Science.gov

Sample records for hits gdp growth

  1. A Rho GDP Dissociation Inhibitor Produced by Apoptotic T-Cells Inhibits Growth of Mycobacterium tuberculosis

    PubMed Central

    Venkatasubramanian, Sambasivan; Dhiman, Rohan; Paidipally, Padmaja; Cheekatla, Satyanarayana S.; Tripathi, Deepak; Welch, Elwyn; Tvinnereim, Amy R.; Jones, Brenda; Theodorescu, Dan; Barnes, Peter F.; Vankayalapati, Ramakrishna

    2015-01-01

    In this study, we found that a subpopulation of CD4+CD25+ (85% Foxp3+) cells from persons with latent tuberculosis infection (LTBI) inhibits growth of M. tuberculosis (M. tb) in human monocyte-derived macrophages (MDMs). A soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by apoptotic CD4+CD25+ (85% Foxp3+) cells is responsible for this inhibition of M. tb growth in human macrophages and in mice. M. tb-expanded CD4+CD25+Foxp3+D4GDI+ cells do not produce IL-10, TGF-β and IFN-γ. D4GDI inhibited growth of M. tb in MDMs by enhancing production of IL-1β, TNF-α and ROS, and by increasing apoptosis of M. tb-infected MDMs. D4GDI was concentrated at the site of disease in tuberculosis patients, with higher levels detected in pleural fluid than in serum. However, in response to M. tb, PBMC from tuberculosis patients produced less D4GDI than PBMC from persons with LTBI. M. tb-expanded CD4+CD25+ (85% Foxp3+) cells and D4GDI induced intracellular M. tb to express the dormancy survival regulator DosR and DosR-dependent genes, suggesting that D4GDI induces a non-replicating state in the pathogen. Our study provides the first evidence that a subpopulation of CD4+CD25+ (85% Foxp3+) cells enhances immunity to M. tb, and that production of D4GDI by this subpopulation inhibits M. tb growth. PMID:25659138

  2. Carbon dioxide emissions, GDP, energy use, and population growth: a multivariate and causality analysis for Ghana, 1971-2013.

    PubMed

    Asumadu-Sarkodie, Samuel; Owusu, Phebe Asantewaa

    2016-07-01

    In this study, the relationship between carbon dioxide emissions, GDP, energy use, and population growth in Ghana was investigated from 1971 to 2013 by comparing the vector error correction model (VECM) and the autoregressive distributed lag (ARDL). Prior to testing for Granger causality based on VECM, the study tested for unit roots, Johansen's multivariate co-integration and performed a variance decomposition analysis using Cholesky's technique. Evidence from the variance decomposition shows that 21 % of future shocks in carbon dioxide emissions are due to fluctuations in energy use, 8 % of future shocks are due to fluctuations in GDP, and 6 % of future shocks are due to fluctuations in population. There was evidence of bidirectional causality running from energy use to GDP and a unidirectional causality running from carbon dioxide emissions to energy use, carbon dioxide emissions to GDP, carbon dioxide emissions to population, and population to energy use. Evidence from the long-run elasticities shows that a 1 % increase in population in Ghana will increase carbon dioxide emissions by 1.72 %. There was evidence of short-run equilibrium relationship running from energy use to carbon dioxide emissions and GDP to carbon dioxide emissions. As a policy implication, the addition of renewable energy and clean energy technologies into Ghana's energy mix can help mitigate climate change and its impact in the future. PMID:27030236

  3. Applications of the Time-Varying Multi-Hazard Index to Armed Conflicts and GDP Growth Rate

    NASA Astrophysics Data System (ADS)

    Isanuk, M.; Skorik, A.; Lerner-Lam, A.

