93 research outputs found

    Search for the Sagittarius Tidal Stream of Axion Dark Matter around 4.55 Ό\mueV

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    We report the first search for the Sagittarius tidal stream of axion dark matter around 4.55 ÎŒ\mueV using CAPP-12TB haloscope data acquired in March of 2022. Our result excluded the Sagittarius tidal stream of Dine-Fischler-Srednicki-Zhitnitskii and Kim-Shifman-Vainshtein-Zakharov axion dark matter densities of ρa≳0.184\rho_a\gtrsim0.184 and ≳0.025\gtrsim0.025 GeV/cm3^{3}, respectively, over a mass range from 4.51 to 4.59 ÎŒ\mueV at a 90% confidence level.Comment: 6 pages, 7 Figures, PRD Letter accepte

    Principles of genetic circuit design

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    Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Pan-cancer analysis of whole genomes

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    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

    International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

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    Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

    Report on industrial attachment with Siemens Medical Instruments Pte Ltd

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    This report shall give an account of my work and the experiences gained during my internship with the Siemens Medical Instruments Pte. Ltd. (SMI) from 5 January 2009 to 5 June 2009. The first part of the report will give an overview about SMI and hearing instrument standards. Some common hearing instrument terms will also be discussed in this section followed by the description of the hearing instruments measurements performed in SMI. The main part of the report will discuss about the progress of the four projects involved and the task completed. The main focus of my work is the supporting of Pendo project, where I learnt about the Product Lifecycle Management of a hearing aid project from conceptual to product release. The project also allows me to experiment with the ferrite beads to suppress Electromagnetic Interference (EMI) and expose to the reliability tests conducted in all manufacturing companies. I am also heavily involved in the Active Telecoil bonus project where investigation into cost-effective in-house built of active telecoil without compromising of performance is done. This is the project where I could better relate my electronics knowledge learnt from the University to the project.

    Far field prediction of radiated emission from pcb using near-field measurement

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    This report presents a new near field to far field transformation by using a statistical model approach that has yet to be introduced in the EMC community. The report begins with the introduction of near field to far field transformation which includes the background, motivation, objectives and scope of the project. Next, it will provide theoretical background on the EMC topics and the relationship between near field and far field. The advantages of near field to far field transformation approach are numerous and the transformation has received considerable attention and vast interest from the EMC community over the last few years. A few different approaches will thus be presented in the literature review in chapter two. The main body of the report discusses in detail the methodology of computing far field prediction using two different types of averaging methods. The mathematical principles and reasons behind each averaging method were explained in chapter three and the transformation results will be presented in chapter four, where predicted and actual measure far fields were compared and analyzed in depth. Lastly, the report will end with a conclusion to explain each averaging method and decide on the final approach used and recommendation for future work.Bachelor of Engineerin

    A model-based analysis of evacuation strategies in hospital emergency departments

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    Evacuation planning for emergency incidents is an essential preparedness for Emergency Departments (ED) which normally contains patients with severe illness and limited mobility. However, the preparedness can be challenging due to a lack of empirical data and difficulties conducting physical drills. We propose an agent-based model to simulate the evacuation process in the EDs containing medical staff, rescuers, visitors and various types of patients. In a case study, we apply the model to a peak hour scenario of the ED of the largest hospital in Singapore. Two rescue strategies with different behavior sequences of medical staff as suggested by the practitioners are evaluated. The simulation results show that prioritizing preparation of all the patients generates less total evacuation time but leads to fewer evacuated cases in the first 20 minutes and more serious congestion compared to one-by-one transfer of individual patients.National Research Foundation (NRF)Submitted/Accepted versionThis research is supported by National Research Foundation (NRF) Singapore, GOVTECH under its Virtual Singapore program Grant No. NRF2017VSG-AT3DCM001-031
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