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- Butler-Laporte, G, et al.
(författare)
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Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
- 2022
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 18:11, s. e1010367-
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Tidskriftsartikel (refereegranskat)abstract
- Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
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- Rehman, S., et al.
(författare)
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Experimental Investigation of Temperature Effect on Corrosive Sulfur Formation in Transformers
- 2017
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Ingår i: IEEE transactions on dielectrics and electrical insulation. - : IEEE. - 1070-9878 .- 1558-4135. ; 24:5, s. 3201-3206
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents experimental findings of the effect of temperature on corrosive sulfur formation in transformers. To conduct the experimental study, new transformer oil was randomly selected and heated at 40, 60, 80, 120, and 150 degrees C temperature for 72 hours each along with copper strips wrapped with insulation paper and immersed in oil in accordance with IEC-62535 standard test covered conductor deposition (CCD). The oil, copper strips, and the insulation paper samples were evaluated using gas chromatography-sulfur chemiluminescence detector (GC-SCD), X-ray fluorescence spectroscopy (XRF), inductively coupled plasma optical emission spectrometry (ICP), and scanning electron microscopy (SEM) tests after 72 hours exposure at each temperature. The values so obtained, were analyzed and effect of temperature on various parameters was studied individually and as well as collectively. It was found that temperature plays an important role on corrosive sulfur formation process inside the transformers and hence the temperature of the oil should be kept within the allowed operating ranges for avoiding unforeseen failures.
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- Rehman, Shafiqur, et al.
(författare)
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Study of Limit Concentrations of DBDS and Sulfur Mercaptan in Power Transformers
- 2016
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Ingår i: 2016 IEEE ELECTRICAL INSULATION CONFERENCE (EIC). - : IEEE conference proceedings. - 9781467387064 ; , s. 37-39
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Konferensbidrag (refereegranskat)abstract
- The study presents the results of experimental investigation of finding out the limit concentrations of DBDS and sulfur mercaptan for safe and prolonged operation of power transformers in the local environmental conditions of Saudi Arabia. For experimental investigation of limit concentrations of DBDS and sulfur mercaptan, new oil free of sulfur compounds was acquired. Four specimens of this were spiked with 2.2, 3.9, 5.4 and 10.2 ppm of DBDS and another four with free sulfur mercaptan RSH concentrations of 0.00, 0.52, 1.07, 2.13, and 7.10 ppm. The covered conductor deposition (CCD) tests were performed in accordance with IEC 62535 method on all the specimens. The experimental results indicated that the concentration of DBDS should always be <5 ppm and sulfur mercaptan <1 ppm in the new oils before putting in to the service.
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- Al-Wathinani, Ahmed M, et al.
(författare)
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A Cross-Sectional Study on the Flood Emergency Preparedness among Healthcare Providers in Saudi Arabia.
- 2021
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- This study used a descriptive cross-sectional methodology to measure healthcare workers' knowledge, attitudes, perceptions, and willingness to respond to a flood scenario in Saudi Arabia. A validated survey was distributed to collect data using a convenience sampling technique through multiple social media platforms. A total of 227 participants were included in this study: 52% of them were aged between 26 to 34 years, 74% were residents from Riyadh, and 52.4% worked in nursing divisions. A significant number of respondents (73.2%) had positive perceptions towards their hospitals' ability to provide an effective response to a flood, 89% were willing to report to work following a flood, and 90% of participants reported the need to develop both guidelines and training for flood disaster preparedness. Preparation and successful flood mitigation in the hospital setting requires staff that have both knowledge and training in emergency management. One way to obtain such readiness is through competency-based training, including both table-top and full-scale live exercises. Although the willingness to respond to such a flooding emergency was high among staff, the development of guidelines and educational programs is needed in order to develop the competencies and skills sets to improve disaster preparedness response and preparedness efforts.
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- Roberts, AG, et al.
(författare)
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NMR-Derived Models of Amidopyrine and Its Metabolites in Complexes with Rabbit Cytochrome P450 2B4 Reveal a Structural Mechanism of Sequential N-Dealkylation
- 2011
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Ingår i: BIOCHEMISTRY. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 50:12, s. 2123-2134
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Tidskriftsartikel (refereegranskat)abstract
- To understand the molecular basis of sequential N-dealkylation by cytochrome P450 2B enzymes, we studied the binding of amidopyrine (AP) as well as the metabolites of this reaction, desmethylamidopyrine (DMAP) and aminoantipyrine (AAP), using the X-ray crystal structure of rabbit P450 2B4 and two nuclear magnetic resonance (NMR) techniques: saturation transfer difference (STD) spectroscopy and longitudinal (T1) relaxation NMR. Results of STD NMR of AP and its metabolites bound to P450 2B4 were similar, suggesting that they occupy similar niches within the enzyme’s active site. The model-dependent relaxation rates (RM) determined from T1 relaxation NMR of AP and DMAP suggest that the N-linked methyl is closest to the heme. To determine the orientation(s) of AP and its metabolites within the P450 2B4 active site, we used distances calculated from the relaxation rates to constrain the metabolites to the X-ray crystal structure of P450 2B4. Simulated annealing of the complex revealed that the metabolites do indeed occupy similar hydrophobic pockets within the active site, while the N-linked methyls are free to rotate between two binding modes. From these bound structures, a model of N-demethylation in which the N-linked methyl functional groups rotate between catalytic and noncatalytic positions was developed. This study is the first to provide a structural model of a drug and its metabolites complexed to a cytochrome P450 based on NMR and to provide a structural mechanism for how a drug can undergo sequential oxidations without unbinding. The rotation of the amide functional group might represent a common structural mechanism for N-dealkylation reactions for other drugs such as the local anesthetic lidocaine.
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