A computationally efficient approach for generating RVEs of various inclusion/fiber shapes

A computationally efficient method for generating virtual periodic representative volume element (RVE), capable of handling arbitrary inclusion shapes, is developed. A universal collision/overlap detection and repair method is proposed, where each inclusion shape is represented as a union of n-Spheres (UnS). A constrained optimization problem is formulated and solved to remove inclusion overlaps; a closed-form solution is derived for calculating the degree of inclusions overlap and its gradient vector with respect to inclusion position. RVE generation is illustrated with circular, spherical, four non-circular and four non-spherical inclusion shapes. Computational efficiency is demonstrated using an elaborate RVE generation time study. The generated RVEs are evaluated using various statistical metrics; results confirm the random distribution of inclusions. Effective properties of RVEs, representing unidirectional composites, are determined using homogenization with various fibre cross-section shapes; obtained mechanical properties have shown transverse isotropy

Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells

B cell responses are critical for antiviral immunity. However, a comprehensive picture of antigen-specific B cell differentiation, clonal proliferation, and dynamics in different organs after infection is lacking. Here, by combining single-cell RNA and B cell receptor (BCR) sequencing of antigen-specific cells in lymph nodes, spleen, and lungs after influenza infection in mice, we identify several germinal center (GC) B cell subpopulations and organ-specific differences that persist over the course of the response. We discover transcriptional differences between memory cells in lungs and lymphoid organs and organ-restricted clonal expansion. Remarkably, we find significant clonal overlap between GC-derived memory and plasma cells. By combining BCR-mutational analyses with monoclonal antibody (mAb) expression and affinity measurements, we find that memory B cells are highly diverse and can be selected from both low- and high-affinity precursors. By linking antigen recognition with transcriptional programming, clonal proliferation, and differentiation, these finding provide important advances in our understanding of antiviral immunity

SMAR1 binds to T(C/G) repeatvand inhibits tumor progression by regulating miR-371-373 cluster

Chromatin architecture and dynamics are regulated by various histone and non-histone proteins. The matrix attachment region binding proteins (MARBPs) play a central role in chromatin organization and function through numerous regulatory proteins. In the present study, we demonstrate that nuclear matrix protein SMAR1 orchestrates global gene regulation as determined by massively parallel ChIPsequencing. The study revealed that SMAR1 binds to T(C/G) repeat and targets genes involved in diverse biological pathways. We observe that SMAR1 binds and targets distinctly different genes based on the availability of p53. Our data suggest that SMAR1 binds and regulates one of the imperative microRNA clusters in cancer and metastasis, miR-371-373. It negatively regulates miR-371-373 transcription as confirmed by SMAR1 overexpression and knockdown studies. Further, deletion studies indicate that a ~200 bp region in the miR-371-373 promoter is necessary for SMAR1 binding and transcriptional repression. Recruitment of HDAC1/mSin3A complex by SMAR1, concomitant with alteration of histone marks results in downregulation of the miRNA cluster. The regulation of miR-371-373 by SMAR1 inhibits breast cancer tumorigenesis and metastasis as determined by in vivo experiments. Overall, our study highlights the binding of SMAR1 to T(C/G) repeat and its role in cancer through miR-371-37

Adaptive preconditioning in neurological diseases -­ therapeutic insights from proteostatic perturbations

International audienceIn neurological disorders, both acute and chronic neural stress can disrupt cellular proteostasis, resulting in the generation of pathological protein. However in most cases, neurons adapt to these proteostatic perturbations by activating a range of cellular protective and repair responses, thus maintaining cell function. These interconnected adaptive mechanisms comprise a 'proteostasis network' and include the unfolded protein response, the ubiquitin proteasome system and autophagy. Interestingly, several recent studies have shown that these adaptive responses can be stimulated by preconditioning treatments, which confer resistance to a subsequent toxic challenge - the phenomenon known as hormesis. In this review we discuss the impact of adaptive stress responses stimulated in diverse human neuropathologies including Parkinson´s disease, Wolfram syndrome, brain ischemia, and brain cancer. Further, we examine how these responses - and the molecular pathways they recruit - might be exploited for therapeutic gai

Transforming Business Strategies of Manufacturing Industries Through Reshoring

The global market explores the best business strategy which enables them to excel by attaining their goals and objectives. The outsourcing phenomenon was practiced by various manufacturing industries to increase their profit margins. The outsourcing tide seems to be reversing since the past few years. The reason behind this transforming scenario is the recent trend of reshoring. The potential benefits of reshoring were highlighted by the some of the manufacturing industries as they are enjoying the fruitful results of reshoring. The research paper aims to provide an in depth analysis of various outsourcing factors that are enforcing the change in business strategies to reshoring. The reshoring drivers play a crucial role in determining the path for cultivating the best business practices. The outsourcing factors of the major manufacturing industries are individually analyzed and evaluated to determine their impact levels on the performance of the manufacturing industries. The assessment of these factors projects the different trends of the outsourcing factors that have a detrimental effect on the transforming business strategies. The research paper provides a framework for the reshoring strategies that is believed to drive the manufacturing business