induced Transcriptomic/ epi-Transcriptomic Reshaping (PITTR) of host cells to counter cellular stress. We present a novel experimental model and our preliminary findings of trypsin- primed Caco-2 cells (CPT) that result in translational halt comparable to cells grown under serum-starvation conditions (CSS). CPT at escalating trypsin concentration (CPT- EC) induce upregulation of selective proteins that majorly map to ribosomal, RNA transport, and spliceosome ribonucleoproteins (RNPs). The inclusion of proinflammatory IL1-b to CPT (CPT- IL) resulted in global overexpression of proteins comparable to Caco-2 cells cultured in growth-factor rich serum conditions (CFBS), indicating a likely de-repression of trypsin- induced translational halt. Caco-2 cells display abortive interferon proteome under differential trypsin conditions (CPT, CPT-EC and CPT-IL), which is marked by complete lack of INF generation despite induction of intermediate ISGs, suggestive of protease (trypsin)- dependent regulation of INF response. Viruses regulate the proteome of stress granules (SGs) that are induced to cope transient translational halt as a central adaptive response to pathogen induced cellular stress. The integral components of SGs include non-translating mRNA, ribonucleoproteins (RNPs) and RNA binding proteins (RBPs), which together form biological condensates through a biophysical process involving weak electrostatic interactions through intrinsically disordered regions in RBPs resulting in liquid- liquid phase separation. We compared the CPT- EC proteome to the Mammalian Stress Granules Proteome (MSGP) database to explore potential RBPs that could possibly regulate INF response (and could act as potential anti-viral targets). Notably, differentially upregulated RNPs and potential RBPs from ISG family including ADAR and PRKRA, and RNA helicases implicated in viral pathogenesis were found to be upregulated in the CPT- EC proteome further strengthening the role of proteases (trypsin) in regulating INF pathways independent of the pathogen. We propose that the supplementation of viable SARS-CoV-2 viral loads to trypsin- primed host cells could recapitulate an infectious disease model, which may closely phenocopy pathogen- driven inflammation and signaling events. Based on the global downregulation of seven SERPINS (serine protease inhibitors) linked to thromboinflammation in our LCMS profiling data, we support the candidature of serine protease inhibitors for protease mediated viral pathologies. COVID-19 is increasingly linked to coagulopathy and resemblance to Neutrophil Extracellular Trap (NET) related thromboinflammatory features; SERPIN A1AT (alpha 1 antitrypsin) being a potent neutrophil- elastase inhibitor and a negative regulator of coagulation complement pathway may be a promising candidate for establishing hemostasis rebalancing in COVID-19 pathology.

Understanding the physical properties of ultramafic rocks is important for evaluating awide variety of petrologic models of the oceanic lithosphere, particularly upper mantle and lower crust. Hydration of oceanic peridotites results in increasing serpentine content, which affects lithospheric physical properties and the global bio/geochemical cycles of various elements. In understanding tectonic, magmatic and metamorphic history of the oceanic crust, interpreting seismic velocities, rock composition and elastic moduli are of fundamental importance. In this study we show that as serpentine content increases, density decreases linearly with a slope of 7.85. We also correlate increase in serpentine content with a linear decline in shear, bulk and Young’s moduli with slopes of 0.48, 0.77, 0.45 respectively. Our results show that increase in serpentine content of lower crust and forearc mantle could decrease elasticity of lithospehere and result in break-offs. Therefore tectonic processes at peridotite rich slow spreading ridges may be strongly affected by serpentine content, particularly serpentinization may be responsible for discontinuities in thin crust, and formation of weak fault zones.

In this paper, we introduce a new class of Hermite-Fubini numbers and polynomials and investigate some properties of these polynomials. We establish summation formulas of these polynomials by summation techniques series. Furthermore, we derive symmetric identities of Hermite-Fubini numbers and polynomials by using generating functions.

The aim of this article is to extend the local as well as the semi-local convergence analysis of multi-point iterative methods using center Lipschitz conditions in combination with our idea, of the restricted convergence region. It turns out that this way a finer convergence analysis for these methods is obtained than in earlier works and without additional hypotheses. Numerical examples favoring our technique over earlier ones completes this article.

This paper presents a configuration of dual output single phase current source inverter with 6 switches for microgrid applications. The inverter is capable of delivering power to two independent set of loads of equal voltages or different voltages at the load end. The control strategy is based on Integral Sliding Mode Control (ISMC). The remote monitoring of the inverter is performed with cyber infrastructure. The cyber physical test bench is developed based on Reconfigurable I/O processor (NI MyRIO-1900) for control and monitoring of the inverter. The inverter prototype is tested in cyber physical test bench in laboratory conditions. The performance of the inverter is analyzed and monitored through the remote system. Also, the inverter is analyzed with different voltage conditions.

Microbe bioengineering has the potential to improve the nutritional value and health benefits of food products. Modifying microbial cells to produce specific proteins or compounds that can improve human health is one approach. Penicillin and recombinant insulin are two examples of this. The production of recombinant insulin by genetically modified E. coli bacteria has transformed diabetes treatment by providing a consistent and cost-effective source of insulin. Previously, insulin was extracted from the pancreas of animals, which was an expensive process that frequently resulted in impurities that could cause adverse reactions. Bioengineered insulin is now the standard diabetes treatment, providing a safe and effective method of controlling blood glucose levels. Bacteria, for example, can be genetically modified to produce vitamins like B12, which are difficult to obtain from plant sources. Likewise, yeasts can be genetically modified to produce β-carotene, a precursor to vitamin A that is required for vision, immune function, and skin health. Overall, bioengineered microorganisms have the potential to provide significant health benefits by producing essential compounds and proteins. Because of ongoing advances in genetic engineering techniques and understanding microbial metabolism, the possibilities for improving human health through bioengineering are limitless.

Global emerge of zoonotic novel corona virus (COVID-19) became a pandemic and its effect to mankind is talk of the town now a days. This tiny, invisible enemy has affected every country in the world and almost every living directly or indirectly and nationwide complete lockdown has triggered a short-term environmental impact. Since 2003, corona virus came into existence in the form of Severe Acute Respiratory Syndrome (SARS) and more evolved Middle East Respiratory Syndrome (MERS) in 2012. This time, at the end of December 2019, outbreak of novel corona virus COVID-19 (also known as SARS-CoV₂, nCoV-2019) draw attention as global health emergency. World Health Organization (WHO) report says that the outbreak of this virus is so immense, it has already affected 35,57,235 people and caused death to 2,45,150 people worldwide and 46,433 Indians got affected with 1568 death as on 5^th May 2020 (2:00 am) and these numbers are increasing exponentially day by day. Virologist, micro-biologist and science community are hammering their head very hard to find out cure and vaccine against this powerful virus and to prevent mass demise of mankind. In order to curb the spread of COVID-19, Janta curfew on 22.03.2020 and nationwide complete lockdown was implemented in India for 21 days (phase-I, from 25.03.2020 to 14.04.2020) to stop community transmission of third stage, for 19 days (phase-II, 15.04.2020 to 03.05.2020) and 14 days (phase-III, 04.05.2020 to 17.05.2020) complete lockdown to minimize the community transmission effect. During complete lockdown and quarantine period a drastic change in Earth’s atmosphere, including reduction in emission of greenhouse gases, air pollution (~50% fall in air quality index), noise pollution, water pollution and solid waste pollution, have been recorded by government agencies as well as private agencies. In this paper we considered data of Janta curfew, phase-I and phase-II lockdown to link between geological and environmental aspect related to environmental impact due to emerge of COVID-19 and massive reduction in pollution level during complete lockdown in India. We propose future lockdown strategies to minimize the emission of greenhouse gas by ~100 Mt to ~200Mt (3.33% to 6.66%) of GHG_total per year by 2-4 days per month nationwide lockdown or ~70 Mt to ~140 Mt (2.33% to 4.66%) of GHG_total per year by 2-4 days per month complete lockdown of energy sectors only.

The Wind Energy Conversion System (WECS) plays an inevitable role across the world. In particular, the attention for Permanent Magnet Synchronous Generators (PMSGs) connected with wind farm is popular. This paper deals with the literature review that describes the recent advances, progresses and innovatory trends on PMSGs for WECS. Comparison between geared and direct-driven conversion systems and the classification of electrical machines used in WECS are discussed. A detailed analysis on the design aspects considering various topologies of PMSGs are encompassed in the literature. The PMSG design and optimization problems are solved by field computation techniques and optimized by using Soft Computing (SC) techniques .The three-dimensional, finite element software platform for the analysis and design of PMSGs is discussed. This paper also deals with the interdisciplinary modeling, analysis, and optimization of PMSG using Finite Element Analysis (FEM) and SC techniques. Finally, PMSGs are reviewed and compared for further exploration.

This paper investigates the performance of dual hop UAV-assisted communication channels, employing a decode and forward relay architecture. The system utilizes Terahertz (THz) communication in the primary hop and Visible Light Communication (VLC) in the secondary hop. We conduct a thorough analysis by deriving closed-form expressions for end to end bit error rate (BER). Furthermore, we employ a Monte Carlo approach to generate best fitting curves and validate our numerical expressions with simulation results. Evaluation via BER and outage probability demonstrates the proposed system’s effectiveness. The outcomes of this research offer valuable insights into the feasibility and limitations of UAV-assisted THz- VLC systems.

Modern climatic changes have an impact on the bearing capacity of permafrost soils at the base of the foundations of buildings and structures in the urbanized territories of the Arctic and Subarctic. The activation of cryogenic processes leads to the destruction of the infrastructure of human settlements and, as a result, to social, economic, environmental consequences for the population. Based on the results of geothermy of frozen and thawing soil, GPR profiling of the territory of the city of Anadyr, it was concluded that the main risks of permafrost degradation are associated with the spread of hydrogenic melt zones. Maps of soil temperature in imaginary cross-sectional with a depth of 3, 5 and 10 m were compiled; maps of the capacity of thawing soils and the permafrost aquifer; a map of zones of dangerous spread of exogenous cryogenic processes. A permafrost monitoring system in the territory of Anadyr has been substantiated, which will consist of an automated network of observations of soil temperature in 35 wells at the border and at the epicenter of 20 zones of dangerous development of exogenous cryogenic processes and 12 control GPR profiles at the intersection of linear hydrogenic taliks.

Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there is a need to discover innovative therapeutic approaches to counteract DOX-induced cardiotoxicity (DIC). MSC-Exos have shown to reduce apoptosis and cardiac fibrosis and promote cardiomyocyte proliferation in myocardial infracted mice. However, the effect of MSC-Exos on ameliorating DOX-induced pyroptosis has not been investigated. In this current study H9c2 were first exposed to DOX to stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, with further analysis performed through immunocytochemistry, western blotting, and RT-PCR. Our data depicted that post-treatment with MSC-Exos significantly (p<0.05) reduced the HMGB1/TLR4 axis, inflammasome formation (NLRP3), pyroptotic markers (caspase-1, IL-1β, and IL-18), and the pyroptotic executioner (GSDMD) in DOX-treated H9c2 cells. In conclusion, our data shows that MSC-Exos attenuates inflammation-induced pyroptosis in our in vitro DIC model. Our findings indicate that MSC-Exos may serve as a promising therapeutic intervention for mitigating DIC, as they maintain the therapeutic capabilities of MSCs while circumventing the drawbacks associated with traditional stem cell therapy.

Boron carbide (B4C) powders with defined stoichiometry, high crystallinity, minimal impurity content, and a fine particle size are imperative for realizing the exceptional properties of this compound in advanced high-technology applications. Nevertheless, achieving the desired stoi-chiometry and particle size using traditional synthesis methods, which rely on prolonged, high-temperature processes, can be challenging. The primary objective of this study is to syn-thesize fine B4C powders characterized by high crystallinity and a sub-micron particle size, em-ploying a fast, and energy-efficient method. B4C powders are synthesized from elemental boron and carbon in a high-frequency induction heating furnace using the Electromagnetic Induction Synthesis (EMIS) method. The rapid heating rate achieved through contactless heating promotes the ignition and propagation of the exothermic chemical reaction between boron and carbon. Additionally, electromagnetic effects accelerate atomic diffusion, allowing the reaction to be completed in an exceptionally short timeframe. The grain size and crystallinity of B4C can be finely tuned by adjusting various process parameters, including the post-ignition holding temperature and the duration of heating. As a result, fine B4C powders can be synthesized in under 10 minutes. Moreover, these synthesized B4C powders exhibit high resistance to oxidation when exposed to air.

Keywords: Аrtificial neural network, electric drive system, database, stability, training algorithm, technological mechanisms.

Recently a measure termed F* was described, as an interpretable transformation of the F measure, also known as the Dice coefficient. Using elementary mathematical methods, it is shown that F* is in fact identical to a previously described measure, monotonically related to the F measure, and variously termed in previous publications, dating from the late 19^th to the late 20^th century, as the ratio of verification, the Jaccard similarity measure or index, the threat score, the Tanimoto index, and the critical success index. The origins of these different terms in different disciplines (weather forecasting, ecology, machine learning) may explain the repeated independent redescription of this measure.

The effectiveness of a recently proposed methodology in the identification of damage in planar, multi-storey, Reinforced Concrete (RC) moment-frames, which develop a plastic-yield mechanism on their beams, is showcased here via the examining of a group of such existing multi-storey frames with three or more unequal spans. According to the methodology, the diagram of the instantaneous Eigen-Frequencies of the frame in the nonlinear regime is drawn as a function of the inelastic seismic roof displacement by performing a sequence of pushover and instantaneous modal analyses with gradually increasing target displacement. Using this key-diagram, the locations of severe seismic damage in an existing moment-frame can be evaluated if the instantaneous fundamental eigen-frequency of the damaged frame, at an analysis step within the nonlinear area, is known in advance by “the monitoring and the identification of frequencies” using a local network of uniaxial accelerometers. This is a hybrid technique because both procedures, the instrumental Monitoring of the structure and the Pushover analysis on the frame (M and P technique), are combined. Moreover, the damage image of the planar multi-storey moment-frame is illustrated, and the lateral stiffness matrix of the damaged frame is calculated with high accuracy.

This research paper presents an enhanced economic load dispatch (ELD) approach using the Teaching-Learning-Based Optimization (TLBO) algorithm for 10 thermal units, examining the impact of Plug-in Electric Vehicles (PEVs) in different charging scenarios. The TLBO algorithm is utilized to optimize the ELD problem, considering the complexities associated with thermal units. The integration of PEVs in the load dispatch optimization is investigated, and different charging profiles and probability distributions are defined for PEVs in various scenarios, including overall charging profile, off-peak charging, peak charging, and stochastic charging. These tables allow for the modeling and analysis of PEV charging behavior and power requirements within the power system. By incorporating PEVs, additional controllable resources are introduced, enabling more effective load management and grid stability. The comparative analysis showcases the advantages of the TLBO-based ELD model with PEVs, demonstrating the potential of coordinated dispatch strategies leveraging PEV storage and controllability. This paper emphasizes the importance of integrating PEVs into the load dispatch optimization process, utilizing the TLBO algorithm, to achieve economic and reliable power system operation while considering different PEV charging scenarios.

The article introduces the reader to the new thermodynamic potential of classical thermodynamics, called the J-potential. For the case of a homogeneous system, it vanishes, but it perfectly serves multiphase (heterogeneous) systems. The J-potential is especially important for the thermodynamics of capillary systems in colloidal science. The J-potential simplifies the derivation of the Neumann and Young equations, and has found application in the thermodynamics of thin films and the theory of strength of materials. In this work, for example, it was used to study the dependence of the chemical potential of a substance of a small bubble on the bubble size.

With the advent of COVID19, the attitude of health authorities around the world, led mainly by the West, demanded a level of proof as evidence for cheap, non-patented remedies while promoting expensive, patented, and untested remedies by using emergency use authorization and special provisions afforded to the status of a pandemic emergency. Western science has neither a tested nor a valid historical basis of a logical system that informs to authenticate scientific practices. Here we use a logical heuristic derived from ancient Buddhist logic, which is consistent with the conduct of modern science. We applied the heuristic to show that enough evidence was available for using cost-effective early therapies such as vitamin D supplementation as a public health measure during the first half of 2020. Strong supporting evidence has since accumulated. Apart from political and financial decisions incompatible with science and other conflicts of interest, a critical barrier to evaluating and approving early therapies appears to be the fallacy that the randomized controlled trial (RCT) is the superior proof method in medical hypotheses, including those for nutrients. Logically, no reason exists why properly designed retrospective, ecological, and naturalistic studies with adequate sample sizes and applied appropriate statistical methods would not be as valid as RCTs, especially when elucidating a causative factor instead of treatment. That assertion is particularly true for nutrient deficiencies, interventions, and other cost-effective therapies. Leading health authorities’ failure or refusal to consider other study types (because of either poor logic or vested interest) probably contributed to the spread of misinformation, symptomatic disease, complications, and deaths from COVID19. Partial immunity derived from vaccines and the later development of more contagious variants—and thus a sense of acceptance that SARS-CoV-2 had progressed from a pandemic to an endemic—shows the hollowness of the initial promotions and mandates of vaccines as a cure. Adequate knowledge was available in 2020 to advise that SARS-CoV-2 will continue to mutate, with variants emerging a few times per year, making the vaccine less effective. Emerging evidence confirms that natural immunity better protects against new variants than vaccination against the spike protein. Had vitamin D been adopted as part of the public health measure through a broader supplementation program in 2020 or even today (through sun exposure or as a prophylactic or adjunct therapy early on), the viral spread and symptomatic disease may have been suppressed, with minimal lockdowns and quarantine, and economic harm. The pandemic could have been halted with a significantly reduced need for hospitalization, complications, and deaths, potentially saving millions of lives.

Since the process of waste recycling generates dust and flammable gas during fragmentation, there is always a risk of fire resulting therefrom, and fire does, in fact, frequently occur. However, research on disaster management at recycling facilities deals only with the problem of processing systems from a technical point of view, but it does not suggest concrete alternatives from a management point of view. Therefore, in this study, we analyzed the influence of the disaster response network of a waste recycling center at the organizational level based on the concept of the cognitive accuracy of a network when considering administrative aspects. Through this analysis, we confirmed that factors affecting the influence of the network exist, such that the entire network and the networks of different levels of position are different. We suggest that this can be improved by deploying members who perform formal tasks at the center of the network so that everyone can agree political approach.

Burning woody biomass for energy is gaining attention due to environmental issues associated with fossil fuels and carbon emission. The carbon released from burning wood is absorbed by plants and is carbon neutral. The purpose of this study was to investigate the combustion characteristics (heat calorific values and ash contents) of three timbers: Araucaria cunninghamii, Instia bijuga and Pometia pinnata and recommend for fuelwood. The test samples were sawdust particles (treatment) and solid woods (control) extracted from the heartwoods. The sawdust particles were oven-dried, sieved and pelletized into pellets using a hand-held pelletizing device, thus, forming cylindrical dimension (volume 1178.57 mm3, oven dry density 0.0008 g/mm3). While the solid woods were cubed and oven-dried (volume 1000.00 mm3, oven dry density 0.001 g/mm3). Prior to combustion in a semi-automatic bomb calorimeter, 90 test specimens (15 replicates per treatment and control per species) were conditioned to 14 % moisture content (at temperature 105 ºC) and weighed to a constant (unit) mass (1.0 g). The heat energy outputs and ash residues (of treatments) were analyzed statistically. The results indicated variability in heat energy outputs and ash residues between test specimens of the three species. Comparatively, the treatment specimens of A. cunninghamii produced higher calorific value (18.546 kJ/g) than the control (18.376 kJ/g) whilst the treatment specimens of I. bijuga and P. pinnata generated lower heat calorific values (17.124 kJ/g and 18.822 kJ/g) than the control (18.415 kJ/g and 20.659 kJ/g), respectively. According to ash content analysis, A. cunninghamii generated higher residues (6.3%) followed by P. pinnata (4.5%) and I. bijuga (2.8%). The treatment specimens of the three species could not meet the standard heat energy requirement (20.0 kJ/g) and thus, were unsuitable for fuelwood. However, the control specimens of P. pinnata generated equivalent heat energy (20.659 kJ/g) and could be a potential fuelwood.

