Massively Parallel Sequencing of Human Urinary Exosome/Microvesicle RNA Reveals a Predominance of Non-Coding RNA

Intact RNA from exosomes/microvesicles (collectively referred to as microvesicles) has sparked much interest as potential biomarkers for the non-invasive analysis of disease. Here we use the Illumina Genome Analyzer to determine the comprehensive array of nucleic acid reads present in urinary microvesicles. Extraneous nucleic acids were digested using RNase and DNase treatment and the microvesicle inner nucleic acid cargo was analyzed with and without DNase digestion to examine both DNA and RNA sequences contained in microvesicles. Results revealed that a substantial proportion (∼87%) of reads aligned to ribosomal RNA. Of the non-ribosomal RNA sequences, ∼60% aligned to non-coding RNA and repeat sequences including LINE, SINE, satellite repeats, and RNA repeats (tRNA, snRNA, scRNA and srpRNA). The remaining ∼40% of non-ribosomal RNA reads aligned to protein coding genes and splice sites encompassing approximately 13,500 of the known 21,892 protein coding genes of the human genome. Analysis of protein coding genes specific to the renal and genitourinary tract revealed that complete segments of the renal nephron and collecting duct as well as genes indicative of the bladder and prostate could be identified. This study reveals that the entire genitourinary system may be mapped using microvesicle transcript analysis and that the majority of non-ribosomal RNA sequences contained in microvesicles is potentially functional non-coding RNA, which play an emerging role in cell regulation

Photon Management in Two-Dimensional Disordered Media

Elaborating reliable and versatile strategies for efficient light coupling between free space and thin films is of crucial importance for new technologies in energy efficiency. Nanostructured materials have opened unprecedented opportunities for light management, notably in thin-film solar cells. Efficient coherent light trapping has been accomplished through the careful design of plasmonic nanoparticles and gratings, resonant dielectric particles and photonic crystals. Alternative approaches have used randomly-textured surfaces as strong light diffusers to benefit from their broadband and wide-angle properties. Here, we propose a new strategy for photon management in thin films that combines both advantages of an efficient trapping due to coherent optical effects and broadband/wide-angle properties due to disorder. Our approach consists in the excitation of electromagnetic modes formed by multiple light scattering and wave interference in two-dimensional random media. We show, by numerical calculations, that the spectral and angular responses of thin films containing disordered photonic patterns are intimately related to the in-plane light transport process and can be tuned through structural correlations. Our findings, which are applicable to all waves, are particularly suited for improving the absorption efficiency of thin-film solar cells and can provide a novel approach for high-extraction efficiency light-emitting diodes

Predicting residue-wise contact orders in proteins by support vector regression

BACKGROUND: The residue-wise contact order (RWCO) describes the sequence separations between the residues of interest and its contacting residues in a protein sequence. It is a new kind of one-dimensional protein structure that represents the extent of long-range contacts and is considered as a generalization of contact order. Together with secondary structure, accessible surface area, the B factor, and contact number, RWCO provides comprehensive and indispensable important information to reconstructing the protein three-dimensional structure from a set of one-dimensional structural properties. Accurately predicting RWCO values could have many important applications in protein three-dimensional structure prediction and protein folding rate prediction, and give deep insights into protein sequence-structure relationships. RESULTS: We developed a novel approach to predict residue-wise contact order values in proteins based on support vector regression (SVR), starting from primary amino acid sequences. We explored seven different sequence encoding schemes to examine their effects on the prediction performance, including local sequence in the form of PSI-BLAST profiles, local sequence plus amino acid composition, local sequence plus molecular weight, local sequence plus secondary structure predicted by PSIPRED, local sequence plus molecular weight and amino acid composition, local sequence plus molecular weight and predicted secondary structure, and local sequence plus molecular weight, amino acid composition and predicted secondary structure. When using local sequences with multiple sequence alignments in the form of PSI-BLAST profiles, we could predict the RWCO distribution with a Pearson correlation coefficient (CC) between the predicted and observed RWCO values of 0.55, and root mean square error (RMSE) of 0.82, based on a well-defined dataset with 680 protein sequences. Moreover, by incorporating global features such as molecular weight and amino acid composition we could further improve the prediction performance with the CC to 0.57 and an RMSE of 0.79. In addition, combining the predicted secondary structure by PSIPRED was found to significantly improve the prediction performance and could yield the best prediction accuracy with a CC of 0.60 and RMSE of 0.78, which provided at least comparable performance compared with the other existing methods. CONCLUSION: The SVR method shows a prediction performance competitive with or at least comparable to the previously developed linear regression-based methods for predicting RWCO values. In contrast to support vector classification (SVC), SVR is very good at estimating the raw value profiles of the samples. The successful application of the SVR approach in this study reinforces the fact that support vector regression is a powerful tool in extracting the protein sequence-structure relationship and in estimating the protein structural profiles from amino acid sequences

