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Experimental and computational analysis for thermo-erosive stability assessment of ZrB2-SiC based multiphase composites
No full textHigh temperature erosion tests were conducted on spark plasma sintered ZrB2-SiC based multiphase ceramic composites at 1073 K in thermo-erosive environment for 1200 s with a net energy deposition per unit area of 50.5 MJ/m(2). The thermo-erosive mechanisms were qualitatively discussed using XRD and SEM-EDS analyses. Efforts were made to assess feasibility of identified reactions at the computed temperatures to support reaction mechanism for oxide formation in eroded region. Finite element (FE) analysis with high-quality structural elements was used to determine the spatial temperature and stress distribution in the eroded region. Taken together, the present study highlights the significance of combined approach of computational and experimental analysis in understanding the thermo-erosive-structural stability in applications where erosion can limit the performance of ceramic composites
A hybrid finite element formulation for large-deformation contact mechanics
No full textAs is well-known, displacement-based finite elements are prone to the `locking' problem. Thus, employing them for solving contact mechanics problems involving thin structures and almost incompressible materials might require a significant amount of computational effort. Hybrid elements which are based on a two-field Hellinger-Reissner variational principle are known to provide an effective remedy for this locking problem associated with displacement based elements. In this work, we employ the hybrid finite element methodology along with the mortar method towards developing an efficient and robust finite element contact strategy for frictionless two dimensional and axisymmetric problems. The proposed contact formulation can effectively model the contact interaction of thin as well as thick geometries as well as contact between bodies made of almost incompressible materials. Further, for accurate estimation of the contact pressure, a new projection technique is proposed. We demonstrate the excellent coarse mesh accuracy of the proposed formulation through various examples
Fluctuating fortunes: genomes and habitat reconstructions reveal global climate-mediated changes in bats' genetic diversity
No full textOver the last approximately 2.6 Myr, Earth's climate has been dominated by cyclical ice ages that have profoundly affected species' population sites, but the impact of impending anthropogenic climate change on species' extinction potential remains a worrying problem. We investigated 11 bat species from different taxonomic, ecological and geographical backgrounds using combined information from palaeoclimatic habitat reconstructions and genomes to analyse biotic impacts of historic climate change. We discover tightly correlated fluctuations between species' historic distribution and effective population size, identity trugivores as particularly susceptible to global warming, pinpoint large insectivores as having overall low effective population size and flag the onset of the Holocene (approx. 10-12 000 years ago) as the period with the generally lowest effective population sites across the last approximately 1 Myr. Our study show's that combining genomic and palaeoclimatological approaches reveals effects of climatic shifts on genetic diversity and may help predict impacts of future climate change
Structural and functional studies on Salmonella typhimurium pyridoxal kinase: the first structural evidence for the formation of Schiff base with the substrate
No full textA large number of enzymes depend on the ubiquitous cofactor pyridoxal 5 ` phosphate (PLP) for their activity. Pyridoxal kinase (PLK) is the key enzyme involved in the synthesis of PLP from the three forms of vitamin B-6 via the salvage pathway. In the present work, we determined the unliganded structure of StPLK in a monoclinic form and its ternary complex with bound pyridoxal (PL), ADP and Mg2+ in two different tetragonal crystal forms (Form I and Form II). We found that, in the ternary complex structure of StPLK, the active site Lys233 forms a Schiff base linkage with the substrate (PL). Although formation of a Schiff base with the active site Lys229 was demonstrated in the Escherichia coli enzyme based on biochemical studies, the ternary complex of StPLK represents the first crystal structure where the Schiff bond formation has been observed. We also identified an additional site for PLP binding away from the active site in one of the ternary complexes (crystal Form I), suggesting a probable route for the product release. This is the first ternary complex structure where the modeled gamma-phosphate of ATP is close enough to PL for the phosphorylation of the substrate. StPLK prefers PL over pyridoxamine as its substrate and follows a sequential mechanism of catalysis. Surface plasmon resonance studies suggest that StPLK interacts with apo-PLP-dependent enzymes with mu m affinity supporting the earlier proposed direct transfer mechanism of PLP from PLK to PLP-dependent enzymes
Preferential binding and re-organization of nanoscale domains on model lipid membranes by pore-forming toxins: insight from STED-FCS
No full textPotential nanodomains in cellular membranes are widely believed to be targeted by proteins and other biomolecules to enable execution of critical cellular functions. However, characterization of these nanodomains remains elusive, primarily due to the diffraction limit of a conventional optical microscope. Herein using super-resolution STED microscopy coupled with fluorescence correlation spectroscopy (STED-FCS), we provide experimental evidence of lipid nanodomains present in model membranes comprised of phosphocholine-cholesterol binary mixture, and its reorganization induced by pore-forming toxins (PFTs). In this study, we used two different types of PFTs, namely alpha-PFT (cytolysis A) and beta-PFT (listeriolysin O), that preferentially associate as well as reorganize cholesterol-containing saturated and unsaturated phosphocholine membranes. The emergence of nanodomains due to the lipid-lipid and lipid-PFT interactions was quantified at a length scales of similar to 50-150nm using FCS diffusion law enabled by variation of spot sizes in the super-resolution STED microscopy. Our results shed light on the usefulness of super-resolution microscopy to quantify the underlying nanoscale domains in model membranes with implications for a wide variety of membrane-mediated cellular events observed in real cell membranes