Branching patterns are ubiquitous in nature, consequently over the years many researchers have tried to characterize the complexity of their structures. Due to their hierarchical nature and resemblance to fractal trees, they are often thought to have fractal properties, however their non-homogeneity (i.e., lack of strict self-similarity) is often ignored. In this paper we review and examine the use of the box-counting and sandbox methods to estimate the fractal dimensions of branching structures. We highlight the fact that these methods rely on an assumption of self-similarity that is not present in branching structures due to their non-homogeneous nature. Looking at the local slopes of the log-log plots used by these methods reveals the problems caused by the non-homogeneity. Finally, we examine the role of the canopies (endpoints or limit points) of branching structures in the estimation of their fractal dimensions.

Glufosinate, a glutamine synthetase (GS) inhibitor, often provides variable weed control depending on environmental conditions such as light, temperature and humidity at the time of application. Midday applications normally provide improved efficacy compared to applications at dawn or dusk. We investigated the physiological, molecular, and biochemical basis for the time-of-day effect on glufosinate efficacy in Amaranthus palmeri. GS1 and GS2 gene expression and protein abundance were assessed in different parts (young leaves, old leaves, and roots) of plants incubated in the dark compared to those in the light. The turnover of GS total activity was also evaluated overtime following glufosinate treatment at midday compared to dusk application. The results suggest that GS in A. palmeri is less expressed and less abundant in the dark compared to in the light. Midday application of glufosinate under intense light conditions in the hours following application provide full control of A. palmeri plants. Consequently, these plants are unable to recover GS activity by de novo protein synthesis. Full activity of GS is required for complete inhibition by the irreversible inhibitor glufosinate. Therefore, glufosinate applications should always be performed in the middle of the day when sunlight is intense, to prevent weed escapes from the herbicide treatment.

The inaccurate estimates of linear prediction coefficient (LPC) and noise variance introduce bias in Kalman filter (KF) gain and degrades speech enhancement performance. The existing methods proposed a tuning of the biased Kalman gain particularly in stationary noise condition. This paper introduces a tuning of the KF gain for speech enhancement in real-life noise conditions. First, we estimate noise from each noisy speech frame using a speech presence probability (SPP) method to compute the noise variance. Then construct a whitening filter (with its coefficients computed from the estimated noise) and employed to the noisy speech, yielding a pre-whitened speech, from where the speech LPC parameters are computed. Then construct KF with the estimated parameters, where the robustness metric offsets the bias in Kalman gain during speech absence to that of the sensitivity metric during speech presence to achieve better noise reduction. Where the noise variance and the speech model parameters are adopted as a speech activity detector. The reduced-biased Kalman gain enables the KF to minimize the noise effect significantly, yielding the enhanced speech. Objective and subjective scores on NOIZEUS corpus demonstrates that the enhanced speech produced by the proposed method exhibits higher quality and intelligibility than some benchmark methods.

Pulmonary arterial hypertension is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors, and likely gene x environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 36% of pediatric-onset idiopathic PAH (IPAH) compared to ~11% of adult-onset IPAH. De novo variants are frequently associated with PAH in children, and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, the increased etiologic heterogeneity, poorer prognosis and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

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.

The current Coronavirus Disease 19 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, is unprecedented in recent history and threatens the lives and livelihoods of billions worldwide. The rapid spread and lack of modern parallels have left governments, health agencies, and the public racing to understand how to best mitigate and ultimately suppress the pandemic, but we are still working to understand the strengths and weaknesses of various interventions at our disposal. Few issues have been as contentious as the public use of face masks to control the pandemic’s spread. There is ongoing debate about their effectiveness, but an increasing body of evidence suggests that masks could be a useful in preventing the spread of coronavirus, leading several governments and health agencies to review and revise their policies. Here, we review the theory and evidence behind use of masks. The theory behind masks is that they prevent the spread of viral particles by infected persons, and inhalation of viral particles by uninfected persons. Even assuming masks are not 100% effective in preventing infection, they may reduce severity of infection by reducing viral dosing. Laboratory studies suggest masks may be effective in stopping both exhalation and inhalation of viral particles. However, real-world studies provided limited evidence for the use of masks in controlling influenza transmission and highlight potential problems associated with their misuse, such as poor compliance or improper use. Evidence for efficacy of face masks against the first SARS virus, SARS-CoV-1, implies that they may be effective against the current outbreak of SARS-Cov-2 virus. This is important as mathematical modeling suggests that even small reductions of in transmission rates can make a large difference over time, potentially slowing the pace of viral pandemics and limiting their spread. Perhaps the strongest argument for the use of masks is that countries with early adoption of masks have tended to see flatter pandemic curves, even without strict nationwide lockdowns. There is little evidence that respirators are more effective than surgical masks, but this may be due to misuse or poor compliance. Studies suggest some non-medical masks perform on par with medical masks. Improvised masks are less effective than medical masks, but may provide better protection than nothing at all. While many governments now encourage the use of improvised face coverings, more will need to be known about material, design, and who needs to wear masks, and when, to ensure effectiveness. Proper use of masks will also be important; if masks are used improperly or infrequently they may provide limited protection. It is important that public health policy makers consider the debate and the potential of masks as part of multi-faceted coronavirus control strategies.

NIRS uses the relative absorption of light at 850nm and 760nm, to determine skeletal muscle oxygen saturation. Previous studies have used the ratio of both signals to report muscle oxygen saturation. Purpose: To evaluate the different approaches used to represent muscle oxygen saturation, and to evaluate the pulsations of the O₂heme and Heme signal. Method: Twelve participants, ages 20-29years were tested on the forearm flexor muscles using continuous wave NIRS at rest. Measurements were taken during 2-3mins rest, during physiological calibration (5-minuts Ischemia) and during reperfusion. Results: There was a significant difference in pulse size between O₂heme and Heme signal at the three locations (p < 0.05). Resting oxygen saturation was 58.8+9.2%, 69.6+3.9%, and 89.2+6.9% when calibrated using O₂heme, TSI, and Heme, respectively. Conclusion: The difference in magnitude of O₂heme and Heme pulse with each heartbeat might suggest different anatomical locations of these signals, which propose calibrating with just one of the signals instead of the ratio of both. Calculations of physiological calibration must account for increased blood volume in the tissue, because of the changes in blood volume which appear to be primarily from the O₂heme signal. Resting oxygen levels calibrated with Heme agrees with theoretical oxygen saturation.

Data on the seasonally dry tropical forests of Mexico have been examined in the light of statistical mechanics. The results suggest a division into two classes of species. There are drifting populations of a cosmopolitan class capable of existing in most dry forest sites; these have a statistical distribution previously only observed (globally) for populations of alien species. A high proportion of species found only at a single site are endemic and these prefer sites comparatively low in species richness.

In this review paper, we present a pellucid proof of how x tanh(x/µ) approximates |x|and is better than √x² +µ  when we are concernedwith accuracy.

Analysis of the hourly Canadian Prairie data for the past 60 years has transformed our quantitative understanding of land-atmosphere-cloud coupling. The key reason is that trained observers made hourly estimates of opaque cloud fraction that obscures the sun, moon or stars, following the same protocol for 60 years at all stations. These 24 daily estimates of opaque cloud data are of sufficient quality that they can be calibrated against Baseline Surface Radiation Network data to give the climatology of the daily short-wave, longwave and total cloud forcing (SWCF, LWCF and CF). This key radiative forcing has not been available previously for climate datasets. Net cloud radiative forcing reverses sign from negative in the warm season to positive in the cold season, when reflective snow reduces the negative SWCF below the positive LWCF. This in turn leads to a large climate discontinuity with snow cover, with a systematic cooling of 10°C or more with snow cover. In addition, snow cover transforms the coupling between cloud cover and the diurnal range of temperature. In the warm season, maximum temperature increases with decreasing cloud, while minimum temperature barely changes; while in the cold season with snow cover, maximum temperature decreases with decreasing cloud and minimum temperature decreases even more. In the warm season, the diurnal ranges of temperature, relative humidity, equivalent potential temperature and the pressure height of the lifting condensation level are all tightly coupled to opaque cloud cover. Given over 600 station-years of hourly data, we are able to extract, perhaps for the first time, the coupling between cloud forcing and the warm season imbalance of the diurnal cycle; which changes monotonically from a warming and drying under clear skies to a cooling and moistening under cloudy skies with precipitation. Because we have the daily cloud radiative forci, which is large, we are able to show that the memory of water storage anomalies, from precipitation and the snowpack, goes back many months. The spring climatology shows the memory of snowfall back through the entire winter, and the memory in summer goes back to the months of snowmelt. Lagged precipitation anomalies modify the thermodynamic coupling of the diurnal cycle to the cloud forcing, and shift the diurnal cycle of mixing ratio which has a double peak. The seasonal extraction of the surface total water storage is a large damping of the interannual variability of precipitation anomalies in the growing season. The large land-use change from summer fallow to intensive cropping, which peaked in the early 1990s, has led to a coupled climate response that has cooled and moistened the growing season, lowering cloud-base, increasing equivalent potential temperature, and increasing precipitation. We show a simplified energy balance of the Prairies during the growing season and its dependence on reflective cloud.