The Look-back Time Evolution of Far-Ultraviolet Flux from the Brightest Cluster Elliptical Galaxies at z < 0.2

We present the GALEX UV photometry of the elliptical galaxies in Abell clusters at moderate redshifts (z < 0.2) for the study of the look-back time evolution of the UV upturn phenomenon. The brightest elliptical galaxies (M_r < -22) in 12 remote clusters are compared with the nearby giant elliptical galaxies of comparable optical luminosity in the Fornax and Virgo clusters. The sample galaxies presented here appear to be quiescent without signs of massive star formation or strong nuclear activity, and show smooth, extended profiles in their UV images indicating that the far-UV (FUV) light is mostly produced by hot stars in the underlying old stellar population. Compared to their counterparts in nearby clusters, the FUV flux of cluster giant elliptical galaxies at moderate redshifts fades rapidly with ~ 2 Gyrs of look-back time, and the observed pace in FUV - V color evolution agrees reasonably well with the prediction from the population synthesis models where the dominant FUV source is hot horizontal-branch stars and their progeny. A similar amount of color spread (~ 1 mag) in FUV - V exists among the brightest cluster elliptical galaxies at z ~ 0.1, as observed among the nearby giant elliptical galaxies of comparable optical luminosity.Comment: Accepted for publication in the Special GALEX ApJ Supplement, December 200

Gaugino Anomaly Mediated SUSY Breaking: phenomenology and prospects for the LHC

We examine the supersymmetry phenomenology of a novel scenario of supersymmetry (SUSY) breaking which we call Gaugino Anomaly Mediation, or inoAMSB. This is suggested by recent work on the phenomenology of flux compactified type IIB string theory. The essential features of this scenario are that the gaugino masses are of the anomaly-mediated SUSY breaking (AMSB) form, while scalar and trilinear soft SUSY breaking terms are highly suppressed. Renormalization group effects yield an allowable sparticle mass spectrum, while at the same time avoiding charged LSPs; the latter are common in models with negligible soft scalar masses, such as no-scale or gaugino mediation models. Since scalar and trilinear soft terms are highly suppressed, the SUSY induced flavor and CP-violating processes are also suppressed. The lightest SUSY particle is the neutral wino, while the heaviest is the gluino. In this model, there should be a strong multi-jet +etmiss signal from squark pair production at the LHC. We find a 100 fb^{-1} reach of LHC out to m_{3/2}\sim 118 TeV, corresponding to a gluino mass of \sim 2.6 TeV. A double mass edge from the opposite-sign/same flavor dilepton invariant mass distribution should be visible at LHC; this, along with the presence of short-- but visible-- highly ionizing tracks from quasi-stable charginos, should provide a smoking gun signature for inoAMSB.Comment: 30 pages including 14 .eps figure

Engineering Schottky contacts in open-air fabricated heterojunction solar cells to enable high performance and ohmic charge transport.

The efficiencies of open-air processed Cu2O/Zn(1-x)Mg(x)O heterojunction solar cells are doubled by reducing the effect of the Schottky barrier between Zn(1-x)Mg(x)O and the indium tin oxide (ITO) top contact. By depositing Zn(1-x)Mg(x)O with a long band-tail, charge flows through the Zn(1-x)Mg(x)O/ITO Schottky barrier without rectification by hopping between the sub-bandgap states. High current densities are obtained by controlling the Zn(1-x)Mg(x)O thickness to ensure that the Schottky barrier is spatially removed from the p-n junction, allowing the full built-in potential to form, in addition to taking advantage of the increased electrical conductivity of the Zn(1-x)Mg(x)O films with increasing thickness. This work therefore shows that the Zn(1-x)Mg(x)O window layer sub-bandgap state density and thickness are critical parameters that can be engineered to minimize the effect of Schottky barriers on device performance. More generally, these findings show how to improve the performance of other photovoltaic system reliant on transparent top contacts, e.g., CZTS and CIGS.This work was supported by EPSRC of the UK (award number RG3717)This is the accepted manuscript. The final version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/am5058663

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio