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Highly magnetized super-Chandrasekhar white dwarfs and their consequences
No full textSince 2012, we have been exploring possible existence of highly magnetized significantly super-Chandrasekhar white dwarfs with a new mass limit. This explains several observations, e.g. peculiar over-luminous type Ia supernovae, some white dwarf pulsars, soft gamma-ray repeaters and anomalous X-ray pulsars, which otherwise puzzled us enormously. We have proceeded to uncover the underlying issues by exploiting the enormous potential in quantum, classical and relativistic effects lying with magnetic fields present in white dwarfs. We have also explored the issues related to the stability and gravitational radiation of these white dwarfs
Elucidating molecular events underlying topography mediated cardiomyogenesis of stem cells on 3D nanofibrous scaffolds
No full textToward engineering a cardiac patch, the objective of this work was to assess stem cell response to a three-dimensional (3D) nanofibrous scaffold and probe the underlying molecular mechanisms including both cell signaling and epigenetic changes. Cardiomyogenesis of human mesenchymal stem cells (hMSCs) in 3D poly(epsilon-caprolactone) (PCL) nanofibers and macroporous scaffolds was compared with two-dimensional (2D) PCL films. In addition, nanofiber mats of PCL and its blend with gelatin (PCL-Gel) were prepared with fibers of random or unidirectional alignment to assess the roles of topography (fibrous architecture and its alignment) and biochemical cue (cell-adhesive sites) in directing cell functions. Cells on 3D random nanofibers, exhibited elevated expression of known cardiac markers such as cardiac actinin, cardiac troponin and beta-myocardial heavy chain compared to cells on 2D films suggesting enhanced differentiation that was further accentuated on the aligned fibers. 3D macroporous scaffolds did not enhance the cardiomyogenic differentiation. However, minimal differences were noted between cells on PCL and PCL-Gel fibers, irrespective of alignment. Co-culture with neonatal rat cardiomyocytes induced beating in the differentiated cells. The use of small molecule inhibitors revealed that cytoskeletal elements F-actin, microtubules and downstream ROCK protein are essential for the cardiomyogenesis of hMSCs on the nanofibers. The activation of ERK, AKT and mTOR was observed during cardiomyogenesis. Interestingly, enhanced differentiation on the aligned nanofibers was associated with increased level of the histone deacytelase SIRT6 and decreased level of the acetylated histone H3K9 suggesting a role for epigenetic regulation. This study demonstrates that aligned nanofibrous scaffolds augment cardiomyogenic differentiation wherein topography plays a critical role in driving stem cell function. In addition, this study offers insight into molecular pathways driving the cellular response
APPROXIMATING NASH EQUILIBRIA AND DENSE SUBGRAPHS VIA AN APPROXIMATE VERSION OF CARATHEODORY'S THEOREM
No full textWe present algorithmic applications of an approximate version of Caratheodory's theorem. The theorem states that given a set of vectors X in R-d, for every vector in the convex hull of X there exists an epsilon-close (under the p-norm distance for 2 <= p < infinity) vector that can be expressed as a convex combination of at most b vectors of X, where the bound b depends on epsilon and the norm p and is independent of the dimension d. This theorem can be derived by instantiating Maurey's lemma, early references to which can be found in the work of Pisier (1981) and Carl (1985). However, in this paper we present a self-contained proof of this result. Using this theorem we establish that in a bimatrix game with n x n payoff matrices A, B, if the number of nonzero entries in any column of A + B is at most s then an epsilon-Nash equilibrium of the game can be computed in time n(O(log s/epsilon 2)). This, in particular, gives us a polynomial-time approximation scheme for Nash equilibrium in games with fixed column sparsity s. Moreover, for arbitrary bimatrix games the running time of our algorithm matches the best-known upper bound, which was obtained by Lipton, Markakis, and Mehta (2003). The theorem also leads to an additive approximation algorithm for the normalized densest k-subgraph problem. Given a graph with n vertices and maximum degree d, our algorithm determines a size-k subgraph with normalized density within epsilon of the optimal in time n(O(log s/epsilon 2))
Spatiotemporal Modulation of ERK Activation by GPCRs
No full textERK1/2 (extracellular signal-regulated protein kinases) are the nodal proteins that regulate diverse cellular functions primarily in response to activation from receptor tyrosine kinases (RTKs). Not only is ERK activated through a variety of RTKs, but noncanonical signaling through GPCRs also activates them. Such multimodal activation allows appropriate integration of many inputs to critical cell fate decisions such as proliferation and differentiation that MAP kinases typically regulate. MAP kinases also regulate many polar responses such as apoptosis and proliferation, dedifferentiation-differentiation, and the diversity in the outcomes though the same terminal molecule can be explained based on differences in the activation dynamics and rates. However, two processes have now been established as drivers for most of the diversity recorded in the outcomes of MAP kinase signaling. These parameters are cellular compartmentalization, i.e., spatial confinement of the molecules participating in a pathway and changes in the kinetics of the activation-deactivation, i.e., temporal regulation. While phosphorylation is the key to activating responses, specifically for ERK, the terminal MAP kinase, it is the spatiotemporal dynamics that governs the outcome generated by it. This chapter reviews our present understanding of the spatial and temporal regulation of MAP kinase cascade and the ERK activity, specifically through GPCRs
The three-point Pick-Nevanlinna interpolation problem on the polydisc
No full textWe give a necessary and sufficient condition for the existence of a holomorphic interpolant, for prescribed three-point Pick-Nevanlinna data. This is equivalent, due to results of Agler-McCarthy and Knese, to the existence of an interpolating rational inner function on the unit polydisc. Characterizing the latter reduces the search for a three-point interpolant to finding a single rational inner function that satisfies a certain positivity condition and arises from a polynomial of a very special form. This in turn relies on a pair of results on the factorization of rational inner functions
