21 research outputs found
Robust estimation of bacterial cell count from optical density
Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
New genetic loci link adipose and insulin biology to body fat distribution.
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
Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.
OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis
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
Modelling and developing conflict-aware scheduling on large-scale data centres
Large-scale data centres are the growing trend for modern computing systems. Since a large-scale data centre has to manage a large number of machines and jobs, deploying multiple independent schedulers (termed as distributed schedulers in literature) to make scheduling decisions simultaneously has been shown as an effective way to speed up the processing of large quantity of submitted jobs and data. The key drawback of distributed schedulers is that since these schedulers schedule different jobs independently, the scheduling decisions made by different schedulers may conflict with each other due to the possibility that different scheduling decisions refer to the same subset of the resources in the data centre. Conflicting scheduling decisions cause additional scheduling attempts and consequently increase the scheduling cost. More resources each scheduler demands, higher scheduling cost may incur and longer job response times the users may experience. It is useful to investigate the balanced points in terms of resource demands for each of independent schedulers, so that the distributed schedulers can all achieve decent job performance without experiencing undesired resource competition. To address this issue, we model distributed scheduling and resource conflict using the game theory and conduct the quantitative analysis about scheduling cost and job performance. Further, based on the analysis, we develop the conflict-aware scheduling strategies to reduce the scheduling cost and improve job performance. We have conducted the simulation experiments with workload trace and also real experiments on Amazon Web Services(AWS). The experimental results verify the effectiveness of the proposed modelling approach and scheduling strategies
Modelling and developing conflict-aware scheduling on large-scale data centres
Large-scale data centres are the growing trend for modern computing systems. Since a large-scale data centre has to manage a large number of machines and jobs, deploying multiple independent schedulers (termed as distributed schedulers in literature) to make scheduling decisions simultaneously has been shown as an effective way to speed up the processing of large quantity of submitted jobs and data. The key drawback of distributed schedulers is that since these schedulers schedule different jobs independently, the scheduling decisions made by different schedulers may conflict with each other due to the possibility that different scheduling decisions refer to the same subset of the resources in the data centre. Conflicting scheduling decisions cause additional scheduling attempts and consequently increase the scheduling cost. More resources each scheduler demands, higher scheduling cost may incur and longer job response times the users may experience. It is useful to investigate the balanced points in terms of resource demands for each of independent schedulers, so that the distributed schedulers can all achieve decent job performance without experiencing undesired resource competition. To address this issue, we model distributed scheduling and resource conflict using the game theory and conduct the quantitative analysis about scheduling cost and job performance. Further, based on the analysis, we develop the conflict-aware scheduling strategies to reduce the scheduling cost and improve job performance. We have conducted the simulation experiments with workload trace and also real experiments on Amazon Web Services(AWS). The experimental results verify the effectiveness of the proposed modelling approach and scheduling strategies
High-Performance Plasmonic Nanolasers with a Nanotrench Defect Cavity for Sensing Applications
Recent developments
in small footprint plasmonic nanolasers show
promise for active optical sensing with potential applications in
various fields, including real-time and label-free biochemical sensing,
and gas detection. In this study, we demonstrate a novel hybrid plasmonic
crystal nanolaser that features a ZnO nanowire placed on Al grating
surfaces with a nanotrench defect nanocavity. The lasing action of
gain-assisted defect nanocavity overcomes the ohmic loss parasitically
in the plasmonic nanostructures. Therefore, the plasmonic nanolaser
exhibits an extremely small mode volume, a narrow linewidth Δλ,
and a high Purcell factor that can facilitate the strong interaction
between light and matter. This can be used as a refractive index sensor
and is highly sensitive to local changes in the refractive indices
of ambient materials. By careful design, the near-ultraviolet nanolaser
sensors have significant sensing performances of glucose solutions,
revealing a high sensitivity of 249 nm/RIU and high resolution, with
a figure of merit of 1132, at the resonant wavelength of 373 nm
Chemical-to-Electricity Carbon: Water Device
The ability to release, as electrical energy, potential energy stored at the water:carbon interface is attractive, since water is abundant and available. However, many previous reports of such energy converters rely on either flowing water or specially designed ionic aqueous solutions. These requirements restrict practical application, particularly in environments with quiescent water. Here, a carbon-based chemical-to-electricity device that transfers the chemical energy to electrical form when coming into contact with quiescent deionized water is reported. The device is built using carbon nanotube yarns, oxygen content of which is modulated using oxygen plasma-treatment. When immersed in water, the device discharges electricity with a power density that exceeds 700 mW m-2 , one order of magnitude higher than the best previously published result. X-ray absorption and density functional theory studies support a mechanism of operation that relies on the polarization of sp2 hybridized carbon atoms. The devices are incorporated into a flexible fabric for powering personal electronic devices.S.H., Y.Z., L.Q., and L.Z. contributed equally to this work. This work was supported by the Ministry of Science and Technology (Grant No. 2016YFA0203302), the National Natural Science Foundation of China (Grant Nos. 21634003, 51573027, 51403038, 51673043, and 21604012), and the Science and Technology Commission of Shanghai Municipality (Grant Nos. 16JC1400702, 15XD1500400, and 15JC1490200). The sample fabrication was performed at the Fudan Nano-fabrication Laboratory. This work has also benefited from the X-ray Micro-Analysis and Spherical Grating Monochromator beamlines at Canadian Light Source. The authors thank Oleksandr Voznyy, Y. H. Wang, and G. F. Zheng for fruitful discussions and the equipment assistance, and thank X. H. Tao for the circuit design
Enhanced multi-carbon alcohol electroproduction from CO via modulated hydrogen adsorption
The electrocatalytic upgrading of CO to higher-value fuels provides a promising route to multi-carbon alcohol products. Here, the authors show that high alcohol selectivity and activity can be achieved by incorporating palladium in copper