    2004-12-01

    The time-varying Multi-Hazard Index has many potential applications for comparisons against quantitative measures of sustainable development. We have compared the time-varying severity of multiple natural hazards against time-varying socio-economic data for selected countries. Our analysis compares Gross Domestic Product (GDP) growth and armed conflict occurrence against multiple hazard severity as measured by an empirical time-varying multiple hazard index. The purpose of these analyses is to establish and characterize correlations between the Multi-Hazard Index and trends in GDP and conflicts over the past 25 years. To analyze the relationship between natural hazards and armed conflicts, the Multi-Hazard Index was correlated against the number of conflicts at each intensity level for individual countries. A preliminary analysis was performed studying the apparent relationship as well as the possible existence of time lags. In a similar although more quantitative analysis, the GDP data was correlated against the Multi-Hazard Index for a particular country at different time lags. Analysis involving the conflict datasets yielded varying results from country to country. Colombia shows the strongest correlation, with all positive values of the Multi-Hazard Index followed by an escalation in conflict intensity. The results for other countries are more difficult to interpret as certain years show increases in the number of conflicts at one intensity level and a decrease for other intensity levels. Some issues that need to be addressed include the coding of the intensity for the conflict data, the dating for both conflicts and hazards, and the use of national boundaries as geographic extents. The degree of correlation between GDP growth and the Multi-Hazard Index varies from country to country as well. Our calculations for Honduras show an extremely high correlation, for example, implying a strong economic sensitivity to natural hazards, whereas for China no significant

  4. National Income Inequality and Declining GDP Growth Rates Are Associated with Increases in HIV Diagnoses among People Who Inject Drugs in Europe: A Panel Data Analysis

    PubMed Central

    Nikolopoulos, Georgios K.; Fotiou, Anastasios; Kanavou, Eleftheria; Richardson, Clive; Detsis, Marios; Pharris, Anastasia; Suk, Jonathan E.; Semenza, Jan C.; Costa-Storti, Claudia; Paraskevis, Dimitrios; Sypsa, Vana; Malliori, Melpomeni-Minerva; Friedman, Samuel R.; Hatzakis, Angelos

    2015-01-01

    Background There is sparse evidence that demonstrates the association between macro-environmental processes and drug-related HIV epidemics. The present study explores the relationship between economic, socio-economic, policy and structural indicators, and increases in reported HIV infections among people who inject drugs (PWID) in the European Economic Area (EEA). Methods We used panel data (2003–2012) for 30 EEA countries. Statistical analyses included logistic regression models. The dependent variable was taking value 1 if there was an outbreak (significant increase in the national rate of HIV diagnoses in PWID) and 0 otherwise. Explanatory variables included the growth rate of Gross Domestic Product (GDP), the share of the population that is at risk for poverty, the unemployment rate, the Eurostat S80/S20 ratio, the Gini coefficient, the per capita government expenditure on health and social protection, and variables on drug control policy and drug-using population sizes. Lags of one to three years were investigated. Findings In multivariable analyses, using two-year lagged values, we found that a 1% increase of GDP was associated with approximately 30% reduction in the odds of an HIV outbreak. In GDP-adjusted analyses with three-year lagged values, the effect of the national income inequality on the likelihood of an HIV outbreak was significant [S80/S20 Odds Ratio (OR) = 3.89; 95% Confidence Interval (CI): 1.15 to 13.13]. Generally, the multivariable analyses produced similar results across three time lags tested. Interpretation Given the limitations of ecological research, we found that declining economic growth and increasing national income inequality were associated with an elevated probability of a large increase in the number of HIV diagnoses among PWID in EEA countries during the last decade. HIV prevention may be more effective if developed within national and European-level policy contexts that promote income equality, especially among vulnerable

  5. Heat resistance and salt hypersensitivity in Lactococcus lactis due to spontaneous mutation of llmg_1816 (gdpP) induced by high-temperature growth.

