Paleozoic to Cenozoic sedimentary bedrock geology and lithostratigraphy of Singapore

A new lithostratigraphical framework for Singapore is proposed, based on the analysis of c. 20,000 m of core recovered from 121 c. 205 m deep boreholes and augmented with 218 field localities from across Singapore. The new framework describes a succession dating from the Carboniferous to the Quaternary. New U-Pb detrital zircon dates and fossil analysis were used to constrain the ages of key sedimentary units. The oldest known sedimentary rocks in Singapore are found to be the deformed Carboniferous (Mississippian) Sajahat Formation. These are succeeded by the newly erected, Middle and Upper Triassic, marine to continental Jurong Group and Sentosa Group successions that accumulated in the southern part of the Semantan Basin. The Jurong Group comprises four formations: the Tuas Formation, the Pulau Ayer Chawan Formation, the Pandan Formation and the Boon Lay Formation. The Sentosa Group contains two formations: the Tanjong Rimau Formation and the Fort Siloso Formation. In Singapore, the depositional record during this time is related to late Permian to Triassic arc magmatism in the southern part of the forearc basin to the Sukhothai Arc. The Jurong and Sentosa groups were deformed and weakly metamorphosed during the final stages of the Late Triassic to Early Jurassic orogenic event, deformation that led to the formation of the syn-orogenic conglomerates of the Buona Vista Formation. Following this, two distinct Lower Cretaceous sedimentary successions overstepped the Jurong and Sentosa group strata, including the Kusu Formation and the Bukit Batok Formation, both deposited in the southern part of the Tembeling Basin. A series of Neogene to Quaternary formations overly the Mesozoic and Palaeozoic stratigraphy, including the Fort Canning Formation, Bedok Formation and the Kallang Group

Novel Smart N95 Filtering Facepiece Respirator with Real-time Adaptive Fit Functionality and Wireless Humidity Monitoring for Enhanced Wearable Comfort

The widespread emergence of the COVID-19 pandemic has transformed our lifestyle, and facial respirators have become an essential part of daily life. Nevertheless, the current respirators possess several limitations such as poor respirator fit because they are incapable of covering diverse human facial sizes and shapes, potentially diminishing the effect of wearing respirators. In addition, the current facial respirators do not inform the user of the air quality within the smart facepiece respirator in case of continuous long-term use. Here, we demonstrate the novel smart N-95 filtering facepiece respirator that incorporates the humidity sensor and pressure sensory feedback-enabled self-fit adjusting functionality for the effective performance of the facial respirator to prevent the transmission of airborne pathogens. The laser-induced graphene (LIG) constitutes the humidity sensor, and the pressure sensor array based on the dielectric elastomeric sponge monitors the respirator contact on the face of the user, providing the sensory information for a closed-loop feedback mechanism. As a result of the self-fit adjusting mode along with elastomeric lining, the fit factor is increased by 3.20 and 5 times at average and maximum respectively. We expect that the experimental proof-of-concept of this work will offer viable solutions to the current commercial respirators to address the limitations.Comment: 20 pages, 5 figures, 1 table, submitted for possible publicatio

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

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