The dietary pattern that characterizes the Western diet is strongly associated with obesity and related metabolic diseases, but biological mechanisms supporting these associations remain largely unknown. We argue that the Western diet promotes inflammation that arises from both structural and behavioral changes in the resident microbiome. The environment created in the gut by ultra-processed foods, a hallmark of the Western diet, is an evolutionarily unique selection ground for microbes that can promote diverse forms of inflammatory disease. Recognizing the importance of the microbiome in the development of diet-related disease has implications for future research, public dietary advice as well as food production practices. Research into food patterns suggests that whole foods are a common denominator of diets associated with a low level of diet-related disease. Hence, by studying how ultra-processing changes the properties of whole foods and how these foods affect the gut microbiome, more useful dietary guidelines can be made. Innovations in food production should be focusing on enabling health in the super-organism of man and microbe, and stronger regulation of potentially hazardous components of food products is warranted.

A low-cost data logging platform is presented for environmental monitoring projects that provides long-term operation in remote or submerged environments. Three premade “breakout boards” from the open-source Arduino ecosystem are assembled into the core of the platform. The components are selected based on low-cost and ready availability, making the loggers easy to build and modify without specialized tools, or a significant background in electronics. Power optimization techniques are explained. The platform has proven to be highly reliable, and capable of operating for more than a year on standard AA batteries. The flexibility of the system is illustrated with two ongoing field studies recording drip rates in a cave, and water flow in a flooded cave system.

Many species of plants are found in regions to which they are alien. Their global distributions are characterised by a family of exponential functions of the kind that arise in elementary statistical mechanics (an example in ecology is MacArthur's broken stick). We show here that all these functions are quantitatively reproduced by a model containing a single parameter – some global resource partitioned at random on the two axes of species number and site number. A dynamical model generating this equilibrium is a two fold stochastic process and suggests a curious and interesting biological interpretation in terms of niche structures fluctuating with time and productivity; with sites and species highly idiosyncratic. Idiosyncrasy implies that attempts to identify a priori those species likely to become naturalized are unlikely to be successful. Although this paper is primarily concerned with a particular problem in population biology, the two fold stochastic process may be of more general interest.

Abstract: The study focuses on how socio-economic and demographic indicators affect fertilization sustainability (excessive amount of fertilization). Principally we aim to examine the significance magnitude of the effects of three socio-demographic variables such as traditional way of fertilization, rental land farming, and farmers’ younger age on over-fertilization in Bangladesh and other developing countries. In 1960s, Bangladesh state authority launched a campaign ‘Grow more Food’ to feed huge numbers of population and thus the farmers are provided chemical fertilizers and pesticides at a subsidized low price. Farmers began to use huge amount of fertilizers for gaining high yields and continued it to present causing environmental woes a lot. We interview (face-to-face, focus group discussion, and phone interview) 210 Bangladesh farmers in 2016 by semi-structured questionnaire. Data has been analyzed using General Linear Model (GLM) in Univariate Analysis of Variance. The study found the effect of traditional way of fertilization on excessive amount of fertilization is strongly significant at 1% level. Apart from, rental land farming and farmers’ younger age have a significant influence on over- fertilization; though their significance level (5% and 10% respectively) is quasi-strong. Policy makers can be able to formulate fertilizer policy on the basis of these findings.

Three different populations of sulfated polysaccharides can be found in the cell wall of the red alga Botryocladia occidentalis. In a previous work, the structures of the two more sulfated polysaccharides were revised. In this work, NMR-based structural analysis was performed on the least sulfated polysaccharide and its chemically modified derivatives. Results have revealed the presence of both 4-linked α- and 3-linked β-galactose units having the following chemical features: more than half of the total galactose units are not sulfated, the α-units occur primarily as 3,6-anhydro-galactose units either 2-O-methylated or 2-O-sulfated, and the β-galactose units can be 4-O-sulfated or 2,4-O-disulfated. SPR-based results indicated weaker binding of the least sulfated galactan to thrombin, factor Xa, and antithrombin, but stronger binding to heparin cofactor II than unfractionated heparin. This report together with our previous publication completes the structural characterization of the three polysaccharides found in the cell wall of the red alga B. occidentalis and correlates the impact of their composing chemical groups with the levels of interaction with the blood co-factors.

Abiotic stresses, including drought, salinity, cold, heat, and heavy metals, extensively reduce global agricultural production. Approaches such as conventional breeding and transgenic breeding have been widely used to cope with these environmental stresses. The clustered regularly interspaced short palindromic repeat- Cas (CRISPR/Cas) based gene-editing tool has revolutionized due to its simplicity, accessibility, adaptability, flexibility, and wide applicability. This system has a great potential to build up crop varieties with enhanced tolerance against abiotic stresses. In this review, we summarize the most recent findings on understanding the mechanism of abiotic stress response in plants and the application of CRISPR/Cas mediated gene-editing system towards enhanced tolerance to drought, salinity, cold, heat, and heavy metals stresses. Furthermore, in this review, we highlighted the recent advancements in prime editing and base editing tools for crop improvement.

The genus Fritillaria belongs to the widely distributed family Liliaceae. The bulbs of Fritillaria ussuriensis and Fritillaria cirrhosa are valuable herbaceous medicinal ingredients. However, they are still used indiscriminately in herbal medicine. Identification and molecular phylogenic analysis of Fritillaria species is therefore required. Here, we report the complete chloroplast (cp) genome sequences of F. ussuriensis and F. cirrhosa. The two Fritillaria cp genomes were 151,524 and 151,083 bp in length, respectively, including a pair of inverted repeat regions (52,678 and 52,156 bp) separated by a large single copy region (81,732 and 81,390 bp) and small single copy region (17,114 and 17,537 bp). A total of 111 genes in F. ussuriensis and 112 in F. cirrhosa comprised 77 protein-coding genes in F. ussuriensis and 78 in F. cirrhosa, 30 tRNA genes, and four rRNA genes. The gene order, content, and orientation of the two Fritillaria cp genomes exhibited the general structure of flowering plants, and were similar to those of other Fritillaria species. Comparison of the six Fritillaria species’ cp genomes indicated seven highly divergent regions in intergenic spacers and in the matK, rpoC1, rpoC2, ycf1, ycf2, ndhD, and ndhF coding regions. We established the position of the six species through phylogenic analysis. The complete chloroplast genome sequences of two Fritillaria species will be useful genomics resources for identification of Fritillaria species and for studying the phylogenetic relationship among Fritillaria species within the Liliaceae family.

The new diprotic ligand 3,5-di-tert-butylsalicylaldehyde 4-ethyl-3-thiosemicarbazone, abbreviated H2(3,5-t-Bu2)-sal4eT, exists as the thio-keto tautomer and adopts the E-configuration with respect to the imine double bond as evidenced by single-crystal X-ray analysis and corroborated by spectroscopic characterisation. Upon treatment with Cu(OAc)2·H2O in the presence of either 2,9-dimethyl-1,10-phenanthroline (2,9-Me2-phen) or 1,10-phenanthroline (phen) as a co-ligand in MeOH, this thiosemicarbazone undergoes conformational transformation (relative donor-atom orientations: syn,anti → syn,syn) concomitantly with tautomerization and double deprotonation to afford the ternary copper(II) complexes [Cu{(3,5-t-Bu2)-sal4eT}(2,9-Me2-phen)] (1) and [Cu2{3,5-t-Bu2)-sal4eT}2(phen)] (2). Crystallographic elucidation has revealed that complex 1 is a centrosymmetric dimer of mononuclear copper(II) complex molecules brought about by intermolecular H-bonding. The coordination geometry at the copper(II) centre is best described as distorted square pyramidal in accord with the trigonality index (τ = 0.14). The co-ligand adopts an axial-equatorial coordination mode; hence there is a disparity between its two Cu–N coordinate bonds arising from weakening of the apical one as a consequence of the tetragonal distortion. The axial X-band ESR spectrum of complex 1 is consistent with retention of this structure in solution. Complex 2 is a centrosymmetric dimer of dinuclear copper(II) complex molecules exhibiting intermolecular H-bonding and π-π-stacking interactions. The two copper(II) centres, which are 4.8067(18) Å apart and bridged by the thio-enolate nitrogen of the quadridentate thiosemicarbazonate ligand, display two different coordination geometries, one distorted square planar (τ4 = 0.082) and the other distorted square pyramidal (τ5 = 0.33). Such dinuclear copper(II) thiosemicarbazone complexes, which are crystallographically characterised, are extremely rare. In vitro, complexes 1 and 2 outperform cisplatin as antiproliferative agents in terms of potency and selectivity towards HeLa and MCF-7 cancer cell lines.

The climate crisis is developing to a life-changing event on a global level. Health promotion with the aim to increase the health status of individuals, independent from the present health status has been developed on scientific basis at least for the last eight decades and follows. There are some basic principles, which are prerequisites for both, health promotion and climate protection. Those principles include (1) sustainability, (2) orientation on determinants, and (3) requirement of in-dividual as well as community approaches. People are generally aiming to protect their lifestyle habits (e.g. traveling, consumer habits) and personal properties (e.g. car, house) by easy solution with as little effort as possible, and this can affect both, health and climate. To reduce the emission of greenhouse gases and to protect our environment, changes towards a sustainable lifestyle have to be embed into everybody’s mind. Examples for domains, that need to be addressed in health promotion as well as in climate protection include education/ knowledge/ (health) literacy, physical activity, nutrition and dietary habits, mental health, and social capital. If health promo-tion fails to tackle those domains, this will continue to drive climate crisis. And climate change, in turn, will affect health. On the other hand, developing and promoting health resources in the domains mentioned could again help to mitigate the health-damaging effects of climate change.

In the contemporary era, there has been a notable surge in the systematic utilization of therapeutic drugs that exhibit stimulus-responsive drug release patterns in specific target areas. However, challenges such as premature drug release and limited biocompatibility persist. To address these issues, the application of a lipid coating on mesoporous silica nanoparticles (MSNs) has emerged as a promising strategy. This lipid coating not only enhances the stability and biocompatibility of nanocarriers but also facilitates targeted drug delivery to diseased cells while minimizing drug release throughout the body. MSNs, renowned for their unique attributes including high porosity, morphology, and controllable pore size, have been widely recognized as suitable platforms for drug/gene delivery systems. Furthermore, graphene-based nanomaterials such as graphene oxide and reduced graphene oxide have garnered significant interest in the fields of biology and biomedicine. These materials possess exceptional characteristics such as a large surface area, distinct surface properties, high biocompatibility, and pH sensitivity, making them ideal candidates for incorporating drugs, genes, photosensitizers, and other cargo to design innovative drug delivery systems. This study aims to emphasize the ongoing efforts and advancements in enhancing the capacity and versatility of nanocomposites comprising graphene MSN composites for applications in drug delivery.