    PubMed

    Smith, William M; Pham, Thi Huong; Lei, Lin; Dou, Junchao; Soomro, Aijaz H; Beatson, Scott A; Dykes, Gary A; Turner, Mark S

    2012-11-01

    During construction of several gene deletion mutants in Lactococcus lactis MG1363 which involved a high-temperature (37.5°C) incubation step, additional spontaneous mutations were observed which resulted in stable heat resistance and in some cases salt-hypersensitive phenotypes. Whole-genome sequencing of one strain which was both heat resistant and salt hypersensitive, followed by PCR and sequencing of four other mutants which shared these phenotypes, revealed independent mutations in llmg_1816 in all cases. This gene encodes a membrane-bound stress signaling protein of the GdpP family, members of which exhibit cyclic dimeric AMP (c-di-AMP)-specific phosphodiesterase activity. Mutations were predicted to lead to single amino acid substitutions or protein truncations. An independent llmg_1816 mutant (Δ1816), created using a suicide vector, also displayed heat resistance and salt hypersensitivity phenotypes which could be restored to wild-type levels following plasmid excision. L. lactis Δ1816 also displayed improved growth in response to sublethal concentrations of penicillin G. High-temperature incubation of a wild-type industrial L. lactis strain also resulted in spontaneous mutation of llmg_1816 and heat-resistant and salt-hypersensitive phenotypes, suggesting that this is not a strain-specific phenomenon and that it is independent of a plasmid integration event. Acidification of milk by the llmg_1816-altered strain was inhibited by lower salt concentrations than the parent strain. This study demonstrates that spontaneous mutations can occur during high-temperature growth of L. lactis and that inactivation of llmg_1816 leads to temperature resistance and salt hypersensitivity. PMID:22923415

  6. Heat Resistance and Salt Hypersensitivity in Lactococcus lactis Due to Spontaneous Mutation of llmg_1816 (gdpP) Induced by High-Temperature Growth

    PubMed Central

    Smith, William M.; Pham, Thi Huong; Lei, Lin; Dou, Junchao; Soomro, Aijaz H.; Beatson, Scott A.; Dykes, Gary A.

    2012-01-01

    During construction of several gene deletion mutants in Lactococcus lactis MG1363 which involved a high-temperature (37.5°C) incubation step, additional spontaneous mutations were observed which resulted in stable heat resistance and in some cases salt-hypersensitive phenotypes. Whole-genome sequencing of one strain which was both heat resistant and salt hypersensitive, followed by PCR and sequencing of four other mutants which shared these phenotypes, revealed independent mutations in llmg_1816 in all cases. This gene encodes a membrane-bound stress signaling protein of the GdpP family, members of which exhibit cyclic dimeric AMP (c-di-AMP)-specific phosphodiesterase activity. Mutations were predicted to lead to single amino acid substitutions or protein truncations. An independent llmg_1816 mutant (Δ1816), created using a suicide vector, also displayed heat resistance and salt hypersensitivity phenotypes which could be restored to wild-type levels following plasmid excision. L. lactis Δ1816 also displayed improved growth in response to sublethal concentrations of penicillin G. High-temperature incubation of a wild-type industrial L. lactis strain also resulted in spontaneous mutation of llmg_1816 and heat-resistant and salt-hypersensitive phenotypes, suggesting that this is not a strain-specific phenomenon and that it is independent of a plasmid integration event. Acidification of milk by the llmg_1816-altered strain was inhibited by lower salt concentrations than the parent strain. This study demonstrates that spontaneous mutations can occur during high-temperature growth of L. lactis and that inactivation of llmg_1816 leads to temperature resistance and salt hypersensitivity. PMID:22923415

  7. Modification of epidermal growth factor-like repeats with O-fucose. Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase.

    PubMed

    Wang, Y; Shao, L; Shi, S; Harris, R J; Spellman, M W; Stanley, P; Haltiwanger, R S

