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Soft Computing (SC) technique consisting of several fields of Artificial Intelligence namely, Artificial Neural Networks (ANNs), Fuzzy Logic (FL), Genetic Algorithms (GA), Machine Learning (ML) and Probabilistic Reasoning (PR) is a new paradigm in computing based on a creative mix of comparatively newer computing techniques. Here, we have taken into consideration several important schemes/ programs of selected sectors pertaining to different Central Ministries/ Departments of Government of India and observed that proper Knowledge Management System (KMS) can be developed and implemented in such cases using ANN based soft computing input output model as an effective tool for the same. Further, we have analyzed how various input and output parameters (both physical and financial) associated with each such selected scheme/ program are related to each other in the light of their basic objectives and the way these can be appropriately represented by an ANN based soft computing input output model in which the expected outputs corresponding to certain inputs can be calculated/ estimated.

Mutual funds are one of the safest options to invest money in the stock market or to buy assets. Past and present analysis of the mutual fund investing scenario is very crucial to gain an insight about the future performance. This paper aims to forecast the Net Asset Values of an efficient Indian Equity Mutual Funds portfolio using the Auto-Regressive Integrated Moving Average model. The Equity Mutual funds which are operational on or before January 2015 are considered and their monthly Net Asset Values are collected from January 2015 – December 2019. The portfolio is constructed by allocating weightage to the funds ensuring minimum risk. The stationarity of the Net Asset Value for each fund constituting the portfolio is tested using the Augmented Dickey-Fuller test. An appropriate Auto-Regressive Integrated Moving Average model is fitted to each of these funds and the models are validated using the Ljung Box test. The models with the lowest Akaike's Information Criteria value and significant coefficients are selected as the appropriate model. The Net Asset Values for the first six months of the year 2020 are forecasted for each fund using the selected model and the forecasts are found to be quite appropriate. Thus, this study will help investors in their future investments.

Background: The beneficial metabolic effects of the PPARγ agonist rosiglitazone (Rosi) are associated with anti-inflammatory changes in adipose tissue macrophages (ATMs) . One study aim was to characterize the in vivo Rosi-induced phenotypic switch of ATMs using a variety of macrophage markers, including the lipid-associated macrophage markers CD9 and Trem2. As a second aim, since ATM-derived exosomes can exert insulin-sensitizing or desensitizing effects dependent on ATM cell context, we assessed the effects of ATM exosomes from Rosi-treated obese mice on in vitro insulin actions. Research Design and Method: ATMs were isolated from 4 months HFD/obese mice treated for the last month with Rosi (60 mg/kg HFD) compared to HFD or chow-fed controls. Among CD11b+F4/80+ or CD64+ macrophages, we identified pro-inflammatory (“M1-like” CD11c+ and/or CD9+) , anti-inflammatory (“M2-like” CD11c-CD206+) and lipid-associated (CD9+ and/or Trem2+) ATMs by flow cytometry. Bone marrow-derived macrophages (BMDMs) were treated in vitro with µM Rosi for 24h. 3T3-L1 adipocytes, L6 myotubes, and primary hepatocytes were cultured 24h with exosomes isolated from ATMs of Rosi treated obese mice or in vitro Rosi treated BMDMs and then assessed for insulin sensitivity. Results: Rosi treatment reduced adipose tissue inflammation, as seen by reduced numbers of pro-inflammatory (“M1-like”) ATMs and increased the Trem2 signature in “M2-like” ATMs. Importantly, Rosi directly induced Trem2 expression in vitro in BMDMs. Additionally, exosomes isolated from Rosi-treated obese mice or M1 BMDMs increased glucose uptake and insulin signalling (pAKT) in adipocytes and myotubes and reduced glucose production in hepatocytes compared to control exosomes. Conclusion: Our data indicate that Trem2 is a PPARγ target gene. Since exosomes from Rosi treated ATMs or BMDMs enhance cellular insulin action, this could provide a new explanation for the well-known insulin-sensitizing effects of PPARγ agonists. Disclosure T.V.Rohm: None. F.C.G.Reis: None. R.Isaac: None. M.Paszek: None. G.Bandyopadhyay: None. J.M.Olefsky: None. Funding Swiss National Science Foundation (SNF) Early Postdoc.Mobility grant (to T.R.) .

Background & Aims Liver CRIg+ (complement receptor of the immunoglobulin superfamily) macrophages play a critical role in filtering bacteria and their products from circulation. Translocation of microbiota-derived products from an impaired gut barrier contributes to the development of obesity-associated tissue inflammation and insulin resistance. However, the critical role of CRIg+ macrophages in clearing microbiota-derived products from the bloodstream in the context of obesity is largely unknown. Methods We performed studies with CRIg–/–, C3–/–, cGAS–/–, and their wild-type littermate mice. The CRIg+ macrophage population and bacterial DNA abundance were examined in both mouse and human liver by either flow cytometric or immunohistochemistry analysis. Gut microbial DNA–containing extracellular vesicles (mEVs) were adoptively transferred into CRIg–/–, C3–/–, or wild-type mice, and tissue inflammation and insulin sensitivity were measured in these mice. After coculture with gut mEVs, cellular insulin responses and cGAS/STING-mediated inflammatory responses were evaluated. Results Gut mEVs can reach metabolic tissues in obesity. Liver CRIg+ macrophages efficiently clear mEVs from the bloodstream through a C3-dependent opsonization mechanism, whereas obesity elicits a marked reduction in the CRIg+ macrophage population. Depletion of CRIg+ cells results in the spread of mEVs into distant metabolic tissues, subsequently exacerbating tissue inflammation and metabolic disorders. Additionally, in vitro treatment of obese mEVs directly triggers inflammation and insulin resistance of insulin target cells. Depletion of microbial DNA blunts the pathogenic effects of intestinal EVs. Furthermore, the cGAS/STING pathway is crucial for microbial DNA–mediated inflammatory responses. Conclusions Deficiency of CRIg+ macrophages and leakage of intestinal EVs containing microbial DNA contribute to the development of obesity-associated tissue inflammation and metabolic diseases.

