Benchmarking performance of machine and deep learning-based methodologies for Urdu text document classification

Neural Computing and Applications - In order to provide benchmark performance for Urdu text document classification, the contribution of this paper is manifold. First, it provides a publicly...     

Analysis of time-dependent flow-sensitive PC-MRI data

Many flow visualization techniques, especially integration-based methods, are problematic when the measured data exhibit noise and discretization issues. Particularly, this is the case for flow-sensitive phase-contrast magnetic resonance imaging (PC-MRI) data sets which not only record anatomic information, but also time-varying flow information. We propose a novel approach for the visualization of such data sets using integration-based methods. Our ideas are based upon finite-time Lyapunov exponents (FTLE) and enable identification of vessel boundaries in the data as high regions of separation. This allows us to correctly restrict integration-based visualization to blood vessels. We validate our technique by comparing our approach to existing anatomy-based methods as well as addressing the benefits and limitations of using FTLE to restrict flow. We also discuss the importance of parameters, i.e., advection length and data resolution, in establishing a well-defined vessel boundary. We extract appropriate flow lines and surfaces that enable the visualization of blood flow within the vessels. We further enhance the visualization by analyzing flow behavior in the seeded region and generating simplified depictions.     

A code tagging approach to software product line development

Software product line engineering seeks to systematise reuse when developing families of similar software systems so as to minimise development time, cost and defects. To realise variability at the code level, product line methods classically advocate usage of inheritance, components, frameworks, aspects or generative techniques. However, these might require unaffordable paradigm shifts for developers if the software was not thought at the outset as a product line. Furthermore, these techniques can be conflicting with a company’s coding practices or external regulations. These concerns were the motivation for the industry–university collaboration described in this paper in which we developed a minimally intrusive coding technique based on tags. The approach was complemented with traceability from code to feature diagrams which were exploited for automated configuration. It is supported by a toolchain and is now in use in the partner company for the development of flight-grade satellite communication software libraries.     

Double necking in polymer tensile deformation

After initial necking of tensile polymer samples the deformation front moves along the gauge length at a stress which is smaller than the yield stress. The still undeformed parts of the sample are therefore subjected to conditions which favour deformation by a creep mechanism. If the extension rate is right, secondary necking becomes possible. Boundary conditions are discussed.     

Analysis of grain boundary movement analogous to dislocation movement – both with a matrix having precipitates

In the present investigation it has been shown exemplarily for an austenite microstructure containing carbonitrides that the specific restraining force of a grain boundary due to the distribution of precipitates can be described by a modified Orowan's law, so that the grain boundary movement is considered to be analogous to the dislocation movement. This is achieved by using a modified restraining force F_r (corresponding to the cubic geometry of the particles), a detailed thermodynamic analysis of the precipitates (in this case, carbonitrides) and selected relation for the interparticle spacing L_a. The specific restraining force and the interparticle spacing depend on temperature within the austenite range. Each temperature is attached to a couple (F_r/L_a). The plot F_r against shows straight lines for each steel and from their average slope, a shear module G' of grain boundaries, which is about 64300 N·cm^?2, is obtained. Hence, it is possible to describe the specific restraining force of a grain boundary with the help of Orowan's law or as it is conventionally done by using Zener's modell. At a critical temperature T*, which is different for each steel, the specific restraining force is equal to the driving force of the grain boundary. The corresponding values of L_a are also different for each steel and the steel which is the most resistant to grain coarsening is allowed to have the greatest value of L_a which still retains the capacity of impeding grain coarsening.     

Energy Metabolites as Biomarkers in Ischemic and Dilated Cardiomyopathy

With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10⁻⁶). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.     

Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE

Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, and with clinical and serologic disease parameters of SLE. Compared to healthy controls (HC), CD38 expression levels in SLE were significantly increased on circulating plasmacytoid dendritic cells, CD14⁺⁺CD16⁺ monocytes, CD56⁺ CD16^dim natural killer cells, marginal zone-like IgD⁺CD27⁺ B cells, and on CD4⁺ and CD8⁺ memory T cells. Correlation analyses revealed coordinated CD38 expression between individual innate and memory T cell subsets in SLE but not HC. However, CD38 expression levels were heterogeneous across patients, and no correlation was found between CD38 expression on immune cell subsets and the disease activity index SLEDAI-2K or established serologic and immunological markers of disease activity. In conclusion, we identified widespread changes in CD38 expression on SLE immune cells that highly correlated over different leukocyte subsets within individual patients, but was heterogenous within the population of SLE patients, regardless of disease severity or clinical manifestations. As anti-CD38 treatment is being investigated in SLE, our results may have important implications for the personalized targeting of pathogenic leukocytes by anti-CD38 monoclonal antibodies.     

Mapping and Modelling Single Scan Track Formation in Direct Metal Selective Laser Melting

When a laser beam scans the surface of a metallic powder bed, the resulting track may be continuous with a crescent shape cross-section, continuous with an elliptical section, discontinuously irregularly broken, discontinuously balled or only partially melted. This paper reports experimental observations of what CO₂laser powers and scan speeds lead to what type of track, for M2 and H13 tools steels and 314S stainless steel powder beds. It also presents measurements of bed physical properties relevant to predicting the behaviour and the results of modelling that agree with the experiments. The results are placed in the broader context of selective laser melting build strategies     

Elucidation of the Clustered Nano-Architecture of Radiation-Induced DNA Damage Sites and Surrounding Chromatin in Cancer Cells: A Single Molecule Localization Microscopy Approach

In cancer therapy, the application of (fractionated) harsh radiation treatment is state of the art for many types of tumors. However, ionizing radiation is a “double-edged sword”—it can kill the tumor but can also promote the selection of radioresistant tumor cell clones or even initiate carcinogenesis in the normal irradiated tissue. Individualized radiotherapy would reduce these risks and boost the treatment, but its development requires a deep understanding of DNA damage and repair processes and the corresponding control mechanisms. DNA double strand breaks (DSBs) and their repair play a critical role in the cellular response to radiation. In previous years, it has become apparent that, beyond genetic and epigenetic determinants, the structural aspects of damaged chromatin (i.e., not only of DSBs themselves but also of the whole damage-surrounding chromatin domains) form another layer of complex DSB regulation. In the present article, we summarize the application of super-resolution single molecule localization microscopy (SMLM) for investigations of these structural aspects with emphasis on the relationship between the nano-architecture of radiation-induced repair foci (IRIFs), represented here by γH2AX foci, and their chromatin environment. Using irradiated HeLa cell cultures as an example, we show repair-dependent rearrangements of damaged chromatin and analyze the architecture of γH2AX repair clusters according to topological similarities. Although HeLa cells are known to have highly aberrant genomes, the topological similarity of γH2AX was high, indicating a functional, presumptively genome type-independent relevance of structural aspects in DSB repair. Remarkably, nano-scaled chromatin rearrangements during repair depended both on the chromatin domain type and the treatment. Based on these results, we demonstrate how the nano-architecture and topology of IRIFs and chromatin can be determined, point to the methodological relevance of SMLM, and discuss the consequences of the observed phenomena for the DSB repair network regulation or, for instance, radiation treatment outcomes.     

Functional and Molecular Properties of DYT-SGCE Myoclonus-Dystonia Patient-Derived Striatal Medium Spiny Neurons

Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca²⁺ content and lower frequency of spontaneous Ca²⁺ signals in SGCE MSNs. Blocking of voltage-gated Ca²⁺ channels by verapamil was less efficient in suppressing KCl-induced Ca²⁺ peaks of SGCE MSNs. Ca²⁺ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca²⁺ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia.