Mapping single-cell sequencing profiles to comprehensive reference datasets provides a powerful alternative to unsupervised analysis. However, most reference datasets are constructed from single-cell ...RNA-sequencing data and cannot be used to annotate datasets that do not measure gene expression. Here we introduce 'bridge integration', a method to integrate single-cell datasets across modalities using a multiomic dataset as a molecular bridge. Each cell in the multiomic dataset constitutes an element in a 'dictionary', which is used to reconstruct unimodal datasets and transform them into a shared space. Our procedure accurately integrates transcriptomic data with independent single-cell measurements of chromatin accessibility, histone modifications, DNA methylation and protein levels. Moreover, we demonstrate how dictionary learning can be combined with sketching techniques to improve computational scalability and harmonize 8.6 million human immune cell profiles from sequencing and mass cytometry experiments. Our approach, implemented in version 5 of our Seurat toolkit ( http://www.satijalab.org/seurat ), broadens the utility of single-cell reference datasets and facilitates comparisons across diverse molecular modalities.
Well-being and HRM in the changing workplace Kowalski, Tina H. P.; Loretto, Wendy
International journal of human resource management,
09/2017, Letnik:
28, Številka:
16
Journal Article
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In a fast changing and fast-paced global workplace, where maintaining competitive advantage is paramount to success, identifying ways of sustaining employee well-being is of increasing importance to ...a range of stakeholders, both within the context of work and beyond. Within the workplace, well-being is important not only to individual employees in terms of maintaining their own good health, but also to managers and organisations as there is evidence to suggest that poor well-being at work can have adverse effects on performance and overall productivity. Beyond the workplace, health service providers must manage the potential burden of poor individual and population health, exacerbated in many nations by ageing workforces. Given the existing evidence linking employee well-being to key organisational outcomes such as performance and productivity, identifying ways to enhance employee well-being is, arguably, a core function of contemporary human resource professionals. However, the juxtaposition of an increased focus on well-being at work and the current business climate of needing to do more with less can pose significant challenges for HRM professionals in contemporary organisations. In this paper we examine some of the key issues of pertinence to researchers in the field of HRM and well-being, and propose a number of areas for future research.
We analyze, within a dipole model, the final, inclusive HERA DIS cross section data in the low x region, using fully correlated errors. We show that these highest precision data are very well ...described within the dipole model framework starting from Q2 values of 3.5 GeV2 to the highest values of Q2=250 GeV2. To analyze the saturation effects we evaluated the data including also the very low 0.35<Q2 GeV2 region. The fits including this region show a preference of the saturation ansatz.
We analyse the high precision HERA F2 data in the low-x, x<0,01, and very-low-x, x<0.001, regions using λ-fits. λ is a measure of the rate of rise of F2 defined by F2∝(1/x)λ. We show that λ ...determined in these two regions, at various Q2 values, is systematically smaller in the very-low-x region as compared to the low-x region. We discuss some possible physical interpretations of this effect.
Even as biomarker-based approaches are adopted for diagnosis of fungal infections, culture-based methods remain valuable for the identification of specific etiological agents and determination of ...antifungal susceptibility 1. ...when obtainable, infectious organisms are observed as macroscopic colony biofilms in clinical settings. ...we discuss the importance of investigating recurring and distinct fungal macroscopic morphologies for furthering our understanding of host–fungal interactions. ...white–gray–opaque phenotype switching alters the yeast cellular morphology and colony morphotypes as a result of transcriptional rewiring 14. In either case, the change in macroscopic colony morphology may be indicative that a key genetic factor associated with virulence has been changed in the microbe under study. ...defining the genetic mechanisms driving morphological change should be an important goal for future research.
We show that the enhancement of the saturation scale in large nuclei relative to the proton is significantly influenced by the effects of quantum evolution and the impact parameter dependence of ...dipole cross sections in high energy QCD. We demonstrate that there is a strong A dependence in diffractive deeply inelastic scattering and discuss its sensitivity to the measurement of the recoil nucleus.
The frequency of antifungal resistance, particularly to the azole class of ergosterol biosynthetic inhibitors, is a growing global health problem. Survival rates for those infected with resistant ...isolates are exceptionally low. Beyond modification of the drug target, our understanding of the molecular basis of azole resistance in the fungal pathogen Aspergillus fumigatus is limited. We reasoned that clinically relevant antifungal resistance could derive from transcriptional rewiring, promoting drug resistance without concomitant reductions in pathogenicity. Here we report a genome-wide annotation of transcriptional regulators in A. fumigatus and construction of a library of 484 transcription factor null mutants. We identify 12 regulators that have a demonstrable role in itraconazole susceptibility and show that loss of the negative cofactor 2 complex leads to resistance, not only to the azoles but also the salvage therapeutics amphotericin B and terbinafine without significantly affecting pathogenicity.