Mitigation of winding resonance triggered by oscillatory transient over voltages is one of the key challenges in designing high-voltage transformer windings. Internal resonance is typically an issue with high-voltage transformers with homogeneous winding, manifesting identical natural frequency for the uniform winding sections. Self-capacitance grading can be a possible remedy to resonance issue which incorporates diversification in the natural frequencies of winding disk coils. Practical implementation of this concept is however difficult due to economic and design constraints. This study proposes a practical method of implementing the concept of natural frequency diversification by use of ‘multi-graded inter-winding electrostatic shields’. The concept, theory, design and implementation of the proposed winding method have been presented in this study. A scaled-down prototype of a typical high-voltage transformer has been developed to illustrate the real-time implementation of the proposed method. Both simulation and experimental results established that the proposed winding can effectively suppress oscillatory characteristics under transient over voltages and overcome winding resonance.

An effort was made in forecasting year wise estimated foreign exchange reserves of India with the help of past data of relevant parameters, using back propagation type of artificial neural networks methodology of soft computing. The results indicates that in a particular financial year if we know the values of foreign direct investments, total expenditure on all plan schemes and special plan schemes of department of commerce, export to import ratio, average import duty rate and GDP of India, then estimation of the likely value of foreign exchange reserves for that particular year can be made by this method.

Agriculture is an important sector of the Indian economy. In the present paper an attempt has been made to theoretically explore the development of an agricultural knowledge management system (KMS) in respect of various micro irrigation techniques for agriculture, as well as relevant crop-/region-specific agricultural practices in different regions of the country, as the same has been observed to be very much necessary for the overall benefits of wider cross section of farmers, agricultural scientists, economists, and other stakeholders in the domain. It is further observed that artificial neural networks (ANNs), which are a part of soft computing techniques, can be used as a KMS tool for effective management of various sub sectors of agriculture. In this context, it has been shown that use of ANNs as a KMS tool can improve the effectiveness of applications of the above mentioned agricultural KMS by accurately forecasting the year-wise estimated yield of food grains of India with the help of past data of various relevant parameters.

Obesity is characterized by a state of chronic, unresolved inflammation in insulin-targeted tissues. Obesity-induced inflammation causes accumulation of proinflammatory macrophages in adipose tissue and liver. Proinflammatory cytokines released from tissue macrophages inhibits insulin sensitivity. Obesity also leads to inflammation-induced endoplasmic reticulum (ER) stress and insulin resistance. In this scenario, based on the data (specifically patterns) generated by our in vivo experiments on both diet-induced obese (DIO) and normal chow diet (NCD) mice, we developed an in silico state space model to integrate ER stress and insulin signaling pathways. Computational results successfully followed the experimental results for both DIO and NCD conditions. Chromogranin A (CgA) peptide catestatin (CST: hCgA 352 - 372 ) improves obesity-induced hepatic insulin resistance by reducing inflammation and inhibiting proinflammatory macrophage infiltration. We reasoned that the anti-inflammatory effects of CST would alleviate ER stress. CST decreased obesity-induced ER dilation in hepatocytes and macrophages. On application of Proportional-Integral-Derivative (PID) controllers on the in silico model, we checked whether the reduction of phosphorylated PERK resulting in attenuation of ER stress, resembling CST effect, could enhance insulin sensitivity. The simulation results clearly pointed out that CST not only decreased ER stress but also enhanced insulin sensitivity in mammalian cells. In vivo experiment validated the simulation results by depicting that CST caused decrease in phosphorylation of UPR signaling molecules and increased phosphorylation of insulin signaling molecules. Besides simulation results predicted that enhancement of AKT phosphorylation helps in both overcoming ER stress and achieving insulin sensitivity. These effects of CST were verified in hepatocyte culture model.

The human lung plays vital roles in respiration, host defense and basic physiology. Recent technological advancements such as single-cell RNA sequencing and genetic lineage tracing have revealed novel cell types and enriched functional properties of existing cell types in lung. The time has come to take a new census. Initiated from members of the NHLBI-funded LungMAP Consortium and aided by experts in the lung biology community, we synthesized current data into a comprehensive and practical cellular census of the lung. Identities of cell types in the normal lung are captured in individual cell cards with delineation of function, markers, developmental lineages, heterogeneity, regenerative potential, disease links and key experimental tools. This publication will serve as the starting point of a live, up-to-date guide for lung research at https://lungmap.net/cell-cards-browser/. We hope that this Lung CellCards will promote the community-wide effort to establish, maintain and restore respiratory health.