    2001-10-26

    The O-fucose modification is found on epidermal growth factor-like repeats of a number of cell surface and secreted proteins. O-Fucose glycans play important roles in ligand-induced receptor signaling. For example, elongation of O-fucose on Notch by the beta1,3-N-acetylglucosaminyltransferase Fringe modulates the ability of Notch to respond to its ligands. The enzyme that adds O-fucose to epidermal growth factor-like repeats, GDP-fucose protein O-fucosyltransferase (O-FucT-1), was purified previously from Chinese hamster ovary (CHO) cells. Here we report the isolation of a cDNA that encodes human O-FucT-1. A probe deduced from N-terminal sequence analysis of purified CHO O-FucT-1 was used to screen a human heart cDNA library and expressed sequence tag and genomic data bases. The cDNA contains an open reading frame encoding a protein of 388 amino acids with a predicted N-terminal transmembrane sequence typical of a type II membrane orientation. Likewise, the mouse homolog obtained from an expressed sequence tag and 5'-rapid amplification of cDNA ends of a mouse liver cDNA library encodes a type II transmembrane protein of 393 amino acids with 90.4% identity to human O-FucT-1. Homologs were also found in Drosophila and Caenorhabditis elegans with 41.2 and 29.4% identity to human O-FucT-1, respectively. The human gene (POFUT1) is on chromosome 20 between PLAGL2 and KIF3B, near the centromere at 20p11. The mouse gene (Pofut1) maps near Plagl2 on a homologous region of mouse chromosome 2. POFUT1 gene transcripts were expressed in all tissues examined, consistent with the widespread localization of the modification. Expression of a soluble form of human O-FucT-1 in insect cells yielded a protein of the predicted molecular weight with O-FucT-1 kinetic and enzymatic properties similar to those of O-FucT-1 purified from CHO cells. The identification of the gene encoding protein O-fucosyltransferase I now makes possible mutational strategies to examine the functions of the

  8. Beyond GDP: Classifying Alternative Measures for Progress

    ERIC Educational Resources Information Center

    Bleys, Brent

    2012-01-01

    Both the potential pitfalls of macro-economic policies focused on stimulating economic growth and the problems involved in using GDP as a measure of well-being or economic welfare have long been recognized by economists and researchers from other social sciences. Therefore, it is no surprise that alternative measures for policy-making have been…

  9. Prediction of Malaysian monthly GDP

    NASA Astrophysics Data System (ADS)

    Hin, Pooi Ah; Ching, Soo Huei; Yeing, Pan Wei

    2015-12-01

    The paper attempts to use a method based on multivariate power-normal distribution to predict the Malaysian Gross Domestic Product next month. Letting r(t) be the vector consisting of the month-t values on m selected macroeconomic variables, and GDP, we model the month-(t+1) GDP to be dependent on the present and l-1 past values r(t), r(t-1),…,r(t-l+1) via a conditional distribution which is derived from a [(m+1)l+1]-dimensional power-normal distribution. The 100(α/2)% and 100(1-α/2)% points of the conditional distribution may be used to form an out-of sample prediction interval. This interval together with the mean of the conditional distribution may be used to predict the month-(t+1) GDP. The mean absolute percentage error (MAPE), estimated coverage probability and average length of the prediction interval are used as the criterions for selecting the suitable lag value l-1 and the subset from a pool of 17 macroeconomic variables. It is found that the relatively better models would be those of which 2 ≤ l ≤ 3, and involving one or two of the macroeconomic variables given by Market Indicative Yield, Oil Prices, Exchange Rate and Import Trade.

  10. The SVT Hit Buffer

    SciTech Connect

    Belforte, S.; Dell`Orso, M.; Donati, S.

    1996-06-01

    The Hit Buffer is part of the Silicon Vertex Tracker, a trigger processor dedicated to the reconstruction of particle trajectories in the Silicon Vertex Detector and the Central Tracking Chamber of the Collider Detector at Fermilab. The Hit Buffer is a high speed data-traffic node, where thousands of words are received in arbitrary order and simultaneously organized in an internal structured data base, to be later promptly retrieved and delivered in response to specific requests. The Hit Buffer is capable of processing data at a rate of 25 MHz, thanks to the use of special fast devices like Cache-Tag RAMs and high performance Erasable Programmable Logic Devices from the XILINX XC7300 family.

  11. Characterization of GDP-Fucose

    PubMed Central

    James, Douglas W.; Jones, Russell L.

