T-helper 2 Cytokines, Transforming Growth Factor β1, and Eosinophil Products Induce Fibrogenesis and Alter Muscle Motility in Patients with Eosinophilic Esophagitis

PubMed Central

Rieder, Florian; Nonevski, Ilche; Ma, Jie; Ouyang, Zhufeng; West, Gail; Protheroe, Cheryl; DePetris, Giovanni; Schirbel, Anja; Lapinski, James; Goldblum, John; Bonfield, Tracey; Lopez, Rocio; Harnett, Karen; Lee, James; Hirano, Ikuo; Falk, Gary; Biancani, Piero; Fiocchi, Claudio

2014-01-01

BACKGROUND & AIMS Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEF), muscle cells (HEMC), and esophageal muscle strips to eosinophil-derived products. METHODS Biopsies were collected via endoscopy from the upper, middle and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls). Primary cultures of esophageal fibroblasts and muscle cells were derived from 12 freshly resected human esophagectomy specimens. Eosinophil distribution was investigated by histologic analyses of full-thickness esophageal tissue. Active secretion of EoE-related mediators was assessed from medium underlying mucosal biopsy cultures. We quantified production of fibronectin and collagen I by HEF and HEMC in response to eosinophil products. We also measured expression of ICAM1 and VCAM1 by, and adhesion of human eosinophils to, HEF and HEMC. Eosinophil products were tested in an esophageal muscle contraction assay. RESULTS Activated eosinophils were present in all esophageal layers. Significantly higher concentrations of eosinophil-related mediators were spontaneously secreted in mucosal biopsies from patients with EoE than controls. Exposure of HEF and HEMC to increasing concentrations of eosinophil products or co-culture with eosinophils caused HEF and HEMC to increase secretion of fibronectin and collagen I; this was inhibited by blocking transforming growth factor (TGF)β1 and p38 mitogen-activated protein kinase (MAKP) signaling. Eosinophil binding to HEF and HEMC increased following incubation of mesenchymal cells with eosinophil-derived products, and decreased following blockade of TGFβ1 and p38MAPK blockade. Eosinophil products reduced electrical field-induced contraction of esophageal muscle strips, but not acetylcholine-induced contraction. CONCLUSION In an analysis of tissues samples from patients with EoE, we linked the presence and activation state of eosinophils in EoE with altered fibrogenesis and motility of esophageal fibroblasts and muscle cells. This process might contribute to the development of dysphagia. PMID:24486052

T-helper 2 cytokines, transforming growth factor β1, and eosinophil products induce fibrogenesis and alter muscle motility in patients with eosinophilic esophagitis.

PubMed

Rieder, Florian; Nonevski, Ilche; Ma, Jie; Ouyang, Zhufeng; West, Gail; Protheroe, Cheryl; DePetris, Giovanni; Schirbel, Anja; Lapinski, James; Goldblum, John; Bonfield, Tracey; Lopez, Rocio; Harnett, Karen; Lee, James; Hirano, Ikuo; Falk, Gary; Biancani, Piero; Fiocchi, Claudio

2014-05-01

Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEFs), human esophageal muscle cells (HEMCs), and esophageal muscle strips to eosinophil-derived products. Biopsy specimens were collected via endoscopy from the upper, middle, and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls). Primary cultures of esophageal fibroblasts and muscle cells were derived from 12 freshly resected human esophagectomy specimens. Eosinophil distribution was investigated by histologic analyses of full-thickness esophageal tissue. Active secretion of EoE-related mediators was assessed from medium underlying mucosal biopsy cultures. We quantified production of fibronectin and collagen I by HEF and HEMC in response to eosinophil products. We also measured the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by, and adhesion of human eosinophils to, HEFs and HEMCs. Eosinophil products were tested in an esophageal muscle contraction assay. Activated eosinophils were present in all esophageal layers. Significantly higher concentrations of eosinophil-related mediators were secreted spontaneously in mucosal biopsy specimens from patients with EoE than controls. Exposure of HEFs and HEMCs to increasing concentrations of eosinophil products or co-culture with eosinophils caused HEFs and HEMCs to increase secretion of fibronectin and collagen I; this was inhibited by blocking transforming growth factor β1 and p38 mitogen-activated protein kinase signaling. Eosinophil binding to HEFs and HEMCs increased after incubation of mesenchymal cells with eosinophil-derived products, and decreased after blockade of transforming growth factor β1 and p38 mitogen-activated protein kinase blockade. Eosinophil products reduced electrical field-induced contraction of esophageal muscle strips, but not acetylcholine-induced contraction. In an analysis of tissues samples from patients with EoE, we linked the presence and activation state of eosinophils in EoE with altered fibrogenesis and motility of esophageal fibroblasts and muscle cells. This process might contribute to the development of dysphagia. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effects of Surfactants on the Preparation of Nanocellulose-PLA Composites

PubMed Central

Immonen, Kirsi; Lahtinen, Panu; Pere, Jaakko

2017-01-01

Thermoplastic composite materials containing wood fibers are gaining increasing interest in the manufacturing industry. One approach is to use nano- or micro-size cellulosic fibrils as additives and to improve the mechanical properties obtainable with only small fibril loadings by exploiting the high aspect ratio and surface area of nanocellulose. In this study, we used four different wood cellulose-based materials in a thermoplastic polylactide (PLA) matrix: cellulose nanofibrils produced from softwood kraft pulp (CNF) and dissolving pulp (CNFSD), enzymatically prepared high-consistency nanocellulose (HefCel) and microcellulose (MC) together with long alkyl chain dispersion-improving agents. We observed increased impact strength with HefCel and MC addition of 5% and increased tensile strength with CNF addition of 3%. The addition of a reactive dispersion agent, epoxy-modified linseed oil, was found to be favorable in combination with HefCel and MC. PMID:29149057

Development and Use of the Hydrologic Ensemble Forecast System by the National Weather Service to Support the New York City Water Supply

NASA Astrophysics Data System (ADS)

Shedd, R.; Reed, S. M.; Porter, J. H.

2015-12-01

The National Weather Service (NWS) has been working for several years on the development of the Hydrologic Ensemble Forecast System (HEFS). The objective of HEFS is to provide ensemble river forecasts incorporating the best precipitation and temperature forcings at any specific time horizon. For the current implementation, this includes the Global Ensemble Forecast System (GEFS) and the Climate Forecast System (CFSv2). One of the core partners that has been working with the NWS since the beginning of the development phase of HEFS is the New York City Department of Environmental Protection (NYCDEP) which is responsible for the complex water supply system for New York City. The water supply system involves a network of reservoirs in both the Delaware and Hudson River basins. At the same time that the NWS was developing HEFS, NYCDEP was working on enhancing the operations of their water supply reservoirs through the development of a new Operations Support Tool (OST). OST is designed to guide reservoir system operations to ensure an adequate supply of high-quality drinking water for the city, as well as to meet secondary objectives for reaches downstream of the reservoirs assuming the primary water supply goals can be met. These secondary objectives include fisheries and ecosystem support, enhanced peak flow attenuation beyond that provided natively by the reservoirs, salt front management, and water supply for other cities. Since January 2014, the NWS Northeast and Middle Atlantic River Forecast Centers have provided daily one year forecasts from HEFS to NYCDEP. OST ingests these forecasts, couples them with near-real-time environmental and reservoir system data, and drives models of the water supply system. The input of ensemble forecasts results in an ensemble of model output, from which information on the range and likelihood of possible future system states can be extracted. This type of probabilistic information provides system managers with additional information not available from deterministic forecasts and allows managers to better assess risk, and provides greater context for decision-making than has been available in the past. HEFS has allowed NYCDEP water supply managers to make better decisions on reservoir operations than they likely would have in the past, using only deterministic forecasts.

Interactions Between Suspended Kaolinite Deposition and Hyporheic Exchange Flux Under Losing and Gaining Flow Conditions

NASA Astrophysics Data System (ADS)

Fox, Aryeh; Packman, Aaron I.; Boano, Fulvio; Phillips, Colin B.; Arnon, Shai

2018-05-01

Fine particle deposition and streambed clogging affect many ecological and biogeochemical processes, but little is known about the effects of groundwater flow into and out of rivers on clogging. We evaluated the effects of losing and gaining flow on the deposition of suspended kaolinite clay particles in a sand streambed and the resulting changes in rates and patterns of hyporheic exchange flux (HEF). Observations of clay deposition from the water column, clay accumulation in the streambed sediments, and water exchange with the bed demonstrated that clay deposition in the bed substantially reduced both HEF and the size of the hyporheic zone. Clay deposition and HEF were strongly coupled, leading to rapid clogging in areas of water and clay influx into the bed. Local clogging diverted exchanged water laterally, producing clay deposit layers that reduced vertical hyporheic flow and favored horizontal flow. Under gaining conditions, HEF was spatially constrained by upwelling water, which focused clay deposition in a small region on the upstream side of each bed form. Because the area of inflow into the bed was smallest under gaining conditions, local clogging required less clay mass under gaining conditions than neutral or losing conditions. These results indicate that losing and gaining flow conditions need to be considered in assessments of hyporheic exchange, fine particle dynamics in streams, and streambed clogging and restoration.

Development of a Ground-Based Analog to the Advanced Resistive Exercise Device Aboard the International Space Station

NASA Technical Reports Server (NTRS)

Newby, Nathaniel J.; Scott-Pandorf, M. M.; Caldwell, E.; DeWitt, J.K.; Fincke, R.; Peters, B.T.

2010-01-01

NASA and Wyle engineers constructed a Horizontal Exercise Fixture (HEF) that was patented in 2006. Recently modifications were made to HEF with the goal of creating a device that mimics squat exercise on the Advanced Resistive Exercise Device (ARED) and can be used by bed rest subjects who must remain supine during exercise. This project posed several engineering challenges, such as how best to reproduce the hip motions (we used a sled that allowed hip motion in the sagittal plane), how to counterweight the pelvis against gravity (we used a pulley and free-weight mechanism), and how to apply large loads (body weight plus squat load) to the shoulders while simultaneously supporting the back against gravity (we tested a standard and a safety bar that allowed movement in the subject s z-axis, both of which used a retractable plate for back support). METHODS An evaluation of the HEF was conducted with human subjects (3F, 3M), who performed sets of squat exercises of increasing load from 10-repetition maximum (RM) up to 1-RM. Three pelvic counterweight loads were tested along with each of the two back-support squat bars. Data collection included 3-dimensional ground reaction forces (GRF), muscle activation (EMG), body motion (video-based motion capture), and subjective comments. These data were compared with previous ground-based ARED study data. RESULTS All subjects in the evaluation were able to perform low- to high-loading squats on the HEF. Four of the 6 subjects preferred a pelvic counterweight equivalent to 60 percent of their body weight. Four subjects preferred the standard squat bar, whereas 2 female subjects preferred the safety bar. EMG data showed muscle activation in the legs and low back typical of squat motion. GRF trajectories and eccentric-concentric loading ratios were similar to ARED. CONCLUSION: Squat exercise performed on HEF approximated squat exercise on ARED.

Aspirin increases susceptibility of Helicobacter pylori to metronidazole by augmenting endocellular concentrations of antimicrobials.

PubMed

Zhang, Xiao-Ping; Wang, Wei-Hong; Tian, Yu; Gao, Wen; Li, Jiang

2009-02-28

To investigate the mechanisms of aspirin increasing the susceptibility of Helicobacter pylori (H pylori) to metronidazole. H pylori reference strain 26695 and two metronidazole-resistant isolates of H pylori were included in this study. Strains were incubated in Brucella broth with or without aspirin (1 mmol/L). The rdxA gene of H pylori was amplified by PCR and sequenced. The permeability of H pylori to antimicrobials was determined by analyzing the endocellular radioactivity of the cells after incubated with [7-(3)H]-tetracycline. The outer membrane proteins (OMPs) of H pylori 26695 were depurated and analyzed by SDS-PAGE. The expression of 5 porins (hopA, hopB, hopC, hopD and hopE) and the putative RND efflux system (hefABC) of H pylori were analyzed using real-time quantitative PCR. The mutations in rdxA gene did not change in metronidazole resistant isolates treated with aspirin. The radioactivity of H pylori increased when treated with aspirin, indicating that aspirin improved the permeability of the outer membrane of H pylori. However, the expression of two OMP bands between 55 kDa and 72 kDa altered in the presence of aspirin. The expression of the mRNA of hopA, hopB, hopC, hopD, hopE and hefA, hefB, hefC of H pylori did not change when treated with aspirin. Although aspirin increases the susceptibility of H pylori to metronidazole, it has no effect on the mutations of rdxA gene of H pylori. Aspirin increases endocellular concentrations of antimicrobials probably by altering the OMP expression.

