28 research outputs found
DESIGN AND OPERATION OF MICROGRID
The need for new generation systems has motivated the development of microgrids. This new concept may provide significant benefits such as losses compensation, achieving high degree of efficiency and reliability to the transmission and distribution networks. This novel idea provides more advantages about Microgrids like general structure and different topologies. Also an original methodology for facilitating its design is proposed. Finally Simulink model of Microgrid is designed and then analyzed.Â
Comparison of predictive protocols in chest pain patients in a tertiary care hospital in Karachi, Pakistan
Background: The most challenging aspect in evaluation of a patient presenting with chest pain in the Emergency Department (ED) is diagnosis of acute cardiac ischemia (ACI). Various decisions aids have been developed to aid the ED physician in the diagnosis of chest pain. Three different predictive protocols – the Goldman protocol, ACI-TIPI, and the Troponin protocol are used in predicting the occurrence of ACI. None of these decision aids have been tested in the Pakistani population, where risk factors and prevalence of CAD are much different than what is seen in other regions of the world.Aims: The aim of this study was to compare how three different predictive protocols for ACI fared in the Pakistani population.Methods:This retrospective case series included a consecutive sample of 212 patients who presented to the ED with symptoms of chest pain or its equivalent. Patient data was collected and retrospectively analyzed with each predictive protocol to analyze sensitivity, specificity, PPV, and NPV of each protocol.Results: 63% of patients were diagnosed with ACI. The sensitivities of the Goldman, ACI-TIPI, and Troponin protocols were 94%, 98%, and 38% respectively. The specificities of the Goldman, ACI-TIPI, and Troponin protocols were 14%, 29%, and 95% respectively. Conclusion: Sensitivities from a small sample size show promise in the use of predictive protocols for chest pain in the Pakistani population. However, prospective studies on a larger level need to be conducted to validate these findings
PP2A and Its Inhibitors in Helper T-Cell Differentiation and Autoimmunity
Protein phosphatase 2A (PP2A) is a highly complex heterotrimeric Ser/Thr phosphatase that regulates many cellular processes. The role of PP2A as a tumor suppressor has been extensively studied and reviewed. However, emerging evidence suggests PP2A constrains inflammatory responses and is important in autoimmune and neuroinflammatory diseases. Here, we reviewed the existing literature on the role of PP2A in T-cell differentiation and autoimmunity. We have also discussed the modulation of PP2A activity by endogenous inhibitors and its small-molecule activators as potential therapeutic approaches against autoimmunity
DESIGN AND OPERATION OF MICROGRID
The need for new generation systems has motivated the development of microgrids. This new concept may provide significant benefits such as losses compensation, achieving high degree of efficiency and reliability to the transmission and distribution networks. This novel idea provides more advantages about Microgrids like general structure and different topologies. Also an original methodology for facilitating its design is proposed. Finally Simulink model of Microgrid is designed and then analyzed.
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Potential effects of the COVID-19 pandemic on future birth rate
Here, we examine the potential effect of the COVID-19 pandemic on future birth rates. This highly contagious disease originated in China, and rapidly spread worldwide, leading to extensive lockdown policies being implemented globally with the aim of containing the infection rates and its serious attendant consequences. Based on previous extant literature, this paper overviews the potential demographic consequences of the current progressively widespread epidemic on conception and fertility as driven by the data obtained during similar prior incidents. In general, epidemics manifest a common pattern as far as their impact on population, which is remarkably similar to natural disasters, i.e., a steep decline in birth rates followed by gradual increases and then followed by a baby boom. Additionally, we have also depicted how economic conditions, mental health, fear, and mortality may also influence future birth rates
Long Intergenic Noncoding RNA MIAT as a Regulator of Human Th17 Cell Differentiation