    1979-01-01

    The peripheral root cap cells of corn (cv. SX-17A) secrete a fucose-rich, high molecular weight, polysaccharide slime via the dictyosome pathway. To study the synthesis of this polysaccharide, a technique for isolating and assaying GDP-fucose:polysaccharide fucosyl transferase activity was developed. Corn roots were excised from germinated seeds, incubated 12 hours at 10 C in water, and ground in 100 millimolar Tris or Pipes buffer (pH 7.0) with or without 0.5 molar sucrose. The membrane-bound enzyme was solubilized by sonication in the presence of 2 molar urea and 1.5% (v/v) Triton X-100 and assayed by monitoring the incorporation of GDP-[14C]fucose into endogenous acceptors. Optimum enzyme activity is expressed at pH 7.0 and 30 C in the presence of 0.8% (v/v) Triton X-100. The enzyme does not require divalent cations for activation and is inhibited by concentrations of MnCl2 or MgCl2 greater than 1 millimolar. Corn root cap slime will serve as an exogenous acceptor for the enzyme if it is first hydrolyzed in 5 millimolar trifluoroacetic acid for 60 minutes at 18 pounds per square inch, 121 C. This procedure prepares the acceptor by removing terminal fucose residues from the slime molecule. Kinetics of fucose release during hydrolysis of native slime and in vitro synthesized product suggests that the two polymers possess similar linkages to fucose. PMID:16661104

  12. But Can You Hit?

    ERIC Educational Resources Information Center

    Johnson, R. E.

    2009-01-01

    The author shares a story told to him by a colleague more than thirty years ago. The dean of a midsized American university was explaining the path to tenure to a roomful of newly appointed assistant professors. "We know you boys can all "field"," he declared. "Now we want to see if you can hit." A lot has changed over the intervening decades. If…

  13. The Arabidopsis Golgi-localized GDP-L-fucose transporter is required for plant development

    PubMed Central

    Rautengarten, Carsten; Ebert, Berit; Liu, Lifeng; Stonebloom, Solomon; Smith-Moritz, Andreia M.; Pauly, Markus; Orellana, Ariel; Scheller, Henrik Vibe; Heazlewood, Joshua L.

    2016-01-01

    Nucleotide sugar transport across Golgi membranes is essential for the luminal biosynthesis of glycan structures. Here we identify GDP-fucose transporter 1 (GFT1), an Arabidopsis nucleotide sugar transporter that translocates GDP-L-fucose into the Golgi lumen. Using proteo-liposome-based transport assays, we show that GFT preferentially transports GDP-L-fucose over other nucleotide sugars in vitro, while GFT1-silenced plants are almost devoid of L-fucose in cell wall-derived xyloglucan and rhamnogalacturonan II. Furthermore, these lines display reduced L-fucose content in N-glycan structures accompanied by severe developmental growth defects. We conclude that GFT1 is the major nucleotide sugar transporter for import of GDP-L-fucose into the Golgi and is required for proper plant growth and development. PMID:27381418

  14. The Arabidopsis Golgi-localized GDP-L-fucose transporter is required for plant development.

    PubMed

    Rautengarten, Carsten; Ebert, Berit; Liu, Lifeng; Stonebloom, Solomon; Smith-Moritz, Andreia M; Pauly, Markus; Orellana, Ariel; Scheller, Henrik Vibe; Heazlewood, Joshua L

    2016-01-01

    Nucleotide sugar transport across Golgi membranes is essential for the luminal biosynthesis of glycan structures. Here we identify GDP-fucose transporter 1 (GFT1), an Arabidopsis nucleotide sugar transporter that translocates GDP-L-fucose into the Golgi lumen. Using proteo-liposome-based transport assays, we show that GFT preferentially transports GDP-L-fucose over other nucleotide sugars in vitro, while GFT1-silenced plants are almost devoid of L-fucose in cell wall-derived xyloglucan and rhamnogalacturonan II. Furthermore, these lines display reduced L-fucose content in N-glycan structures accompanied by severe developmental growth defects. We conclude that GFT1 is the major nucleotide sugar transporter for import of GDP-L-fucose into the Golgi and is required for proper plant growth and development. PMID:27381418