A small molecule autophagy inducer exerts cytoprotection against alpha-synuclein toxicity
No full textalpha-synucleopathies are protein-misfolding disorders occur primarily due to aggregation and toxicity of alpha-synuclein. This study characterized the small molecule AGK2 as a modifier of alpha-synuclein mediated toxicity in an autophagy dependent manner in both yeast and mammalian cell line models. In yeast system, AGK2 enhances autophagy to clear toxic alpha-synuclein aggregates in an autophagy dependent manner. Autophagy flux analyses revealed that AGK2 induces autophagy especially autolysosomes. Importantly, AGK2 induces autophagy in an mTOR independent manner. These features enable AGK2 to exert cytoprotective potential against a-synuclein mediated toxicity in different model systems
Subcortical connectivity correlates selectively with attention's effects on spatial choice bias
No full textNeural mechanisms of attention are extensively studied in the neocortex; comparatively little is known about how subcortical regions contribute to attention. The superior colliculus (SC) is an evolutionarily conserved, subcortical (midbrain) structure that has been implicated in controlling visuospatial attention. Yet how the SC contributes mechanistically to attention remains unknown. We investigated the role of the SC in attention, combining model-based psychophysics, diffusion imaging, and tractography in human participants. Specifically, we asked whether the SC contributes to enhancing sensitivity (d') to attended information, or whether it contributes to biasing choices (criteria) in favor of attended information. We tested human participants on a multialternative change detection task, with endogenous spatial cueing, and quantified sensitivity and bias with a recently developed multidimensional signal detection model (m-ADC model). At baseline, sensitivity and bias exhibited complementary patterns of asymmetries across the visual hemifields: While sensitivity was consistently higher for detecting changes in the left hemifield, bias was higher for reporting changes in the right hemifield. Remarkably, white matter connectivity of the SC with the neocortex mirrored this pattern of asymmetries. Specifically, the asymmetry in SC-cortex connectivity correlated with the asymmetry in choice bias, but not in sensitivity. In addition, SC-cortex connectivity strength could predict cueing-induced modulation of bias, but not of sensitivity, across individuals. In summary, the SC may be a key node in an evolutionarily conserved network for controlling choice bias during visuospatial attention
Critical Sublattice Symmetry Breaking: A Universal Criterion for Dirac Cone Splitting
No full textSublattice symmetry breaking has been identified as the necessary condition for bandgap opening in monolayer graphene-on-substrate heterostructures. In many of them, however, in spite of sublattice symmetry breaking, the Dirac cone of graphene remains preserved. Here, we report using first-principles density functional theory (DFT) and a simple tight-binding (TB) model that the presence of more than 50% symmetrically inequivalent carbon atoms is required to split the Dirac cone. Additionally, we find that the Dirac cone must also lie within the bandgap of the other 2D layer to get a semiconducting (nonmetallic) heterostructure. The robustness of these two criteria has been validated in a series of heterostructures of graphene. The simplicity and robustness of the proposed model provide a useful design principle for materials scientists and engineers, thus potentially expanding the applicability of graphene bilayer heterostructures to a multitude of semiconductor devices
Perovskite Ceramics as New-Generation Materials for Orthopedic Applications
No full textThe piezoelectric properties of ferroelectric ceramics have been widely investigated in the materials science community, but relatively less is known about such properties of natural living system. Inspired by the knowledge that the piezoelectric properties influence the metabolic activities of natural bone, the design and development of bone-mimicking electrically active synthetic orthopedic implant materials has gained an excellent distinction in the biomaterials community. In this perspective, the present article briefly reviews the origin of fundamental electrical responses in natural bone along with their biological consequences. In this sequence, the potentiality of multifunctional electrically active perovskites (CaTiO3, BaTiO3, Na0.5K0.5NbO3 etc.) as promising bone substitute has been discussed. The results of several published studies from the author's research group are summarized to highlight the cytocompatibility and histocompatibility of those perovskites. Further, the influence of incorporation of these piezoelectric materials as secondary phases in a bioactive matrix in improving the electromechanical response of composite has also been discussed briefly. It is perceived that this review will stimulate further research to explore the biomedical applications of these functional oxides
Sirtuin 6 mediated stem cell cardiomyogenesis on protein coated nanofibrous scaffolds
No full textThe cellular niche provides combination of biomolecular and biophysical cues to control stem cell fate. Three-dimensional (3D) aligned nanofibrous scaffolds can effectively augment stem cell cardiomyogenesis. This work aims to understand the role of biomolecular signals from extracellular matrix (ECM) proteins and leverage them to further promote cardiomyogenesis on nanofibrous scaffolds. Human mesenchymal stem cells (hMSCs) were cultured on 3D aligned polycaprolactone scaffolds coated with different ECM proteins. Among multiple coatings tested, collagen coated fibers were most effective in promoting cardiomyogenesis as determined from increased expression of cardiac biomarkers and intracellular calcium flux. At molecular level, enhanced differentiation on collagen coated fibers was associated with an increased level of sirtuin 6 (SIRT6). Depletion of SIRT6 using siRNA attenuated the differentiation process through activation of Wnt signaling pathway. This study, thus, demonstrates that protein coated scaffolds can augment cardiomyogenic differentiation of stem cells through a combination of topographical and biomolecular signals