Aim: Defects in hepatic glycogen synthesis contribute to post-prandial hyperglycaemia in type 2 diabetic patients. Chromogranin A (CgA) peptide Catestatin (CST: hCgA 352-372) improves glucose tolerance in insulin-resistant mice. Here, we seek to determine whether CST induces hepatic glycogen synthesis. Methods: We determined liver glycogen, glucose-6-phosphate (G6P), uridine diphosphate glucose (UDPG) and glycogen synthase (GYS2) activities; plasma insulin, glucagon, noradrenaline and adrenaline levels in wild-type (WT) as well as in CST knockout (CST-KO) mice; glycogen synthesis and glycogenolysis in primary hepatocytes. We also analysed phosphorylation signals of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-dependent kinase-1 (PDK-1), GYS2, glycogen synthase kinase-3β (GSK-3β), AKT (a kinase in AKR mouse that produces Thymoma)/PKB (protein kinase B) and mammalian/mechanistic target of rapamycin (mTOR) by immunoblotting. Results: CST stimulated glycogen accumulation in fed and fasted liver and in primary hepatocytes. CST reduced plasma noradrenaline and adrenaline levels. CST also directly stimulated glycogenesis and inhibited noradrenaline and adrenaline-induced glycogenolysis in hepatocytes. In addition, CST elevated the levels of UDPG and increased GYS2 activity. CST-KO mice had decreased liver glycogen that was restored by treatment with CST, reinforcing the crucial role of CST in hepatic glycogenesis. CST improved insulin signals downstream of IR and IRS-1 by enhancing phospho-AKT signals through the stimulation of PDK-1 and mTORC2 (mTOR Complex 2, rapamycin-insensitive complex) activities. Conclusions: CST directly promotes the glycogenic pathway by (a) reducing glucose production, (b) increasing glycogen synthesis from UDPG, (c) reducing glycogenolysis and (d) enhancing downstream insulin signalling.

Portfolio formation holds paramount importance in the process of the investment decision making since, a single door investment (SDI) option is much riskier than a multiple door investment (MDI) option. Among available financial instruments, the stock market (SM) has allured investors because of its liquidity and growth opportunities. However, the effectiveness of the investment decision is largely reflected in the selection of the constituent elements of the portfolio by an investor while trading off risk and return. In this paper, after an initial level selection of for formulating a possible portfolio by using Perceptual Map (PM), we have applied DEA to calculate the efficiency of the stocks at the risk-return interface based on the market performance. In order to ascertain that the stock selection is logical and worthwhile, we further probe the fundamental performances over a time period of five consecutive financial years using the method of Multi-Criteria Decision Analysis (MCDA) framework based on the Complex Proportional Assessment (COPRAS) method, where, the criteria weights are calculated by using the entropy method. A consistency is visible in the yearly fundamental performances and a significant pattern with regard to the portfolio selection.

Contains fulltext : 206959.pdf (Publisher’s version ) (Closed access) We have previously shown that the chromogranin A (CgA)-derived peptide catestatin (CST: hCgA352-372) inhibits nicotine-induced secretion of catecholamines from the adrenal medulla and chromaffin cells. In the present study, we seek to determine whether CST regulates dense core (DC) vesicle (DCV) quanta (catecholamine and chromogranin/secretogranin proteins) during acute (0.5-h treatment) or chronic (24-h treatment) cholinergic (nicotine) or peptidergic (PACAP, pituitary adenylyl cyclase activating polypeptide) stimulation of PC12 cells. In acute experiments, we found that both nicotine (60 muM) and PACAP (0.1 muM) decreased intracellular norepinephrine (NE) content and increased (3)H-NE secretion, with both effects markedly inhibited by co-treatment with CST (2 muM). In chronic experiments, we found that nicotine and PACAP both reduced DCV and DC diameters and that this effect was likewise prevented by CST. Nicotine or CST alone increased expression of CgA protein and together elicited an additional increase in CgA protein, implying that nicotine and CST utilize separate signaling pathways to activate CgA expression. In contrast, PACAP increased expression of CgB and SgII proteins, with a further potentiation by CST. CST augmented the expression of tyrosine hydroxylase (TH) but did not increase intracellular NE levels, presumably due to its inability to cause post-translational activation of TH through serine phosphorylation. Co-treatment of CST with nicotine or PACAP increased quantal size, plausibly due to increased synthesis of CgA, CgB and SgII by CST. We conclude that CST regulates DCV quanta by acutely inhibiting catecholamine secretion and chronically increasing expression of CgA after nicotinic stimulation and CgB and SgII after PACAPergic stimulation.

Objectives: To investigate the impact of four dimensions on organizational culture in Heterogeneous Industries which includes: Training and Development, Reward and Recognition and Teamwork and Communication over employees commitment. Methods and Analysis: This research was conducted among employees covered under ten heterogeneous Industries located in Jharkhand, West Bengal, Bihar, Gujarat and Karnataka states in India. 242 random population samples were collected under this study. Initially, we have observed the Reliability analysis on the data set to make the information more reliable and authentic. Thereafter Factor analysis using statistical software (SPSS) version 20.2 was applied. Findings: On the basis of a response from the two categories of Management Staff (Jr Management and Senior with Middle Management) within ten Heterogeneous industries serving in the field of Service, Manufacturing and Infrastructure in different states in India, Reliability Analysis and Factor analysis was tested. A questionnaire developed by Lau and Idris, (2001) and Ooi and Arumugam (2006) have been evolved with some modification. Initially, the questionnaire has been framed on the basis of the Training and Development (TandD) with 6 Questions, Reward and Recognition(RandR) with 8 Questions, Team Work (TW) with 7 Questions, and Organizational Communication (OC) with 6 Questions and Employees Commitment (EC) with 10 Questions. After having the Reliability analysis and Factor Analysis on the basis of responses using 5 point Likert Scale (from 1 to5) of the relevant questions on the application of statistical tools showed reasonably significant on the determination of the attributes of various dimensions of organizational culture. Application: Empirical study covers both type of Industries and hence its outcome and implications will provide a better understanding of the cultural issue to such organizations and help them in carving out future strategy. Keywords: Heterogeneous Industries in India, Organizational Commitment, Organizational Culture, Reliability Analysis and Factor Analysis

