Open Access Repository of IISc Research Publications

    Association of variants in HTRA1 and NOTCH3 with MRI-defined extremes of cerebral small vessel disease in older subjects

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    We report a composite extreme phenotype design using distribution of white matter hyperintensities and brain infarcts in a population-based cohort of older persons for gene-mapping of cerebral small vessel disease. We demonstrate its application in the 3C-Dijon whole exome sequencing (WES) study (n = 1924, n(WESextremes) = 512), with both single variant and gene-based association tests. We used other population-based cohort studies participating in the CHARGE consortium for replication, using whole exome sequencing (n(WES) = 2,868, n(WESextremes) = 956) and genome-wide genotypes (n(GW) = 9924, n(GWextremes) = 3308). We restricted our study to candidate genes known to harbour mutations for Mendelian small vessel disease: NOTCH3, HTRA1, COL4A1, COL4A2 and TREX1. We identified significant associations of a common intronic variant in HTRA1, rs2293871 using single variant association testing (P-discovery = 8.21 x 10(-5), P-replication = 5.25 x 10(-3), P-combined = 4.72 x 10(-5)) and of NOTCH3 using gene-based tests (P-discovery = 1.61 x 10(-2), P-replication = 3.99 x 10(-2), P-combined = 5.31 x 10(-3)). Follow-up analysis identified significant association of rs2293871 with small vessel ischaemic stroke, and two blood expression quantitative trait loci of HTRA1 in linkage disequilibrium. Additionally, we identified two participants in the 3C-Dijon cohort (0.4%) carrying heterozygote genotypes at known pathogenic variants for familial small vessel disease within NOTCH3 and HTRA1. In conclusion, our proof-of-concept study provides strong evidence that using a novel composite MRI-derived phenotype for extremes of small vessel disease can facilitate the identification of genetic variants underlying small vessel disease, both common variants and those with rare and low frequency. The findings demonstrate shared mechanisms and a continuum between genes underlying Mendelian small vessel disease and those contributing to the common, multifactorial form of the disease

    Reliability analysis of near-surface disposal facility using subset simulation

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    Near-surface disposal facility is intended for the disposal of low-level nuclear wastes. The reliability analysis of this facility is carried out to estimate the efficiency of the system in containing the nuclear wastes. Subset simulation, an advanced simulation technique, is used for the reliability analysis of the system, and the bootstrap method of resampling is used to quantify uncertainties in sampling. Further, Sobol indices are used for sensitivity analysis. In the present analysis, radionuclide diffusion model is used assuming diffusion of radionuclides through the multibarrier system to reach the aquifer, and in the aquifer, the contaminant transport model is used for determining the radionuclide concentration at different distances from the source

    Enantioselective Direct Vinylogous Allylic Alkylation of 4-Methylquinolones under Iridium Catalysis

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    The first enantioselective vinylogous allylic alkylation of 4-methylquinolones has been developed. This iridium-catalyzed reaction introduces an allyl group at the gamma-position of 4-methyl-2-quinolones with exclusive branched selectivity and an excellent level of enantioselectivity. This in turn allows for the enantioselective synthesis of gamma-allylquinolines and related nitrogenous heterocycles. This is the first application of 4-methylquinolones in an enantioselective transformation

    Work fluctuation relations for a dragged Brownian particle in active bath

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    We study the work distribution of a Brownian particle diffusing in an environment of active particles and being trapped in a harmonic potential, the center of which is subjected to a time-dependent protocol. Employing phase space path integral technique we find an expression of work distribution for any generic model of active noise. Here we consider two active noise models - Gaussian correlated and Poisson white, each of which can represent some physical systems. For both the cases, it is found that transient fluctuation relation of work is not applicable though at steady state it holds by defining a renormalized temperaturer tau(r) in place of bath temperature. Interestingly, tau(r) is the same for both the models and can be expressed in terms of diffusivities of active and thermal noises. For correlated Gaussian bath, an alternative approach is presented. Analogous to the formalism given by Hatano and Sasa (2001), we obtain a work like quantity from nonequilibrium potential with the inclusion of a new stationary parameter Omega. With proper choice of Omega, a steady-state fluctuation relation, namely Jarzynski equality is satisfied

    A comprehensive review on analysis of nanocomposites: from manufacturing to properties characterization

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    The study of nanocomposites in its diverse scientific fields has increased dramatically over the years with numerous theoretical and experimental techniques emerging and redefining the process of synthesis, analysis and cost control methodologies of nanocomposites. The present review is an attempt to identify the various methodologies, techniques, theories and formulations that are used in nanocomposite technology. As an overall qualitative appreciation it is possible to conclude that the diversity of processes involved in the manufacture and analysis of nanocomposites, impacts them differently, influencing their physical nature, chemical behaviour, biological interactions, optical properties and production costs which consequently may introduce some constraints to their application. Hence, a critical review on the best methodology would remain inconclusive. This work intends to collect and relate publications on different fields of the nanocomposites technology and application fields, aiming at contributing to achieve a wide perspective of different aspects of the nanocomposites processes and theories and with this, being an aid to ease and raise the production and analysis of nanocomposites to a higher level

