Structural and molecular basis of the assembly of the TRPP2/PKD1 complex

Mutations in PKD1 and TRPP2 account for nearly all cases of autosomal dominant polycystic kidney disease (ADPKD). These 2 proteins form a receptor/ion channel complex on the cell surface. Using a combination of biochemistry, crystallography, and a single-molecule method to determine the subunit composition of proteins in the plasma membrane of live cells, we find that this complex contains 3 TRPP2 and 1 PKD1. A newly identified coiled-coil domain in the C terminus of TRPP2 is critical for the formation of this complex. This coiled-coil domain forms a homotrimer, in both solution and crystal structure, and binds to a single coiled-coil domain in the C terminus of PKD1. Mutations that disrupt the TRPP2 coiled-coil domain trimer abolish the assembly of both the full-length TRPP2 trimer and the TRPP2/PKD1 complex and diminish the surface expression of both proteins. These results have significant implications for the assembly, regulation, and function of the TRPP2/PKD1 complex and the pathogenic mechanism of some ADPKD-producing mutations

Relative entropy and the stability of shocks and contact discontinuities for systems of conservation laws with non BV perturbations

We develop a theory based on relative entropy to show the uniqueness and L^2 stability (up to a translation) of extremal entropic Rankine-Hugoniot discontinuities for systems of conservation laws (typically 1-shocks, n-shocks, 1-contact discontinuities and n-contact discontinuities of large amplitude) among bounded entropic weak solutions having an additional trace property. The existence of a convex entropy is needed. No BV estimate is needed on the weak solutions considered. The theory holds without smallness condition. The assumptions are quite general. For instance, strict hyperbolicity is not needed globally. For fluid mechanics, the theory handles solutions with vacuum.Comment: 29 page

Single Nucleotide Polymorphism (SNP) Detection and Genotype Calling from Massively Parallel Sequencing (MPS) Data

Massively parallel sequencing (MPS), since its debut in 2005, has transformed the field of genomic studies. These new sequencing technologies have resulted in the successful identification of causal variants for several rare Mendelian disorders. They have also begun to deliver on their promise to explain some of the missing heritability from genome-wide association studies (GWAS) of complex traits. We anticipate a rapidly growing number of MPS-based studies for a diverse range of applications in the near future. One crucial and nearly inevitable step is to detect SNPs and call genotypes at the detected polymorphic sites from the sequencing data. Here, we review statistical methods that have been proposed in the past five years for this purpose. In addition, we discuss emerging issues and future directions related to SNP detection and genotype calling from MPS data

Wigner Crystals Phases in Bilayer Quantum Hall Systems

(This is a substantially shortened version of the original abstract:) The Wigner crystal phase diagram of the bilayer systems have been studied using variational methods. Five crystal phases are obtained. As the layer spacing increases, the system will undergo a sequence of phase transitions. A common feature of most bilayer Wigner crystals is that they have mixed (pseudo-spin) ferromagnetic and antiferromagnetic order.Comment: 19 figures. Figures will be provided upon request. Submitted in PRB in Nov 94

Generic properties of a quasi-one dimensional classical Wigner crystal

We studied the structural, dynamical properties and melting of a quasi-one-dimensional system of charged particles, interacting through a screened Coulomb potential. The ground state energy was calculated and, depending on the density and the screening length, the system crystallizes in a number of chains. As a function of the density (or the confining potential), the ground state configurations and the structural transitions between them were analyzed both by analytical and Monte Carlo calculations. The system exhibits a rich phase diagram at zero temperature with continuous and discontinuous structural transitions. We calculated the normal modes of the Wigner crystal and the magneto-phonons when an external constant magnetic field $B$ is applied. At finite temperature the melting of the system was studied via Monte Carlo simulations using the $modified$ $Lindemann$ $criterion$ (MLC). The melting temperature as a function of the density was obtained for different screening parameters. Reentrant melting as a function of the density was found as well as evidence of directional dependent melting. The single chain regime exhibits anomalous melting temperatures according to the MLC and as a check we study the pair correlation function at different densities and different temperatures, formulating a different criterion. Possible connection with recent theoretical and experimental results are discussed and experiments are proposed.Comment: 13 pages text, 21 picture