•The performance of eigenvector calculation using the ELPA library improves on new architectures.•A modern object-oriented API brings new possibilities of the use of the library.•An autotuning ...process leads to significant reduction of the time-to-solution of applications.•The performance of scientific applications can be improved by using the new ELPA library.
The solution of (generalized) eigenvalue problems for symmetric or Hermitian matrices is a common subtask of many numerical calculations in electronic structure theory or materials science. Depending on the scientific problem, solving the eigenvalue problem can easily amount to a sizeable fraction of the whole numerical calculation, and quite often is even the dominant part by far. For researchers in the field of computational materials science, an efficient and scalable solution of the eigenvalue problem is thus of major importance. The ELPA-library (Eigenvalue SoLvers for Petaflop-Applications) is a well-established dense direct eigenvalue solver library, which has proven to be very efficient and scalable up to very large core counts. It is in a wide-spread production use on a large variety of HPC systems worldwide, and is applied by many codes in the field of materials science. In this paper, we describe the latest optimizations of the ELPA-library for new HPC architectures of the Intel Skylake processor family with an AVX-512 SIMD instruction set, or for HPC systems accelerated with recent GPUs. Apart from those direct hardware-related optimizations, we also describe a complete redesign of the API in a modern modular way, which, apart from a much simpler and more flexible usability, leads to a new path to access system-specific performance optimizations. In order to ensure optimal performance for a particular scientific setting or a specific HPC system, the new API allows the user to influence in a straightforward way the internal details of the algorithms and of performance-critical parameters used in the ELPA-library. On top of that, we introduce an autotuning functionality, which allows for finding the best settings in a self-contained automated way, without the need of much user effort. In situations where many eigenvalue problems with similar settings have to be solved consecutively, the autotuning process of the ELPA-library can be done “on-the-fly”, without the need of preceding the simulation with an “artificial” autotuning step. Practical applications from materials science which rely on reaching a numerical convergence limit by so-called self-consistency iterations can profit from the on-the-fly autotuning. On some examples of scientific interest, simulated with the FHI-aims application, the advantages of the latest optimizations of the ELPA-library are demonstrated.
Evidence exists demonstrating the negative impacts of chronic musculoskeletal pain on key measures of gait. Despite neck pain being the second most common musculoskeletal pain condition, there is a ...paucity of evidence exploring the impacts of neck pain specifically on these outcomes. The aims of this work were to systematically review the current evidence of the associations between chronic neck pain and measures of gait health and to conduct meta-analysis for quantitative assessment of the effect sizes under different walking conditions.
Systematic review was conducted following PRISMA guidelines. Databases searched included MEDLINE, Embase, Web of Science, CINAHL, and PEDro. Eligible study designs included observational studies consisting of an exposure group with chronic neck pain and control group without chronic neck pain and primary outcomes relating to gait health. For outcomes amenable to meta-analysis, a random-effects model was used to derive summary estimates of Hedge's g depicted graphically with forest plots. Other gait outcomes were narratively summarized. Risk of bias was also assessed.
The original search yielded 1918 articles; 12 met final eligibility criteria including 10 cross-sectional studies. Outcomes were grouped first by the five domains of gait: pace, rhythm, asymmetry, variability, and postural control; and second by the tested walking conditions. Meta-analyses for gait speed revealed large effect-sizes indicating that individuals with chronic neck pain had slower measures of gait and lower measures of cadence. Gait outcomes that were narratively summarized supported these findings.
The quantitative and qualitative findings of this systematic review and meta-analysis suggest a negative impact of CNNP on measures of gait health, particularly gait speed, under various walking conditions. However, broad interpretation of these results should be cautious. Testing gait under dual task conditions may be particularly sensitive to the impact of CNNP, and future work is needed to better understand how pain disrupts this important functionality of the locomotor system. Additionally, consideration should be made to assess measures of variability and investigate these relationships in the older adult population.
HERAFitter Alekhin, S.; Behnke, O.; Belov, P. ...
The European physical journal. C, Particles and fields,
07/2015, Letnik:
75, Številka:
7
Journal Article
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HERAFitter is an open-source package that provides a framework for the determination of the parton distribution functions (PDFs) of the proton and for many different kinds of analyses in Quantum ...Chromodynamics (QCD). It encodes results from a wide range of experimental measurements in lepton–proton deep inelastic scattering and proton–proton (proton–antiproton) collisions at hadron colliders. These are complemented with a variety of theoretical options for calculating PDF-dependent cross section predictions corresponding to the measurements. The framework covers a large number of the existing methods and schemes used for PDF determination. The data and theoretical predictions are brought together through numerous methodological options for carrying out PDF fits and plotting tools to help to visualise the results. While primarily based on the approach of collinear factorisation, HERAFitter also provides facilities for fits of dipole models and transverse-momentum dependent PDFs. The package can be used to study the impact of new precise measurements from hadron colliders. This paper describes the general structure of HERAFitter and its wide choice of options.
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