BackgroundFor many practical hypothesis testing (H-T) applications, the data are correlated and/or with heterogeneous variance structure. The regressiont-test for weighted linear mixed-effects regression (LMER) is a legitimate choice because it accounts for complex covariance structure; however, high computational costs and occasional convergence issues make it impractical for analyzing high-throughput data. In this paper, we propose computationally efficient parametric and semiparametric tests based on a set of specialized matrix techniques dubbed as the PB-transformation. The PB-transformation has two advantages: 1. The PB-transformed data will have a scalar variance-covariance matrix. 2. The original H-T problem will be reduced to an equivalent one-sample H-T problem. The transformed problem can then be approached by either the one-sample Studentst-test or Wilcoxon signed rank test.ResultsIn simulation studies, the proposed methods outperform commonly used alternative methods under both normal and double exponential distributions. In particular, the PB-transformedt-test produces notably better results than the weighted LMER test, especially in the high correlation case, using only a small fraction of computational cost (3 versus 933 seconds). We apply these two methods to a set of RNA-seq gene expression data collected in a breast cancer study. Pathway analyses show that the PB-transformedt-test reveals more biologically relevant findings in relation to breast cancer than the weighted LMER test․.ConclusionsAs fast and numerically stable replacements for the weighted LMER test, the PB-transformed tests are especially suitable for “messy” high-throughput data that include both independent and matched/repeated samples. By using our method, the practitioners no longer have to choose between using partial data (applying paired tests to only the matched samples) or ignoring the correlation in the data (applying two sample tests to data with some correlated samples).

Microalgae are the unicellular or multicellular photosynthetic microorganisms that can efficiently fix carbon dioxide (CO2) from various sources such as the environment, industrial flue gas, and some carbonate salts. In the present study, one green microalgal strain and a cyanobacterial consortium were used separately for the sequestration of CO2 at different pHs (7–11), at different initial concentrations of CO2 (5–20%), and at various inoculum sizes (5–12.5%). The maximum sequestration of CO2 was found to be 74.37 ± 0.49% and 71.12 ± 0.05% at 5% and 15% CO2 for green algae and cyanobacterial consortium. The biomass generated after sequestration of CO2 was utilized for the synthesis of biomolecules.

Hepatocytes have important roles in liver iron homeostasis, abnormalities in which are tightly associated with liver steatosis and fibrosis. Here, we show that non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are characterized by iron-deficient hepatocytes and iron overload in hepatic stellate cells (HSCs). Iron deficiency enhances hepatocyte lipogenesis and insulin resistance through HIF2α-ATF4 signaling. Elevated secretion of iron-containing hepatocyte extracellular vesicles (EVs), which are normally cleared by Kupffer cells, accounts for hepatocyte iron deficiency and HSC iron overload in NAFLD/NASH livers. Iron accumulation results in overproduction of reactive oxygen species that promote HSC fibrogenic activation. Conversely, blocking hepatocyte EV secretion or depleting EV iron cargo restores liver iron homeostasis, concomitant with mitigation of NAFLD/NASH-associated liver steatosis and fibrosis. Taken together, these studies show that iron distribution disorders contribute to the development of liver metabolic diseases.

Nonalcoholic steatohepatitis (NASH) is a liver disease associated with significant morbidity. Kupffer cells (KCs) produce endogenous miR-690 and, via exosome secretion, shuttle this miRNA to other liver cells, such as hepatocytes, recruited hepatic macrophages (RHMs), and hepatic stellate cells (HSCs). miR-690 directly inhibits fibrogenesis in HSCs, inflammation in RHMs, and de novo lipogenesis in hepatocytes. When an miR-690 mimic is administered to NASH mice in vivo, all the features of the NASH phenotype are robustly inhibited. During the development of NASH, KCs become miR-690 deficient, and miR-690 levels are markedly lower in mouse and human NASH livers than in controls. KC-specific KO of miR-690 promotes NASH pathogenesis. A primary target of miR-690 is NADK mRNA, and NADK levels are inversely proportional to the cellular miR-690 content. These studies show that KCs play a central role in the etiology of NASH and raise the possibility that miR-690 could emerge as a therapeutic for this condition.

Hypertension is associated with inflammation and excessive production of catecholamines. Hypertensive patients have reduced plasma levels of CST (catestatin)—a bioactive cleavage product of the prohormone CgA (chromogranin A). In mouse models, hypertension symptoms can be reduced by administration of CST, but the role of CST in the regulation of cardiovascular function is unknown. In this study, we generated mice with KO (knockout) of the region of the CgA gene coding for CST (CST-KO) and found that CST-KO mice are not only hypertensive as predicted but also display left ventricular hypertrophy, have marked macrophage infiltration of the heart and adrenal gland, and have elevated levels of proinflammatory cytokines and catecholamines. Intraperitoneal injection with CST reversed these phenotypes, and ischemic preconditioning-induced cardioprotection was also abolished in CST-KO mice. Experiments with chlodronate depletion of macrophages and bone marrow transfer showed that macrophages produce CST and that the antihypertensive effects of CST are mediated, in part, via CST’s immunosuppression of macrophages as a form of feedback inhibition. The data thus implicate CST as a key autocrine attenuator of the cardiac inflammation in hypertension by reducing macrophage inflammation.