The Influenza A Virus PB2, PA, NP, and M Segments Play a Pivotal Role during Genome Packaging

PubMed Central

Gao, Qinshan; Chou, Yi-Ying; Doğanay, Sultan; Vafabakhsh, Reza; Ha, Taekjip

2012-01-01

The genomes of influenza A viruses consist of eight negative-strand RNA segments. Recent studies suggest that influenza viruses are able to specifically package their segmented genomes into the progeny virions. Segment-specific packaging signals of influenza virus RNAs (vRNAs) are located in the 5′ and 3′ noncoding regions, as well as in the terminal regions, of the open reading frames. How these packaging signals function during genome packaging remains unclear. Previously, we generated a 7-segmented virus in which the hemagglutinin (HA) and neuraminidase (NA) segments of the influenza A/Puerto Rico/8/34 virus were replaced by a chimeric influenza C virus hemagglutinin/esterase/fusion (HEF) segment carrying the HA packaging sequences. The robust growth of the HEF virus suggested that the NA segment is not required for the packaging of other segments. In this study, in order to determine the roles of the other seven segments during influenza A virus genome assembly, we continued to use this HEF virus as a tool and analyzed the effects of replacing the packaging sequences of other segments with those of the NA segment. Our results showed that deleting the packaging signals of the PB1, HA, or NS segment had no effect on the growth of the HEF virus, while growth was greatly impaired when the packaging sequence of the PB2, PA, nucleoprotein (NP), or matrix (M) segment was removed. These results indicate that the PB2, PA, NP, and M segments play a more important role than the remaining four vRNAs during the genome-packaging process. PMID:22532680

Aspirin increases susceptibility of Helicobacter pylori to metronidazole by augmenting endocellular concentrations of antimicrobials

PubMed Central

Zhang, Xiao-Ping; Wang, Wei-Hong; Tian, Yu; Gao, Wen; Li, Jiang

2009-01-01

AIM: To investigate the mechanisms of aspirin increasing the susceptibility of Helicobacter pylori (H pylori) to metronidazole. METHODS: H pylori reference strain 26 695 and two metronidazole-resistant isolates of H pylori were included in this study. Strains were incubated in Brucella broth with or without aspirin (1 mmol/L). The rdxA gene of H pylori was amplified by PCR and sequenced. The permeability of H pylori to antimicrobials was determined by analyzing the endocellular radioactivity of the cells after incubated with [7-3H]-tetracycline. The outer membrane proteins (OMPs) of H pylori 26 695 were depurated and analyzed by SDS-PAGE. The expression of 5 porins (hopA, hopB, hopC, hopD and hopE) and the putative RND efflux system (hefABC) of H pylori were analyzed using real-time quantitative PCR. RESULTS: The mutations in rdxA gene did not change in metronidazole resistant isolates treated with aspirin. The radioactivity of H pylori increased when treated with aspirin, indicating that aspirin improved the permeability of the outer membrane of H pylori. However, the expression of two OMP bands between 55 kDa and 72 kDa altered in the presence of aspirin. The expression of the mRNA of hopA, hopB, hopC, hopD, hopE and hefA, hefB, hefC of H pylori did not change when treated with aspirin. CONCLUSION: Although aspirin increases the susceptibility of H pylori to metronidazole, it has no effect on the mutations of rdxA gene of H pylori. Aspirin increases endocellular concentrations of antimicrobials probably by altering the OMP expression. PMID:19248190

DNA replication restart and cellular dynamics of Hef helicase/nuclease protein in Haloferax volcanii.

PubMed

Lestini, Roxane; Delpech, Floriane; Myllykallio, Hannu

2015-11-01

Understanding how frequently spontaneous replication arrests occur and how archaea deal with these arrests are very interesting and challenging research topics. Here we will described how genetic and imaging studies have revealed the central role of the archaeal helicase/nuclease Hef belonging to the XPF/MUS81/FANCM family of endonucleases in repair of arrested replication forks. Special focus will be on description of a recently developed combination of genetic and imaging tools to study the dynamic localization of a functional Hef::GFP (Green Fluorescent Protein) fusion protein in the living cells of halophilic archaea Haloferax volcanii. As Archaea provide an excellent and unique model for understanding how DNA replication is regulated to allow replication of a circular DNA molecule either from single or multiple replication origins, we will also summarize recent studies that have revealed peculiar features regarding DNA replication, particularly in halophilic archaea. We strongly believe that fundamental knowledge of our on-going studies will shed light on the evolutionary history of the DNA replication machinery and will help to establish general rules concerning replication restart and the key role of recombination proteins not only in bacteria, yeast and higher eukaryotes but also in archaea. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Major Risks, Uncertain Outcomes: Making Ensemble Forecasts Work for Multiple Audiences

NASA Astrophysics Data System (ADS)

Semmens, K. A.; Montz, B.; Carr, R. H.; Maxfield, K.; Ahnert, P.; Shedd, R.; Elliott, J.

2017-12-01

When extreme river levels are possible in a community, effective communication of weather and hydrologic forecasts is critical to protect life and property. Residents, emergency personnel, and water resource managers need to make timely decisions about how and when to prepare. Uncertainty in forecasting is a critical component of this decision-making, but often poses a confounding factor for public and professional understanding of forecast products. In 2016 and 2017, building on previous research about the use of uncertainty forecast products, and with funding from NOAA's CSTAR program, East Carolina University and Nurture Nature Center (a non-profit organization with a focus on flooding issues, based in Easton, PA) conducted a research project to understand how various audiences use and interpret ensemble forecasts showing a range of hydrologic forecast possibilities. These audiences include community residents, emergency managers and water resource managers. The research team held focus groups in Jefferson County, WV and Frederick County, MD, to test a new suite of products from the National Weather Service's Hydrologic Ensemble Forecast System (HEFS). HEFS is an ensemble system that provides short and long-range forecasts, ranging from 6 hours to 1 year, showing uncertainty in hydrologic forecasts. The goal of the study was to assess the utility of the HEFS products, identify the barriers to proper understanding of the products, and suggest modifications to product design that could improve the understandability and accessibility for residential, emergency managers, and water resource managers. The research team worked with the Sterling, VA Weather Forecast Office and the Middle Atlantic River Forecast center to develop a weather scenario as the basis of the focus group discussions, which also included pre and post session surveys. This presentation shares the findings from those focus group discussions and surveys, including recommendations for revisions to HEFS products to improve accessibility of the forecast tools for various audiences. The presentation will provide a broad perspective on the range of graphic design considerations that affected how the public responded to products and will provide an overview of lessons learned about how product design can influence decision-making by users.

Structure of coronavirus hemagglutinin-esterase offers insight into corona and influenza virus evolution

PubMed Central

Zeng, Qinghong; Langereis, Martijn A.; van Vliet, Arno L. W.; Huizinga, Eric G.; de Groot, Raoul J.

2008-01-01

The hemagglutinin-esterases (HEs) are a family of viral envelope glycoproteins that mediate reversible attachment to O-acetylated sialic acids by acting both as lectins and as receptor-destroying enzymes (RDEs). Related HEs occur in influenza C, toro-, and coronaviruses, apparently as a result of relatively recent lateral gene transfer events. Here, we report the crystal structure of a coronavirus (CoV) HE in complex with its receptor. We show that CoV HE arose from an influenza C-like HE fusion protein (HEF). In the process, HE was transformed from a trimer into a dimer, whereas remnants of the fusion domain were adapted to establish novel monomer–monomer contacts. Whereas the structural design of the RDE-acetylesterase domain remained unaltered, the HE receptor-binding domain underwent remodeling to such extent that the ligand is now bound in opposite orientation. This is surprising, because the architecture of the HEF site was preserved in influenza A HA over a much larger evolutionary distance, a switch in receptor specificity and extensive antigenic variation notwithstanding. Apparently, HA and HEF are under more stringent selective constraints than HE, limiting their exploration of alternative binding-site topologies. We attribute the plasticity of the CoV HE receptor-binding site to evolutionary flexibility conferred by functional redundancy between HE and its companion spike protein S. Our findings offer unique insights into the structural and functional consequences of independent protein evolution after interviral gene exchange and open potential avenues to broad-spectrum antiviral drug design. PMID:18550812

Morbidity and mortality in first-degree relatives of C282Y homozygous probands with clinically detected haemochromatosis compared with the general population: the HEmochromatosis FAmily Study (HEFAS).

PubMed

Jacobs, E M G; Hendriks, J C M; Marx, J J M; van Deursen, C Th B M; Kreeftenberg, H G; de Vries, R A; Stalenhoef, A F H; Verbeek, A L M; Swinkels, D W

2007-12-01

Family screening has been suggested as a sophisticated model for the early detection of HFE-related hereditary haemochromatosis (HH). However, until now, controlled studies on the morbidity and mortality in families with HH are lacking. Data on iron parameters, morbidity and mortality were collected from 224 dutch C282Y-homozygous probands with clinically overt HH and 735 of their first-degree family members, all participating in the HEmochromatosis fAmily study (HEfAs). These data were compared with results obtained from an age- and gender-matched normal population. HEfAs and controls filled in similar questionnaires on demographics, lifestyle factors, health, morbidity and mortality. A significantly higher proportion of the HEfAs first-degree family members reported to be diagnosed with haemochromatosis-related diseases: 45.7 vs 19.4% of the matched normal population (McNemar p<0.001). Mortality among siblings, children and parents in the HEFAS population was similar to that in the relatives of matched control. In this study we show that, morbidity among first-degree family members of C282Y-homozygous probands previously diagnosed with clinically proven HH is higher than that in an age- and gender-matched normal population. Further studies are needed to definitely connect these increase morbidity figures to increase prevalenc of the C282Y mutated HFE-gene and elevated serum iron indices.

Principle of radial transport in low temperature annular plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yunchao, E-mail: yunchao.zhang@anu.edu.au; Charles, Christine; Boswell, Rod

2015-07-15

Radial transport in low temperature annular plasmas is investigated theoretically in this paper. The electrons are assumed to be in quasi-equilibrium due to their high temperature and light inertial mass. The ions are not in equilibrium and their transport is analyzed in three different situations: a low electric field (LEF) model, an intermediate electric field (IEF) model, and a high electric field (HEF) model. The universal IEF model smoothly connects the LEF and HEF models at their respective electric field strength limits and gives more accurate results of the ion mobility coefficient and effective ion temperature over the entire electricmore » field strength range. Annular modelling is applied to an argon plasma and numerical results of the density peak position, the annular boundary loss coefficient and the electron temperature are given as functions of the annular geometry ratio and Paschen number.« less

Enhanced bacterial efflux system is the first step to the development of metronidazole resistance in Helicobacter pylori.

PubMed

Tsugawa, Hitoshi; Suzuki, Hidekazu; Muraoka, Hiroe; Ikeda, Fumiaki; Hirata, Kenro; Matsuzaki, Juntaro; Saito, Yoshimasa; Hibi, Toshifumi

2011-01-14

Although metronidazole (Mtz) is an important component of Helicobacter pylori eradication regimens, it has been pointed out that the increasing use of Mtz may result in increase in the incidence of Mtz-resistant strains. The present study was designed to examine the initial mechanism of resistance acquisition of H. pylori to Mtz. After 10 Mtz-susceptible strains were cultured on plates containing sub-inhibitory concentrations of Mtz, the MIC of Mtz for 9 of the 10 strains increased to levels of the Mtz-resistant strains. In the Mtz-resistance-induced strains, the expression of the TolC efflux pump (hefA) was significantly increased under Mtz exposure, without the reduction of the Mtz-reductive activity. Our finding suggests that overexpression of hefA may be the initial step in the acquisition of Mtz resistance in H. pylori. Copyright © 2010 Elsevier Inc. All rights reserved.

