Dissecting the physiology and pathophysiology of glucagon-like peptide-1

Copyright © 2018 Paternoster and Falasca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. An aging world population exposed to a sedentary life style is currently plagued by chronic metabolic diseases, such as type-2 diabetes, that are spreading worldwide at an unprecedented rate. One of the most promising pharmacological approaches for the management of type 2 diabetes takes advantage of the peptide hormone glucagon-like peptide-1 (GLP-1) under the form of protease resistant mimetics, and DPP-IV inhibitors. Despite the improved quality of life, long-term treatments with these new classes of drugs are riddled with serious and life-threatening side-effects, with no overall cure of the disease. New evidence is shedding more light over the complex physiology of GLP-1 in health and metabolic diseases. Herein, we discuss the most recent advancements in the biology of gut receptors known to induce the secretion of GLP-1, to bridge the multiple gaps into our understanding of its physiology and pathology

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Performance of the CMS muon trigger system in proton-proton collisions at √s = 13 TeV

The muon trigger system of the CMS experiment uses a combination of hardware and software to identify events containing a muon. During Run 2 (covering 2015-2018) the LHC achieved instantaneous luminosities as high as 2 × 10 cm s while delivering proton-proton collisions at √s = 13 TeV. The challenge for the trigger system of the CMS experiment is to reduce the registered event rate from about 40 MHz to about 1 kHz. Significant improvements important for the success of the CMS physics program have been made to the muon trigger system via improved muon reconstruction and identification algorithms since the end of Run 1 and throughout the Run 2 data-taking period. The new algorithms maintain the acceptance of the muon triggers at the same or even lower rate throughout the data-taking period despite the increasing number of additional proton-proton interactions in each LHC bunch crossing. In this paper, the algorithms used in 2015 and 2016 and their improvements throughout 2017 and 2018 are described. Measurements of the CMS muon trigger performance for this data-taking period are presented, including efficiencies, transverse momentum resolution, trigger rates, and the purity of the selected muon sample. This paper focuses on the single- and double-muon triggers with the lowest sustainable transverse momentum thresholds used by CMS. The efficiency is measured in a transverse momentum range from 8 to several hundred GeV

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

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

Offline web application subtitle editor

The Covid-19 pandemic has led to a sudden shift in online learning. Regardless of how clear a recording is, students may still miss important keywords or misunderstand concepts. This is where transcription comes in, it provides clarification to both educators and students, and allows educators to focus on overarching topics since time is saved from answering semantical or repeated questions. By providing students with access to content of the lesson in different forms, institutions can provide distinguished online lessons that match traditional in-class lessons. Magor is a transcription tool developed by SCSE’s Speech and Indexing Laboratory that is aimed to provide transcription services to educators in NTU. It is an existing software that will be built on in this report. We will explore new features that can be added into Magor through an analysis of existing transcription tools and their features that are potentially useful in our use case. At the same time, testing of Magor will be conducted to identify and fix areas of improvements or bugs in the software. In the implementation stage, various methods will be explored and the most suitable solution will be chosen for each problem identified. The report will then be concluded with future work to be done in Magor, in terms of new features that can be added and existing areas of improvements or bugs that should be fixed. The issues addressed throughout the duration of this project has significantly improved the performance of Magor and can possibly result in increased adoption rates of its transcription service across other faculties in NTU.Bachelor of BusinessBachelor of Engineering (Computer Science

Strain-induced degradation and recovery of flexible NbOx-based threshold switching device

Abstract We investigate the functionality of NbOx-based selector devices on a flexible substrate. It was observed that the failure mechanism of cyclic tensile strain is from the disruption of atom arrangements, which essentially led to the crack formation of the film. When under cyclic compressive strain, buckling delamination of the film occurs as the compressed films have debonded from their neighboring layers. By implementing an annealing process after the strain-induced degradation, recovery of the device is observed with reduced threshold and hold voltages. The physical mechanism of the device is investigated through Poole–Frenkel mechanism fitting, which provides insights into the switching behavior after mechanical strain and annealing process. The result demonstrates the potential of the NbOx device in flexible electronics applications with a high endurance of up to 105 cycles of cyclic bending strain and the recovery of the device after degradation