  15. Hurricane Iris Hits Belize

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Hurricane Iris hit the small Central American country of Belize around midnight on October 8, 2001. At the time, Iris was the strongest Atlantic hurricane of the season, with sustained winds up to 225 kilometers per hour (140 mph). The hurricane caused severe damage-destroying homes, flooding streets, and leveling trees-in coastal towns south of Belize City. In addition, a boat of American recreational scuba divers docked along the coast was capsized by the storm, leaving 20 of the 28 passengers missing. Within hours the winds had subsided to only 56 kph (35 mph), a modest tropical depression, but Mexico, Guatemala, El Salvador, and Honduras were still expecting heavy rains. The above image is a combination of visible and thermal infrared data (for clouds) acquired by a NOAA Geostationary Operational Environmental Satellite (GOES-8) on October 8, 2001, at 2:45 p.m., and the Moderate-resolution Imaging Spectroradiometer (MODIS) (for the color of the ground). The three-dimensional view is from the south-southeast (north is towards the upper left). Belize is off the image to the left. Image courtesy Marit Jentoft-Nilsen, NASA GSFC Visualization Analysis Lab

  16. Metabolic engineering of Corynebacterium glutamicum to produce GDP-L-fucose from glucose and mannose.

    PubMed

    Chin, Young-Wook; Park, Jin-Byung; Park, Yong-Cheol; Kim, Kyoung Heon; Seo, Jin-Ho

    2013-06-01

    Wild-type Corynebacterium glutamicum was metabolically engineered to convert glucose and mannose into guanosine 5'-diphosphate (GDP)-L-fucose, a precursor of fucosyl-oligosaccharides, which are involved in various biological and pathological functions. This was done by introducing the gmd and wcaG genes of Escherichia coli encoding GDP-D-mannose-4,6-dehydratase and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase, respectively, which are known as key enzymes in the production of GDP-L-fucose from GDP-D-mannose. Coexpression of the genes allowed the recombinant C. glutamicum cells to produce GDP-L-fucose in a minimal medium containing glucose and mannose as carbon sources. The specific product formation rate was much higher during growth on mannose than on glucose. In addition, the specific product formation rate was further increased by coexpressing the endogenous phosphomanno-mutase gene (manB) and GTP-mannose-1-phosphate guanylyl-transferase gene (manC), which are involved in the conversion of mannose-6-phosphate into GDP-D-mannose. However, the overexpression of manA encoding mannose-6-phosphate isomerase, catalyzing interconversion of mannose-6-phosphate and fructose-6-phosphate showed a negative effect on formation of the target product. Overall, coexpression of gmd, wcaG, manB and manC in C. glutamicum enabled production of GDP-L-fucose at the specific rate of 0.11 mg g cell(-1) h(-1). The specific GDP-L-fucose content reached 5.5 mg g cell(-1), which is a 2.4-fold higher than that of the recombinant E. coli overexpressing gmd, wcaG, manB and manC under comparable conditions. Well-established metabolic engineering tools may permit optimization of the carbon and cofactor metabolisms of C. glutamicum to further improve their production capacity. PMID:23404100

  17. Heat Waves Hit Seniors Hardest

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_160425.html Heat Waves Hit Seniors Hardest Risk of high-temperature trouble ... much of the Northeast struggles with a heat wave that isn't expected to ease until the ...

  18. Micronutrient deficiencies in early childhood can lower a country's GDP: The Myanmar example.

    PubMed

    Win, Aung Zaw

    2016-01-01

    Myanmar (Burma) is a developing country in South East Asia. While Myanmar is among the 20 countries where 80% of the world's malnourished children live, its military consumes the majority of the national budget. Children who are malnourished between conception and age two are at high risk for impaired physical and mental development, which adversely affects the country's productivity and growth. Myanmar is facing three major micronutrient deficiencies which are iodine, iron and vitamin A deficiencies. The three micronutrient deficiencies can cost about 2.4% of the country's GDP. Children are the future of Myanmar and persistent micronutrient deficiencies will hamper its economic growth and lower its GDP. PMID:26421387