Verification of temperature, precipitation, and streamflow forecasts from the NOAA/NWS Hydrologic Ensemble Forecast Service (HEFS): 1. Experimental design and forcing verification

NASA Astrophysics Data System (ADS)

Brown, James D.; Wu, Limin; He, Minxue; Regonda, Satish; Lee, Haksu; Seo, Dong-Jun

2014-11-01

Retrospective forecasts of precipitation, temperature, and streamflow were generated with the Hydrologic Ensemble Forecast Service (HEFS) of the U.S. National Weather Service (NWS) for a 20-year period between 1979 and 1999. The hindcasts were produced for two basins in each of four River Forecast Centers (RFCs), namely the Arkansas-Red Basin RFC, the Colorado Basin RFC, the California-Nevada RFC, and the Middle Atlantic RFC. Precipitation and temperature forecasts were produced with the HEFS Meteorological Ensemble Forecast Processor (MEFP). Inputs to the MEFP comprised ;raw; precipitation and temperature forecasts from the frozen (circa 1997) version of the NWS Global Forecast System (GFS) and a climatological ensemble, which involved resampling historical observations in a moving window around the forecast valid date (;resampled climatology;). In both cases, the forecast horizon was 1-14 days. This paper outlines the hindcasting and verification strategy, and then focuses on the quality of the temperature and precipitation forecasts from the MEFP. A companion paper focuses on the quality of the streamflow forecasts from the HEFS. In general, the precipitation forecasts are more skillful than resampled climatology during the first week, but comprise little or no skill during the second week. In contrast, the temperature forecasts improve upon resampled climatology at all forecast lead times. However, there are notable differences among RFCs and for different seasons, aggregation periods and magnitudes of the observed and forecast variables, both for precipitation and temperature. For example, the MEFP-GFS precipitation forecasts show the highest correlations and greatest skill in the California Nevada RFC, particularly during the wet season (November-April). While generally reliable, the MEFP forecasts typically underestimate the largest observed precipitation amounts (a Type-II conditional bias). As a statistical technique, the MEFP cannot detect, and thus appropriately correct for, conditions that are undetected by the GFS. The calibration of the MEFP to provide reliable and skillful forecasts of a range of precipitation amounts (not only large amounts) is a secondary factor responsible for these Type-II conditional biases. Interpretation of the verification results leads to guidance on the expected performance and limitations of the MEFP, together with recommendations on future enhancements.

An optimal structure for a 34-meter millimeter-wave center-fed BWG antenna: The Cross-Box concept

NASA Technical Reports Server (NTRS)

Chuang, K. L.

1988-01-01

An approach to the design of the planned NASA/JPL 34 m elevation-over-azimuth (Az-El) antenna structure at the Venus site (DSS-13) is presented. The antenna structural configuration accommodates a large (2.44 m) beam waveguide (BWG) tube centrally routed through the reflector-alidade structure, an elevation wheel design, and an optimal structural geometry. The design encompasses a cross-box elevation wheel-reflector base substructure that preserves homology while satisfying many constraints, such as structure weight, surface tolerance, stresses, natural frequency, and various functional constraints. The functional requirements are set to ensure that microwave performance at millimeter wavelengths is adequate. The cross-box configuration was modeled, optimized, and found to satisfy all DSN HEF baseline antenna specifications. In addition, the structure design was conceptualized and analyzed with an emphasis on preserving the structure envelope and keeping modifications relative to the HEF antennas to a minimum, thus enabling the transferability of the BWG technology for future retrofitting. Good performance results were obtained.

Dendrosomal curcumin inhibits metastatic potential of human SW480 colon cancer cells through Down-regulation of Claudin1, Zeb1 and Hef1-1 gene expression.

PubMed

Dehghan Esmatabadi, Mohammad Javad; Farhangi, Baharak; Safari, Zahra; Kazerooni, Hanif; Shirzad, Hadi; Zolghadr, Fatemeh; Sadeghizadeh, Majid

2015-01-01

Colon cancer is one of the leading causes of cancer-associated death worldwide. The prognosis for advanced colorectal cancers remains dismal, mainly due to the propensity for metastatic progression. Accordingly, there is a need for effective anti-metastasis therapeutic agents. Since a great body of research has indicated anticancer effects for curcumin, we investigated the effects of dendrosomal curcumin (DNC) on cellular migration and adhesion of human SW480 cells and possible molecular mechanisms involved. Different methods were applied in this study including MTT, Scratch and adhesion assays as well as real-time PCR and transwell chamber assays. Based on the results obtained, DNC inhibits metastasis by decreasing Hef 1, Zeb 1 and Claudin 1 mRNA levels and can reduce SW480 cell proliferation with IC50values of 15.9, 11.6 and 7.64 μM at 24, 48 and 72 h post-treatment. Thus it might be considered as a safe formulation for therapeutic purpose in colorectal cancer cases.

Metabolic strategies of beer spoilage lactic acid bacteria in beer.

PubMed

Geissler, Andreas J; Behr, Jürgen; von Kamp, Kristina; Vogel, Rudi F

2016-01-04

Beer contains only limited amounts of readily fermentable carbohydrates and amino acids. Beer spoilage lactic acid bacteria (LAB) have to come up with metabolic strategies in order to deal with selective nutrient content, high energy demand of hop tolerance mechanisms and a low pH. The metabolism of 26 LAB strains of 6 species and varying spoilage potentialwas investigated in order to define and compare their metabolic capabilities using multivariate statistics and outline possible metabolic strategies. Metabolic capabilities of beer spoilage LAB regarding carbohydrate and amino acids did not correlate with spoilage potential, but with fermentation type (heterofermentative/homofermentative) and species. A shift to mixed acid fermentation by homofermentative (hof) Pediococcus claussenii and Lactobacillus backii was observed as a specific feature of their growth in beer. For heterofermentative (hef) LAB a mostly versatile carbohydrate metabolism could be demonstrated, supplementing the known relevance of organic acids for their growth in beer. For hef LAB a distinct amino acid metabolism, resulting in biogenic amine production, was observed, presumably contributing to energy supply and pH homeostasis.

SHIP2 Regulates Lumen Generation, Cell Division, and Ciliogenesis through the Control of Basolateral to Apical Lumen Localization of Aurora A and HEF 1.

PubMed

Hamze-Komaiha, Ola; Sarr, Sokavuth; Arlot-Bonnemains, Yannick; Samuel, Didier; Gassama-Diagne, Ama

2016-12-06

Lumen formation during epithelial morphogenesis requires the creation of a luminal space at cell interfaces named apical membrane-initiation sites (AMISs). This is dependent upon integrated signaling from mechanical and biochemical cues, vesicle trafficking, cell division, and processes tightly coupled to ciliogenesis. Deciphering relationships between polarity determinants and lumen or cilia generation remains a fundamental issue. Here, we report that Src homology 2 domain-containing inositol 5-phosphatase 2 (SHIP2), a basolateral determinant of polarity, regulates RhoA-dependent actin contractility and cell division to form AMISs. SHIP2 regulates mitotic spindle alignment. SHIP2 is expressed in G1 phase, whereas Aurora A kinase is enriched in mitosis. SHIP2 binds Aurora A kinase and the scaffolding protein HEF1 and promotes their basolateral localization at the expense of their luminal expression connected with cilia resorption. Furthermore, SHIP2 expression increases cilia length. Thus, our findings offer new insight into the relationships among basolateral proteins, lumen generation, and ciliogenesis. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Influences of Coupled Hydrologic and Microbial Processes on River Corridor Biogeochemistry and Ecology

NASA Astrophysics Data System (ADS)

Scheibe, T. D.; Song, H. S.; Stegen, J.; Graham, E.; Bao, J.; Goldman, A.; Zhou, T.; Crump, A.; Hou, Z.; Hammond, G. E.; Chen, X.; Huang, M.; Zhang, X.; Nelson, W. C.; Garayburu-Caruso, V. A.

2017-12-01

The exchange of water between rivers and surrounding subsurface environments (hydrologic exchange flows or HEFs) is a vital aspect of river ecology and watershed function. HEFs play a key role in water quality, nutrient cycling, and ecosystem health, and they modulate water temperatures and enhance exchange of terrestrial and aquatic nutrients, which lead to elevated biogeochemical activity. However, these coupled hydrologic and microbiological processes are not well understood, particularly in the context of large managed river systems with highly variable discharge, and are poorly represented in system-scale quantitative models. Using the 75 km Hanford Reach of the Columbia River as the research domain, we apply high-resolution flow simulations supported by field observations to understand how variable river discharge interacts with hydromorphic and hydrogeologic structures to generate HEFs and distributions of subsurface residence times. We combine this understanding of hydrologic processes with microbiological activity measurements and reactive transport models to elucidate the holistic impacts of variable discharge on river corridor (surface and subsurface) ecosystems. In particular, our project seeks to develop and test new conceptual and numerical models that explicitly incorporate i) the character (chemical speciation and thermodynamics) of natural organic matter as it varies along flow paths and through mixing of groundwater and surface water, and ii) the history-dependent response of microbial communities to varying time scales of inundation associated with fluctuations in river discharge. The results of these high-resolution mechanistic models are guiding formulation and parameterization of reduced-order models applicable at reach to watershed scales. New understanding of coupled hydrology and microbiology in the river corridor will play a key role in reduction of uncertainties associated with major Earth system biogeochemical fluxes, improving predictions of environmental and human impacts on water quality and riverine ecosystems, and supporting environmentally responsible management of linked energy-water systems.

Naval War College Research Guide, 1984-1985.

DTIC Science & Technology

1984-08-01

Washington: 1980. OECD N 4. Organization for Economic Cooperation and Develop- ment, Economic Surveys: Greece (Paris: 1983), p. 50. B Organization for...Amr, i iCa-In naItI ()n SC ca 1no t , mnU St 1not and Will not pefrmit beP es--tablishment o)f ano1()ther 1 Comm111U nis:t r- ;mcn t inr t hef Wes t

Do Deregulated Cas Proteins Induce Genomic Instability in Early-Stage Ovarian Cancer

DTIC Science & Technology

2006-12-01

use Western blot analysis of tumor lysates to correlate expression of HEF1, p130Cas, Aurora A, and phospho-Aurora A. This analysis is in progress. In...and importantly, evaluated a number of different detection/image analysis systems to ensure reproducible quantitative results. We have used a pilot...reproducible Interestingly, preliminary statistical analysis using Spearman and Pearson correlation indicates at least one striking correlation

Intracellular Protein Delivery for Treating Breast Cancer

DTIC Science & Technology

2012-06-01

are efficiently internalized by mammalian cells lines as characterized by confocal microscopy, and rhodamine-labeled apoptin can be observed in the...To determine the cellular localization of delivered proteins, confocal images were taken with HeLa, MCF-7, or HEF cells incubated with 20 nM of S-S...and analyzed by Nikon NIS Element software. Fluorescence images were acquired on a Yokogawa spinning-disk confocal scanner system using a Nikon

A Matched Field Processing Framework for Coherent Detection Over Local and Regional Networks

DTIC Science & Technology

2011-06-01

Northern Finland Seismological Network, FN) and to the University of Helsinki for data from the VRF and HEF stations (part of the Finnish seismograph ...shows the results of classification with the FK measurement . Most of the events are incorrectly assigned to one particular mine (K2 – Rasvumchorr...generalization of the single-phase matched field processing method that encodes the full structure of the entire wavefield? What would this

Development and intra-institutional and inter-institutional validation of a comprehensive new hepatobiliary software: Part 1--Liver and gallbladder function.