Heartland virus (HRTV) is an emerging tick-borne bandavirus that is capable of causing severe disease characterized by acute thrombocytopenia and lymphopenia. The virus is endemic to the eastern United States, and is carried by the Lone Star tick (Amblyomma americanum). Since its discovery in 2009, at least 60 human infections have been recorded across this area, with an overall 5-10\% estimated mortality rate. All infections reported thus far have occurred following a known tick bite or exposure to tick-infested areas, but the possibility of nosocomial transmission has not been ruled out. Despite relatively high rates of seroprevalence among certain wildlife species such as white-tailed deer, the reservoir species for HRTV remains unknown, as the virus has never been isolated from any mammalian wildlife species. Furthermore, how the virus is transmitted to its vector species in nature remains unknown, though laboratory studies have confirmed both horizontal and vertical transmission of HRTV in A. americanum. In addition, the recent 2017 introduction of the Asian longhorned tick (Haemaphysalis longicornis) to the US has raised concerns about possible spillover of HRTV into a new tick species that has been confirmed to be a competent vector for HRTV in the laboratory. Thus, an increased awareness of its clinical presentation is needed, and further research is urgently required to establish the natural transmission cycle and develop new countermeasures for this novel zoonotic pathogen

The purpose of this research was to examine the act of business schools in the Palestinian universities by their study plans in achieving sustainable development goals (SDGs) (G1, G4, G8, G9, G12, G16, G17), due to their strong relationship with business sector in the local market, in addition to examining whether the graduates of business schools have the required competencies and required skills for the local market. This research is descriptive in nature and a survey questionnaire was designed to collect data from faculty members and employers. The results indicate that business schools in the Palestinian universities have incorporated sustainable development goals in their study plans to a medium-to-high degree, with a higher emphasis on Quality Education. Graduates from these programs are perceived to possess the required competencies and skills by the employers in the local market, with a medium-to-high level of alignment with the SDGs, especially in the area Quality Education. There was no significant difference between the perceptions of university faculty members and employers in the local market regarding the fit of business school graduates' competencies and skills with the local market needs in relation to the SDGs. However, there were significant differences in the areas of accountability and transparency principles, economic and industrial challenges, partnerships for the goals, international standardization, and capacity building in operational expertise. It is recommended that business schools in Palestinian universities continue to prioritize the integration of sustainable development goals in their study plans and align the competencies and skills of their graduates with the needs of the local market. The areas of significant difference between university faculty members and employers in the local market present opportunities for further collaboration and dialogue to better meet the needs of the local market and achieve sustainable development goals.

In this study, machine learning was used to predict and analyze the behavior of occupants in Gifu City residences during winter. Global warming is currently progressing worldwide, and it is important to control greenhouse gas emissions from the perspective of adaptation and mitigation. Occupant behavior is highly individualized and must be analyzed to accurately determine a building's energy consumption. The accuracy of heating behavior prediction has been studied using three different methods: logistic regression, support vector machine (SVM), and deep neural network (DNN). The generalization ability of the support vector machine and the deep neural network was improved by parameter tuning. Parameter tuning of the SVM showed that the values of C and gamma affected the prediction accuracy. The prediction accuracy improved by approximately 11.9 %, confirming the effectiveness of parameter tuning on SVM. Parameter tuning of the DNN showed that the values of layer and neuron affected the prediction accuracy. Although parameter tuning also improved the prediction accuracy of DNN, and the rate of increase was lower than that of SVM.

Evaluation of market connectedness and asymmetric volatility spillover has recently seen a surge in financial risk analytics and portfolio diversification. We carried out a meta-literature review on connectedness and spillovers, providing solid insight into the research field and robust guidelines for future investigation. The review consists of a quantitative bibliometric analysis of 594 papers and a qualitative content analysis of 77 papers covering 1991 to 2021. The results of the meta-citation analysis shows that Diebold's Spillover index (2007) is the predominant method in most works as far as market connectedness and spillover is concerned. With an extensive review, we answered the following objectives (1) Analyze the most influential authors, journals, and publications, (2) Understand the research streams and most studied streams, (3) Understand the theme structure and thematic evolution, and keyword trends, (4) Examine the pattern of collaboration, and most productive affiliations, (5) Explore future research directions and untapped areas. The content analysis revealed the following important research streams in the current literature (1) Asymmetries in the market connectedness, (2) Influence of Macro Factors in the market connectedness and spillover, (3) the Role of Oil in market spillovers and hedging portfolios, (4) Dynamic cross-market connectedness and spillovers. The ongoing financial turmoil and market advancements make market connectedness a vital research topic; thus, our work would significantly contribute to macroeconomic policymakers, researchers and hedging investors.

Satellite-based broad-scale (i.e., global and continental) human settlement data offer foundational information for diverse applications spanning climate hazard mitigation, sustainable development monitoring, spatial epidemiology, and demographic modeling. While many human settlement products report exceptional detection accuracies above 85%, there is a substantial blind spot in that product validation is typically centered on large urban areas rather than rural, small-scale settlements that are home to 3.4 billion people. In this study, we make use of a data-rich collection of 30 refugee settlements in Uganda to produce a targeted assessment of small-scale settlement detection by four broad-scale human settlement products: Global Human Settlements Built-Up Sentinel-2 (GHS-BUILT-S2), World Settlement Footprint (WSF), High Resolution Settlement Layer (HRSL), and Geo-Referenced Infrastructure and Demographic Data for Development (GRID3). We measured each product’s areal coverage within refugee settlements, assessed product detection accuracies in comparison to an independent dataset of 317,416 refugee settlement building footprints, and examined agreement between products. For refugee settlements established before 2016, the human settlement products had a low median F1-Score (F1) of 0.24, a high median false alarm rate of 0.59, and tended to only agree at locations of highest building density. Individually, WSF entirely overlooked 8 of the 30 study refugee settlements (median F1=0.17); GHS-BUILT-S2 underestimated the building footprint area by a median 50% (F1=0.15); GRID3 overestimated the building footprint area by a median 280% (F1=0.38); and HRSL underestimated the median area by 7% (F1=0.34). All products suffer from low detection accuracy and high false alarm rates, but GRID3 and HRSL, based on 0.5 meter resolution imagery, offer better detection accuracy than GHS-BUILT S2 and WSF, which are based on 10-30 meter resolution imagery. These results show that human settlement products have far to go in providing an accurate depiction of small-scale refugee settlements and would benefit from incorporating refugee settlements in training and validation of broad-scale human settlement detection.

There is little understanding of patients' experiences and perceptions with satisfaction by health professionals such as medical and dental clinicians. Furthermore, patient satisfaction is not well understood. The objective of this article is to better understand patients' satisfaction with their medical and dental care. The methods of the current article are based on a narrative review of the literature strategy. Patient satisfaction's multidimensional nature has been established since the perceived reasons for satisfaction varied widely among patients. Many aspects of the treatment influence participant satisfaction at different stages of the intervention's process. An improved understanding of the basis for managing patients' expectations with information reiteratively and efficiently may ultimately reduce patients' potential for negative feelings toward the medical and dental treatment experience. The consumerist method may misrepresent the concept of satisfaction in health service.

In this article, the effect of substitution of Zr and Ga in Dy2Fe17 prepared by arc melting technique are studied. The substitution of Zr and Ga in Dy2Fe17 was found to have an important effect on their structure and magnetic properties. The Rietveld analysis conformed that the crystalline system wereTh2Ni17 structure. Lattice parameters a (Å) and c (Å), unit cell volume (Å3), bonding distance (Å) were calculated by using Rietveld analysis. The unit cell volume of Dy2Fe17-xZrx and Dy2Fe16Ga1-xZrx increase linearly with the Zr and Ga substitution. The substitution of Zr and Ga are limited up to x=1 in order to avoid the decrease in saturation magnetization. The Curie temperature (Tc) of Dy2Fe17-xZrx and Dy2Fe16Ga1-xZrx are found to be Zr content dependent. The Curie temperature is found to be increasing first and then decrease for higher Zr content. The maximum curie temperature was observed 510K at x = 0.75 for Dy2Fe17-xZrx and 505.1 K at x = 0.5 for Dy2Fe17-xZrx which are102 K and 97 K higher than Dy2Fe17. The room temperature Mössbauer analysis shows the decrease in average hyperfine field and increase in isomer shift with Zr doping.

The impact of snow darkening by deposition of light absorbing aerosols (LAAs) on snow cover over the Himalaya-Tibetan-Plateau (HTP) and influence on the Asian monsoon are investigated using the NASA Goddard Earth Observing System Model Version 5 (GEOS-5). We find that during April-May-June, deposition of LAAs on snow leads to a reduction in surface albedo, initiating a sequence of feedback processes, starting with increased surface solar radiation, rapid snowmelt in HTP and warming of the surface and upper troposphere, followed by enhanced low-level southwesterlies and increased dust loading over the Himalayas-Indo-Gangetic Plain. The warming is amplified by increased dust aerosol heating, and subsequently amplified by latent heating from enhanced precipitation over the Himalaya foothills and northern India, via the Elevated Heat Pump (EHP) effect during June-July-August. The reduced snow cover in the HTP anchors the enhanced heating over the Tibetan Plateau and its southern slopes, in conjunction with an enhancement of the Tibetan Anticyclone, and the development of an anomalous Rossby wavetrain over East Asia, leading to weakening of the subtropical westerly jet, and northward displacement and intensification of the Mei-Yu rainbelt. Our results suggest that atmosphere-land heating by LAAs, particularly desert dust play a fundamental role in physical processes underpinning the snow-monsoon relationship proposed by Blandford more than a century ago.

A robust hydrological assessment is challenging in regions where human interference, within all aspects of the hydrological system, significantly alters the flow regime of rivers. The challenge was to extend a large-scale water resources model, GWAVA, to better represent water resources without increasing the model complexity. A groundwater and a regulated reservoir routine were incorporated into GWAVA using modifications of the existing AMBHAS-1D and Hanasaki methodologies, respectively. The groundwater routine can be varied in complexity when sufficient input data is available but fundamentally is driven by three input parameters. The reservoir routine was extended to account for the presence of large, regulated reservoirs using two calibratable parameters. The additional groundwater processes and reservoir regulation was tested in two highly anthropogenically influenced basins in India: the Cauvery and Narmada. The inclusion of the revised groundwater routine improved the simulation of streamflow in the headwater catchments and was successful in improving the representation of the baseflow component. In addition, the model was able to produce a time series of daily groundwater levels, recharge to groundwater and groundwater abstraction. The regulated reservoir routine improved the simulation of streamflow in catchments downstream of major reservoirs, where the streamflow was largely reflective of reservoir releases, when calibrated using downstream observed streamflow records. The model was able to provide a more robust representation of the annual volume and daily outflow released from the major reservoirs and simulate the major reservoir storages adequately. The addition of one-dimensional groundwater processes and a regulated reservoir routine proved successful in improving the model performance and traceability of water balance components, without excessively increasing the model complexity and input data requirements.

We review time expansion wave theory and refine our model showing it to accurately match observed cosmological luminosity data. The theory augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension that we observe as the expansion of the universe. This leads us to explain mass creation, the speed of light limit, gravity, black holes without singularities and other macroscopic effects. Our model leads to an expansion velocity of 6.87 0.36 × 106 ms-1, which results in a Hubble expansion rate constant of 71.3 3.7 km/s/Mpc. Because of the finite window of time in which we exist, an extra a degree of freedom is available leading to interesting interpretations at the subatomic level. At this size range, then a spin is allowed within the time dimension explaining why wave particle duality occurs and explains the electromagnetic force and other quantum mechanical properties. It provides a solution to the double slit conundrum and can explain how quantum entangled partners can behave in a quantum way and pass seemingly time-defying information. The potential quantitative origin of the fine structure constant which governs the size of the electromagnetic force is also strongly indicated by this theory.

Herpesviruses produce a plethora of pleomorphic and heterogeneous particle populations. The composition and biological role of these is not understood. Detailed analysis has been challenging due to the lack of multidimensional identification and purification methodologies. Fluorescence-activated cell sorting (FACS), originally developed to sort objects with at least ten thousand-fold larger volumes, has recently been applied to cellular exosomes as well as viral particles and has been dubbed nanoscale flow cytometry or “flow virometry”. In comparison to other nanoparticles, herpesvirus concentrations can be measured with high precision using simple culturing methods. Here, we used this unique capability to evaluate a standard FACS sorter. We demonstrate that detection and separation capabilities were insufficient to distinguish infectious fluorescent viral populations from populations lacking fluorescence and infectivity. Moreover, fluorescent populations did not contain single virus particles but mostly aggregates. On top, analysis of viral samples by flow cytometry was confounded by swarm detection, as multiple objects are measured simultaneously and interpreted as a single object. Despite these technical difficulties, comparison of crude supernatant to gradient purified HCMV revealed that infectious virus is a minor proportion of the particles released from infected cells. Our data stress the need for a set of standardized controls and protocols when applying FACS to biological nanoparticles and highlights technical challenges that need to be solved before flow virometry can achieve its full potential.

The government of Nepal (GoN) has developed and implemented climate policies, plans and frameworks such as NAPA, National Climate Change Policy, LAPA and currently in the process of developing National Adaptation Plans (NAPs). These policies and plans are in different states of its implementation with diverse opinions and perceptions of the stakeholders. The paper has explored these opinions and experiences of climate experts in Nepal on state of climate policies, inter-linkages, roles and responsibilities of ministries/departments, important factors and subjective indicators for effective implementation of the policies. Altogether 30 experts responded the questionnaire sent via the email, LinkedIn and Skype Interview in the 1^st phase of Delphi research technique. The experiences of these experts range from 2-30 years representing government, non-government sectors, media and independent experts. As per most of the experts interviewed, the policies and plans are progressing in strategic direction with national and local priorities. The LAPA is the pioneer framework to address the local climatic issues, originated in Nepal. However, lack of clarity on roles/responsibilities and coordination among the ministries/departments; clear mechanisms for implementation of these policies; lack of sensitization, decentralization and delegation of finance and technologies; capacity of the stakeholders are the major challenges identified.

Metabolomics profiling for accurate and reliable quantification of organic acids that carry a carboxylic acid functional group in complex biological samples, remains a major analytical challenge in clinical chemistry research. Several procedural barriers associated with quantification of clinically important carboxylic containing metabolites (CCMs) including spontaneous decarboxylation during ionization, poor chromatographic resolution, and retention on a reverse-phase column, limit the sensitivity, specificity, and reproducibility of multiple-reaction monitoring (MRM) based LC-MS assay development. We report a targeted metabolomics-based analytical method for the quantification of CCMs using phenylenediamine derivatization. Accurate and sensitive quantification of CCMs is successfully demonstrated in an array of biological matrices. Recovery of metabolites from different matrices (plasma, serum, urine, saliva, tissues, and cell extracts), ranged from 90% to 105%, with all the CVs ≤ 10%. The method showed linearity over a broad dynamic range from 0.1 ng/mL to 10 µg/mL with linear regression coefficients of 0.99 for most of the metabolites tested herein, that covers broad-based applicability with the analysis of biological samples. In most cases the LODs were as low as 0.01 ng/mL. The phenylenediamine-based derivatization of carboxyl acid library consisting of more than 70 endogenous metabolites was constructed for metabolite identification, which spanned more than 40 biological pathways. The library included a wide-variety of structurally variant CCMs such as amino acids/conjugates, short to medium chain organic acids, di/tri-carboxylic acids/conjugates, fatty acids and some ring-containing CCMs. We compared the CCMs profiles of pancreatic cancer cells with normal pancreatic epithelial cells to test and validate the biological utility of this method. The comparative profiling between cancerous and normal cells resulted in the identification of potential biomarkers in pancreatic cancer, and their correlation with several key metabolic pathways such as central carbon energy metabolism, protein metabolism, including TCA cycle, glycolysis, Gln-Glu pathway, and biosynthesis of amino acids and unsaturated fatty acids was established. The method, described herein, for the first time enables the sensitive and highly specific quantification of CCMs on small sample size with high reproducibility in a high throughput manner. Given the biological and functional significance of this class of metabolites, this mass spectrometry based targeted quantitative assay, fills an important gap and is likely to support a wide range of applications for basic, clinical, and translational research.

Permeability is an important transport property of porous materials, and its accurate evaluation is relevant in studying applied tasks such as CO2 injection into reservoirs and investigating groundwater quality issues. This study examines the dependence of permeability on total and connected porosity, hydraulic tortuosity, specific surface area, and mean pore radius based on the data of 408 cubic sub-volumes extracted from heterogeneous and naturally fractured cylindrical carbonate samples before and after injection of HCl solutions into them. These parameters were computed using pore-scale modeling of fluid flow. It has been shown that permeability correlates well with porosity and mean pore radius with correlation coefficients of R2≈0.65-0.79 for heterogeneous samples. It was found that the presence of natural fractures significantly influenced the relationship between permeability and other parameters. The relationship between permeability k, tortuosity τ, and specific surface area S is described by power laws k~τ-α and k~S-β, with coefficients α and β substantially exceeding those in the Kozeny-Carman equation. It was also found that there is a parabolic relationship between connected and total porosities both before and after rock dissolution with R2≈0.96-0.99. This allowed for estimation of percolation threshold porosity that are in good agreement with the literature data.

Sleep-disordered breathing affects the growth and development, mental aspect, and learning ability of affected children. Postoperative scarring causes anteroposterior and vertical develop-mental disorders of the maxilla. Obstructive apnea is likely to occur due to the influence on the maxillofacial and airway morphology. In this study, we investigated the sleep-respiratory dynamics of school-aged children with unilateral cleft lip and palate by performing a simple over-night sleep study, maxillofacial morphology and airway analysis using lateral cranial radiographs, and model analysis. Children with unilateral cleft lip and palate showed a significantly higher respiratory event index (REI) than normal children; the maxilla was located in the posterior position in terms of maxillofacial morphology, and airway morphology showed narrow values for all distance measurement items. Moreover, the width and length of the dental arch and the width of the alveolar base arch were significantly smaller. Furthermore, there was a negative correlation between REI and SNA, ANB, REI, and alveolar base arch width. Children with unilateral cleft lip and palate are more likely than normal children to develop sleep-disordered breathing due to in-creased airway resistance caused by undergrowth of the maxilla and narrowing of the upper airway and oral volume.

The narrow process window during intercritical annealing and discontinuous yielding have limited the commercialisation of medium Mn steels. In this study, a double annealing process based on the commercial continuous annealing line is proposed. The cold-rolled medium Mn steels were first fully austenitized and quenched during the first annealing, followed by the intercritical annealing for reverted austenite transformation. The microstructure of duplex lath-shaped austenite and ferrite is produced and the steel exhibit a desirable continuous yielding during tensile deformation. Al is added into the medium Mn steel to enlarge the process window and to improve partitioning efficiency of Mn. The produced steel is more robust with temperature fluctuation during the industrial process due to the enlarged intercritical region. Mn partitioning is more efficient owing to elevated annealing temperature, which results in the improvement of ductility in the Al-added steel with increased austenite stability.

COVID-19, a contagious disease caused by the novel coronavirus SARS-CoV-2, emerged in 2019 and quickly became a pandemic, infecting more than 700 million people worldwide. The disease incidence, morbidity and mortality rates have started to decline since the development of effective vaccines against the virus and the widespread immunization of the population. SARS-CoV-2 vaccines are associated with minor local or systemic adverse reactions, while serious adverse effects are rare. Thyroid-related disorders have been reported after vaccination for COVID-19, and Graves’ disease (GD) is the second most common amongst them. Thyroid eye disease (TED), an extrathyroidal manifestation of GD is rarely observed post COVID-19 vaccination. All TED cases followed mRNA-based vaccinations, but two new onset mild TED cases post viral vector vaccine (ChAdox1nCoV-19) have also been reported. We report the case of a 63-year-old woman who presented with new onset hyperthyroidism and moderate-to-severe and active TED ten days after she received the first dose of a viral vector vaccine against SARS-CoV-2. This is the first case of moderate-to-severe TED after such a vaccine. Our patient was initially treated with intravenous glucocorticoids and subsequently with intravenous rituximab, due to no response. The disease was rendered inactive after rituximab, but constant diplopia persisted, and the patient was referred for rehabilitative surgery.

Real time condition monitoring and precision health assessment system is a mandatory need for effective maintenance program in industrial sector. Rapid advancement in the information technology and other engineering technologies have invited more proactive attention from research and development in industrial sectors and particularly in condition monitoring of machines and related Industrial processes. In this work, the drill bit condition monitoring techniques have been developed based on the wavelet analysis and artificial neural network (ANN) as automatic drill bit fault detection and classification. An experimental work has been conducted to capture the vibration signals for analysis. In this experiment, the CNC drill machine is used with high carbon steel drill bit and mild steel material as work piece. The cutting condition parameters are kept constant and the wear level is changed. The Data Acquisition system (DAQ) with Lab VIEW software is used to capture the vibration signals for drill bit with different wear conditions. The captured vibrations data are analyzed using continuous wavelet transform (CWT) with Morlet wavelet and Daubechies wavelet as a prime function. In general, the CWT coefficient is used to generate the inputs features to ANN for automatic tool condition classification, with two outputs (0, 1) for healthy and (1, 0) for faulty. The results show the effectiveness of the combed WT and ANN for automatic classification of tool wear conditions with high success rate.

Groundwater is an important role of the environment in natural resources. The major sources of groundwater contamination in this study were open discharges of domestic sewage, inadequate sewerage system, open defecation, septic tanks, soak pits, contaminated water pools, unorganized solid waste dumping and use of fertilizers, pesticides for agriculture deteriorated the condition. In this present study revealed that the physical and chemical characteristics of ground water in different areas of Kannur district in Kerala have been determined different seasons with respect to its suitability for drinking and agricultural purposes. For this study the groundwater samples were collected during pre-monsoon and post-monsoon seasons from 70 wells representing the entire the study area. The groundwater samples were analyzed for Physico-chemical characteristics using standard techniques in laboratory and compared with standards. The samples were analyzed with reference to the WHO and BIS standards. The groundwater quality information of the entire study area have been prepared using statistical and GIS technique for all the parameters. This paper proved in GIS will be helpful for measuring, monitoring and managing the groundwater pollution in the study area and suggested to protect groundwater resources in the environment.

Ionizing radiation exposure is known to induce molecular and cellular injury, inflicting a cascade of potentially catastrophic events leading to tissue and organ damage. Metabolomic analysis allows for the identification and quantification of small molecules downstream of genomic changes induced by radiation exposure. We aimed to characterize metabolomic changes that underscore the prefinal stage of lethally irradiated rhesus nonhuman primates (NHPs). Peripheral blood was drawn at baseline, post-exposure as well as at the preterminal stage of NHPs (immediately prior to death in moribund NHPs), which did not survive exposure with 7.2 Gy total-body radiation (LD70/60). Herein, we analyzed global metabolomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in plasma samples of NHPs collected at various timepoints in relation to irradiation. The overall goal was to identify metabolic shifts present immediately prior to death. Our findings, for the first time, show that radiation induced significant time dependent metabolic perturbations when compared to pre-irradiation samples, particularly in the glycerophospholipid metabolism and steroid hormone biosynthesis and metabolism pathways. These findings provide valuable insights for identifying biomarkers for lethality, which may be helpful for triage during a mass casualty scenario.

Neuronal cell fate is predominantly controlled by the effects of growth factors, such as neurotrophins, and the activation of a variety of signaling pathways acting through neurotrophin receptors, namely Trk and p75 (p75NTR). Despite their beneficial effects on brain function, their therapeutic use is compromised, due to their polypeptidic nature and blood–brain-barrier impermeability. To overcome these limitations, our previous studies have proven that DHEA-derived synthetic analogs can act like neurotrophins, lacking endocrine side effects. The present study focuses on the biological characterization of a newly synthesized analog, ENT-A044, and its role on inducing cell specific functions of p75NTR. We show that ENT-A044 can induce cell death and phosphorylation of JNK protein by activating p75NTR. Additionally, ENT-A044 can induce the phosphorylation of TrkB receptor, indicating that our molecule can activate both neurotrophin receptors, leading towards the protection of neuronal populations that express both receptors. Furthermore, the present study demonstrates for the first time the expression of p75NTR in human induced Pluripotent Stem Cells - derived Neural Progenitor Cells (hiPSCs - derived NPCs) and receptor-dependent cell death induced by ENT-A044 treatment. In conclusion, ENT-A044 could be proven a lead molecule for the development of novel pharmacological agents, aiming on new therapeutic approaches and research tools, by controlling p75NTR actions.

There are potential overlapping distributions of the protozoan parasite Leishmania and the parasitic helminth Schistosoma mansoni in eastern Africa most notably in endemic regions in the Sudan and Kenya. In murine model studies, the Th₁-Th₂ model of CD4+ T helper cell differentiation is a well-established paradigm for understanding the basis of protective versus pathogenic immune responses in the concomitance state that result in enhanced pathological changes and impaired parasite resolution. In complementation to the experimental studies, the concern for presages of human leishmaniases and schistosomiasis co-infections occurring is increased by their chronicity, displacement of people between endemic areas owing to conflict, climatic changes due to human activities, the spread through irrigation, pisciculture, water conservation schemes and human mobility in pursuit of economic dynamics and resources. Based on diseases prevalence, epidemiology and analyzing the associated risk factors undercurrents, several portents of comorbidity in Kenya are pinpointed. Taking into consideration the limited local resources and diminished surveillance of the areas affected by the two neglected tropical diseases, the discourse concludes that elimination of the diseases is still a challenge. There is need for pilot studies and/or elaborate field surveillance of concomitance and development strategies to mitigate the impending defy in Kenya and beyond.

Globally, an approximate of 380,000 patients succumbed to death due to the pandemic COVID-19 which also infected more than six million people since December 2019. Not sparing anyone, COVID-19 infections are widely reported among healthcare professionals, sanitation workers and researchers too while global leaders and various governments are providing their best in defending their citizens against this airborne and contact spread virus. In order to contain the virus and protect millions of lives from this deadly coronavirus, there is a need to have a combination of advanced engineering technology and medical facilities. Application of applied science, engineering and technology diffuse almost every aspect of contemporary living. Grasping the fundamentals to determine humanity's most imperative and forthcoming challenges is essential. Artificial Intelligence, the technology that learns, adapts and reciprocates the actions according to the situations, finds optimum position in the fight against corona virus and acts as a powerful tool against this pandemic. In this research article, the authors discusses how Artificial Intelligence (AI) can be leveraged to fight the deadly virus. The research paper further discusses the efficient utilization of AI across the globe to help in testing, treating and serving the population in these hard times. This manuscript focuses on the potential impact of the process in which AI can be implemented to prevent, test and treat.

Nanoporous membranes promise energy-efficient water desalination. Hexagonal boron nitride (h-BN), like graphene, exhibits outstanding physical and chemical properties, making it a promising candidate for water treatment. We employed Car–Parrinello molecular dynamics simulations to establish accurate modeling of Na+ and Cl- permeation through hydrogen passivated nanopores in graphene and h-BN membranes. In these complex systems the classical potentials cannot properly account for the physics at play. We demonstrate that ion separation works well for the h-BN by imposing a barrier of 0.13 eV and 0.24 eV for Na+ and Cl- permeation respectively, compared to the graphene where the Cl- ion faces a negative barrier of 0.68 eV and is prone toward blockade and Na+ permeation is associated with a slightly negative barrier of 0.03 eV. From the change in the solvation shell, we get the following trend: Na/h-BN > Na/G > Cl/G > Cl/h-BN. We argue that the trend in the permeation barrier changes to Cl-h-BN > Na-h-BN > Na-G > Cl-G due to a combination of several interactions, including the distortion of the water network induced by the ions, the ion-water interaction, and the ion-nanopore interaction. Overall, the desalination performance of h-BN surpasses that of their graphene counterparts.

The signaling complex around voltage-gated sodium (Nav) channels includes accessory proteins and kinases crucial for regulating neuronal firing. Previous studies showed that one such kinase, WEE1—critical to the cell cycle—selectively modulates Nav1.2 channel activity through the accessory protein fibroblast growth factor 14 (FGF14). Here, we tested whether WEE1 exhibits crosstalk with the AKT/GSK3 pathway for coordinated regulation of FGF14/Nav1.2 channel complex assembly and function. Using the in-cell split luciferase complementation assay (LCA), we found that the WEE1 inhibitor II and GSK3 inhibitor XIII reduce FGF14/Nav1.2 complex formation, while the AKT inhibitor triciribine increases it. However, combining WEE1 inhibitor II with either one of the other two inhibitors abolished its effect on FGF14/Nav1.2 complex formation. Whole-cell voltage-clamp recordings of sodium currents (INa) in HEK293 cells co-expressing Nav1.2 channels and FGF14-GFP showed that WEE1 inhibitor II significantly suppresses peak INa density, both alone and in the presence of triciribine or GSK3 inhibitor XIII, despite the latter inhibitors’ opposite effects on INa. Additionally, WEE1 inhibitor II slowed the tau of fast inactivation, and caused depolarizing shifts in the voltage dependence of activation and inactivation. These phenotypes either prevailed or were additive when combined with triciribine but were outcompeted when both WEE1 inhibitor II and GSK3 inhibitor XIII were present. Concerted regulation by WEE1 inhibitor II, triciribine and GSK3 inhibitor XIII were also observed on long-term inactivation and use-dependence of Nav1.2 currents. Overall, these findings suggest a complex role for WEE1 kinase—in concert with the AKT/GSK3 pathway—in regulating the Nav1.2 channelosome.

