671 research outputs found
Environmental toxicity, redox signaling and lung inflammation:the role of glutathione
Full text linkGlutathione (gamma-glutamyl-cysteinyl-glycine, GSH) is the most abundant intracellular antioxidant thiol and is central to redox defense during oxidative stress. GSH metabolism is tightly regulated and has been implicated in redox signaling and also in protection against environmental oxidant-mediated injury. Changes in the ratio of the reduced and disulfide form (GSH/GSSG) can affect signaling pathways that participate in a broad array of physiological responses from cell proliferation, autophagy and apoptosis to gene expression that involve H(2)O(2) as a second messenger. Oxidative stress due to oxidant/antioxidant imbalance and also due to environmental oxidants is an important component during inflammation and respiratory diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and asthma. It is known to activate multiple stress kinase pathways and redox-sensitive transcription factors such as Nrf2, NF-kappaB and AP-1, which differentially regulate the genes for pro-inflammatory cytokines as well as the protective antioxidant genes. Understanding the regulatory mechanisms for the induction of antioxidants, such as GSH, versus pro-inflammatory mediators at sites of oxidant-directed injuries may allow for the development of novel therapies which will allow pharmacological manipulation of GSH synthesis during inflammation and oxidative injury. This article features the current knowledge about the role of GSH in redox signaling, GSH biosynthesis and particularly the regulation of transcription factor Nrf2 by GSH and downstream signaling during oxidative stress and inflammation in various pulmonary diseases. We also discussed the current therapeutic clinical trials using GSH and other thiol compounds, such as N-acetyl-l-cysteine, fudosteine, carbocysteine, erdosteine in environment-induced airways disease
Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease
Full text linkChronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD
Dietary polyphenols mediated regulation of oxidative stress and chromatin remodeling in inflammation
Full text linkDiabetes Datasets
No full textThese datasets were used to develop machine and deep learning classifiers to predict diabetes. The two datasets were separately used to compare how each classifier performed during model training and testing phases.Both datasets are publicly accessible and can be cited as follows:P. Turney, Pima Indians diabetes data set, UCI ML Repository. Originally from: National Institute of Diabetes and Digestive and Kidney Diseases (1990).M. Islam, R. Ferdousi, S. Rahman, H. Y. Bushra, Likelihood prediction of diabetes at early stage using data mining techniques, in: Computer Vision and Machine Intelligence in Medical Image Analysis, Springer, 2020, pp. 113–125. doi:10.1007/978-981-13-8798-2_12
Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2 reduction
Full text linkAbnormal lung inflammation and oxidant burden are associated with a significant reduction in histone deacetylase 2 (HDAC2) abundance and steroid resistance. We hypothesized that Nrf2 regulates steroid sensitivity via HDAC2 in response to inflammation in mouse lung. Furthermore, HDAC2 deficiency leads to steroid resistance in attenuating lung inflammatory response, which may be due to oxidant/antioxidant imbalance. Loss of antioxidant transcription factor Nrf2 resulted in decreased HDAC2 level in lung, and increased inflammatory lung response which was not reversed by steroid. Thus, steroid resistance or inability of steroids to control lung inflammatory response is dependent on Nrf2-HDAC2 axis. These findings have implications in steroid resistance, particularly during the conditions of oxidative stress when the lungs are more susceptible to inflammatory response, which is seen in patients with chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, and inflammatory bowel disease
Herméneutique coranique et objectivité du sens (la critique philosophique de Fazlur Rahman dans la Turquie contemporaine)
No full textSe revendiquant d E. Betti dans le débat qu il eut avec H.-G. Gadamer, Fazlur Rahman propose une herméneutique du double mouvement afin de connaître avec certitude le sens objectif du Coran. Ainsi, l interprète, dont la démarche est historiciste, doit d abord chercher les finalités morales du texte, identifiées à l intention divine. Cette interprétation méthodologique nécessite la connaissance du contexte de la révélation, dont Rahman souligne l historicité. Puis, cette signification sera appliquée à la situation présente en dépassant le sens littéral. Or une critique philosophique d inspiration gadamérienne a été adressée à Rahman dans la Turquie contemporaine, où il lui a été reproché de ne pas tenir compte de l historicité de l interprète qui l empêche de connaître objectivement les intentions de l auteur. Il s agit moins de condamner toute interprétation à un inévitable subjectivisme que de montrer que Rahman présente sa propre subjectivité comme objective. L herméneutique philosophique s opposant à cette approche épistémologique veut donc remettre en question la prétention à la maîtrise du sens du texte qui, étant donné sa sacralité, ne saurait être assujetti à l interprète. Le Coran ne pouvant être objectivé, le lecteur doit renoncer à l idée d une unique bonne méthode, et se laisser transformer par le texte avec lequel son rapport est avant tout ontologique. Dès lors, la relation qu entretient l interprète avec les multiples lectures du Coran, passées et présentes, permet de réinvestir la créativité d une tradition d interprétations et de penser avec Paul Ricœur la possibilité d un conflit bienveillant des méthodes, incluant l approche rahmanienne elle-même.Using E. Betti s arguments in his debate with H.