High-resolution numerical simulation of 2D nonlinear wave structures in electromagnetic fluids with absorbing boundary conditions

AbstractHere we show how the full set of governing equations for the dynamics of charged-particle fluids in an electromagnetic field may be solved numerically in order to model nonlinear wave structures propagating in two dimensions. We employ a source-term adaptation and two-fluid extension of the second-order high-resolution central scheme of Balbas et al. (2004) [1]. The model employed is a 2D extension of that used by Baboolal and Bharuthram (2007) [5] in studies of 1D shocks and solitons in a two-fluid plasma under 3D electromagnetic fields. Further, we outline the use of free-flow boundary conditions to obtain stable wave structures over sufficiently long modelling times. As illustrative results, we examine the formation and evolution of shock-like and soliton structures of the magnetosonic mode

Entropy Stable Numerical Schemes for Two-Fluid Plasma Equations

Two-fluid ideal plasma equations are a generalized form of the ideal MHD equations in which electrons and ions are considered as separate species. The design of efficient numerical schemes for the these equations is complicated on account of their non-linear nature and the presence of stiff source terms, especially for high charge to mass ratios and for low Larmor radii. In this article, we design entropy stable finite difference schemes for the two-fluid equations by combining entropy conservative fluxes and suitable numerical diffusion operators. Furthermore, to overcome the time step restrictions imposed by the stiff source terms, we devise time-stepping routines based on implicit-explicit (IMEX)-Runge Kutta (RK) schemes. The special structure of the two-fluid plasma equations is exploited by us to design IMEX schemes in which only local (in each cell) linear equations need to be solved at each time step. Benchmark numerical experiments are presented to illustrate the robustness and accuracy of these schemes.Comment: Accepted in Journal of Scientific Computin

Gene expression signatures of synovial fluid multipotential stromal cells (MSCs) in advanced knee osteoarthritis and following knee joint distraction

Osteoarthritis (OA) is the most common musculoskeletal disorder. Although joint replacement remains the standard of care for knee OA patients, knee joint distraction (KJD), which works by temporarily off-loading the joint for 6–8 weeks, is becoming a novel joint-sparing alternative for younger OA sufferers. The biological mechanisms behind KJD structural improvements remain poorly understood but likely involve joint-resident regenerative cells including multipotent stromal cells (MSCs). In this study, we hypothesized that KJD leads to beneficial cartilage-anabolic and anti-catabolic changes in joint-resident MSCs and investigated gene expression profiles of synovial fluid (SF) MSCs following KJD as compared with baseline. To obtain further insights into the effects of local biomechanics on MSCs present in late OA joints, SF MSC gene expression was studied in a separate OA arthroplasty cohort and compared with subchondral bone (SB) MSCs from medial (more loaded) and lateral (less loaded) femoral condyles from the same joints. In OA arthroplasty cohort (n = 12 patients), SF MSCs expressed lower levels of ossification- and hypotrophy-related genes [bone sialoprotein (IBSP), parathyroid hormone 1 receptor (PTH1R), and runt-related transcription factor 2 (RUNX2)] than did SB MSCs. Interestingly, SF MSCs expressed 5- to 50-fold higher levels of transcripts for classical extracellular matrix turnover molecules matrix metalloproteinase 1 (MMP1), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and tissue inhibitor of metalloproteinase-3 (TIMP3), all (p < 0.05) potentially indicating greater cartilage remodeling ability of OA SF MSCs, compared with SB MSCs. In KJD cohort (n = 9 patients), joint off-loading resulted in sustained, significant increase in SF MSC colonies’ sizes and densities and a notable transcript upregulation of key cartilage core protein aggrecan (ACAN) (weeks 3 and 6), as well as reduction in pro-inflammatory C–C motif chemokine ligand 2 (CCL2) expression (weeks 3 and 6). Additionally, early KJD changes (week 3) were marked by significant increases in MSC chondrogenic commitment markers gremlin 1 (GREM1) and growth differentiation factor 5 (GDF5). In combination, our results reveal distinct transcriptomes on joint-resident MSCs from different biomechanical environments and show that 6-week joint off-loading leads to transcriptional changes in SF MSCs that may be beneficial for cartilage regeneration. Biomechanical factors should be certainly considered in the development of novel MSC-based therapies for OA