Objective Recent evidence indicates that inhibition of prolyl hydroxylase domain (PHD) proteins can exert beneficial effects to improve metabolic abnormalities in mice and humans. However, the underlying mechanisms are not clearly understood. This study was designed to address this question. Methods A pan-PHD inhibitor compound was injected into WT and liver-specific hypoxia-inducible factor (HIF)-2α KO mice, after onset of obesity and glucose intolerance, and changes in glucose and glucagon tolerance were measured. Tissue-specific changes in basal glucose flux and insulin sensitivity were also measured by hyperinsulinemic euglycemic clamp studies. Molecular and cellular mechanisms were assessed in normal and type 2 diabetic human hepatocytes, as well as in mouse hepatocytes. Results Administration of a PHD inhibitor compound (PHDi) after the onset of obesity and insulin resistance improved glycemic control by increasing insulin and decreasing glucagon sensitivity in mice, independent of body weight change. Hyperinsulinemic euglycemic clamp studies revealed that these effects of PHDi treatment were mainly due to decreased basal hepatic glucose output and increased liver insulin sensitivity. Hepatocyte-specific deletion of HIF-2α markedly attenuated these effects of PHDi treatment, showing PHDi effects are HIF-2α dependent. At the molecular level, HIF-2α induced increased Irs2 and cyclic AMP-specific phosphodiesterase gene expression, leading to increased and decreased insulin and glucagon signaling, respectively. These effects of PHDi treatment were conserved in human and mouse hepatocytes. Conclusions Our results elucidate unknown mechanisms for how PHD inhibition improves glycemic control through HIF-2α-dependent regulation of hepatic insulin and glucagon sensitivity., Highlights • PHD inhibitor treatment improves glycemic control in obese glucose-intolerant mice. • PHD inhibitor treatment decreases liver glucagon sensitivity in obese mice. • The effects of PHD inhibition on glycemic control is hepatocyte HIF-2α-dependent. • PHD inhibitor treatment stimulates HIF-2α-dependent cAMP-specific PDE expression. • In human and mouse hepatocytes, PHD inhibitor treatment suppresses glucagon signaling.

AimDefects in hepatic glycogen synthesis contribute to postprandial hyperglycemia in type 2 diabetic (T2D) patients. Chromogranin A (CgA) peptide Catestatin (CST: hCgA352-372) has been shown to improve glucose tolerance in insulin-resistant mice. Here, we seek to determine whether CST also reduces hyperglycemia by increasing hepatic glycogen synthesis.MethodsWe determined liver glycogen, glucose-6-phosphate (G6P), uridine diphosphate glucose (UDPG), and glycogen synthase (GYS2) activities; plasma insulin, glucagon, norepinephrine (NE), and epinephrine (EPI) levels in fed and fasted liver of lean and obese mice as well as in CST knockout (CST-KO) mice after treatments with saline, CST, or insulin. We also determined glycogen synthesis and glycogenolysis in primary hepatocytes. In addition, we analyzed phosphorylation signals of Insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylinositol dependent kinase-1 (PDK-1), GYS2, glycogen synthase kinase-3β (GSK-3β), AKT (an enzyme in AKR mouse that produces Thymoma)/PKB (protein kinase B) and mTOR (mammalian/mechanistic target of rapamycin) by immunoblotting.ResultsCST stimulated glycogen accumulation in fed and fasted liver and in primary hepatocytes. CST reduced plasma NE and EPI levels, suggesting that CST promotes glycogenesis by inhibiting catecholamine-induced glycogenolysis. CST also directly stimulated glycogenesis and inhibited NE and EPI-induced glycogenolysis in hepatocytes. CST elevated the levels of UDPG and increased GYS2 activity, thus redirecting G6P to the glycogenic pathway. CST-KO mice had decreased liver glycogen that was restored by treatment with CST, reinforcing the crucial role of CST in hepatic glycogenesis. CST can improve insulin signals downstream of insulin receptor IR and IRS-1 by enhancing phospho-AKT signals through stimulation of PDK-1 and mTORC2 (mTOR complex 2) activities.ConclusionsWe conclude that CST directly promotes the glycogenic pathway and reduces plasma glucose levels in insulin-resistant mice by (i) reducing glucose production, (ii) increasing glycogen synthesis from UDPG, and (iii) reducing glycogenolysis. This is achieved by enhancing downstream insulin signaling.

In a P2P mobile cloud (PMC), an ad-hoc cloud is formed using the closely adjacent smart mobile devices (SMD). Here, a resource-deficient SMD user seeks its neighbouring resource-rich SMDs’ help to carry out a resource-wanting job. To maintain reliability and QoS of the PMC, it is necessary to be assured of the availability of the SMDs before submitting a job request. If the job is distributed to multiple SMDs, instead of assessing the availability of a single SMD, the availability of a group of SMDs is required for a certain period of time. The objective of the paper is to find a stable group of SMD users to increase the QoS of PMC. We aim to propose a novel mobility prediction method to assess the probability of a group of SMD users to be relatively static with respect to each other. We propose an algorithm to estimate the relative stability of an SMD with respect to its neighbourhood over a period of time, irrespective of its geographical location. We assess the short-term relative stability between a group of SMD users as well as the long-term mobility pattern between them. For mobility calculation, we have used real user traces from the UCSD dataset. The estimated results are analyzed and validated using different metrics.