T helper 17 (Th17) cells protect against fungal and bacterial infections and are implicated in autoimmunity. Several long intergenic noncoding RNAs (lincRNA) are induced during Th17 differentiation, however, their contribution to Th17 differentiation is poorly understood. We aimed to characterize the function of the lincRNA Myocardial Infarction Associated Transcript (MIAT) during early human Th17 cell differentiation. We found MIAT to be upregulated early after induction of human Th17 cell differentiation along with an increase in the chromatin accessibility at the gene locus. STAT3, a key regulator of Th17 differentiation, directly bound to the MIAT promoter and induced its expression during the early stages of Th17 cell differentiation. MIAT resides in the nucleus and regulates the expression of several key Th17 genes, including IL17A, IL17F, CCR6 and CXCL13, possibly by altering the chromatin accessibility of key loci, including IL17A locus. Further, MIAT regulates the expression of protein kinase C alpha (PKC alpha), an upstream regulator of IL17A. A reanalysis of published single-cell RNA-seq data showed that MIAT was expressed in T cells from the synovium of RA patients. Our results demonstrate that MIAT contributes to human Th17 differentiation by upregulating several genes implicated in Th17 differentiation. High MIAT expression in T cells of RA patient synovia suggests a possible role of MIAT in Th17 mediated autoimmune pathologies
CIP2A Constrains Th17 Differentiation by Modulating STAT3 Signaling
Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) is an oncogene and a potential cancer therapy target protein. Accordingly, a better understanding of the physiological function of CIP2A, especially in the context of immune cells, is a prerequisite for its exploitation in cancer therapy. Here, we report that CIP2A negatively regulates interleukin (IL)-17 production by Th17 cells in human and mouse. Interestingly, concomitant with increased IL-17 production, CIP2A-deficient Th17 cells had increased strength and duration of STAT3 phosphorylation. We analyzed the interactome of phosphorylated STAT3 in CIP2A-deficient and CIP2A-sufficient Th17 cells and indicated together with genome-wide gene expression profiling, a role of Acylglycerol Kinase (AGK) in the regulation of Th17 differentiation by CIP2A. We demonstrated that CIP2A regulates the strength of the interaction between AGK and STAT3, and thereby modulates STAT3 phosphorylation and expression of IL-17 in Th17 cells
Quantitative genome-scale metabolic modeling of human CD4+ T cell differentiation reveals subset-specific regulation of glycosphingolipid pathways
T cell activation, proliferation, and differentiation involve metabolic reprogramming resulting from the interplay of genes, proteins, and metabolites. Here, we aim to understand the metabolic pathways involved in the activation and functional differentiation of human CD4+ T cell subsets (T helper [Th]1, Th2, Th17, and induced regulatory T [iTreg] cells). Here, we combine genome-scale metabolic modeling, gene expression data, and targeted and non-targeted lipidomics experiments, together with in vitro gene knockdown experiments, and show that human CD4+ T cells undergo specific metabolic changes during activation and functional differentiation. In addition, we confirm the importance of ceramide and glycosphingolipid biosynthesis pathways in Th17 differentiation and effector functions. Through in vitro gene knockdown experiments, we substantiate the requirement of serine palmitoyltransferase (SPT), a de novo sphingolipid pathway in the expression of proinflammatory cytokines (interleukin [IL]-17A and IL17F) by Th17 cells. Our findings provide a comprehensive resource for selective manipulation of CD4+ T cells under disease conditions characterized by an imbalance of Th17/natural Treg (nTreg) cells.</p
Histatin peptides: Pharmacological functions and their applications in dentistry
YesThere are many human oral antimicrobial peptides responsible for playing important
roles including maintenance, repairing of oral tissues (hard or soft) and defense against oral
microbes. In this review we have highlighted the biochemistry, physiology and proteomics of human
oral histatin peptides, secreted from parotid and submandibular salivary glands in human. The significance
of these peptides includes capability for ionic binding that can kill fungal Candida albicans.
They have histidine rich amino acid sequences (7–12 family members; corresponding to residues
12–24, 13–24, 12–25, 13–25, 5–11, and 5–12, respectively) for Histatin-3. However, Histatin-3 can
be synthesized proteolytically from histatin 5 or 6. Due to their fungicidal response and high
biocompatibility (little or no toxicity), these peptides can be considered as therapeutic agents with
most probable applications for example, artificial saliva for denture wearers and salivary gland
dysfunction conditions. The objectives of current article are to explore the human histatin peptides
for its types, chemical and biological aspects. In addition, the potential for therapeutic bio-dental
applications has been elaborated.King Saud Universit