Glacial Aerodynamic Roughness Estimates:Uncertainty, Sensitivity, and Precision in Field Measurements

Calculation of the sensible and latent heat (turbulent) fluxes is required in order to close the surface energy budget of glaciers and model glacial melt. The aerodynamic roughness length, z0, is a key parameter in the bulk approach to calculating sensible heat flux; yet, z0 is commonly considered simply as a tuning parameter or generalized between surfaces and over time. Spatially and temporally distributed observations of z0 over ice are rare. Both direct (from wind towers and sonic anemometers) and indirect (from microtopographic surveys) measurements of z0 are subject to sensitivities and uncertainties that are often unstated or overlooked. In this study, we present a quantitative evaluation of aerodynamic profile-based and microtopographic methods and their effect on z0 using data collected from Storglaciären and Sydöstra Kaskasatjäkkaglaciären, Tarfala Valley, Arctic Sweden. Aggressive data filters discard most of the wind tower data but still produce realistic z0 values of 1.9 mm and 2 mm. Despite uncertainty introduced by scale and resolution dependence, microtopographic methods produced estimates of z0 comparable to wind tower values and those found on similar surfaces. We conclude that (1) in the absence of direct turbulent flux measurements from sonic anemometers, the profile and microtopographic methods provide realistic z0 values, (2) both 2D and 3D microtopographic methods are dependent on scale, resolution, and the chosen detrending method, and (3) careful calibration of these parameters could enable glacier-wide investigations of z0 from remotely sensed data, including those increasingly available from satellite platforms

Developing a novel geophysical tool to investigate the influence of vegetation on slope stability

Vegetation is important for managing shallow geotechnical assets. However, root water uptake-driven changes in slope hydrology and the near-surface (soil water content, matric suction, and hydraulic conductivity) are highly complex. Improved knowledge of these processes is increasingly important as society faces the threat of a greater prevalence of climate-driven extreme rainfall and drought events. Intrinsic factors affect slope stability, including geometry, soil properties, groundwater, and vegetation-driven matric suction. Field evidence shows that engineered slopes are susceptible to hydrometeorological instability mechanisms and pose a potential failure hazard to asset operation and public safety. This study considers the combination of a novel geophysical monitoring system and geotechnical point sensors for use in controlled laboratory conditions to assess the influence of vegetation on soil-water dynamics in the context of geotechnical infrastructure. The geophysical monitoring system, referred to here as PRIME (Proactive Infrastructure Monitoring and Evaluation system), uses electrical resistivity tomography (ERT) technology to non-invasively image changing subsurface moisture-driven processes. The PRIME system and point sensor arrays are being developed for near real-time data acquisition of transient soil moisture conditions in a suite of soil column experiments. Through addressing the challenges associated with designing integrated geophysical-geotechnical laboratory-scale monitoring experiments, this research aims to provide new tools and approaches to further our understanding of vegetation-driven soil moisture movement to better assess slope instability risk

Sites of vulnerability in HCV E1E2 identified by comprehensive functional screening

The E1 and E2 envelope proteins of hepatitis C virus (HCV) form a heterodimer that drives virus-host membrane fusion. Here, we analyze the role of each amino acid in E1E2 function, expressing 545 individual alanine mutants of E1E2 in human cells, incorporating them into infectious viral pseudoparticles, and testing them against 37 different monoclonal antibodies (MAbs) to ascertain full-length translation, folding, heterodimer assembly, CD81 binding, viral pseudoparticle incorporation, and infectivity. We propose a model describing the role of each critical residue in E1E2 functionality and use it to examine how MAbs neutralize infection by exploiting functionally critical sites of vulnerability on E1E2. Our results suggest that E1E2 is a surprisingly fragile protein complex where even a single alanine mutation at 92% of positions disrupts its function. The amino-acid-level targets identified are highly conserved and functionally critical and can be exploited for improved therapies and vaccines

Lower Resting and Exercise-Induced Circulating Angiogenic Progenitors and Angiogenic T-Cells in Older Men

Ageing is associated with a dysfunctional endothelial phenotype, as well as reduced angiogenic capabilities. Exercise exerts beneficial effects on the cardiovascular system, possibly by increasing/maintaining the number and/or function of circulating angiogenic cells (CACs) that are known to decline with age. However, the relationship between cardiorespiratory fitness (CRF) and age related changes in frequency of CACs, as well as the exercise-induced responsiveness of CACs in older individuals has not yet been determined. One hundred and seven healthy male volunteers, aged 18-75 years, participated in the study 1. CRF was estimated using submaximal cycling ergometer test. Circulating endothelial progenitor cells (EPCs), angiogenic T-cells (TANG) and their CXCR4 cell surface receptor expression were enumerated by flow cytometry using peripheral blood samples obtained under resting conditions prior to the exercise test. Study 2 recruited 17 healthy males (8 young, 18-25yrs; 9 older, 60-75yrs) and these participants undertook a 30-minute cycling exercise bout at 70% V ?O2max, with CACs enumerated pre- and immediately post-exercise. Age was inversely associated with both CD34+ progenitor cells (r2=-0.140, p=0.000) and TANG (r2=-0.176, p=0.000) cells, as well as CXCR4-expressing CACs (CD34+, r2=-0.167, p=0.000; EPCs: r2=-0.098, p=0.001; TANG, r2=-0.053, p=0.015). However, after correcting for age, CRF had no relationship with either CAC subset. In addition, older individuals displayed attenuated exercise-induced increases in CD34+ progenitor cells, TANG, CD4+ TANG, and CD8+CXCR4+ TANG cells. Older men display lower CAC levels, which may contribute to increased CVD risk, and older adults display an impaired exercise-induced responsiveness of these cells

The Time-Domain Spectroscopic Survey: Understanding the Optically Variable Sky with SEQUELS in SDSS-III

The Time-Domain Spectroscopic Survey (TDSS) is an SDSS-IV eBOSS subproject primarily aimed at obtaining identification spectra of ~220,000 optically-variable objects systematically selected from SDSS/Pan-STARRS1 multi-epoch imaging. We present a preview of the science enabled by TDSS, based on TDSS spectra taken over ~320 deg^2 of sky as part of the SEQUELS survey in SDSS-III, which is in part a pilot survey for eBOSS in SDSS-IV. Using the 15,746 TDSS-selected single-epoch spectra of photometrically variable objects in SEQUELS, we determine the demographics of our variability-selected sample, and investigate the unique spectral characteristics inherent in samples selected by variability. We show that variability-based selection of quasars complements color-based selection by selecting additional redder quasars, and mitigates redshift biases to produce a smooth quasar redshift distribution over a wide range of redshifts. The resulting quasar sample contains systematically higher fractions of blazars and broad absorption line quasars than from color-selected samples. Similarly, we show that M-dwarfs in the TDSS-selected stellar sample have systematically higher chromospheric active fractions than the underlying M-dwarf population, based on their H-alpha emission. TDSS also contains a large number of RR Lyrae and eclipsing binary stars with main-sequence colors, including a few composite-spectrum binaries. Finally, our visual inspection of TDSS spectra uncovers a significant number of peculiar spectra, and we highlight a few cases of these interesting objects. With a factor of ~15 more spectra, the main TDSS survey in SDSS-IV will leverage the lessons learned from these early results for a variety of time-domain science applications.Comment: 17 pages, 14 figures, submitted to Ap

Long-term geoelectrical monitoring of landslides in natural and engineered slopes

Developments in time-lapse electrical resistivity tomography (ERT) technology are transforming our ability to monitor the subsurface due to purpose-built monitoring instruments, advances in automation and modeling, and the resulting improvements in spatial and temporal resolution. We describe the development of a novel ERT-based remote monitoring system called PRIME that integrates new low-power measurement instrumentation with data delivery, automated data processing and image generation, and web-based information delivery. Due to the sensitivity of ERT to hydrologic processes in the near surface, we focus on the application of PRIME for moisture-driven landslide monitoring. Case examples are considered of landslides in engineered and natural slopes, including those impacting geotechnical assets in rail and highways, where slope hydrology is seen to be controlled by lithology, vegetation, fissuring, and drainage structures. We conclude by taking a forward look at emerging developments in ERT monitoring relating to hardware, software and modeling, and applications

NERO: a biomedical named-entity (recognition) ontology with a large, annotated corpus reveals meaningful associations through text embedding.

Machine reading (MR) is essential for unlocking valuable knowledge contained in millions of existing biomedical documents. Over the last two decades1,2, the most dramatic advances in MR have followed in the wake of critical corpus development3. Large, well-annotated corpora have been associated with punctuated advances in MR methodology and automated knowledge extraction systems in the same way that ImageNet4 was fundamental for developing machine vision techniques. This study contributes six components to an advanced, named entity analysis tool for biomedicine: (a) a new, Named Entity Recognition Ontology (NERO) developed specifically for describing textual entities in biomedical texts, which accounts for diverse levels of ambiguity, bridging the scientific sublanguages of molecular biology, genetics, biochemistry, and medicine; (b) detailed guidelines for human experts annotating hundreds of named entity classes; (c) pictographs for all named entities, to simplify the burden of annotation for curators; (d) an original, annotated corpus comprising 35,865 sentences, which encapsulate 190,679 named entities and 43,438 events connecting two or more entities; (e) validated, off-the-shelf, named entity recognition (NER) automated extraction, and; (f) embedding models that demonstrate the promise of biomedical associations embedded within this corpus

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

Impact of Immunization Technology and Assay Application on Antibody Performance – A Systematic Comparative Evaluation

Antibodies are quintessential affinity reagents for the investigation and determination of a protein's expression patterns, localization, quantitation, modifications, purification, and functional understanding. Antibodies are typically used in techniques such as Western blot, immunohistochemistry (IHC), and enzyme-linked immunosorbent assays (ELISA), among others. The methods employed to generate antibodies can have a profound impact on their success in any of these applications. We raised antibodies against 10 serum proteins using 3 immunization methods: peptide antigens (3 per protein), DNA prime/protein fragment-boost (“DNA immunization”; 3 per protein), and full length protein. Antibodies thus generated were systematically evaluated using several different assay technologies (ELISA, IHC, and Western blot). Antibodies raised against peptides worked predominantly in applications where the target protein was denatured (57% success in Western blot, 66% success in immunohistochemistry), although 37% of the antibodies thus generated did not work in any of these applications. In contrast, antibodies produced by DNA immunization performed well against both denatured and native targets with a high level of success: 93% success in Western blots, 100% success in immunohistochemistry, and 79% success in ELISA. Importantly, success in one assay method was not predictive of success in another. Immunization with full length protein consistently yielded the best results; however, this method is not typically available for new targets, due to the difficulty of generating full length protein. We conclude that DNA immunization strategies which are not encumbered by the limitations of efficacy (peptides) or requirements for full length proteins can be quite successful, particularly when multiple constructs for each protein are used