PubMed

Krishnamurthy, Gerbail T; Krishnamurthy, Shakuntala; Gambhir, Sanjiv Sam; Rodrigues, Cesar; Rosenberg, Jarrett; Schiepers, Christiaan; Buxton-Thomas, Muriel

2009-12-01

To develop a software tool for quantification of liver and gallbladder function, and to assess the repeatability and reproducibility of measurements made with it. The software tool developed with the JAVA programming language uses the JAVA2 Standard Edition framework. After manual selection of the regions of interest on a 99mTc hepatic iminodiacetic acid study, the program calculates differential hepatic bile flow, basal duodeno-gastric bile reflux (B-DGBR), hepatic extraction fraction (HEF) of both the lobes with deconvolutional analysis and excretion half-time with nonlinear least squares fit. Gallbladder ejection fraction, ejection period (EP), ejection rate (ER), and postcholecystokinin (CCK) DGBR are calculated after stimulation with CCK-8. To assess intra-observer repeatability and intra-observer reproducibility, measurements from 10 normal participants were analyzed twice by three nuclear medicine technologists at the primary center. To assess inter-site reproducibility, measurements from a superset of 24 normal participants were also assessed once by three observers at the primary center and single observer at three other sites. For the 24 control participants, mean+/-SD of hepatic bile flow into gallbladder was 63.87+/-28.7%, HEF of the right lobe 100+/-0%, left lobe 99.43+2.63%, excretion half-time of the right lobe 21.50+6.98 min, left lobe 28.3+/-11.3 min. Basal DGBR was 1.2+/-1.0%. Gallbladder ejection fraction was 80+/-11%, EP 15.0+/-3.0 min, ER 5.8+/-1.6%/min, and DGBR-CCK 1.3+/-2.3%. Left and right lobe HEF was virtually identical across readers. All measures showed high repeatability except for gallbladder bile flow, basal DGBR, and EP, which exhibited marginal repeatability. Ejection fraction exhibited high reproducibility. There was high concordance among the three primary center observers except for basal DGBR, EP, and ER. Concordance between the primary site and one of the other sites was high, one was fair, and one was poor. New United States Food and Drug Administration-approved personal computer-based Krishnamurthy Hepato-Biliary Software for quantification of the liver and gallbladder function shows promise for consistently repeatable and reproducible results both within and between institutions, and may help to promote universal standardization of data acquisition and analysis in nuclear hepatology.

Silicone Oil Swelling Slippery Surfaces Based on Mussel-Inspired Magnetic Nanoparticles with Multiple Self-Healing Mechanisms.

PubMed

Jin, Biyu; Liu, Mingzhu; Zhang, Qinghua; Zhan, Xiaoli; Chen, Fengqiu

2017-10-03

In this work, a novel substrate building block, magnetic Fe 3 O 4 nanoparticles armed with dopamine molecules were developed via mussel-inspired metal-coordination bonds. Combined with glycidyl methacrylate, polydimethylsiloxane propyl ether methacrylate, and diethylenetriamine, the original silicone oil swelling slippery liquid-infused porous surfaces (SLIPS) were first prepared by reversible coordinate bonds and strong covalent bonds cross-linking process. The matrix mechanical characteristics and surface physicochemical properties were systematically investigated. Results showed that the mechanical property of copolymer matrix and surface wettability of SLIPS can be remarkably recovered, which were due to the synergistic interactions of magnetic nanoparticles' intrinsic photothermal effect, reversible Fe-catechol coordination, and diffused lubricating liquid. After irradiating with sunlamp for 2 h and sequentially healing for 10 h under ambient conditions, the crack almost disappeared under optical microscopy with 78.25% healing efficiency (HEf) of toughness, and surface slippery was completely retrieved to water droplets. The efficient self-heal of copolymer matrix (66.5% HEf after eighth cutting-healing cycle) and recovering of slipperiness (SA < 5° and 5° < SA < 17° after fourth and eighth cutting-centrifuging-healing cycles, respectively) would extend longevity of SLIPS when subjected to multiple damages. Moreover, the prepared SLIPS displayed superb self-cleaning and liquid-repellent properties to a wide range of particulate contaminants and fluids.

Dynamic gadoxetate-enhanced MRI for the assessment of total and segmental liver function and volume in primary sclerosing cholangitis.

PubMed

Nilsson, Henrik; Blomqvist, Lennart; Douglas, Lena; Nordell, Anders; Jacobsson, Hans; Hagen, Karin; Bergquist, Annika; Jonas, Eduard

2014-04-01

To evaluate dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) for the assessment of global and segmental liver volume and function in patients with primary sclerosing cholangitis (PSC), and to explore the heterogeneous distribution of liver function in this patient group. Twelve patients with primary sclerosing cholangitis (PSC) and 20 healthy volunteers were examined using DHCE-MRI with Gd-EOB-DTPA. Segmental and total liver volume were calculated, and functional parameters (hepatic extraction fraction [HEF], input relative blood-flow [irBF], and mean transit time [MTT]) were calculated in each liver voxel using deconvolutional analysis. In each study subject, and incongruence score (IS) was constructed to describe the mismatch between segmental function and volume. Among patients, the liver function parameters were correlated to bile duct obstruction and to established scoring models for liver disease. Liver function was significantly more heterogeneously distributed in the patient group (IS 1.0 versus 0.4). There were significant correlations between biliary obstruction and segmental functional parameters (HEF rho -0.24; irBF rho -0.45), and the Mayo risk score correlated significantly with the total liver extraction capacity of Gd-EOB-DTPA (rho -0.85). The study demonstrates a new method to quantify total and segmental liver function using DHCE-MRI in patients with PSC. Copyright © 2013 Wiley Periodicals, Inc.

Field testing of the experimental wood preservative N'N-naphtaloylhydroxylamine : five and eight years results

Treesearch

Frederick Green; Rachel A. Arango; Stan T. Lebow

2010-01-01

Field trials were designed to evaluate the ability of the experimental wood preservative N’N-naphthaloylhydroxylamine (NHA) to inhibit fungal decay and termite damage at the USDA Harrison Experimental Forest (HEF) in Saucier, MS. Twenty replicate 19 x 19 x 457 mm (0.75 x 0.75 x 18 in.) southern yellow pine stakes and 10 replicate 19 x 19 x 76 mm (0.75 x 0.75 x 3 in.)...

Reference Manual: Navy Message Words and Word Frequencies.

DTIC Science & Technology

1981-12-29

ADJUDGED 8 ADJUST 14 ADJUSTED 7 ADJUSTMENT 3 ADJUSTMENTS 7 ADM 4 ADMIN 2 ADMINISTER 4 ADMINISTERED 4 ADMINISTRATION 3 ADMINISTRATIVE 2 ADMINISTRATIVELY ...I ADMINISTRATORS I ADMINSUPU 25 ADMIRAL I ADMIT 13 ADMITTED I ADMITTING 5 ADMSG 2 ADOLF 1 ADOLPH 4 ADOPT 1 ADOPTION 2 ADP 2 ADRESSE (Fr.) 4 ADRIAN 2...HEADWAITER 6 HEALTH 3 HEAR 3 HEARD 9 HEARING I HEART 2 HEAT 4 HEATH 3 HEATHROW 4 HEAVILY 9 HEAVY 2 HEAZLITT 1 HEBRIDES 7 HED 2 HEE 3 HEF 2 HEFFRON 2

Effect of biofilm formation by clinical isolates of Helicobacter pylori on the efflux-mediated resistance to commonly used antibiotics.

PubMed

Attaran, Bahareh; Falsafi, Tahereh; Ghorbanmehr, Nassim

2017-02-21

To evaluate the role of biofilm formation on the resistance of Helicobacter pylori ( H. pylori ) to commonly prescribed antibiotics, the expression rates of resistance genes in biofilm-forming and planktonic cells were compared. A collection of 33 H. pylori isolates from children and adult patients with chronic infection were taken for the present study. The isolates were screened for biofilm formation ability, as well as for polymerase chain reaction (PCR) reaction with HP1165 and hp1165 efflux pump genes. Susceptibilities of the selected strains to antibiotic and differences between susceptibilities of planktonic and biofilm-forming cell populations were determined. Quantitative real-time PCR (qPCR) analysis was performed using 16S rRNA gene as a H. pylori -specific primer, and two efflux pumps-specific primers, hp1165 and hefA . The strains were resistant to amoxicillin, metronidazole, and erythromycin, except for one strain, but they were all susceptible to tetracycline. Minimum bactericidal concentrations of antibiotics in the biofilm-forming cells were significantly higher than those of planktonic cells. qPCR demonstrated that the expression of efflux pump genes was significantly higher in the biofilm-forming cells as compared to the planktonic ones. The present work demonstrated an association between H. pylori biofilm formation and decreased susceptibility to all the antibiotics tested. This decreased susceptibility to antibiotics was associated with enhanced functional activity of two efflux pumps: hp1165 and hefA .

Flow and residence times of dynamic river bank storage and sinuosity-driven hyporheic exchange

USGS Publications Warehouse

Gomez-Velez, J.D.; Wilson, J.L.; Cardenas, M.B.; Harvey, Judson

2017-01-01

Hydrologic exchange fluxes (HEFs) vary significantly along river corridors due to spatiotemporal changes in discharge and geomorphology. This variability results in the emergence of biogeochemical hot-spots and hot-moments that ultimately control solute and energy transport and ecosystem services from the local to the watershed scales. In this work, we use a reduced-order model to gain mechanistic understanding of river bank storage and sinuosity-driven hyporheic exchange induced by transient river discharge. This is the first time that a systematic analysis of both processes is presented and serves as an initial step to propose parsimonious, physics-based models for better predictions of water quality at the large watershed scale. The effects of channel sinuosity, alluvial valley slope, hydraulic conductivity, and river stage forcing intensity and duration are encapsulated in dimensionless variables that can be easily estimated or constrained. We find that the importance of perturbations in the hyporheic zone's flux, residence times, and geometry is mainly explained by two-dimensionless variables representing the ratio of the hydraulic time constant of the aquifer and the duration of the event (Γd) and the importance of the ambient groundwater flow ( ). Our model additionally shows that even systems with small sensitivity, resulting in small changes in the hyporheic zone extent, are characterized by highly variable exchange fluxes and residence times. These findings highlight the importance of including dynamic changes in hyporheic zones for typical HEF models such as the transient storage model.

Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI.

PubMed

Nilsson, Henrik; Blomqvist, Lennart; Douglas, Lena; Nordell, Anders; Jonas, Eduard

2010-10-01

Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) is a gadolinium-based hepatocyte-specific contrast agent for magnetic resonance imaging (MRI). The aim of this study was to determine whether the hepatic uptake and excretion of Gd-EOB-DTPA differ between patients with primary biliary cirrhosis (PBC) and healthy controls, and whether differences could be quantified. Gd-EOB-DTPA-enhanced liver MRI was performed in 20 healthy volunteers and 12 patients with PBC. The uptake of Gd-EOB-DTPA was assessed using traditional semi-quantitative parameters (C(max) , T(max) and T(1/2) ), as well as model-free parameters derived after deconvolutional analysis (hepatic extraction fraction [HEF], input-relative blood flow [irBF] and mean transit time [MTT]). In each individual, all parameters were calculated for each liver segment and the median of the segmental values was used to define a global liver median (GLM). Although the PBC patients had relatively mild disease according to their Model for End-stage Liver Disease (MELD), Child-Pugh and Mayo risk scores, they had significantly lower HEF and shorter MTT values compared with the healthy controls. These differences significantly increased with increasing MELD and Child-Pugh scores. Dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) has a potential role as an imaging-based liver function test. The high spatial resolution of MRI enables hepatic function to be assessed on segmental and sub-segmental levels. © 2010 International Hepato-Pancreato-Biliary Association.

Ensemble Streamflow Forecast Improvements in NYC's Operations Support Tool

NASA Astrophysics Data System (ADS)

Wang, L.; Weiss, W. J.; Porter, J.; Schaake, J. C.; Day, G. N.; Sheer, D. P.