Lung MAP HTC - BioRepository for Investigation of Neonatal Diseases of the Lung (BRINDL) 702.B.3 Combined SOP and Worksheet HTC_Lung_Tissue_Digestion_0100616rev061220 Purpose and Scope of the Procedure or Laboratory Assay 1.To dissociate and isolate single cell suspensions from human lung samples to meet the standards and needs of the Human Tissue Core. 2.This protocol covers manual gross dissociation of pieces of lung tissue (lobes or cubes) followed by enzymatic digestion and freezer storage as mixed populations of filtered and counted cells for which viability has been determined. 3.A separate protocol details the technique of freezing, thawing and further identifying and sorting these mixed cell populations. Scientific Principles or Validation of Procedure 1.Fujino et al. Am J Respir Cell Mol Biol. 2012 Apr;46(4):422-30 2.Barkauskas, C. E., Cronce, M. J., Rackley, C. R., Bowie, E. J., Keene, D. R., Stripp, B. R., ... & Hogan, B. L. (2013). Type 2 alveolar cells are stem cells in adult lung. The Journal of clinical investigation, 123(7), 3025.

BACKGROUND & AIMS: Liver CRIg+ (complement receptor of the immunoglobulin superfamily) macrophages play a critical role in filtering bacteria and their products from circulation. Translocation of microbiota-derived products from an impaired gut barrier contributes to the development of obesity-associated tissue inflammation and insulin resistance. However, the critical role of CRIg+ macrophages in clearing microbiota-derived products from bloodstream in the context of obesity is largely unknown. METHODS: We performed studies with CRIg(−/−), C3(−/−), cGAS(−/−), and their wildtype littermate mice. CRIg+ macrophage population and bacterial DNA abundance were examined in both mouse and human liver by either flow cytometric or immunohistochemistry analysis. Gut microbial DNA containing extracellular vesicles (mEVs) were adoptively transferred into CRIg(−/−), C3(−/−), or WT mice, and tissue inflammation and insulin sensitivity were measured in these mice. After cocultured with gut mEVs, cellular insulin responses and cGAS/STING-mediated inflammatory responses were evaluated. RESULTS: Gut mEVs can reach metabolic tissues in obesity. Liver CRIg+ macrophages efficiently clear mEVs from the bloodstream through a C3-dependent opsonization mechanism, while obesity elicits a marked reduction in CRIg+ macrophage population. Depletion of CRIg+ cells results in the spread of mEVs into distant metabolic tissues and subsequently exacerbating tissue inflammation and metabolic disorders. Additionally, in vitro treatment of obese mEVs directly triggers inflammation and insulin resistance of insulin target cells. Depletion of microbial DNAs blunts the pathogenic effects of intestinal EVs. Furthermore, cGAS/STING pathway is crucial for microbial DNA-mediated inflammatory responses. CONCLUSIONS: Deficiency of CRIg+ macrophages and leakage of intestinal EVs containing microbial DNA contribute to the development of obesity-associated tissue inflammation and metabolic diseases.

Hypertension (HTN) is a pandemic associated with inflammation and excessive production of catecholamines. Previous work has shown that hypertensive patients have reduced plasma levels of Catestatin (CST), a bioactive cleavage product of the prohormone Chromogranin A (CgA). Similarly, in mouse models, HTN symptoms can be reduced by administration of CST, but the role of CST in the regulation of cardiovascular function is unknown. In the present study, we generated mice with knockout (KO) of the region of the CgA gene coding for CST (CST-KO) and found that CST-KO mice are not only hypertensive as predicted, but also display left ventricular hypertrophy, have marked macrophage infiltration of the heart and adrenal gland, and have elevated levels of pro-inflammatory cytokines and catecholamines. Additionally, intraperitoneal injection with CST reverses these phenotypes, and ischemic pre-conditioning-induced cardioprotection was also abolished in CST-KO mice. To further explore the relationship between HTN, CST, and macrophages, experiments with chlodronate depletion of macrophages and bone-marrow transfer showed that macrophages produce CST and that the anti-hypertensive effects of CST are mediated in part via immunosuppression of macrophages by CST as a form of feedback inhibition. The data thus implicate CST as a key autocrine attenuator of the cardiac inflammation in HTN by reducing macrophage inflammation.

Investment in Mutual Funds (MF) has generated increasing interest among the investors over last few decades as it provides an opportunity for flexible and transparent choice of funds to diversify risk while having return potential. MF are essentially a portfolio wherein investors’ funds are invested in the securities traded in the capital market while sharing a common objective. However, selection and management of different asset classes pertaining to a particular MF are done by an active fund manager under regulatory supervision. Hence, for an individual investor, it is important to assess the performances of the MF before investment. Performances of MF depend on several criteria based on risk-return measures. Hence, selection of MF is subject to satisfying multiple criteria. In this paper, we have adopted an ensemble approach based on a two-stage framework. Our sample consists of the open ended equity large cap funds (direct plan) in India. In the first stage,the efficiencies of the funds are analyzed using DEA for primary selection of the funds. In order to rank the funds based on risk and return parameters for investment portfolio formulation, we have used MABAC approach in the second stage wherein criteria weights have been calculated using the Entropy method.

This study has tried to see what factors do play a significant role in the B-School selection process of an aspirant. The study also would like to see the constituent elements of the factors which come to the mind of the prospective takers, herein, the prospective students. The study pursued here has significant relevance in its purpose as it is one of its kind in this country, and that the rising market demands a study which would be helpful to the pursuant as well as the service providers. The existing management institutions in the country are challenged for their survival. This study intends to make their work easier by identifying the most important factors which the ‘prospective candidates’ look for while selecting their B-School. For this purpose, we have conducted an Exploratory Factor Analysis (EFA) on the responses obtained from a sample of 594 respondents through questionnaire based survey and interviews. Further, in order to ascertain the results, we have done the Confirmatory Factor Analysis (CFA) using Structural Equation Modeling (SEM) approach of the first order type. The result of SEM conforms to that of EFA.

