136 research outputs found
Microwave Components with MEMS Switches
RF MEMS switches with metal-metal contacts are being developed for microwave applications where broadband, high linearity performance is required. These switches provide less than 0.2 dB insertion loss through 40 GHz. This paper describes the integration of these switches into selected microwave components such as reconfigurable antenna elements, tunable filters, switched delay lines, and SPDT switches. Microwave and millimeter wave measured results from these circuits are presented
Slideflow: Deep Learning for Digital Histopathology with Real-Time Whole-Slide Visualization
Deep learning methods have emerged as powerful tools for analyzing
histopathological images, but current methods are often specialized for
specific domains and software environments, and few open-source options exist
for deploying models in an interactive interface. Experimenting with different
deep learning approaches typically requires switching software libraries and
reprocessing data, reducing the feasibility and practicality of experimenting
with new architectures. We developed a flexible deep learning library for
histopathology called Slideflow, a package which supports a broad array of deep
learning methods for digital pathology and includes a fast whole-slide
interface for deploying trained models. Slideflow includes unique tools for
whole-slide image data processing, efficient stain normalization and
augmentation, weakly-supervised whole-slide classification, uncertainty
quantification, feature generation, feature space analysis, and explainability.
Whole-slide image processing is highly optimized, enabling whole-slide tile
extraction at 40X magnification in 2.5 seconds per slide. The
framework-agnostic data processing pipeline enables rapid experimentation with
new methods built with either Tensorflow or PyTorch, and the graphical user
interface supports real-time visualization of slides, predictions, heatmaps,
and feature space characteristics on a variety of hardware devices, including
ARM-based devices such as the Raspberry Pi
N′-[(E)-2,6-Dichlorobenzylidene]pyrazine-2-carbohydrazide
The title compound, C12H8Cl2N4O, is non-planar, the dihedral angle formed between the pendant pyrazine and benzene rings being 12.55 (11)°. An intramolecular N—H⋯N hydrogen bond occurs. The amide groups self-associate via N—H⋯O hydrogen bonding, forming supramolecular chains with base vector [101], which are stabilized by C—H⋯O contacts. C—H⋯N interactions are formed orthogonal to the chains
Comparison of variant calling methods for whole genome sequencing data in dairy cattle
Accurate identification of SNPs from next-generation sequencing data is crucial for high-quality downstream analysis. Whole genome sequence data of 65 key ancestors of genotyped Swiss dairy populations were available for investigation (24 billion reads, 96.8% mapped to UMD31, 12x coverage). Four publically available variant calling programmes were assessed and different levels of pre-calling handling for each method were tested and compared. SNP concordance was examined with Illumina’s BovineHD Genotyping BeadChip®. Depending on variant calling software used, between 16,894,054 and 22,048,382 SNP were identified (multi-sample calling). A total of 14,644,310 SNP were identified by all four variant callers (multi-sample calling). InDel counts ranged from 1,997,791 to 2,857,754; 1,708,649 InDels were identified by all four variant callers. A minimum of pre-calling data handling resulted in the highest non-reference sensitivity and the lowest non-reference discrepancy rates
Uncertainty-Informed Deep Learning Models Enable High-Confidence Predictions for Digital Histopathology
A model's ability to express its own predictive uncertainty is an essential
attribute for maintaining clinical user confidence as computational biomarkers
are deployed into real-world medical settings. In the domain of cancer digital
histopathology, we describe a novel, clinically-oriented approach to
uncertainty quantification (UQ) for whole-slide images, estimating uncertainty
using dropout and calculating thresholds on training data to establish cutoffs
for low- and high-confidence predictions. We train models to identify lung
adenocarcinoma vs. squamous cell carcinoma and show that high-confidence
predictions outperform predictions without UQ, in both cross-validation and
testing on two large external datasets spanning multiple institutions. Our
testing strategy closely approximates real-world application, with predictions
generated on unsupervised, unannotated slides using predetermined thresholds.
Furthermore, we show that UQ thresholding remains reliable in the setting of
domain shift, with accurate high-confidence predictions of adenocarcinoma vs.