2013-12-01

Like most other water supply utilities, New York City's Department of Environmental Protection (DEP) has operational challenges associated with drought and wet weather events. During drought conditions, DEP must maintain water supply reliability to 9 million customers as well as meet environmental release requirements downstream of its reservoirs. During and after wet weather events, DEP must maintain turbidity compliance in its unfiltered Catskill and Delaware reservoir systems and minimize spills to mitigate downstream flooding. Proactive reservoir management - such as release restrictions to prepare for a drought or preventative drawdown in advance of a large storm - can alleviate negative impacts associated with extreme events. It is important for water managers to understand the risks associated with proactive operations so unintended consequences such as endangering water supply reliability with excessive drawdown prior to a storm event are minimized. Probabilistic hydrologic forecasts are a critical tool in quantifying these risks and allow water managers to make more informed operational decisions. DEP has recently completed development of an Operations Support Tool (OST) that integrates ensemble streamflow forecasts, real-time observations, and a reservoir system operations model into a user-friendly graphical interface that allows its water managers to take robust and defensible proactive measures in the face of challenging system conditions. Since initial development of OST was first presented at the 2011 AGU Fall Meeting, significant improvements have been made to the forecast system. First, the monthly AR1 forecasts ('Hirsch method') were upgraded with a generalized linear model (GLM) utilizing historical daily correlations ('Extended Hirsch method' or 'eHirsch'). The development of eHirsch forecasts improved predictive skill over the Hirsch method in the first week to a month from the forecast date and produced more realistic hydrographs on the tail end of high flow periods. These improvements allowed DEP to more effectively manage water quality control and spill mitigation operations immediately after storm events. Later on, post-processed hydrologic forecasts from the National Weather Service (NWS) including the Advanced Hydrologic Prediction Service (AHPS) and the Hydrologic Ensemble Forecast Service (HEFS) were implemented into OST. These forecasts further increased the predictive skill over the initial statistical models as current basin conditions (e.g. soil moisture, snowpack) and meteorological forecasts (with HEFS) are now explicitly represented. With the post-processed HEFS forecasts, DEP may now truly quantify impacts associated with wet weather events on the horizon, rather than relying on statistical representations of current hydrologic trends. This presentation will highlight the benefits of the improved forecasts using examples from actual system operations.

Defense Health Care. Reimbursement of Hospitals Not Meeting CHAMPUS (Civilian Health and Medical Program of the Uniformed Services) Copayment Requirements.

DTIC Science & Technology

1988-06-01

8217JntedState* General AccouýLg Office __ Rteport to Congmesoa Commitee A,""FILE COPYAD-A197 876 DF7-EANSE HEF.ALTHl L’W Reimbur emen--t Of I...Secretary of Defense grant a waiver from CHAMPUS copayment requirements and be approved, tuader certain criteria, to be reimbursed for care to...that a provider waives patient copayments, it denies the provider’s claim for reimbursement . . In fiscal year 1987, cHAmpus payments to civilian

Impacts of Freshets on Hyporheic Exchange Flow under Neutral Conditions

NASA Astrophysics Data System (ADS)

Singh, T.; Wu, L.; Worman, A. L. E.; Hannah, D. M.; Krause, S.; Gomez-Velez, J. D.

2016-12-01

Hyporheic zones (HZs) are characterized by the exchange of water, solutes, momentum and energy between streams and aquifers. Hyporheic exchange flow (HEF) is driven by pressure gradients along the sediment-water interface, which in turn are caused by interactions between channel flow and bed topography. With this in mind, changes in channel flow can have significant effects in the hydrodynamic and transport characteristics of HZs. While previous research has improved our understanding of the drivers and controls of HEF, little attention has been paid to the potential impacts of transient dynamic hydrologic forcing, such as freshets. In this study, we use a two-dimensional, homogeneous flow and transport model with a time-varying pressure distribution at the sediment-water interface to explore the dynamic development of HZ characteristics in response to discharge fluctuations (i.e., freshets). With this model, we explore a wide range of plausible scenarios for discharge and bed geometry. Our modelling results show that a single freshet alters the spatial extent and penetration of the HZ, though quantitatively different, when investigated using hydrological (streamlines/flow field) and geochemical (>90% of surface water in streambed) approaches of HZ. We summarize the results of a detailed sensitivity analysis where the effects of hydraulic geometry (slope, amplitude of the streambed), flood characteristics (duration, skewness and magnitude of the flood wave) and biogeochemical timescales (time-scale for oxygen consumption) on the HZ's extent, mean age, and oxic/anoxic zonation are explored. Taking into consideration these multiple morphological characteristics along with variable hydrological controls has clear potential to facilitate process understanding and upscaling.

Cerebral sex dimorphism and sexual orientation.

PubMed

Manzouri, Amirhossein; Savic, Ivanka

2018-03-01

The neurobiology of sexual orientation is frequently discussed in terms of cerebral sex dimorphism (defining both functional and structural sex differences). Yet, the information about possible cerebral differences between sex-matched homo and heterosexual persons is limited, particularly among women. In this multimodal MRI study, we addressed these issues by investigating possible cerebral differences between homo and heterosexual persons, and by asking whether there is any sex difference in this aspect. Measurements of cortical thickness (Cth), subcortical volumes, and functional and structural resting-state connections among 40 heterosexual males (HeM) and 40 heterosexual females (HeF) were compared with those of 30 homosexual males (HoM) and 30 homosexual females (HoF). Congruent with previous reports, sex differences were detected in heterosexual controls with regard to fractional anisotropy (FA), Cth, and several subcortical volumes. Homosexual groups did not display any sex differences in FA values. Furthermore, their functional connectivity was significantly less pronounced in the mesial prefrontal and precuneus regions. In these two particular regions, HoM also displayed thicker cerebral cortex than other groups, whereas HoF did not differ from HeF. In addition, in HoM the parietal Cth showed "sex-reversed" values, not observed in HoF. Homosexual orientation seems associated with a less pronounced sexual differentiation of white matter tracts and a less pronounced functional connectivity of the self-referential networks compared to heterosexual orientation. Analyses of Cth suggest that male and female homosexuality are not simple analogues of each other and that differences from heterosexual controls are more pronounced in HoM. © 2017 Wiley Periodicals, Inc.

Detailed comparison of the geodetic and direct glaciological mass balances on an annual time scale at Hintereisferner, Austria

NASA Astrophysics Data System (ADS)

Klug, Christoph; Bollmann, Erik; Galos, Stephan; Kaser, Georg; Prinz, Rainer; Rieg, Lorenzo; Sailer, Rudolf

2016-04-01

The quantification of glacier mass changes is fundamental for glacier monitoring and provides important information for climate change assessments, hydrological applications and sea-level changes. On Alpine glaciers two methods of measuring glacier mass changes are widely applied: the direct glaciological method and the geodetic method. Over the last decades several studies compared the mass balance estimates obtained by both methods to identify and correct stochastic and systematic errors. In almost all of these studies, the time span for comparison between the two methods is about one decade or longer. On Hintereisferner (HEF; Ötztal Alps, Austria) mass balance measurements were initiated in the glaciological year 1952/53, resulting in a consistent mass balance data set with an estimated accuracy of ±0.2 m w.e. a-1. Furthermore, 11 airborne laser scanning (ALS) campaigns were conducted between 2001 and 2011 at HEF, all consistent in accuracy as well as in precision (± 0.04 to 0.10 m for slopes ≤ 50°). This is a world-wide unique ALS dataset of a glacierized alpine catchment. Flight campaigns were performed close to the end of the hydrological year (30th September). Resulting data provide high quality topographic information to derive glacier mass changes by applying the geodetic method. On sub-decadal time-scales such method comparisons are rare, or reveal unexplainable large discrepancies between both mass balance methods. In this study we estimate stochastic and systematic uncertainties of the ALS data for processing volume changes, and quantify methodological differences, such as density assumptions, unequal measurement dates, crevasses and glacier dynamics. Hence, we present a method to compare direct glaciological and geodetic mass balances on an annual basis. In a first step, we calculate the annual geodetic mass balance of HEF between 2001 and 2011, resulting in a thickness change map of the glacier. In a second step, the snow cover, which has eventually built up before the ALS acquisition, is corrected. As snow cover biases are particular uncertain, a statistical approach has been applied to assess combined DTM errors by using the population of DTM differences over stable terrain. This method incorporates all known and unknown error sources from the surface difference in stable areas and uses its median thickness for correction in all altitudinal belts. In addition, intensity data of the ALS surveys are used to classify the optical surface properties into ice and firn zones. The resulting grids with according conversion factors (900 and 700 kg/m³ for ice and firn, respectively) are combined to calculate mass changes. In a last step, the survey dates are adjusted, using numerous field observations. On an annual time scale, the geodetic mass balances of HEF corrected using this approach, correlate well with the results from the homogenized direct glaciological method. Significant deviations occur in years with few measurements in the uppermost areas applying the direct glaciological method, due to strong melt in areas not equipped with ablation stakes (cf. Figure 2 for 2002/03) or inaccessibility due to weather conditions. On the basis of these results, the conventional error risk (e.g. confidence levels), was adopted in order to test the null hypothesis and to check if unexplained discrepancies suggest reanalyses of glaciological mass balances. Regarding the cumulative mass balance, the deviations between the two methods tend to become smaller the longer the period of comparison extends. Averaged between 2001 and 2011 the largest sources of differences are snow cover and density assumptions having high uncertainties in their estimates and/or leading to higher error ranges in the geodetic mass balances. Some errors were found to have a minor impact and are not treated explicitly, such as uncertainties in different glacier outlines used in both methods or the influence of snow covered and snow free crevasses in successive years on the geodetic mass balance.

The evolution of the small x gluon TMD

NASA Astrophysics Data System (ADS)

Zhou, Jian

2016-06-01

We study the evolution of the small x gluon transverse momentum dependent (TMD) distribution in the dilute limit. The calculation has been carried out in the Ji-Ma-Yuan scheme using a simple quark target model. As expected, we find that the resulting small x gluon TMD simultaneously satisfies both the Collins-Soper (CS) evolution equation and the Balitsky-Fadin-Kuraev-Lipatov (BFKL) evolution equation. We thus confirmed the earlier finding that the high energy factorization (HEF) and the TMD factorization should be jointly employed to resum the different type large logarithms in a process where three relevant scales are well separated.

The omega-3 polyunsaturated fatty acid docosahexaenoic acid inhibits proliferation and progression of non-small cell lung cancer cells through the reactive oxygen species-mediated inactivation of the PI3K /Akt pathway.

PubMed

Yin, Yuanqin; Sui, Chengguang; Meng, Fandong; Ma, Ping; Jiang, Youhong

2017-05-03

Docosahexaenoic acid(DHA) inhibits tumor growth and progression in various cancers, including lung cancer. However, the mechanisms involved remain unclear. The aim of this study was to identify the mechanism of DHA in inhibiting progression of non-small cell lung cancer (NSCLC) in vitro. The proliferation of A549 was tested by MTT, and cell apoptosis was analysed using flow cytometer. The migration and invasion were examined respectively by wound healing assay and Transwell invasion assay. The level of ROS (reactive oxygen species, ROS) was checked by DCF (dichlorodihydrofluorescein, DCF) production in cells. The apoptosis associated protein (caspase-3, PARP,Bax,Bcl-2 and survivin) and metastases associated proteins including HEF1, MMP9 and VEGF were detected by Western blot, and the same method was used in the expression of PI3K and Akt. DHA inhibited proliferation and induced apoptosis of A549 cells. Moreover, it suppressed the invasion and metastasis of A549 cells, while downregulating the levels of metastasis-associated proteins, including HEF1, matrix metallopeptidase (MMP9), and vascular endothelial growth factor (VEGF), in a dose -dependent manner. In addition, DHA inactivated Akt phosphorylation. All of these responses were associated with the accumulation of intracellular ROS. DHA downregulated the level of antioxidant enzymes such as catalase, while the antioxidant N-acetyl-cysteine (NAC) reversed the effect of DHA, which further validated our findings. The present study demonstrates that DHA inhibits the development of non-small lung tumors through an ROS-mediated inactivation of the PI3K/Akt signaling pathway.

A Diagnostics Tool to detect ensemble forecast system anomaly and guide operational decisions

NASA Astrophysics Data System (ADS)

Park, G. H.; Srivastava, A.; Shrestha, E.; Thiemann, M.; Day, G. N.; Draijer, S.