Interstitials, Vacancies and Dislocations in Flux-Line Lattices: A Theory of Vortex Crystals, Supersolids and Liquids

We study a three dimensional Abrikosov vortex lattice in the presence of an equilibrium concentration of vacancy, interstitial and dislocation loops. Vacancies and interstitials renormalize the long-wavelength bulk and tilt elastic moduli. Dislocation loops lead to the vanishing of the long-wavelength shear modulus. The coupling to vacancies and interstitials - which are always present in the liquid state - allows dislocations to relax stresses by climbing out of their glide plane. Surprisingly, this mechanism does not yield any further independent renormalization of the tilt and compressional moduli at long wavelengths. The long wavelength properties of the resulting state are formally identical to that of the ``flux-line hexatic'' that is a candidate ``normal'' hexatically ordered vortex liquid state.Comment: 21 RevTeX pgs, 7 eps figures uuencoded; corrected typos, published versio

Flexural behavior of UHPCbeam reinforced with steel-FRP composite bars

YesThis paper numerically investigates flexural performance of Ultra-High Performance Concrete (UHPC) beam reinforced with Steel-Fibre-Reinforced Polymer (FRP) Composite Bars (SFCBs) in terms of flexural stiffness, moment capacity, deflection, ductility and energy dissipation. The effect of various parameters, include the inner steel core area ratio of SFCB, yield strength of inner steel core, elastic modulus and ultimate strength of outer-wrapped FRP, reinforcement ratio, type and strength of concrete were studied. The results demonstrate that the inner steel core area ratio of SFCB, reinforcement ratio and the elastic modulus of SFCB's outer FRP have significant effect on the overall flexural performance of SFCB reinforced UHPC beam. The overall flexural performance of SFCB reinforced UHPC beam is slightly improved by increasing the yield strength of inner steel core of SFCB, but not affected by the ultimate strength of SFCB's outer FRP when specimen occurred compression failure. The results also exhibit that the flexural performance of UHPC beam reinforced with SFCBs is significantly improved when compared to those of reinforced high strength concrete (HSC) beam and normal strength concrete (NSC) beam. The flexural stiffness and the moment capacity of SFCB reinforced UHPC beam at the ultimate point were 2.0 and 2.4 times, respectively, of those of reinforced NSC counterpart.Natural Science Foundation of Jiangsu Province, China (BK20201436), the China Postdoctoral Science Foundation (2018M642335), the Science and Technology Project of Jiangsu Construction System, China (2018ZD047, 2021ZD06), the Science and Technology Project of Gansu Construction System, China (JK2021-19), the National Natural Science Foundation of China (51678514), the Science and Technology Innovation Fund of Yangzhou University, China (2020-65), the Open Foundation of Jiangsu Province Engineering Research Center of Prefabricated Building and Intelligent Construction, China (2021), the Science and Technology Cooperation Fund Project of Yangzhou City and Yangzhou University, China (YZU212105), the Practice and Innovation Plan for Postgraduates in Jiangsu Province, China (SJCX21_1589), the Blue Project Youth Academic Leader of Colleges and Universities in Jiangsu Province, China (2020) and the Deputy General Manager Science and Technology Project of Jiangsu Province, China (FZ20200869). Reference

ROP: dumpster diving in RNA-sequencing to find the source of 1 trillion reads across diverse adult human tissues.

High-throughput RNA-sequencing (RNA-seq) technologies provide an unprecedented opportunity to explore the individual transcriptome. Unmapped reads are a large and often overlooked output of standard RNA-seq analyses. Here, we present Read Origin Protocol (ROP), a tool for discovering the source of all reads originating from complex RNA molecules. We apply ROP to samples across 2630 individuals from 54 diverse human tissues. Our approach can account for 99.9% of 1 trillion reads of various read length. Additionally, we use ROP to investigate the functional mechanisms underlying connections between the immune system, microbiome, and disease. ROP is freely available at https://github.com/smangul1/rop/wiki