Antiphase boundary in antiferromagnetic multiferroic LuMn0.5Fe0.5O3: anomalous ferromagnetism, exchange bias effect and large vertical hysteretic shift
No full textThe emergence of exchange bias effect in Fe3O4 thin films has been since attributed to the presence of anti phase boundary (APB) growth defects despite lack of direct experimental evidence. In the present report, APB induced anomalous weak ferromagnetism and exchange bias property of single-phase antiferromagnetic (AFM) system LuMn0.5Fe0.5O3 (LMFO) is discussed and Fe-57 Mossbauer spectroscopy and high resolution transmission electron microscopy (HRTEM) measurements are used to probe the origin of the observed effect. In addition to the sextet component corresponding to the long range AFM ordering, the measured Mossbauer spectra reveal the presence of a small component (10%-12%) near zero velocity with unusually small internal field. This indicates the presence of APB defects. From micro structural investigations using HRTEM, presence of APB type defects and dislocations are confirmed. In addition to the exchange bias effect, upon field cooling, hysteresis loop exhibits large vertical shift due to strong pinning effect of the APB. Finally we further annealed the optimally sintered sample LMFO and studied the evolution of defects, and their influence on weak ferromagnetism and exchange bias properties. Our present experimental findings may pave the way in creating new functionalities in materials using APB-type growth defects
Why resource history matters: age and oviposition history affect oviposition behaviour in exploiters of a mutualism
No full text1. Acceptance of hosts for oviposition is often hardwired in short-lived insects, but can be dynamic at the individual level due to variation in physiological state determinants such as ageing and prior oviposition. However, the effect of the oviposition history of resources together with time taken to accept less preferred hosts in ageing insects has rarely been investigated. 2. The time taken by parasitic fig wasps to accept resources with different oviposition histories was recorded in order to investigate the effect of wasp physiological state and resource oviposition history on oviposition behaviour. These wasps, which differ in life-history traits, oviposit at specific developmental stages of enclosed fig inflorescences called syconia. 3. Behavioural assays were performed with naive wasps and wasps aged with and without prior oviposition experience. Syconia at the same developmental stage but differing in oviposition history were offered in no-choice assays and the time taken to first oviposition attempt was recorded. 4. One short-lived pro-ovigenic galler species exhibited a decline with age in time taken to accept a syconium for oviposition. The exact timing of the transition from non-acceptance to acceptance of less preferred syconia was determined in terms of the proportion of elapsed life span at the transition; this occurred at 25% of elapsed life span. 5. Longer-lived parasitoids did not show any decline in specificity despite being aged for 50% of their life span. Therefore, host quality, trophic position, egg load and age may individually affect oviposition decisions or have interaction effects
Identification of a co-target for enhancing efficacy of sorafenib in HCC through a quantitative modeling approach
No full textSorafenib (SFB), a multi-kinase inhibitor, is the only approved drug for treating hepatocellular carcinoma (HCC). However, SFB shows low efficacy in many cases. HCC related mortality therefore remains to be high worldwide. SFB, a multi-kinase inhibitor is also known to modulate the redox homeostasis in cancer cells. To understand the effect of SFB on the redox status, a quantitative understanding of the system is necessary. Kinetic modeling of the relevant pathways is a useful approach for obtaining a quantitative understanding of the pathway dynamics and to rank the individual factors based on the extent of influence they wield on the pathway. Here, we report a comprehensive model of the glutathione reaction network (GSH(net)), consisting of four modules and includes SFB-induced redox stress. We compared GSH(net) simulations for HCC of six different etiologies with healthy liver, and correctly identified the expected variations in cancer. Next, we studied alterations induced in the system upon SFB treatment and observed differential H2O2 dynamics in all the conditions. Using metabolic control analysis, we identified glutathione S-transferase (GST) as the enzyme with the highest selective control coefficient, making it an attractive co-target for potentiating the action of SFB across all six etiologies. As a proof-of-concept, we selected ethacrynic acid (EA), a known inhibitor of GST, and verified ex vivo that EA synergistically potentiates the cytotoxic effect of SFB. Being an FDA approved drug, EA is a promising candidate for repurposing as a combination therapy with SFB for HCC treatment
Effect of niobium interlayer in dissimilar friction stir welding of aluminum to titanium
No full textThe most important issue associated with dissimilar welding is the formation of detrimental intermetallics and consequent reduction in mechanical properties of the weld. It was expected that addition of an interlayer would modify the pattern of the intermetallic formation. The present investigation deals with Friction Stir Welding of aluminum (Al) to titanium (Ti) in presence of niobium (Nb) interlayer. X-ray Computed Tomography results highlighted that fine particles of both Ti and Nb are homogeneously distributed. Large Ti particles are substantially fragmented whereas large Nb particles remain as flakes. Microstructural features of the nugget zone indicated a complex mixing of materials. Jointing had been perceived through elemental diffusion at the interfaces of Al/Ti and Ti/Nb. However, Nb restricted the reaction between Al and Ti, and acted as an efficient interlayer to retard the formation of brittle Al3Ti intermetallic phase. Mechanisms of microstructural evolution in Al side of the weld have been identified as Dynamic Recovery, Dynamic Recrystallization and particle stimulated nucleation. Significant improvement in the tensile ductility had been observed due to the presence of finer particles. The presence of Nb in the weld nugget influences the microstructural evolution and tensile properties of the weld by reducing the formation of intermetallics