    Image reconstruction from undersampled confocal microscopy data using multiresolution based maximum entropy regularization

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    We consider the problem of reconstructing 2D images from randomly under-sampled confocal microscopy samples. The well known and widely celebrated total variation regularization, which is the l(1) norm of derivatives, turns out to be unsuitable for this problem; it is unable to handle both noise and under-sampling together. This issue is linked with the notion of phase transition phenomenon observed in compressive sensing research, which is essentially the break-down of total variation methods, when sampling density gets lower than certain threshold. The severity of this breakdown is determined by the so-called mutual incoherence between the derivative operators and measurement operator. In our problem, the mutual incoherence is low, and hence the total variation regularization gives serious artifacts in the presence of noise even when the sampling density is not very low. There has been very few attempts in developing regularization methods that perform better than total variation regularization for this problem. We develop a multi-resolution based regularization method that is adaptive to image structure. In our approach, the desired reconstruction is formulated as a series of coarse-to-fine multi-resolution reconstructions; for reconstruction at each level, the regularization is constructed to be adaptive to the image structure, where the information for adaption is obtained from the reconstruction obtained at coarser resolution level. This adaptation is achieved by using maximum entropy principle, where the required adaptive regularization is determined as the maximizer of entropy subject to the information extracted from the coarse reconstruction as constraints. We also utilize the directionally adaptive second order derivatives for constructing the regularization with directions guided by the given coarse reconstruction, which leads to an improved suppression of artifacts. We demonstrate the superiority of the proposed regularization method over existing ones using several reconstruction examples

    Analytical modelling of spatial deformation pathways in planar and spatial shallow bistable arches

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    We analyse spatial bistable arches and present an analytical model incorporating axial, two transverse bending and torsion energy components. We extend the St. Venant and Michell relationship used in flexural-torsional buckling of planar arches and use it in modelling spatial arches. We study deformation pathways in spatial arches and their effect on critical characteristics of bistability such as back and forth switching forces, and the distance travelled by a point of the arch. We show that not considering spatial deformation leads to incorrect inferences concerning the bistability of planar arches too. Thus, this model serves as a generalized framework for the existing analysis on planar arches since they belong to a subset of spatial arches. Additionally, the effects of eccentric loading on spatial deformations are explored for arches with a range of as-fabricated shapes and boundary conditions, and the results are validated with finite-element analysis

    Peak-to-Average Power Ratio of OTFS Modulation

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    In this letter, we analyze the peak-to-average power ratio (PAPR) of orthogonal time frequency space modulation (OTFS) waveform. Towards this, we consider modulation symbols on an N x M delay-Doppler grid, where N and M are the number of Doppler and delay bins, respectively. We derive an upper bound on the PAPR of the OTFS signal and show that the maximum PAPR grows linearly with N (and not with M, the number of subcarriers, as observed in conventional multicarrier schemes such as OFDM). We analytically characterize the complementary cumulative distribution function (CCDF) of the PAPR of OTFS with rectangular pulse for large values of N. We present the simulated CCDF of the PAPR of OTFS for different pulse shapes and compare it with those of OFDM and generalized frequency division multiplexing (GFDM). It is shown that OTFS can have better PAPR compared to OFDM and GFDM

    Peculiar magnetic states in the double perovskite Nd2NiMnO6

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    We present magnetic measurements on Nd2NiMnO6 which exhibits a well-known insulating paramagnetic state to an insulating ferromagnetic state transition when cooled below 200 K. Beyond this basic fact, there is a great deal of diversity in the reported magnetic properties and interpretation of specific anomalies observed in the magnetic data of this compound below the Curie temperature. We address specifically two anomalies discussed in the past, namely, a spin-glass like behavior observed in some samples near 100 K and a downturn in the magnetization with a lowering of the temperature below approximately 50 K. We show for the first time that the application of an increasing magnetic field can systematically change the low-temperature behavior to make the down-turn in the magnetization into an upturn. With the help of first principle calculations and extensive simulations along with our experimental observations, we provide a microscopic understanding of all magnetic properties observed in this interesting system to point out that the glassiness around 100 K is absent in well-ordered samples and that the low-temperature magnetic anomaly below 50 K is a consequence of a ferromagnetic coupling of the Nd spin moments with the spin of the Ni-Mn ordered sublattice without giving rise to any ordering of the Nd sublattice that remains paramagnetic, contrary to earlier claims. We explain this counter-intuitive interpretation of a ferromagnetic coupling of Nd spins with Ni-Mn spin giving rise to a decrease in the total magnetic moment by noting the less than half-filled 4f occupation of Nd that ensures orbital and spin moments of Nd to be opposite to each other due to the spin-orbit coupling. Since the ground state total magnetic moment of Nd has a contribution from the orbital moment, that is larger than the spin moment, the total moment of Nd is indeed pointing in a direction opposite to the direction of spin moments of the Ni-Mn sublattice as a consequence of the ferromagnetic exchange coupling between Nd and Ni-Mn spins
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