-G. Gadamer, Fazlur Rahman proposes a double movement hermeneutics to know with certainty the objective meaning of the Koran. Thus, the interpreter, whose approach is historicist, must, at first, look for the moral purposes of the text, identified with the divine intention. This methodological interpretation requires the knowledge of the context of the revelation, which Rahman underlines the historicity of. This significance will be applied, secondly, to the present situation by exceeding the literal meaning. However a philosophical critique inspired by Gadamer was sent to Rahman in contemporary Turkey, where he was criticised for not taking into account the historicity of the interpreter that prevents him knowing objectively the intentions of the author. The purpose of this critique is not to condemn any interpretation to an inevitable subjectivism but to show that Rahman presents his own subjectivity as objective. Philosophical hermeneutics, which opposes this epistemological approach, wants to question the claim to control the meaning of the text, which, because of its sacredness, cannot be subjected to the interpreter. As the Koran can not be objectified, the reader must renounce the idea of a single right method and let the text with which his relationship is above all ontological transform him. Therefore, the relation that maintains the interpreter with the multiples readings of the Koran, past and present, allows to reinvest the creativity of a tradition of interpretations and to think with Paul Ricœur about the possibility of a friendly conflict of the methods, including the rahmanian approach itself.PARIS3-BU (751052102) / SudocSudocFranceF
Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation
Full text linkDeficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction
Peer-to-Peer System Design: A Socioeconomic approach
No full textIt has gradually become clear that Peer-to-Peer (P2P) systems should not be conceived in the manner of conventional computing systems. Consequently, over the years, ideas from social science in general and economics in particular have made their way to P2P systems to deal with the novel challenges that such systems throw up. In Chapter 2 of this thesis we examine many of the socioeconomic ideas that have been employed in the literature. We discover that the economic ideas that have been utilized for incentive related works in P2P systems are imbued in the rational action framework. The assumptions entailed in this framework drive the solutions to free-riding in P2P incentive works, and also impinge upon the usage of terms such as fairness, social welfare, etc. Our examination leads us to accomplish three major tasks: 1) We argue for the reconsideration of commonly used concepts and paradigms; 2) We propose novel socioeconomic concepts and approaches for the design of P2P systems; and 3) We open up new areas that could benefit from the use of socioeconomic ideas. In Chapter 3 we take inspiration from opinion gathering techniques such as VoxPopuli; voting tools such as the Ballot Box; and general acceptance of the opinion of \emph{experienced} members of the society, to devise a voting infrastructure to fight spam in Tribler, a P2P media distribution system In Chapter 4 we indicate that private BitTorrent communities that use sharing ratio enforcement for incentivizing contribution from peers, can face problems such as credit crunches. In Chapter 5, we show that such problems are exacerbated when peers do not follow the rational user model. We also present some ways in which these problems can be rectified. In Chapter 6 and 7, we argue for the consideration of alternate viewpoints viz a viz concepts such as fairness, freeriding and social welfare; and for formulation of alternatives to game-theoretic solution concepts for assessing the robustness and performance of distributed protocols. In Chapter 6 we propose effort based incentives with a novel concept of fairness, for improving efficiency and fairness in P2P systems. In Chapter 7 we argue that the goal of most earlier P2P works, of achieving a Nash equilibrium when all peers are rational, is limited. We present Design Space Analysis, a simulation based method that: allows for flexible user behavior assumptions; aims to analyze protocols more comprehensively and not just on a single point in the design space; and provides a tournament based approach for evaluating protocol robustness and performance.Software TechnologyElectrical Engineering, Mathematics and Computer Scienc
Diabetes Datasets
No full textThese datasets were used to develop machine and deep learning classifiers to predict diabetes. The two datasets were separately used to compare how each classifier performed during model training and testing phases.Both datasets are publicly accessible and can be cited as follows:P. Turney, Pima Indians diabetes data set, UCI ML Repository. Originally from: National Institute of Diabetes and Digestive and Kidney Diseases (1990).M. Islam, R. Ferdousi, S. Rahman, H. Y. Bushra, Likelihood prediction of diabetes at early stage using data mining techniques, in: Computer Vision and Machine Intelligence in Medical Image Analysis, Springer, 2020, pp. 113–125. doi:10.1007/978-981-13-8798-2_12.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV
Example of <i>pneu</i>RIP <sup>TM</sup> operation, hardware, and data display.
No full text(A) The pneuRIPTM device uses two bands: one band around the ribcage and one around the abdomen (illustrated by author (TR). (B) The pneuRIPTM wirelessly connects to an iPad and displays data in real-time plots. (C) Typical RIP data from a healthy subject. (D) Typical data from a neuromuscular DMD patient (Image modified from Rahman et al [8]).</p
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