Insight into self concept and motivations of generation C members to participate in collaborative virtual environments

Existing research focuses on Generation C and collaborative virtual environments in the western context. This research aims to discover how the motivation to attain certain self concepts may drive Generation C members in Singapore to participate in collaborative virtual environments, with particular interest in “Second Life”. With Generation C shaping the consumption patterns in the future, this research also aims to provide marketers with insights on how to attract these consumers to join collaborative virtual environments

Impact of interfacial engineering on MgO-based resistive switching devices for low-power applications

In this work, the resistive switching characteristics of MgO/Al2O3-based resistive random-access memory (ReRAM) devices have been reported. Analysis shows the change in dominant conduction mechanism from space-charge-limited conduction to Schottky emission owing to the incorporation of an Al2O3 insertion layer. The MgO/Al2O3 bilayer ReRAM devices exhibit lower power operation (50.6% reduction) and better switching uniformity as compared to single-layer devices, depending on the stack configuration. This can be attributed to the lower oxygen vacancy accumulation and filament confinement at the MgO/Al2O3 interface, resulting in a more controllable switching operation. Further X-ray photoelectron spectroscopy (XPS) depth profile analysis of the bilayer device reveals that the switching dynamics are correlated directly with the oxygen vacancy concentrations. These findings indicate the importance of interfacial layer engineering in improving the resistive switching properties of MgO-based memory devices, thus allowing for low-power applications.Agency for Science, Technology and Research (A*STAR)This work was supported by RIE2020 A*STAR, Singapore AME IAFICP (Grant No. I1801E0030); and EDB-IPP (Grant No. RCA2019-1376)

Efficacy of Interventions That Incorporate Mobile Apps in Facilitating Weight Loss and Health Behavior Change in the Asian Population: Systematic Review and Meta-analysis

BackgroundSmartphone apps have shown potential in enhancing weight management in Western populations in the short to medium term. With a rapidly growing obesity burden in Asian populations, researchers are turning to apps as a service delivery platform to reach a larger target audience to efficiently address the problem. ObjectiveThis systematic review and meta-analysis aims to determine the efficacy of interventions that incorporate apps in facilitating weight loss and health behavior change in the Asian population. MethodsA total of 6 databases were searched in June 2020. The eligible studies included controlled trials in which an app was used in the intervention. The participants were aged 18 years or older and were of Asian ethnicity. A meta-analysis to test intervention efficacy, subgroup analyses, and post hoc analyses was conducted to determine the effects of adding an app to usual care and study duration. The primary outcome was absolute or percentage weight change, whereas the secondary outcomes were changes to lifestyle behaviors. ResultsA total of 21 studies were included in this review, and 17 (81%) were selected for the meta-analysis. The pooled effect size across 82% (14/17) of the randomized controlled trials for weight change was small to moderate (Hedges g=–0.26; 95% CI –0.41 to –0.11), indicating slightly greater weight loss achieved in the intervention group; however, this may not be representative of long-term studies (lasting for more than a year). Supplementing multicomponent usual care with an app led to greater weight loss (Hedges g=–0.28; 95% CI –0.47 to –0.09). Asian apps were largely culturally adapted and multifunctional, with the most common app features being communication with health professionals and self-monitoring of behaviors and outcomes. ConclusionsMore evidence is required to determine the efficacy of apps in the long term and address the low uptake of apps to maximize the potential of the intervention. Future research should determine the efficacy of each component of the multicomponent intervention to facilitate the designing of studies that are most effective and cost-efficient for weight management. Trial RegistrationPROSPERO CRD42020165240; https://tinyurl.com/2db4tvn