2017-12-01

The hydrologic community is moving toward using ensemble forecasts to take uncertainty into account during the decision-making process. The New York City Department of Environmental Protection (DEP) implements several types of ensemble forecasts in their decision-making process: ensemble products for a statistical model (Hirsch and enhanced Hirsch); the National Weather Service (NWS) Advanced Hydrologic Prediction Service (AHPS) forecasts based on the classical Ensemble Streamflow Prediction (ESP) technique; and the new NWS Hydrologic Ensemble Forecasting Service (HEFS) forecasts. To remove structural error and apply the forecasts to additional forecast points, the DEP post processes both the AHPS and the HEFS forecasts. These ensemble forecasts provide mass quantities of complex data, and drawing conclusions from these forecasts is time-consuming and difficult. The complexity of these forecasts also makes it difficult to identify system failures resulting from poor data, missing forecasts, and server breakdowns. To address these issues, we developed a diagnostic tool that summarizes ensemble forecasts and provides additional information such as historical forecast statistics, forecast skill, and model forcing statistics. This additional information highlights the key information that enables operators to evaluate the forecast in real-time, dynamically interact with the data, and review additional statistics, if needed, to make better decisions. We used Bokeh, a Python interactive visualization library, and a multi-database management system to create this interactive tool. This tool compiles and stores data into HTML pages that allows operators to readily analyze the data with built-in user interaction features. This paper will present a brief description of the ensemble forecasts, forecast verification results, and the intended applications for the diagnostic tool.

Genetic manipulation of murine embryonic stem cells with enhanced green fluorescence protein and sulfatase-modifying factor I genes.

PubMed

Zhao, Guoying; Karageorgos, Litsa; Hutchinson, Rhonda G; Hopwood, John J; Hemsley, Kim

2010-05-01

Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder (LSD) in which an absence of sulfamidase results in incomplete degradation and subsequent accumulation of its substrate, heparan sulfate. Most neurodegenerative LSD remain untreatable. However, therapy options, such as gene, enzyme end cell therapy, are under investigation. Previously, we have constructed an embryonic stem (ES) cell line (NS21) that over-expresses human sulphamidase as a potential treatment for murine MPS IIIA. In the present study the sulfatase-modifying factor I (SUMF1) and enhanced green fluorescence protein (eGFP) genes were co-introduced under a cytomegalovirus (CMV) promoter into NS21 cells, to enhance further sulfamidase activity and provide a marker for in vivo cell tracking, respectively. eGFP was also introduced under the control of the human elongation factor-1alpha (hEF-1alpha) promoter to compare the stability of transgene expression. During differentiation of ES cells into glial precursors, SUMF1 was down-regulated and was hardly detectable by day 18 of differentiation. Likewise, eGFP expression was heterogeneous and highly unstable. Use of a human EF-1alpha promoter resulted in more homogeneous eGFP expression, with approximately 50% of cells eGFP positive following differentiation into glial precursors. Compared with NS21 cells, the outgrowth of eGFP-expressing cells was not as confluent when differentiated into glial precursors. Our data suggest that SUMF1 enhances sulfamidase activity in ES cells, hEF-1alpha is a stronger promoter than CMV for ES cells and over-expression of eGFP may affect cell growth and contribute to unstable gene expression.

Scaling Hydrologic Exchange Flows and Biogeochemical Reactions from Bedforms to Basins

NASA Astrophysics Data System (ADS)

Harvey, J. W.; Gomez-Velez, J. D.

2015-12-01

River water moves in and out of the main channel along pathways that are perpendicular to the channel's main axis that flow across or beneath the ground surface. These hydrologic exchange flows (HEFs) are difficult to measure, yet no less important than a river's downstream flow, or exchanges with the atmosphere and deeper groundwater (Harvey and Gooseff, 2015, WRR). There are very few comprehensive investigations of exchange fluxes to understand patterns with river size and relative importance of specific types of exchanges. We used the physically based model NEXSS to simulate multiple scales of hyporheic flow and their cumulative effects on solute reaction in large basins (on the order of Chesapeake Bay basin or larger). Our goal was to explain where and when particular types of hyporheic flow are important in enhancing key biogeochemical reactions, such as organic carbon respiration and denitrification. Results demonstrate that hyporheic flux (expressed per unit area of streambed) varies surprisingly little across the continuum of first-order streams to eighth-order rivers, and vertical exchange beneath small bedforms dominates in comparison with lateral flow beneath gravel bars and meanders. Also, the river's entire volume is exchanged many times with hyporheic flow within a basin, and the turnover length (after one entire river volume is exchanged) is strongly influenced by hydrogeomorphic differences between physiographic regions as well as by river size. The cumulative effects on biogeochemical reactions were assessed using a the reaction significance factor, RSF, which computes the cumulative potential for hyporheic reactions using a dimensionless index that balances reaction progress in a single hyporheic flow path against overall processing efficiency of river turnover through hyporheic flow paths of that type. Reaction significance appears to be strongly dominated by hydrologic factors rather than biogeochemical factors, and seems to be dominated by vertical exchange beneath small bedforms throughout river networks. Future implementations of NEXSS will expand the model to consider flow variation and to consider HEFs beyond hyporheic flow to include exchange with marginal surface waters such as riparian wetlands, floodplains, and ponded water.

Low-noise cryogenic transmission line

NASA Technical Reports Server (NTRS)

Norris, D.

1987-01-01

New low-noise cryogenic input transmission lines have been developed for the Deep Space Network (DSN) at 1.668 GHz for cryogenically cooled Field Effect Transistors (FET) and High Electron Mobility Transistor (HEMT) amplifiers. These amplifiers exhibit very low noise temperatures of 5 K to 15 K, making the requirements for a low-noise input transmission line critical. Noise contribution to the total amplifier system from the low-noise line is less than 0.5 K for both the 1.668-GHz and 2.25-GHz FET systems. The 1.668-GHz input line was installed in six FET systems which were implemented in the DSN for the Venus Balloon Experiment. The 2.25-GHz input line has been implemented in three FET systems for the DSN 34-m HEF antennas, and the design is currently being considered for use at higher frequencies.

A Better ARED Squat

NASA Technical Reports Server (NTRS)

Caldwell, E. E.; Newby, N. J.; Ploutz-Snyder, L.

2014-01-01

The 0-G ARED squat under loads the legs relative to the 1g ARED squat. In 1g the knee extensor/flexor muscles are primarily engaged due to the body's center of gravity is behind the knees during the motion of the squat. As body weight does not play a sufficient role 0 G, a crewmember's load exposure is limited by the load delivered by ARED through the exercise bar. Prescription loads for lowerbody resistance exercise in microgravity aim to include 1-G exercise bar load in addition to the crewmember's Earth body weight (BW); however, pressure points from the bar and the 1BW increased load at the shoulders translating to higher loads on the back have been a historical limitation for shoulders, requiring a decrease in exercise load at the start of the mission. Analogous to crewmembers, bed rest subjects report limitations of exercising with high loads on the back while performing squats on the horizontal exercise fixture (HEF), a custom exercise device that serves as an analog to 0-G ARED. Improvements for increasing loads on the HEF squat were suggested by distributing total exercise load between the hips and the bar1. The same is recommended for the 0-G ARED squat, with using current equipment on the ISS, which include the T2 running harness and T2 bungees. Quantification of this improvement has been accessed through computational modeling. The purpose of this study is to characterize joint torque during a squat with a distribution in exercise load on the ARED in 0 G. The analysis used existing models from NASA's Digital Astronaut Project. The biomechanics squat model was integrated with the ARED model and T2 bungees. The spring constant for the bungees were derived from ground testing. Forward dynamic simulation was performed for various conditions including anchor point attachments on the footplate of the ARED, bar load, hip load, and gravitational environment. The model confirms joint torques at knees is lower relative to 1G conditions primarily because the load delivery system is just with the exercise bar in 0 G. By distributing partial loads through use of the bungees to the hips joint-torque profiles were altered during a squat and provided options to enhance targeting lower-body loading in aims as for an improved countermeasure.

Matrigel immobilization on the shish-kebab structured poly(ɛ-caprolactone) nanofibers for skin tissue engineering

NASA Astrophysics Data System (ADS)

Jing, Xin; Mi, Hao-Yang; Peng, Xiang-Fang; Turng, Lih-Sheng

2016-03-01

Surface properties of tissue engineering scaffolds such as topography, hydrophilicity, and functional groups play a vital role in cell adhesion, migration, proliferation, and apoptosis. First, poly(ɛ-caprolactone) (PCL) shish-kebab scaffolds (PCL-SK), which feature a three-dimensional structure comprised of electrospun PCL nanofibers covered by periodic, self-induced PCL crystal lamellae on the surface, was created to mimic the nanotopography of native collagen fibrils in the extracellular matrix (ECM). Second, matrigel was covalently immobilized on the surface of alkaline hydrolyzed PCL-SK scaffolds to enhance their hydrophilicity. This combined approach not only mimics the nanotopography of native collagen fibrils, but also simulates the surface features of collagen fibrils for cell growth. To investigate the viability of such scaffolds, HEF1 fibroblast cell assays were conducted and the results revealed that the nanotopography of the PCL-SK scaffolds facilitated cell adhesion and proliferation. The matrigel functionalization on PCL-SK scaffolds further enhanced cellular response, which suggested elevated biocompatibility and greater potential for skin tissue engineering applications.

MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA

PubMed Central

Berke, Ian C; Modis, Yorgo

2012-01-01

Melanoma differentiation-associated gene-5 (MDA5) detects viral double-stranded RNA in the cytoplasm. RNA binding induces MDA5 to activate the signalling adaptor MAVS through interactions between the caspase recruitment domains (CARDs) of the two proteins. The molecular mechanism of MDA5 signalling is not well understood. Here, we show that MDA5 cooperatively binds short RNA ligands as a dimer with a 16–18-basepair footprint. A crystal structure of the MDA5 helicase-insert domain demonstrates an evolutionary relationship with the archaeal Hef helicases. In X-ray solution structures, the CARDs in unliganded MDA5 are flexible, and RNA binds on one side of an asymmetric MDA5 dimer, bridging the two subunits. On longer RNA, full-length and CARD-deleted MDA5 constructs assemble into ATP-sensitive filaments. We propose a signalling model in which the CARDs on MDA5–RNA filaments nucleate the assembly of MAVS filaments with the same polymeric geometry. PMID:22314235

Matrigel immobilization on the shish-kebab structured poly(ε-caprolactone) nanofibers for skin tissue engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jing, Xin, E-mail: jingxinscut@gmail.com; Mi, Hao-Yang; Wisconsin Institutes for Discovery, University of Wisconsin-Madison, 53715

Surface properties of tissue engineering scaffolds such as topography, hydrophilicity, and functional groups play a vital role in cell adhesion, migration, proliferation, and apoptosis. First, poly(ε-caprolactone) (PCL) shish-kebab scaffolds (PCL-SK), which feature a three-dimensional structure comprised of electrospun PCL nanofibers covered by periodic, self-induced PCL crystal lamellae on the surface, was created to mimic the nanotopography of native collagen fibrils in the extracellular matrix (ECM). Second, matrigel was covalently immobilized on the surface of alkaline hydrolyzed PCL-SK scaffolds to enhance their hydrophilicity. This combined approach not only mimics the nanotopography of native collagen fibrils, but also simulates the surface featuresmore » of collagen fibrils for cell growth. To investigate the viability of such scaffolds, HEF1 fibroblast cell assays were conducted and the results revealed that the nanotopography of the PCL-SK scaffolds facilitated cell adhesion and proliferation. The matrigel functionalization on PCL-SK scaffolds further enhanced cellular response, which suggested elevated biocompatibility and greater potential for skin tissue engineering applications.« less

Hurwitz numbers and products of random matrices

NASA Astrophysics Data System (ADS)

Orlov, A. Yu.

2017-09-01

We study multimatrix models, which may be viewed as integrals of products of tau functions depending on the eigenvalues of products of random matrices. We consider tau functions of the two-component Kadomtsev-Petviashvili (KP) hierarchy (semi-infinite relativistic Toda lattice) and of the B-type KP (BKP) hierarchy introduced by Kac and van de Leur. Such integrals are sometimes tau functions themselves. We consider models that generate Hurwitz numbers HE,F, where E is the Euler characteristic of the base surface and F is the number of branch points. We show that in the case where the integrands contain the product of n > 2 matrices, the integral generates Hurwitz numbers with E ≤ 2 and F ≤ n+2. Both the numbers E and F depend both on n and on the order of the factors in the matrix product. The Euler characteristic E can be either an even or an odd number, i.e., it can match both orientable and nonorientable (Klein) base surfaces depending on the presence of the tau function of the BKP hierarchy in the integrand. We study two cases, the products of complex and the products of unitary matrices.