Characterization of long and stable de novo single alpha-helix domains provides novel insight into their stability

Naturally-occurring single α-helices (SAHs), are rich in Arg (R), Glu (E) and Lys (K) residues, and stabilized by multiple salt bridges. Understanding how salt bridges promote their stability is challenging as SAHs are long and their sequences highly variable. Thus, we designed and tested simple de novo 98-residue polypeptides containing 7-residue repeats (AEEEXXX, where X is K or R) expected to promote salt-bridge formation between Glu and Lys/Arg. Lys-rich sequences (EK3 (AEEEKKK) and EK2R1 (AEEEKRK)) both form SAHs, of which EK2R1 is more helical and thermo-stable suggesting Arg increases stability. Substituting Lys with Arg (or vice versa) in the naturally-occurring myosin-6 SAH similarly increased (or decreased) its stability. However, Arg-rich de novo sequences (ER3 (AEEERRR) and EK1R2 (AEEEKRR)) aggregated. Combining a PDB analysis with molecular modelling provides a rational explanation, demonstrating that Glu and Arg form salt bridges more commonly, utilize a wider range of rotamer conformations, and are more dynamic than Glu–Lys. This promiscuous nature of Arg helps explain the increased propensity of de novo Arg-rich SAHs to aggregate. Importantly, the specific K:R ratio is likely to be important in determining helical stability in de-novo and naturally-occurring polypeptides, giving new insight into how single α-helices are stabilized

Corrigendum:Local and macroscopic electrostatic interactions in single α-helices

The non-covalent forces that stabilise protein structures are not fully understood. One way to address this is to study equilibria between unfolded states and α-helices in peptides. For these, electrostatic forces are believed to contribute, including interactions between: side chains; the backbone and side chains; and side chains and the helix macrodipole. Here we probe these experimentally using designed peptides. We find that both terminal backbone-side chain and certain side chain-side chain interactions (i.e., local effects between proximal charges, or interatomic contacts) contribute much more to helix stability than side chain-helix macrodipole electrostatics, which are believed to operate at larger distances. This has implications for current descriptions of helix stability, understanding protein folding, and the refinement of force fields for biomolecular modelling and simulations. In addition, it sheds light on the stability of rod-like structures formed by single α-helices that are common in natural proteins including non-muscle myosins

Development and validation of the motivations for selection of medical study (MSMS) questionnaire in India

Background and Objective Understanding medical students' motivation to select medical studies is particularly salient to inform practice and policymaking in countries-such as India-where shortage of medical personnel poses crucial and chronical challenges to healthcare systems. This study aims to develop and validate a questionnaire to assess the motivation of medical students to select medical studies. Methods A Motivation for Selection of Medical Study (MSMS) questionnaire was developed using extensive literature review followed by Delphi technique. The scale consisted of 12 items, 5 measuring intrinsic dimensions of motivations and 7 measuring extrinsic dimensions. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), validity, reliability and data quality checks were conducted on a sample of 636 medical students from six medical colleges of three North Indian states. Results The MSMS questionnaire consisted of 3 factors (subscales) and 8 items. The three principal factors that emerged after EFA were the scientific factor (e.g. research opportunities and the ability to use new cutting edge technologies), the societal factor (e.g. job security) and the humanitarian factor (e.g. desire to help others). The CFA conducted showed goodnessof-fit indices supporting the 3-factor model. Conclusion The three extracted factors cut across the traditional dichotomy between intrinsic and extrinsic motivation and uncover a novel three-faceted motivation construct based on scientific factors, societal expectations and humanitarian needs. This validated instrument can be used to evaluate the motivational factors of medical students to choose medical study in India and similar settings and constitutes a powerful tool for policymakers to design measures able to increase selection of medical curricula