Synapse: Synthetic Application Profiler and Emulator

We introduce Synapse motivated by the needs to estimate and emulate workload execution characteristics on high-performance and distributed heterogeneous resources. Synapse has a platform independent application profiler, and the ability to emulate profiled workloads on a variety of heterogeneous resources. Synapse is used as a proxy application (or "representative application") for real workloads, with the added advantage that it can be tuned at arbitrary levels of granularity in ways that are simply not possible using real applications. Experiments show that automated profiling using Synapse represents application characteristics with high fidelity. Emulation using Synapse can reproduce the application behavior in the original runtime environment, as well as reproducing properties when used in a different run-time environments

Age- and activity-related differences in the abundance of Myosin essential and regulatory light chains in human muscle

Traditional methods for phenotyping skeletal muscle (e.g., immunohistochemistry) are labor-intensive and ill-suited to multixplex analysis, i.e., assays must be performed in a series. Addressing these concerns represents a largely unmet research need but more comprehensive parallel analysis of myofibrillar proteins could advance knowledge regarding age- and activity-dependent changes in human muscle. We report a label-free, semi-automated and time efficient LC-MS proteomic workflow for phenotyping the myofibrillar proteome. Application of this workflow in old and young as well as trained and untrained human skeletal muscle yielded several novel observations that were subsequently verified by multiple reaction monitoring (MRM).We report novel data demonstrating that human ageing is associated with lesser myosin light chain 1 content and greater myosin light chain 3 content, consistent with an age-related reduction in type II muscle fibers. We also disambiguate conflicting data regarding myosin regulatory light chain, revealing that age-related changes in this protein more closely reflect physical activity status than ageing per se. This finding reinforces the need to control for physical activity levels when investigating the natural process of ageing. Taken together, our data confirm and extend knowledge regarding age- and activity-related phenotypes. In addition, the MRM transitions described here provide a methodological platform that can be fine-tuned to suite multiple research needs and thus advance myofibrillar phenotyping

The how and why of lncRNA function: An innate immune perspective.

Next-generation sequencing has provided a more complete picture of the composition of the human transcriptome indicating that much of the "blueprint" is a vastness of poorly understood non-protein-coding transcripts. This includes a newly identified class of genes called long noncoding RNAs (lncRNAs). The lack of sequence conservation for lncRNAs across species meant that their biological importance was initially met with some skepticism. LncRNAs mediate their functions through interactions with proteins, RNA, DNA, or a combination of these. Their functions can often be dictated by their localization, sequence, and/or secondary structure. Here we provide a review of the approaches typically adopted to study the complexity of these genes with an emphasis on recent discoveries within the innate immune field. Finally, we discuss the challenges, as well as the emergence of new technologies that will continue to move this field forward and provide greater insight into the biological importance of this class of genes. This article is part of a Special Issue entitled: ncRNA in control of gene expression edited by Kotb Abdelmohsen

Two-dimensional gel electrophoresis in proteomics: A tutorial

Two-dimensional electrophoresis of proteins has preceded, and accompanied, the birth of proteomics. Although it is no longer the only experimental scheme used in modern proteomics, it still has distinct features and advantages. The purpose of this tutorial paper is to guide the reader through the history of the field, then through the main steps of the process, from sample preparation to in-gel detection of proteins, commenting the constraints and caveats of the technique. Then the limitations and positive features of two-dimensional electrophoresis are discussed (e.g. its unique ability to separate complete proteins and its easy interfacing with immunoblotting techniques), so that the optimal type of applications of this technique in current and future proteomics can be perceived. This is illustrated by a detailed example taken from the literature and commented in detail. This Tutorial is part of the International Proteomics Tutorial Programme (IPTP 2)

Towards Ultimate Parton Distributions at the High-Luminosity LHC

Since its start of data taking, the LHC has provided an impressive wealth of information on the quark and gluon structure of the proton. Indeed, modern global analyses of parton distribution functions (PDFs) include a wide range of LHC measurements of processes such as the production of jets, electroweak gauge bosons, and top quark pairs. In this work, we assess the ultimate constraining power of LHC data on the PDFs that can be expected from the complete dataset, in particular after the High-Luminosity (HL) phase, starting in around 2025. The huge statistics of the HL-LHC, delivering $\mathcal{L}=3$ ab$^{-1}$ to ATLAS and CMS and $\mathcal{L}=0.3$ ab$^{-1}$ to LHCb, will lead to an extension of the kinematic coverage of PDF-sensitive measurements as well as to an improvement in their statistical and systematic uncertainties. Here we generate HL-LHC pseudo-data for different projections of the experimental uncertainties, and then quantify the resulting constraints on the PDF4LHC15 set by means of the Hessian profiling method. We find that HL-LHC measurements can reduce PDF uncertainties by up to a factor of 2 to 4 in comparison to state-of-the-art fits, leading to few-percent uncertainties for important observables such as the Higgs boson transverse momentum distribution via gluon-fusion. Our results illustrate the significant improvement in the precision of PDF fits achievable from hadron collider data alone, and motivate the continuation of the ongoing successful program of PDF-sensitive measurements by the LHC collaborations.Comment: 30 pages, 20 figure

The impact of professional learning on the teaching identities of higher education lecturers

Higher Education is currently undergoing some of the most profound changes in its history. Against a backdrop of increasing marketization, rising levels of student debt and far greater fully online offerings, the higher education lecturer is grappling with new ways of working and high expectations of teaching quality. This 3 year qualitative study based in The Open University UK investigates the ways in which HE distance learning lecturers are approaching professional development and learning, identifying what type of learning may be most effective in creating and sustaining an online teaching identity. The study also examines ways in which resistance discourse is shaping these identities and practices revealing emerging re- conceptualisations of what it means to be an effective and well-motivated distance learning lecturer. The investigation uses a framework for identity analysis which analyses professional identity via the expression of hegemonies, phenomenological, narrative articulations of identity, and a post-modern, constructivist view of identity which is shaped by social interactions and communities of practice. It highlights the importance of personal agency in identity formation. The results revealed a number of insights into the ways in which a combination of resistance discourse, professional learning and reflections from student interactions are shaping new understandings of professional knowledge in this context

High Lundquist Number Simulations of Parker\u27s Model of Coronal Heating: Scaling and Current Sheet Statistics Using Heterogeneous Computing Architectures

Parker\u27s model [Parker, Astrophys. J., 174, 499 (1972)] is one of the most discussed mechanisms for coronal heating and has generated much debate. We have recently obtained new scaling results for a 2D version of this problem suggesting that the heating rate becomes independent of resistivity in a statistical steady state [Ng and Bhattacharjee, Astrophys. J., 675, 899 (2008)]. Our numerical work has now been extended to 3D using high resolution MHD numerical simulations. Random photospheric footpoint motion is applied for a time much longer than the correlation time of the motion to obtain converged average coronal heating rates. Simulations are done for different values of the Lundquist number to determine scaling. In the high-Lundquist number limit (S \u3e 1000), the coronal heating rate obtained is consistent with a trend that is independent of the Lundquist number, as predicted by previous analysis and 2D simulations. We will present scaling analysis showing that when the dissipation time is comparable or larger than the correlation time of the random footpoint motion, the heating rate tends to become independent of Lundquist number, and that the magnetic energy production is also reduced significantly. We also present a comprehensive reprogramming of our simulation code to run on NVidia graphics processing units using the Compute Unified Device Architecture (CUDA) and report code performance on several large scale heterogenous machines