Bioinformatic approaches to augment study of epithelial-to-mesenchymal transition in lung cancer

PubMed Central

Beck, Tim N.; Chikwem, Adaeze J.; Solanki, Nehal R.

2014-01-01

Bioinformatic approaches are intended to provide systems level insight into the complex biological processes that underlie serious diseases such as cancer. In this review we describe current bioinformatic resources, and illustrate how they have been used to study a clinically important example: epithelial-to-mesenchymal transition (EMT) in lung cancer. Lung cancer is the leading cause of cancer-related deaths and is often diagnosed at advanced stages, leading to limited therapeutic success. While EMT is essential during development and wound healing, pathological reactivation of this program by cancer cells contributes to metastasis and drug resistance, both major causes of death from lung cancer. Challenges of studying EMT include its transient nature, its molecular and phenotypic heterogeneity, and the complicated networks of rewired signaling cascades. Given the biology of lung cancer and the role of EMT, it is critical to better align the two in order to advance the impact of precision oncology. This task relies heavily on the application of bioinformatic resources. Besides summarizing recent work in this area, we use four EMT-associated genes, TGF-β (TGFB1), NEDD9/HEF1, β-catenin (CTNNB1) and E-cadherin (CDH1), as exemplars to demonstrate the current capacities and limitations of probing bioinformatic resources to inform hypothesis-driven studies with therapeutic goals. PMID:25096367

The antidiabetic effects of an herbal formula composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin-induced diabetic rats.

PubMed

Hu, Weicheng; Yeo, Jin-Hee; Jiang, Yunyao; Heo, Seong-Il; Wang, Myeong-Hyeon

2013-04-01

A folk prescription consisting of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng has been used in the treatment of diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of the herb formula extract (HFE) composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin (STZ)-induced diabetic rats. The HFE was mixed in the food supply of the healthy and STZ-induced diabetic male Sprague-Dawley rats, and its effects on the body weight, water and food intake, hyperglycemia, hypolipidemic and islet structure were studied. The treatment of the rats with STZ for 6 weeks resulted in marasmus, polydipsia, polyphagia, hyperglycemia and hypoinsulinemia. In addition, the diabetic rats showed an apparent decrease in the insulin immunoreactivity and the number of β-cells in the pancreas. The addition of the HFE to the rats' food supply significantly lowered the serum glucose and the serum triglycerides level and preserved the normal histological appearance of the pancreatic islets. These results indicate that the HEF have a strong antidiabetic potential along with the significant hypoglycemic and hypolipidemic effects, which may be applicable in the pharmaceutical industry.

[Tensile strength of bone fixation of hydroxyapatite coated Schanz screws of the Heidelberg External Fixation System (HEFS)--comparative torque measurements in clinical use and in cadaver tibia].

PubMed

Placzek, R; Deuretzbacher, G; Meiss, A L

2002-12-01

It is claimed in the literature that hydroxyapatite(HA)-coated screws of external fixators have superior fixation strength in bone, which is postulated to lead to a substantial decrease in loosening and infection rates. We report on a study of the maximum torque values developed while inserting and removing 30 HA-coated Schanz screws of 8 Heidelberg external fixation systems applied to the tibia to correct leg length differences and axial deformities. The infection rate was determined in accordance with defined criteria, and was found to be about 20% for the HA-coated screws. Screws without infection showed an extraction torque above insertion torque, screws with infection an extraction torque below. A significant correlation (p = 0.05) was seen between infection and decrease in fixation strength (quotient: loosening torque/tightening torque). To exclude the impact of such biological processes as osteointegration and bone remodelling, the clinical results were compared with the torques measured for coated and uncoated Schanz screws in a human cadaveric tibia. A significantly higher fixation strength in bone was found for HA-coated screws in comparison with uncoated screws (p = 0.002). These data warrant a clinical study directly comparing HA-coated and uncoated Schanz screws.

FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA

PubMed Central

Ali, Abdullah Mahmood; Singh, Thiyam Ramsing; Meetei, Amom Ruhikanta

2009-01-01

Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA crosslinking agents. Eight FA proteins (FANCA, -B, -C, -E, -F, -G, -L and –M) and three non-FA proteins (FAAP100, FAAP24 and HES1) form the FA nuclear core complex that is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. The other three FA proteins, FANCD1/BRCA2, FANCJ/BACH1/BRIP1 and FANCN/PALB2, act in parallel or downstream of the FANCD2-FANCI dimer. Despite the isolation and characterization of several FA proteins, the mechanism by which these proteins protect cells from DNA interstrand crosslinking agents has been unclear. This is because a majority of the FA proteins lack any recognizable functional domains that can provide insight into their function. The recently discovered FANCM (Hef) and FANCJ (BRIP1/BACH1) proteins contain helicase domains, providing potential insight into the role of FA proteins in DNA repair. FANCM with its partner, FAAP24, and FANCJ bind and metabolize a variety of DNA substrates. In this review, we focus on the discovery, structure, and function of the FANCM-FAAP24 and FANCJ proteins. PMID:19379763

1H NMR-Based Metabolomic Analysis of Sub-Lethal Perfluorooctane Sulfonate Exposure to the Earthworm, Eisenia fetida, in Soil

PubMed Central

Lankadurai, Brian P.; Furdui, Vasile I.; Reiner, Eric J.; Simpson, André J.; Simpson, Myrna J.

2013-01-01

1H NMR-based metabolomics was used to measure the response of Eisenia fetida earthworms after exposure to sub-lethal concentrations of perfluorooctane sulfonate (PFOS) in soil. Earthworms were exposed to a range of PFOS concentrations (five, 10, 25, 50, 100 or 150 mg/kg) for two, seven and fourteen days. Earthworm tissues were extracted and analyzed by 1H NMR. Multivariate statistical analysis of the metabolic response of E. fetida to PFOS exposure identified time-dependent responses that were comprised of two separate modes of action: a non-polar narcosis type mechanism after two days of exposure and increased fatty acid oxidation after seven and fourteen days of exposure. Univariate statistical analysis revealed that 2-hexyl-5-ethyl-3-furansulfonate (HEFS), betaine, leucine, arginine, glutamate, maltose and ATP are potential indicators of PFOS exposure, as the concentrations of these metabolites fluctuated significantly. Overall, NMR-based metabolomic analysis suggests elevated fatty acid oxidation, disruption in energy metabolism and biological membrane structure and a possible interruption of ATP synthesis. These conclusions obtained from analysis of the metabolic profile in response to sub-lethal PFOS exposure indicates that NMR-based metabolomics is an excellent discovery tool when the mode of action (MOA) of contaminants is not clearly defined. PMID:24958147

Verification of Ensemble Forecasts for the New York City Operations Support Tool

NASA Astrophysics Data System (ADS)

Day, G.; Schaake, J. C.; Thiemann, M.; Draijer, S.; Wang, L.

2012-12-01

The New York City water supply system operated by the Department of Environmental Protection (DEP) serves nine million people. It covers 2,000 square miles of portions of the Catskill, Delaware, and Croton watersheds, and it includes nineteen reservoirs and three controlled lakes. DEP is developing an Operations Support Tool (OST) to support its water supply operations and planning activities. OST includes historical and real-time data, a model of the water supply system complete with operating rules, and lake water quality models developed to evaluate alternatives for managing turbidity in the New York City Catskill reservoirs. OST will enable DEP to manage turbidity in its unfiltered system while satisfying its primary objective of meeting the City's water supply needs, in addition to considering secondary objectives of maintaining ecological flows, supporting fishery and recreation releases, and mitigating downstream flood peaks. The current version of OST relies on statistical forecasts of flows in the system based on recent observed flows. To improve short-term decision making, plans are being made to transition to National Weather Service (NWS) ensemble forecasts based on hydrologic models that account for short-term weather forecast skill, longer-term climate information, as well as the hydrologic state of the watersheds and recent observed flows. To ensure that the ensemble forecasts are unbiased and that the ensemble spread reflects the actual uncertainty of the forecasts, a statistical model has been developed to post-process the NWS ensemble forecasts to account for hydrologic model error as well as any inherent bias and uncertainty in initial model states, meteorological data and forecasts. The post-processor is designed to produce adjusted ensemble forecasts that are consistent with the DEP historical flow sequences that were used to develop the system operating rules. A set of historical hindcasts that is representative of the real-time ensemble forecasts is needed to verify that the post-processed forecasts are unbiased, statistically reliable, and preserve the skill inherent in the "raw" NWS ensemble forecasts. A verification procedure and set of metrics will be presented that provide an objective assessment of ensemble forecasts. The procedure will be applied to both raw ensemble hindcasts and to post-processed ensemble hindcasts. The verification metrics will be used to validate proper functioning of the post-processor and to provide a benchmark for comparison of different types of forecasts. For example, current NWS ensemble forecasts are based on climatology, using each historical year to generate a forecast trace. The NWS Hydrologic Ensemble Forecast System (HEFS) under development will utilize output from both the National Oceanic Atmospheric Administration (NOAA) Global Ensemble Forecast System (GEFS) and the Climate Forecast System (CFS). Incorporating short-term meteorological forecasts and longer-term climate forecast information should provide sharper, more accurate forecasts. Hindcasts from HEFS will enable New York City to generate verification results to validate the new forecasts and further fine-tune system operating rules. Project verification results will be presented for different watersheds across a range of seasons, lead times, and flow levels to assess the quality of the current ensemble forecasts.

Embryonal Fyn-associated substrate (EFS) and CASS4: The lesser-known CAS protein family members.

PubMed

Deneka, Alexander; Korobeynikov, Vladislav; Golemis, Erica A

2015-10-01

The CAS (Crk-associated substrate) adaptor protein family consists of four members: CASS1/BCAR1/p130Cas, CASS2/NEDD9/HEF1/Cas-L, CASS3/EFS/Sin and CASS4/HEPL. While CAS proteins lack enzymatic activity, they contain specific recognition and binding sites for assembly of larger signaling complexes that are essential for cell proliferation, survival, migration, and other processes. All family members are intermediates in integrin-dependent signaling pathways mediated at focal adhesions, and associate with FAK and SRC family kinases to activate downstream effectors regulating the actin cytoskeleton. Most studies of CAS proteins to date have been focused on the first two members, BCAR1 and NEDD9, with altered expression of these proteins now appreciated as influencing disease development and prognosis for cancer and other serious pathological conditions. For these family members, additional mechanisms of action have been defined in receptor tyrosine kinase (RTK) signaling, estrogen receptor signaling or cell cycle progression, involving discrete partner proteins such as SHC, NSP proteins, or AURKA. By contrast, EFS and CASS4 have been less studied, although structure-function analyses indicate they conserve many elements with the better-known family members. Intriguingly, a number of recent studies have implicated these proteins in immune system function, and the pathogenesis of developmental disorders, autoimmune disorders including Crohn's disease, Alzheimer's disease, cancer and other diseases. In this review, we summarize the current understanding of EFS and CASS4 protein function in the context of the larger CAS family group. Copyright © 2015 Elsevier B.V. All rights reserved.

Topographic measurements of eyelids and orbit in enucleated eyes with hydroxyapatite integrated implant versus PMMA implant.

PubMed

Gradinaru, S; Totir, M; Iancu, R; Leasu, C; Pricopie, S; Yasin, S; Ciuluvica, R; Ungureanu, E

2014-01-01

This study reports our results relating to palpebral eyelid fissure and orbital measurements following evisceration with orbital implantation of hydroxyapatite integrated implant and PMMA implant. This study is a prospective study of 43 patients that underwent evisceration for different ocular affections at University Emergency Hospital Bucharest, Ophthalmology department between January 2009 and September 2010 (Group A comprising of twenty patients had the coralline hydroxyapatite implant -Integrated Ocular Implants, USA and Group B comprising of twenty-three received non-integrated PMMA ocular implants) .The outcomes measured were the degree of exo /enophthalmos, horizontal eyelid fissure and palpebral fissure height at 4 years after surgical intervention related to measurement to the contralateral eye. Horizontal eyelid fissure (HEF) was suffering a shortening of 7.4% in the group B versus the contralateral eye, and only 1.9% in the group A related to the contralateral eye. Eyelid fissure height was greater in the group B with 5.2% regarding the contralateral eye, and 1.2% in group A. The degree of enophthalmia was higher in the group B of 4 mm versus the contralateral eye and lower in group A 1.5 mm regarding the contralateral eye. . Although a hydroxyapatite implant may be not as economic as a PMMA implant, a patient must be warned about the effect on its ocular structures in time and that cosmetic appearance over years will change more dramatically than in the fellow normal eye. Therefore preoperative counseling of the patient is crucial in long term patient satisfaction.