Summary Insulin resistance is a major factor in obesity-linked type 2 diabetes. PPARγ is a master regulator of adipogenesis, and small molecule agonists, termed thiazolidinediones, are potent therapeutic insulin sensitizers. Here, we studied the role of transcriptional co-activator with PDZ-binding motif (TAZ) as a transcriptional co-repressor of PPARγ. We found that adipocyte-specific TAZ knockout (TAZ AKO) mice demonstrate a constitutively active PPARγ state. Obese TAZ AKO mice show improved glucose tolerance and insulin sensitivity compared to littermate controls. PPARγ response genes are upregulated in adipose tissue from TAZ AKO mice and adipose tissue inflammation was also decreased. In vitro and in vivo mechanistic studies revealed that the TAZ-PPARγ interaction is partially dependent on ERK-mediated Ser112 PPARγ phosphorylation. As adipocyte PPARγ Ser112 phosphorylation is increased in obesity, repression of PPARγ activity by TAZ could contribute to insulin resistance. These results identify TAZ as a new factor in the development of obesity-induced insulin resistance.

Decreased adipose tissue oxygen tension and increased HIF-1α expression can trigger adipose tissue inflammation and dysfunction in obesity. Our current understanding of obesity-associated decreased adipose tissue oxygen tension is mainly focused on changes in oxygen supply and angiogenesis. Here, we demonstrate that increased adipocyte O2 demand, mediated by ANT2 activity, is the dominant cause of adipocyte hypoxia. Deletion of adipocyte Ant2 improves obesity-induced intracellular adipocyte hypoxia by decreasing obesity-induced adipocyte oxygen demand, without effects on mitochondrial number or mass, or oligomycin-sensitive respiration. This led to decreased adipose tissue HIF-1α expression and inflammation with improved glucose tolerance and insulin resistance in both a preventative or therapeutic setting. Our results suggest that ANT2 may be a target for the development of insulin sensitizing drugs and that ANT2 inhibition might have clinical utility.

Efficient market hypothesis (EMH), one of the central pillars of modern financial theories, often fails to explain the ?financial anomalies?. One fatal challenge of EMH probably comes from the theoretical assumption of ?rational man?. According to EMH, the fully rational investor may change his demand for financial assets on the basis of available information. According to EMH, at any given point of time, the stock price should reflect all the available information, and predictability of stock returns should be impossible. However, the literature shows ample evidence of abnormal returns related to firm and market specific attributes. In financial literature, these variations are often termed as ?financial anomalies?. Within the framework of behavioural finance, there are research results that contain evidence on predictability of future stock market returns based on financial anomalies (Stanivuk et al., 2012). Value effect and momentum effect are the two prominent financial anomalies (Ho, 2012). This paper explores the predictability of Indian stock market returns using multiple discriminant analysis. Our result shows that the risk premium, momentum and value effect may have significant power for predicting the Indian stock market returns. The validity test of the model also corroborates the impact of financial anomalies over predictability of stock returns.

INTRODUCTION:Governments at all levels have to play a major role in developing urban infrastructure which strengthens the base of an economy. Indian Constitutionhas provided for a three tiers federal structure (Union, State and Local) specifying the powers and responsibilities for all the tires of the governments. Therefore, it is the desired intention of the Constitution that all the tiers of the Governments work in a co -ordinated manner well within limits of the Constitution for urban infrastructure development. Third tier of Governments are generally termed as local self-governments and it has two wings, one which operates in the rural areas and the other in the urban areas. Constitutional status has been provided to these local governments through the 73th and 74th Constitutional Amendment Acts, 1992. Local self-governmentoperating in urban areas are commonly known as "Urban Local Self Governments".Prior to the Amendment Act, the plan for local infrastructure development were used to be drawn by the upper tier governmentswhere local requirement would not be considered. Therefore, the amendment is a direction to the state governments for transfer of power and responsibilities to the local governments with respect to preparation of plans for economic development and social justice, and also for the implementation of development schemes as may be required to enable the local governments to function as institutions of self-government. Unfortunately the issue of empowerment of the local selfgovernments has been left at the discretion of the state governments and as a result legislation primarily aims to make urban local bodies accountable to their stategovernment rather than to the citizens (The World Bank, 2007).Urban Local Self Governments (hereinafter referred to as ULSG) are of three types: (i) Nagar Panchayats for areas in transition from a rural area tourban area; (ii) Municipal Councils for smaller urban areas; (iii) Municipal Corporations for larger urban areas.India is also in the stage of rapid urbanization like other countries in the World and the constitution has provided different and concurrent list of works for different levels of governments. The role of ULGs, after becoming statutorily responsible for providing basic infrastructural facilities and maintenance of the same in the urban areas, has become more and more important.ULSGs find it difficult to balance between the limited financial resources and the unlimited needs for public services. (Tesu, 2011).FINANCIAL ANALYSIS OF ULSGs:ULSGs are statutorily responsible to carry out decentralized functions effectively and this requires presence of two important elements: adequate level of revenue either raised locally or transferred from the central government and the authority to make decisions about expenditures (Meddzi and Gondo, 2010). Finance of ULSGs consists of two major sources: own source and external source. Own source of receipts basically includes tax and non-tax receipts within the assigned power whereas external source constitutes a major portion of grant and assignments from upper tiers including contribution from others, loan from bank or financial institution and fund raised through issue of bonds.Psycharis and Iliopoulou(2016) have commented that local municipalities in Greece have a limited extent of tax or other forms of fiscal autonomy and therefore still rely heavily on fiscally centralized revenue sources. This situation also prevails in the ULSGs in India. Several literaturesshow that the dependency is due to the constitutional imbalance between the enormous functions and legitimate source of finances. ULSGs in India have lowest tax base (property tax, advertisement tax etc.)and upper tiers enjoy higher tax bases. Therefore,funds collected by the upper tiers are devolved to the lower levels of governments but not at the desired level. In order to resolve the imbalance, the amendment act has stated for constitution of state finance commission in every state which in addition to finance commission constituted by the central government. …