squamous cell carcinoma for out-of-distribution, non-lung cancer cohorts
Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector
The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry
Argumentum ad misericordiam - the critical intimacies of victimhood
This article discusses the widespread use of victim tropes in contemporary Anglo-American culture by using cultural theory to analyse key social media memes circulating on Facebook in 2015. Since the growth of social media, victim stories have been proliferating, and each demands a response. Victim narratives are rhetorical, they are designed to elicit pity and shame the perpetrator. They are deployed to stimulate political debate and activism, as well as to appeal to an all-purpose humanitarianism. Victimology has its origins in Law and Criminology, but this paper opens up the field more broadly to think about the cultural politics of victimhood, to consider how the victim-figure can be appropriated by/for different purposes, particularly racial and gender politics, including in the case of Rachel Dolezal, and racial passing. In formulating an ethical response to the lived experience of victims, we need to think about the different kinds of critical intimacies
elicited by such media
Structure of S. aureus HPPK and the Discovery of a New Substrate Site Inhibitor
The first structural and biophysical data on the folate biosynthesis pathway enzyme and drug target, 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (SaHPPK), from the pathogen Staphylococcus aureus is presented. HPPK is the second essential enzyme in the pathway catalysing the pyrophosphoryl transfer from cofactor (ATP) to the substrate (6-hydroxymethyl-7,8-dihydropterin, HMDP). In-silico screening identified 8-mercaptoguanine which was shown to bind with an equilibrium dissociation constant, Kd, of ∼13 µM as measured by isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR). An IC50 of ∼41 µM was determined by means of a luminescent kinase assay. In contrast to the biological substrate, the inhibitor has no requirement for magnesium or the ATP cofactor for competitive binding to the substrate site. The 1.65 Å resolution crystal structure of the inhibited complex showed that it binds in the pterin site and shares many of the key intermolecular interactions of the substrate. Chemical shift and 15N heteronuclear NMR measurements reveal that the fast motion of the pterin-binding loop (L2) is partially dampened in the SaHPPK/HMDP/α,β-methylene adenosine 5′-triphosphate (AMPCPP) ternary complex, but the ATP loop (L3) remains mobile on the µs-ms timescale. In contrast, for the SaHPPK/8-mercaptoguanine/AMPCPP ternary complex, the loop L2 becomes rigid on the fast timescale and the L3 loop also becomes more ordered – an observation that correlates with the large entropic penalty associated with inhibitor binding as revealed by ITC. NMR data, including 15N-1H residual dipolar coupling measurements, indicate that the sulfur atom in the inhibitor is important for stabilizing and restricting important motions of the L2 and L3 catalytic loops in the inhibited ternary complex. This work describes a comprehensive analysis of a new HPPK inhibitor, and may provide a foundation for the development of novel antimicrobials targeting the folate biosynthetic pathway
Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals
peer-reviewedH.D.D., A.J.C., P.J.B. and B.J.H. would like to acknowledge the Dairy Futures
Cooperative Research Centre for funding. H.P. and R.F. acknowledge funding
from the German Federal Ministry of Education and Research (BMBF) within the
AgroClustEr ‘Synbreed—Synergistic Plant and Animal Breeding’ (grant 0315527B).
H.P., R.F., R.E. and K.-U.G. acknowledge the Arbeitsgemeinschaft Süddeutscher
Rinderzüchter, the Arbeitsgemeinschaft Österreichischer Fleckviehzüchter
and ZuchtData EDV Dienstleistungen for providing genotype data. A. Bagnato
acknowledges the European Union (EU) Collaborative Project LowInputBreeds
(grant agreement 222623) for providing Brown Swiss genotypes. Braunvieh Schweiz
is acknowledged for providing Brown Swiss phenotypes. H.P. and R.F. acknowledge
the German Holstein Association (DHV) and the Confederación de Asociaciones
de Frisona Española (CONCAFE) for sharing genotype data. H.P. was financially
supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft
(DFG) (grant PA 2789/1-1). D.B. and D.C.P. acknowledge funding from the
Research Stimulus Fund (11/S/112) and Science Foundation Ireland (14/IA/2576).
M.S. and F.S.S. acknowledge the Canadian Dairy Network (CDN) for providing the
Holstein genotypes. P.S. acknowledges funding from the Genome Canada project
entitled ‘Whole Genome Selection through Genome Wide Imputation in Beef Cattle’ and acknowledges WestGrid and Compute/Calcul Canada for providing
computing resources. J.F.T. was supported by the National Institute of Food and
Agriculture, US Department of Agriculture, under awards 2013-68004-20364 and
2015-67015-23183. A. Bagnato, F.P., M.D. and J.W. acknowledge EU Collaborative
Project Quantomics (grant 516 agreement 222664) for providing Brown Swiss
and Finnish Ayrshire sequences and genotypes. A.C.B. and R.F.V. acknowledge
funding from the public–private partnership ‘Breed4Food’ (code BO-22.04-011-
001-ASG-LR) and EU FP7 IRSES SEQSEL (grant 317697). A.C.B. and R.F.V.
acknowledge CRV (Arnhem, the Netherlands) for providing data on Dutch and
New Zealand Holstein and Jersey bulls.Stature is affected by many polymorphisms of small effect in humans1. In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10−8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP–seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals
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