150,456 research outputs found
Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation
No full textDeficiency 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
Stata code: Additive and intersectional analyses for self-health concerns during the COVID-19 pandemic in Canada
No full textThis repository includes two files: (1) a secondary data file with an analytical sample, "Rahman_2022_Covid19 AnalyticalSample_StatCanadaData2020" and (2) a Stata code file, "Rahman_2022_Covid19_StataCode" .Rahman (2022) wrote Stata code to analyse a sub-sample (N=239143) of Statistics Canada’s publicly available crowdsourcing data for findings presented in a book chapter. The purpose of this chapter was to showcase the contrast between additive and intersectional approaches to examine the COVID-19 impact on intersectional groups of Canadians. See Rahman's (2022) methods section and Supplemental Figure S1 in order to learn about this analytical sample.Statistics Canada (2020a) collected crowdsourcing data online from April 3 to 23, 2020 to understand the impacts of the COVID-19 pandemic in Canada. Statistics Canada’s (2020a; 2020b) publicly available complete data set and their documentation can be downloaded from https://doi.org/10.25318/45250003-eng.REFERENCESRahman, Laila. 2022. Concern for self-health during the COVID-19 pandemic in Canada: How to tell an intersectional story using quantitative data? In D. Woolford, D. Kotsopoulos, and B. Samuels (Eds.), Applied Data Science: Data Translators Across the Disciplines, Springer, Interdisciplinary Applied Sciences. (Accepted for publication).Statistics Canada. (2020a, June 3). Crowdsourcing: Impacts of COVID-19 on Canadians. https://doi.org/10.25318/45250003-engStatistics Canada. (2020b). User guide for the crowdsourcing: Impacts of the COVID-19 on Canadians, public use microdata file. https://doi.org/10.25318/45250003-en
Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease
No full textChronic 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
Environmental toxicity, redox signaling and lung inflammation:the role of glutathione
No full textGlutathione (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
Vitamin D & cognition
No full textThis data is collected from patients attending outpatient geriatric clinic for the evaluation of the association between vitamin D deficiency and cognition
Vitamin D & cognition
No full textThis data is collected from patients attending outpatient geriatric clinic for the evaluation of the association between vitamin D deficiency and cognition
Low-cost on-chip clock jitter measurement scheme
No full textIn this paper, we present a low-cost, on-chip clock jitter digital measurement scheme for high performance microprocessors. It enables in situ jitter measurement during the test or debug phase. It provides very high measurement resolution and accuracy, despite the possible presence of power supply noise (representing a major source of clock jitter), at low area and power costs. The achieved resolution is scalable with technology node and can in principle be increased as much as desired, at low additional costs in terms of area overhead and power consumption. We show that, for the case of high performance microprocessors employing ring oscillators (ROs) to measure process parameter variations (PPVs), our jitter measurement scheme can be implemented by reusing part of such ROs, thus allowing to measure clock jitter with a very limited cost increase compared with PPV measurement only, and with no impact on parameter variation measurement resolution
Dietary polyphenols mediated regulation of oxidative stress and chromatin remodeling in inflammation
No full textMeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
Evaluation framework for public R&D program / Norida Abd Rahman
No full textThere is an increasing pressure on policymakers to demonstrate objectivity in the evaluation of the public R&D investments in order to improve the effectiveness and performance of R&D towards achieving better results. Previous literature indicates that evaluation approach for public R&D program would vary among countries as it is highly contextual in nature and country-specific. This study aimed to examine R&D evaluation practices in the given context, building on the body of knowledge in R&D management and program evaluation. An extended new research in this area shall address the question: How can we evaluate public R&D program for improved performance? The underlying objective of this study was to develop an appropriate framework to evaluate the public R&D program within the given country context. Through application of the conceptual framework to a case study, this study examined the main components and the dynamic process of performance evaluation of the public R&D at program level. This study therefore will demonstrate the importance of program evaluation in improving the performance of the public R&D program. This study employed case study, mixed method design to collect data and address the research question. Logic model and cross case analysis techniques were employed to analyze the case study at both the project and program levels. The findings and results at the project level were then aggregated and synthesized at the program level. There are several findings from this study. Firstly, the study examined the current evaluative practices and identified the requisite key evaluation components and evaluation process needed in evaluating the public R&D program. Secondly, the analysis identified the challenges, issues and knowledge gaps in the current evaluative practice with respect to program evaluation process and program design and delivery in the given context. Thirdly, validation and refinement of thematic key factors from literature has been applied to the case study to determine suitable thematic key factors that were suggested to influence the performance of the public R&D program. Additionally, the results from case study identified the critical missing components and process in the current evaluative practice that are prerequisites to developing an objective evaluation framework. Finally, this research synthesized all the findings and suggested the design of an evaluation framework that is appropriate for the given country context. Guided by the initial conceptual framework, the findings contributed to the development of an objective and systematic evaluation framework for the public R&D program together with improvement plan for the given country context
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