Phytochemical, chromatographic and spectroscopic investigation of Carum copticum seeds and their potential as immunomodulatory agents.

PubMed

Sonar, Pankaj K; Singh, Ranjit; Saraf, Shailendra K

2016-01-01

Carum copticum seeds have been prescribed in the traditional system of medicine for the treatment of immune disorders, such as asthma and rheumatism. The objective of this study was to determine immunomodulatory effects of the alcoholic extract and isolated compounds in Swiss albino mice. Seeds of C. copticum were extracted with 95% v/v alcohol. The immunomodulatory activity of the crude extract was evaluated at the doses of 100, 300, and 500 mg/kg body weight of mice, administered in mice once daily (orally) for 25 days. Volatile oil of C. copticum was isolated by steam distillation and was characterized by GLC and HPLC. Bio-assay-guided fractionation and isolation were carried out and the isolated compounds were characterized and subjected to immunomodulatory activity studies. The n-hexane fraction yielded p-cymene, carvacrol, and α-pinene. The LD50 value of the crude extract was found to be 4500 mg/kg and the values reported for p-cymene, carvacrol, and α-pinene in the literature were 4750, 810, and 3700 mg/kg, respectively. The oral administration of crude extract, n-hexane fraction (HEF), and isolated oils at the dose of 500, 150, and 50 mg/kg body weight, respectively, showed a significant increase in the HA titers, DTH-response, and phagocytosis. The stimulatory effect observed, on humoral and cellular immunity, was compared with the standard (levamisole treated) and control groups. The results obtained in the study endorse the traditional use of the seeds of C. copticum and the isolated constituents act as immunostimulants.

[Genetic diversity and evolution of the influenza C virus].

PubMed

Speranskaia, A S; Mel'nikova, N V; Belenkin, M S; Dmitriev, A A; Oparina, N Iu; Kudriavtseva, A V

2012-07-01

The influenza C virus is spread worldwide and causes diseases of the upper and (less frequently) lower respiratory tract in human. The virus is not pandemic, but it circulates together with pandemic influenza A and B viruses during winter months and has quite similar clinical manifestations. The influenza C virus is also encountered in animals (pigs and dogs) and is known to override the interspecific barriers oftransmssion. The immune system of mammals often fails to recognize new antigenic variants of influenza C virus, which invariably arise in nature, resulting in outbreaks of diseases, although the structure of antigens in influenza C virus in general is much more stable than those of influenza viruses A and B. Variability of genetic information in natural isolates of viruses is determined by mutations, reassortment, and recombination. However, recombination events very rarely occur in genomes of negative-strand RNA viruses, including those of influenza, and virtually have no effect on their evolution. Unambiguous explanations for this phenomenon have thus far not been proposed. There is no proof of recombination processes in the influenza C virus genome. On the contrary, reassortant viruses derived from different strains of influenza C virus frequently appear in vitro and are likely to be common in nature. The genome of influenza C virus comprises seven segments. Based on the comparison of sequences in one of its genes (HEF), six genetic or antigenic lineages of this virus can be distinguished (Yamagata/26/81, Aichi/1/81, Mississippi/80, Taylor/1233/47, Sao Paulo/378/82, and Kanagawa/1/76). However, the available genetic data show that all the seven segments of the influenza C virus genome evolve independently.

Antenna Controller Replacement Software

NASA Technical Reports Server (NTRS)

Chao, Roger Y.; Morgan, Scott C.; Strain, Martha M.; Rockwell, Stephen T.; Shimizu, Kenneth J.; Tehrani, Barzia J.; Kwok, Jaclyn H.; Tuazon-Wong, Michelle; Valtier, Henry; Nalbandi, Reza;

Apigenin inhibits cell proliferation, migration, and invasion by targeting Akt in the A549 human lung cancer cell line.

PubMed

Zhou, Zhongping; Tang, Miaomiao; Liu, Yi; Zhang, Zhuyi; Lu, Rongzhu; Lu, Jian

2017-04-01

Apigenin (APG), a widely distributed flavonoid in vegetables and fruits, with low toxicity, and a nonmutagenic characteristic, has been reported to have many targets. Evidence indicates that APG can inhibit the proliferation, migration, invasion, and metastasis of some tumor cells, but the mechanism, specifically in lung cancer, is unclear. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway regulates a diverse set of cellular functions relevant to the growth and progression of lung cancer, including proliferation, survival, migration, and invasion. Our results showed that APG exerted anti-proliferation, anti-migration, and anti-invasion effects in A549 human lung cancer cells by targeting the PI3K/Akt signaling pathway. 3-(4, 5-dimethylthiszol-2-yl)-2, 5-diphenytetrazolium bromide assay and colony formation assay showed that APG suppressed cell proliferation in a dose-dependent and time-dependent manner. Cell motility and invasiveness were assayed using a wound healing and Transwell assay, suggesting that APG inhibited the migration and invasion of A549 cells. Western blot analyses were carried out to examine the Akt signaling pathways. The results confirmed that APG decreased Akt expression and its activation. Then, cells were transfected with Akt-active and Akt-DN plasmids separately. The migration and invasion of A549 cells were significantly changed, constitutively activating Akt or knocking down Akt, indicating that APG can suppress the migration and invasion of lung cancer cells by modulating the PI3K/Akt signaling pathway. Furthermore, the results indicated that APG not only suppressed phosphorylation of Akt, thereby preventing its activation, but also inhibited its downstream gene expression of matrix metalloproteinases-9, glycogen synthase kinase-3β, and HEF1. Together, APG is a new inhibitor of Akt in lung cancer and a potential natural compound for cancer chemoprevention.

Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth.

PubMed

Iida, Joji; Dorchak, Jesse; Clancy, Rebecca; Slavik, Juliana; Ellsworth, Rachel; Katagiri, Yasuhiro; Pugacheva, Elena N; van Kuppevelt, Toin H; Mural, Richard J; Cutler, Mary Lou; Shriver, Craig D

2015-01-15

There are lines of evidence demonstrating that NEDD9 (Cas-L, HEF-1) plays a key role in the development, progression, and metastasis of breast cancer cells. We previously reported that NEDD9 plays a critical role for promoting migration and growth of MDA-MB-231. In order to further characterize the mechanisms of NEDD9-mediated cancer migration and growth, stable cells overexpressing NEDD9 were generated using HCC38 as a parental cell line which expresses low level of endogenous NEDD9. Microarray studies demonstrated that core proteins of CD44 and Serglycin were markedly upregulated in HCC38(NEDD9) cells compared to HCC38(Vector) cells, while those of Syndecan-1, Syndecan-2, and Versican were downregulated in HCC38(NEDD9). Importantly, enzymes generating chondroitin sulfate glycosaminoglycans (CS) such as CHST11, CHST15, and CSGALNACT1 were upregulated in HCC38(NEDD9) compared to HCC38(Vector). Immunofluorescence studies using specific antibody, GD3G7, confirmed the enhanced expression of CS-E subunit in HCC38(NEDD9). Immunoprecipitation and western blotting analysis demonstrated that CS-E was attached to CD44 core protein. We demonstrated that removing CS by chondroitinase ABC significantly inhibited anchorage-independent colony formation of HCC38(NEDD9) in methylcellulose. Importantly, the fact that GD3G7 significantly inhibited colony formation of HCC38(NEDD9) cells suggests that CS-E subunit plays a key role in this process. Furthermore, treatment of HCC38(NEDD9) cells with chondroitinase ABC or GD3G7 significantly inhibited mammosphere formation. Exogenous addition of CS-E enhanced colony formation and mammosphere formation of HCC38 parental and HCC38(Vector) cells. These results suggest that NEDD9 regulates the synthesis and expression of tumor associated glycocalyx structures including CS-E, which plays a key role in promoting and regulating breast cancer progression and metastasis and possibly stem cell phenotypes. Copyright © 2014 Elsevier Inc. All rights reserved.

The heart of Africa: succeeding against the odds.

PubMed

Sliwa, Karen

2016-12-17

South Africa and other areas of sub-Saharan Africa have in the past 20 years undergone rapid demographical changes, largely due to urbanisation and changes in lifestyle. This rapid change has led to a marked increase in specific cardiac conditions, such as hypertensive heart disease and coronary artery disease (with the highest prevalence in the middle-aged population), in conjunction with a range of other heart diseases, which are historically common in Africa-eg, rheumatic heart disease, cardiomyopathies, and unoperated congenital heart disease. The short supply of well-equipped screening facilities, late diagnosis, and inadequate care at primary, secondary, and tertiary levels have led to a large burden of patients with poorly treated heart failure. Excellent progress has been made in the understanding of the epidemiology, sociodemographical factors, effect of urbanisation, and pathophysiology of cardiac conditions, such as peripartum cardiomyopathy, rheumatic heart disease, and tuberculous pericarditis, which are common in sub-Saharan Africa. This progress has been achieved largely through several studies, such as the Heart of Soweto, THESUS, REMEDY, BA-HEF, Abeokuta-HF, and the PAPUCO studies. Studies on the suitable therapeutic management of several heart conditions have also been done or are underway. In this Lecture, I provide a personal perspective on the evolving burden of cardiac disease, as witnessed since my appointment at Chris Hani Baragwanath Hospital, in Soweto, South Africa, in 1992, which was also the year that the referendum to end apartheid in South Africa was held. Subsequently, a network of cardiologists was formed under the umbrella of the Heart of Africa Studies and the Pan African Cardiac Society. Furthermore, I summarise the major gaps in the health-care system dealing with the colliding epidemic of communicable and non-communicable heart diseases, including cardiac diseases common in peripartum women. I also touch on the fantastic opportunities available for doing meaningful research with enthusiastic colleagues and, thereby, having a large effect, despite the need to be highly innovative in finding much needed funding support. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fanconi anemia: causes and consequences of genetic instability.

PubMed

Kalb, R; Neveling, K; Nanda, I; Schindler, D; Hoehn, H

2006-01-01

Fanconi anemia (FA) is a rare recessive disease that reflects the cellular and phenotypic consequences of genetic instability: growth retardation, congenital malformations, bone marrow failure, high risk of neoplasia, and premature aging. At the cellular level, manifestations of genetic instability include chromosomal breakage, cell cycle disturbance, and increased somatic mutation rates. FA cells are exquisitely sensitive towards oxygen and alkylating drugs such as mitomycin C or diepoxybutane, pointing to a function of FA genes in the defense against reactive oxygen species and other DNA damaging agents. FA is caused by biallelic mutations in at least 12 different genes which appear to function in the maintenance of genomic stability. Eight of the FA proteins form a nuclear core complex with a catalytic function involving ubiquitination of the central FANCD2 protein. The posttranslational modification of FANCD2 promotes its accumulation in nuclear foci, together with known DNA maintenance proteins such as BRCA1, BRCA2, and the RAD51 recombinase. Biallelic mutations in BRCA2 cause a severe FA-like phenotype, as do biallelic mutations in FANCD2. In fact, only leaky or hypomorphic mutations in this central group of FA genes appear to be compatible with life birth and survival. The newly discovered FANCJ (= BRIP1) and FANCM (= Hef ) genes correspond to known DNA-maintenance genes (helicase resp. helicase-associated endonuclease for fork-structured DNA). These genes provide the most convincing evidence to date of a direct involvement of FA genes in DNA repair functions associated with the resolution of DNA crosslinks and stalled replication forks. Even though genetic instability caused by mutational inactivation of the FANC genes has detrimental effects for the majority of FA patients, around 20% of patients appear to benefit from genetic instability since genetic instability also increases the chance of somatic reversion of their constitutional mutations. Intragenic crossover, gene conversion, back mutation and compensating mutations in cis have all been observed in revertant, and, consequently, mosaic FA-patients, leading to improved bone marrow function. There probably is no other experiment of nature in our species in which causes and consequences of genetic instability, including the role of reactive oxygen species, can be better documented and explored than in FA.