The burden of chronic liver disease is globally increasing at an alarming rate. Chronic liver injury leads to liver inflammation and fibrosis (LF) as critical determinants of long-term outcomes such as cirrhosis, liver cancer and mortality. LF is a wound-healing process characterized by excessive deposition of extracellular matrix (ECM) proteins due to the activation of hepatic stellate cells (HSCs). In the healthy liver, quiescent HSCs metabolize and store retinoids. Upon fibrogenic activation, quiescent HSCs transdifferentiate into myofibroblasts, lose their vitamin A, upregulate -smooth muscle actin, and produce pro-inflammatory soluble mediators, collagens, and inhibitors of ECM degradation. Activated HSCs are the main effector cells during hepatic fibrogenesis. In addition, the accumulation and activation of profibrogenic macrophages in response to hepatocyte death play a critical role in the initiation of HSC activation and survival. The main source of myofibroblasts is resident HSCs. Activated HSCs migrate to the site of active fibrogenesis to initiate the formation of a fibrous scar. Single-cell technologies revealed that quiescent HSCs are highly homogenous, while activated HSCs/myofibroblasts are much more heterogeneous. The complex process of inflammation results from the response of various hepatic cells to hepatocellular death and inflammatory signals related to intrahepatic injury pathways or extrahepatic mediators. Inflammatory processes modulate fibrogenesis by activating HSCs and, in turn, drive immune mechanisms via cytokines and chemokines. Increasing evidence also suggests that cellular stress responses contribute to fibrogenesis. Recent data demonstrated that LF can revert even at advanced stages of cirrhosis if the underlying cause is eliminated, which inhibits the inflammatory and profibrogenic cells. However, despite numerous clinical studies on plausible drug candidates, an approved antifibrotic therapy still remains elusive. This state-of-the-art review presents cellular and molecular mechanisms involved in hepatic fibrogenesis and its resolution, as well as comprehensively discusses the drivers linking liver injury to chronic liver inflammation and LF.

The spread of fake news poses a serious threat to public trust and informed decision-making. The emergence of AI-generated fake news exacerbates this issue, as it can be produced more rapidly and convincingly than human-generated content. Addressing this issue, our paper introduces a robust approach to detect AI-generated fake news that is applicable across major disinformation domains: Politics and Elections, Health and Medicine, Science and Technology, and Entertainment and Celebrities. Our models differentiate between AI-generated and human-generated news articles while assessing their truthfulness. Utilizing large language models such as ChatGPT, we curated datasets spanning both AI and human generated fake and genuine news. Following extensive data preprocessing and the application of diverse feature extraction techniques, our models were trained using multiple machine learning algorithms. Our results show the feasibility of accurately identifying AI-generated fake news, thereby adding a significant layer of defense in combating misinformation across various sectors. In addition, we have explored the potential utility of transferable machine learning models trained on data from one domain (e.g., politics), when tested on another domain (e.g., health).

p-Toluenesulfonic acid is commercially available, non-toxic, cheap organic compound with robust stability. p-Toluenesulfonic acid is solid, non-corrosive and a strong organic acid that can be handled easily. Due to this p-toluenesulfonic acid could be the better replacement of other conventional acids like nitric acid, sulfuric acid, perchloric acid and AlCl3 in organic transformations. Moreover, p-toluenesulfonic acid could be used synergistically with other mode of catalysis like transition metal catalysis and photocatalysis. In recent years, the use of this solid organic acid in organic and polymer synthesis has grown tremendously. In this review, we present an overview of p-toluenesulfonic acid promoted various organic reactions with particular emphasis to the more recently reported methods. In some cases, we also detailed the understanding of the reactions by providing the reaction mechanism. Despite these advances, there are still many opportunities for the development of new reactions using PTSA. Industry and academia have become more conscious to adopt sustainable chemical processes using safer reagents and solvents and the use of PTSA in this context is highly significant. This review will inspire researchers for further reaction development employing p-toluenesulfonic acid.

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast and gastric cancers is an important target for monoclonal antibody (mAb) therapy. All therapeutic mAbs, including anti-HER2 mAbs, exhibit adverse effects probably due to the recognition of antigens expressed in normal cells. Therefore, tumor-selective or specific mAbs can be beneficial in reducing the adverse effects. In this study, we established a novel cancer-specific anti-HER2 antibody, named H₂Mab-250/H₂CasMab-2 (IgG₁, kappa). H₂Mab-250 reacted with HER2-positive breast cancer BT-474 and SK-BR-3 cells. Importantly, H₂Mab-250 did not react with non-transformed normal epithelial cells (HaCaT and MCF 10A) and immortalized normal epithelial cells in flow cytometry. In contrast, most anti-HER2 mAbs including H₂Mab-119 (IgG₁, kappa) reacted with both cancer and normal epithelial cells. Furthermore, a core-fucose deleted IgG_2a-type H₂Mab-250 (H₂Mab-250-mG_2a-f) could trigger the antibody-dependent cellular cytotoxicity activity to BT-474, but not to HaCaT cells. Furthermore, H₂Mab-250-mG_2a-f exhibited an in vivo antitumor effect against BT-474 xenograft. Immunohistochemical analysis demonstrated that H₂Mab-250 possesses much higher reactivity to the HER2-positive breast cancer tissues compared to H₂Mab-119, and did not react with normal tissues, including heart, breast, stomach, lung, colon, kidney, and esophagus. The epitope mapping demonstrated that the Trp614 of HER2 domain IV mainly contributes to the recognition by H₂Mab-250. H₂Mab-250 could contribute to the development of chimeric antigen receptor-T or antibody-drug conjugates without adverse effects for breast cancer therapy.

Video lectures are becoming more popular and in demand as online classroom teaching is becoming more prevalent. Massive Open Online Courses (MOOCs), such as NPTEL, have been creating high-quality educational content that is freely accessible to students online. A large number of colleges across the country are now using NPTEL videos in their classrooms. So more video lectures are being recorded, maintained, and uploaded. These videos generally contain information about that video before the lecture begins. We generally observe that these educational videos have metadata containing five to six attributes: Institute Name, Publisher Name, Department Name, Professor Name, Subject Name, and Topic Name. It would be easy to maintain these videos if we could organize them according to their categories. The indexing of these videos based on this information is beneficial for students all around the world to efficiently utilise these videos. In this project, we are trying to get the metadata information mentioned above from the video lectures.

Breast cancer is a serious disease and the second leading cause of cancer-related death among women in the U.S. New treatments for this aggressive disease are urgently needed. Repurposing FDA-approved drugs for cancer treatment is an alternative that saves time and lowers the costs needed for drug development. In this study, we investigated the effects of proguanil, an anti-malarial drug, in breast cancer cells. Proguanil exhibited a significant cytotoxic effect on breast cancer cell lines including patient derived cell lines. Proguanil caused apoptosis through increased production of ROS and consequent decrease of mitochondrial membrane potential, mitochondrial respiration, and ATP production rates. ROS generation by proguanil was up to 3-fold higher when compared to the control. Proguanil treatment increased the expression of Bax, p-H2AX, cleaved-caspase 9, cleaved PARP, and down-regulated bcl-2 and survivin in breast cancer cell lines. The enlargement of 4T1 breast tumors in female Balb/c mice was suppressed by 55% through daily oral administration of 20mg/kg of proguanil. Western blot analyses of proguanil- treated tumors showed increased levels of p-H2AX, Bax, c-PARP, and c-caspase3 compared to control. Proguanil proved to be an efficient in vitro and in-vivo inhibitor of breast cancer cells, hence should be considered further for clinical investigation against breast cancer.

Electroencephalography (EEG) is essential for tracking brain activity and identifying seizure effects. However, epileptic behaviour can only be detected after a specialist has carefully analysed all EEG recordings along with a proper history of the patient. A skilled physician is required for the right epilepsy diagnosis and therapy. But most of the time, patients visit the clinician in the interictal stage with no proper history documented. Therefore, it was essential to the automatic prediction of stages of seizure. K nearest neighbours (KNN) and random forest (RF) models using raw EEG signals, preictal, ictal, postictal, and interictal stages were identified in this study. The possibility of these characteristics is explored by examining how well time-domain signals work in the prediction of epileptic stages using intracranial EEG datasets from Freiburg Hospital (FH), Children's Hospital Boston-Massachusetts Institute of Technology (CHB-MIT), and Temple University Hospital (TUHEEG). To test the viability of this approach, two different types of simulations were carried out on three binary classifications (interictal vs. preictal, interictal vs. ictal, preictal vs. postictal, and interictal vs. postictal), and one four-class problem (interictal vs. preictal vs. ictal vs. postictal) was performed for each model. The average accuracy when using time-domain signals in the FH database was 90.5% and 75.0%; CHB-MIT was 92.87% and 75.9%; and TUHEEG was 94.46% and 76.8%, respectively, for the KNN and RF models.

The origin of an anomalous excess of high-energy (about 100 GeV and higher) positrons in cosmic rays is one of the rare problems in this field which is proposed to be solved with dark matter (DM). Attempts to solve this problem are faced with the issue of having to satisfy the data on cosmic positrons and cosmic gamma-radiation, which inevitably accompanies positron production such as FSR (final state radiation), simultaneously. We have been trying to come up with a solution by means of two approaches: making assumptions (*) about the spatial distribution of the dark matter, and (**) about the physics of its interactions. This work is some small final step of a big investigation regarding the search for gamma suppression by employing the second approach and a model with a doubly charged particle decaying into two positrons (X++→e+e+) is suggested as the most prospective one from those considered before.