Tissue inflammation is a key component of obesity-induced insulin resistance, with a variety of immune cell types accumulating in adipose tissue. Here, we have demonstrated increased numbers of B2 lymphocytes in obese adipose tissue and have shown that high-fat diet-induced (HFD-induced) insulin resistance is mitigated in B cell-deficient (Bnull) mice. Adoptive transfer of adipose tissue B2 cells (ATB2) from wild-type HFD donor mice into HFD Bnull recipients completely restored the effect of HFD to induce insulin resistance. Recruitment and activation of ATB2 cells was mediated by signaling through the chemokine leukotriene B4 (LTB4) and its receptor LTB4R1. Furthermore, the adverse effects of ATB2 cells on glucose homeostasis were partially dependent upon T cells and macrophages. These results demonstrate the importance of ATB2 cells in obesity-induced insulin resistance and suggest that inhibition of the LTB4/LTB4R1 axis might be a useful approach for developing insulin-sensitizing therapeutics.

Chromogranin A (CgA) is widely expressed in endocrine and neuroendocrine tissues as well as in the central nervous system. We observed CgA expression (mRNA and protein) in the gastrocnemius (GAS) muscle and found that performance of CgA-deficientChga-KO mice in treadmill exercise was impaired. Supplementation with CgA inChga-KO mice restored exercise ability suggesting a novel role for endogenous CgA in skeletal muscle function.Chga-KO mice display (i) lack of exercise-induced stimulation of pAKT, pTBC1D1 and phospho-p38 kinase signaling, (ii) loss of GAS muscle mass, (iii) extensive formation of tubular aggregates (TA), (iv) disorganized cristae architecture in mitochondria, (v) increased expression of the inflammatory cytokinesTnfα,Il6andIfnγ, and fibrosis. The impaired maximum running speed and endurance in the treadmill exercise inChga-KO mice correlated with decreased glucose uptake and glycolysis, defects in glucose oxidation and decreased mitochondrial cytochrome C oxidase activity. The lack of adaptation to endurance training correlated with the lack of stimulation of p38MAPK that is known to mediate the response to tissue damage. As CgA sorts proteins to the regulated secretory pathway, we speculate that lack of CgA could cause misfolding of membrane proteins inducing aggregation of sarcoplasmic reticulum (SR) membranes and formation of tubular aggregates that is observed inChga-KO mice. In conclusion, CgA deficiency renders the muscle energy deficient, impairs performance in treadmill exercise and prevents regeneration after exercise-induced tissue damage.

Introduction: Considering morbidity and mortality, depression is a burning issue in the modern civilization. Early diagnosis and treatment significantly reduces the incidence of morbidity and mortality. In this context, the present study was conducted to find the prevalence and associated factors of depression among adult population of Siliguri subdivision, Darjeeling district, West Bengal. Materials and Methods: A community-based cross-sectional study was conducted among adult population (≥18 years) of Siliguri subdivision of Darjeeling district, West Bengal. Thirty-cluster sampling method was used to identify the study participants. Beck's depression inventory–II was used as the screening tool. Binary logistic regression was done to find the associated factors of depression using IBM SPSS software Version 20.0 (Armonk, New York). Results: Overall, 36% of the study participants were depressed and 11% were significantly depressed. In binary logistic regression, female gender, rural resident, and lower educational status were found to be significantly associated with depression. Conclusion: Screening of depression and early identification of associated factors helps in reducing the adverse outcome of depression. More than one-third of the population depressed and there were some modifiable associated factors such as educational status and rural residence.

Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

Serine-rich splicing factor 3 (SRSF3) plays a critical role in liver function and its loss promotes chronic liver damage and regeneration. As a consequence, genetic deletion of SRSF3 in hepatocytes caused progressive liver disease and ultimately led to hepatocellular carcinoma. Here we show that SRSF3 is decreased in human liver samples with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), or cirrhosis that was associated with alterations in RNA splicing of known SRSF3 target genes. Hepatic SRSF3 expression was similarly decreased and RNA splicing dysregulated in mouse models of NAFLD and NASH. We showed that palmitic acid–induced oxidative stress caused conjugation of the ubiquitin-like NEDD8 protein to SRSF3 and proteasome-mediated degradation. SRSF3 was selectively neddylated at lysine 11 and mutation of this residue (SRSF3-K11R) was sufficient to prevent both SRSF3 degradation and alterations in RNA splicing. Lastly, prevention of SRSF3 degradation in vivo partially protected mice from hepatic steatosis, fibrosis, and inflammation. These results highlight a neddylation-dependent mechanism regulating gene expression in the liver that is disrupted in early metabolic liver disease and may contribute to the progression to NASH, cirrhosis, and ultimately hepatocellular carcinoma.