Investigations of a THGEM-based imaging detector

We present the results of our recent studies on a Thick Gas Electron Multiplier (THGEM)-based imaging detector prototype. It consists of two 100x100 mm^2 THGEM electrodes in cascade, coupled to a resistive anode. The event location is recorded with a 2D double-sided readout electrode equipped with discrete delay-lines and dedicated electronics. The THGEM electrodes, produced by standard printed-circuit board and mechanical drilling techniques, a 0.4 mm thick with 0.5 mm diameter holes spaced by 1 mm. Localization resolutions of about 0.7 mm (FWHM) were measured with soft x-rays, in a detector operated with atmospheric-pressure Ar/CH4; good linearity and homogeneity were achieved. We describe the imaging-detector layout, the resistive-anode 2D readout system and the imaging properties. The THGEM has numerous potential applications that require large-area imaging detectors, with high-rate capability, single-electron sensitivity and moderate (sub-mm) localization resolution.Comment: Published in JINST, 22 pages, 18 figure

Using Mendelian randomisation to identify opportunities for type 2 diabetes prevention by repurposing medications used for lipid management

Background: Maintaining a healthy lifestyle to reduce type 2 diabetes (T2D) risk is challenging and additional strategies for T2D prevention are needed. We evaluated several lipid control medications as potential therapeutic options for T2D prevention using tissue-specific predicted gene expression summary statistics in a two-sample Mendelian randomisation (MR) design. Methods: Large-scale European genome-wide summary statistics for lipids and T2D were leveraged in our multi-stage analysis to estimate changes in either lipid levels or T2D risk driven by tissue-specific predicted gene expression. We incorporated tissue-specific predicted gene expression summary statistics to proxy therapeutic effects of three lipid control medications [i.e., statins, icosapent ethyl (IPE), and proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK-9i)] on T2D susceptibility using two-sample Mendelian randomisation (MR). Findings: IPE, as proxied via increased FADS1 expression, was predicted to lower triglycerides and was associated with a 53% reduced risk of T2D. Statins and PCSK-9i, as proxied by reduced HMGCR and PCSK9 expression, respectively, were predicted to lower LDL-C levels but were not associated with T2D susceptibility. Interpretation: Triglyceride lowering via IPE may reduce the risk of developing T2D in populations of European ancestry. However, experimental validation using animal models is needed to substantiate our results and to motivate randomized control trials (RCTs) for IPE as putative treatment for T2D prevention. Funding: Only summary statistics were used in this analysis. Funding information is detailed under Acknowledgments. © 2022Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The Comparison of the culture operation of Artemia franciscana and parthenogenetic species on the sidelines of Qom Salt Lake

Qom Province with an area of 11,238 km^2 , surrounds about 0.68%of the country area and almost situated in the center of the country and enjoys a hot and dry climate . Because of the unique flora and fauna of the region especially the salt pools - hoze- Sultan and salt lakes enjoys a certain ecosystem in the country. Research has done in different parts of Iran and Qom province regarding the Artemia culture in salt lands that showed a great potential in the country and Qom province. The aim of this study that was held in order of Qom fisheries institute and environmental protection organization of that province and scientific leadership of Iranian Artemia Research Center, was the culture of Qom native Artemia and Artemia franciscana ( foreign species ) across Qom salt lake and determining the prevalence of cultured species in this region for this purpose, site selection and climatic and topographic data collection was held at 5 regions of Qom province. This regions were included margins of salt lake, and hoze sultan, shams abad drainage, railway station, and freshwater culture farm at the north east of Qom salt lake. margins of salt lake, and hoze sultan, were suitable for Artemia investment due to suitable climate and vast area, but they had problems in terms of technical facilities and access to areas . Also, the rail way station and plantation industry had dehydration problems. Therefore, after reviewing the field of agricultural water taken along the 45 km of Kashan and Qom Salt Lake were selected for the project because of the salty ecosystem similar to the lake, presence of salt water drainages downstream of the farm , technical facilities and a large area , soil texture and easy access to the area . For this purpose, six pools with 50 square meters near the reservoir pool available were constructed and 70 g native Artemia cysts of Qom and 23/3 g cysts of Artemia franciscana were hatched in Zooks of 10 liters for each pool ea of 50 square meters under standard condition (salinity 35 ppt pH =8, light lux 2000 and temperature 28°C). By calculating the useful volume of water for culture (112 cubic meters) and Hatching efficiency for native Artemia of Qom (40,000) and Artemia franciscana (120,000), the number of 25 nauplii per liter equal to the 2.8 million nauplii were released to each pool with size 4 × 12 m and high slope with area of 50 meter in the floor and 273 meters in the surface . Non- biological and biological studies, including algae and water analysis and population assessments were performed regularly in pools every 2 weeks. the culture period were from July to mid- October, 2009 for a period of 3/5 months. The results of algal study revealed more abundance of Cholestrium, Navicula, Nitzshia algae during culture period (105 days), that Amphora, etraselmis, Cymbella, Senedesmus, Dscillatoria, Gomphonema genera were observed, too. The results of water parameters analysis revealed that they should preserve at salinity 40–50 ppt, pH 8, water hardness 7000- 9000 mg. the results of population assessment showed a larger amounts of female broods of Qom Artemia at days 15,30 and 90 of culture with average number of 120.3, 68.8 and 29.5 per liter, respectively, comparing to Artemia franciscana with average number of 28.8, 17.5 and 7.7 per liter that was significant (p<0.05). The results indicated the greater development and adaptation of native Artemia of Qom at the culture ecosystem of Qom (Kesht va Sanaat Ab Shirin farm at the northeast of Qom salt lake). Harvesting of Artemia biomass of native Qom with the amount of 30 kg/100m^2 showed the production of native Artemia is relatively economic and during culture period (105 days) the mean cyst production for native Qom Artemia and Artemia franciscana were 193 and 123.5 individuals/liter, respectively. It can be concluded that native Qom Artemia enjoys a greater adaptation in growth and development with the arid ecosystem of the region and can be used as a valuable biologic stock in culturing purposes and developing native Artemia strains of the country and investments in construction of Artemia culture pilots in salt areas situated at Qom salt lake

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk