Regulation of T cell differentiation by the TGF-β inhibitor Smad7 and non-Smad pathways

The cytokine transforming growth factor (TGF-β) has a pivotal role in T cell differentiation. Regulation of intracellular signalling pathways during T cell differentiation has been given a great attention recently. Under certain conditions TGF-β inhibits T helper (Th1) and Th2 differentiation or induces regulatory T cell and Th17 development, mainly through the Smad-dependent signalling pathway. In addition to that, growing evidence implicates the involvement of non-Smad signalling pathways in T cell differentiation. Smad7 is the intracellular inhibitor of the canonical TGF-β signalling cascade, but its role in T cell differentiation was unknown. In order to investigate the role of Smad7 in T cell differentiation, we used mice with a T cell specific Smad7 deletion, which allowed us to study the function of Smad7 exclusively in T cells. These Smad7 conditional knockout mice show normal immune homeostasis but less activated T cells in the periphery as compared to control wild type littermates. Smad7 deletion in T cells results in decreased Th1, Th2 and increased Th17 and regulatory T cell differentiation. Smad7 shows no effect on the suppressive capacity of regulatory T cells but exerts effects on the proliferation of responder T cells when challenged with regulatory T cell suppression. Furthermore, Smad7 plays a direct role in priming Th1 differentiation which is associated with T-bet transcription. Upon blocking the canonical TGF-β-Smad signalling pathway, naive T cells differentiate into Th17 cells to a smaller extent. Using a TGF-β downstream signalling phospho-protein antibody array, we show that PI3K/AKT/mTOR and p38 MAPK signalling pathways, which are independent of the canonical TGF-β-Smad cascade, are activated at specific phosphorylation sites during Th17 differentiation. Inhibition of these pathways leads to decreased IL-17 production by Th17 cells. In essence, Smad7 is a major regulator of T cell differentiation. Besides the canonical signalling cascade of TGF-β, naïve T cells use non-Smad pathways to differentiate into the Th17 subset. Signalling through PI3K/AKT/mTOR and p38 MAPK pathways plays a crucial role in this event. This study provides insight into molecular mechanisms of T helper cell differentiation and thus helps to elucidate the pathophysiology of autoimmune diseases like multiple sclerosis which could eventually lead to development of new diagnostic or therapeutic procedures

A New Data-Driven Method to Identify Violent Facial Expression

Human Facial Expressions plays an important role in identifying human actions or intention. Facial expressions can represent any specific action of any person and the pattern of violent behavior of any person strongly depends on the geographic region. Here we have designed an automated system by using a Convolutional Neural Network which can detect whether a person has any intention to commit any crime or not. Here we proposed a new method that can identify criminal intentions or violent behavior of any person before executing crimes more efficiently by using very little data on facial expressions before executing a crime or any violent tasks. Instead of using image features which is a time-consuming and faulty method we used an automated feature selector Convolutional Neural Network model which can capture exact facial expressions for training and then can predict that target facial expressions more accurately. Here we used only the facial data of a specific geographic region which can represent the violent and before-crime before-crime facial patterns of the people of the whole region.Comment: Submitted to the 1st International Conference on Artificial Intelligence, Advanced Materials, and Mechatronics Systems : Submission Number:230

Microgrid Energy Management using Weather Forecasts: Case Study, Discussion and Challenges

The main objective of this study is to demonstrate the integration of weather forecasts which can lead to a significant reduction in energy costs and carbon emissions while ensuring the reliability of the microgrid operation. By serving a small area or a particular building, the incorporation of weather forecasts can considerably increase the efficiency of microgrid energy management. The planning and operation of microgrids can be greatly improved by using weather predictions, which give useful information about upcoming weather conditions. By forecasting future energy demand and supply based on meteorological conditions, Microgrid Energy Management (MEM) is utilized to optimize the energy management decisions in microgrid systems. Making better choices regarding energy generation, storage, and consumption may be aided by the incorporation of weather forecasts, which can offer a more precise and trustworthy estimate of the energy demand and supply. This strategy can result in increased energy efficiency, decreased energy prices, and decreased carbon emissions, all of which are important goals for contemporary power systems. A promising approach for raising energy effectiveness and lowering greenhouse gas emissions in contemporary power networks is MEM. The incorporation of weather forecasts into MEM can improve decision-making regarding energy management by giving a better insight of future energy demand and supply. This essay examines the advantages and disadvantages of using weather forecasts in MEM through the presentation of a case example. By providing valuable information about future weather conditions, weather forecasts this review explain the Optimized Renewable Energy Integration, Improved Energy Storage Utilization, Load Shifting and Demand Response, Efficient Grid Management for reducing reliance on fossil fuels and lowering energy cost and carbon emissions. In order to address the issues related with MEM employing weather forecasts, this study offers potential fixes for increasing the accuracy of weather forecasts and emphasizes the necessity for more research in this area

Direct Simulation Monte Carlo Analysis on Thrust Vectoring of a Supersonic Micro Nozzle using Bypass Mass Injection

Converging diverging micro nozzle is fundamentally intended for flow acceleration through the generation of kinetic energy for the advanced micro-propulsion systems. Such supersonic micro nozzles have significant applications in the launching, propulsion and rapid directional control of the micro-satellites for a better maneuver. Micro scale analysis of such flow devices is extended to the rarefied flow regime. Present study has addressed thrust vectoring in a planar converging-diverging supersonic micro nozzle by the bypass mass injection technique. Direct Simulation Monte Carlo (DSMC) method has been used for numerical modelling. Primary focus is given on the thrust vectoring control of the micro nozzle with a throat height of 20 micro meter and an expansion ratio of 1.7. For the secondary injection, a rectangular channel of 5 different bypass widths (2 - 12 micro meter) is considered for two different outlet pressures (Pout = 10 kPa and 40 kPa) while keeping the inlet pressure (Pin) and temperature (Tin) fixed at 1 atm and 300 k respectively. The physical behavior of the micro nozzle is acknowledged through the analysis of Mach, pressure, temperature and density contours. Numerical results reveal that the secondary flow injection is adapted into the primary flow through the formation of a pressure bump in the diverging section. Moreover, the total mass flow rate, secondary flow percentage, thrust force, the thrust coefficient and specific impulse increase with the bypass channel width. A change in thrust direction is obtained which in turn produces a considerable vectoring effect in the supersonic micro nozzle. The vectoring angle for Pout of 40 kPa peaks at 6 micro meter bypass channel whereas a gradual increase of the vectoring angle with the bypass channel width is observed for Pout = 10 kPa.Comment: Journal paper and it's under revie

Combatting Multidrug Resistance in Bacteria: A Novel Approaches for Assessing Efflux Pumps

In order to defend themselves, bacteria contain efflux pumps that assist in evacuating harmful chemicals outside the cell. Antibiotic-active efflux is one of the main mechanisms of drug resistance in bacteria. Membrane transporters use a variety of unrelated compounds as substrates to mediate the efflux process. Because of this, the presence and activity of efflux pumps have a significant impact on the effectiveness of antibiotics, which contributes to bacteria developing drug resistance. Six samples were used in the investigation, and f; foures were found to be E. coli, while the other two were Klebsiella pneumoniae. These isolates demonstrated efflux pump-mediated multidrug resistance. Notably, these bacteria with the Integron integrase 1 gene, called resistant strains, were resistant to 25 different antibiotics. Including Aztreonam, Ampicillin/Sulbactam, Amoxyclav, Cefepime, Cefepime/Tazobactam, Ampicillin, and Cefotaxime, resistance was observed in both E. coli and Klebsiella pneumoniae. Given the complexity of drug efflux transporters, novel approaches are essential to combat multidrug resistance in bacteria effectively. A glucose-triggered rhodamine 6G (R6G) efflux assay from Sigma-Aldrich, USA, was used to test how well efflux pumps work

Important Factors to Remember when Constructing a Cross-site Scripting Prevention Mechanism

Web application has become an essential part of daily activities to provide easy accessibility that ensures better performance. It is a platform where sensitive information such as username, password, credit card details, operating system and software version etc. is stored that attracts intruders to generate most of their attacks. Intruders can steal valuable data by compromising web application security flaws; Cross Site Scripting (XSS) vulnerability is one of these. Several studies have been conducted in order to prevent the XSS vulnerability. In this research, we searched Scopus Indexed articles published in the last 11 years (between 2008 and 2020) using two keywords (“XSS Attack Prevention” and “XSS Prevention”). The purpose of this study was to conduct a literature review on XSS prevention techniques e.g. strengths and weaknesses, including structural issues and real-time deployment location in order to extract valuable information. This review identified 14 articles among the 25 selected articles that provided various suitable prevention techniques for XSS attacks. Seven articles are based on tools that have been implemented and take into account design, coding, testing, and integrating validation processes, six articles are about server site solutions, and one is about automatic mitigation solutions. As a result, this research will be invaluable in guiding the advancement of XSS prevention techniques