  19. Distributed generation hits market

    SciTech Connect

    1997-10-01

    The pace at which vendors are developing and marketing gas turbines and reciprocating engines for small-scale applications may signal the widespread growth of distributed generation. Loosely defined to refer to applications in which power generation equipment is located close to end users who have near-term power capacity needs, distributed generation encompasses a broad range of technologies and load requirements. Disagreement is inevitable, but many industry observers associate distributed generation with applications anywhere from 25 kW to 25 MW. Ten years ago, distributed generation users only represented about 2% of the world market. Today, that figure has increased to about 4 or 5%, and probably could settle in the 20% range within a 3-to-5-year period, according to Michael Jones, San Diego, Calif.-based Solar Turbines Inc. power generation marketing manager. The US Energy Information Administration predicts about 175 GW of generation capacity will be added domestically by 2010. If 20% comes from smaller plants, distributed generation could account for about 35 GW. Even with more competition, it`s highly unlikely distributed generation will totally replace current market structures and central stations. Distributed generation may be best suited for making market inroads when and where central systems need upgrading, and should prove its worth when the system can`t handle peak demands. Typical applications include small reciprocating engine generators at remote customer sites or larger gas turbines to boost the grid. Additional market opportunities include standby capacity, peak shaving, power quality, cogeneration and capacity rental for immediate demand requirements. Integration of distributed generation systems--using gas-fueled engines, gas-fired combustion engines and fuel cells--can upgrade power quality for customers and reduce operating costs for electric utilities.

  20. Car Hits Boy on Bicycle

    ERIC Educational Resources Information Center

    Ruiz, Michael J.

    2005-01-01

    In this article we present the fascinating reconstruction of an accident where a car hit a boy riding his bicycle. The boy dramatically flew several metres through the air after the collision and was injured, but made a swift and complete recovery from the accident with no long-term after-effects. Students are challenged to determine the speed of…

  1. An Empirical Analysis of Differences in GDP per Capita and the Role of Human Capital

    ERIC Educational Resources Information Center

    Sfakianakis, George; Magoutas, Anastasios I.; Georgopoulos, Demosthenes

    2010-01-01

    Using a generalized production function approach and insights from empirical research on the determinants of growth, this paper assesses the relative importance of specific factors in explaining differences in the levels of per capita GDP. Emphasis is placed on education, physical capital accumulation, the share of the public sector in economic…

  2. Hitting Is Contagious in Baseball: Evidence from Long Hitting Streaks

    PubMed Central

    Bock, Joel R.; Maewal, Akhilesh; Gough, David A.

    2012-01-01

    Data analysis is used to test the hypothesis that “hitting is contagious”. A statistical model is described to study the effect of a hot hitter upon his teammates’ batting during a consecutive game hitting streak. Box score data for entire seasons comprising streaks of length games, including a total observations were compiled. Treatment and control sample groups () were constructed from core lineups of players on the streaking batter’s team. The percentile method bootstrap was used to calculate confidence intervals for statistics representing differences in the mean distributions of two batting statistics between groups. Batters in the treatment group (hot streak active) showed statistically significant improvements in hitting performance, as compared against the control. Mean for the treatment group was found to be to percentage points higher during hot streaks (mean difference increased points), while the batting heat index introduced here was observed to increase by points. For each performance statistic, the null hypothesis was rejected at the significance level. We conclude that the evidence suggests the potential existence of a “statistical contagion effect”. Psychological mechanisms essential to the empirical results are suggested, as several studies from the scientific literature lend credence to contagious phenomena in sports. Causal inference from these results is difficult, but we suggest and discuss several latent variables that may contribute to the observed results, and offer possible directions for future research. PMID:23251507

  3. Modified GDP through health cost analysis of air pollution: The case of Turkey

    SciTech Connect

    Zaim, K.K.

    1999-02-01

    Economic growth and performance is monitored through the gross domestic product (GDP) of a nation. It has long been recognized that the traditionally computed GDP does not account for gains and losses observed due to the consumption of natural resources and environmental services. Hence, the objective of this study is to modify the Turkish GDP by taking social cost associated with air pollution into consideration. To this end health benefits and economic costs of air-quality improvement are estimated. The computations are based on the dose-response coefficients reported in several studies. The results indicate that a decrease in PM{sub 10} and SO{sub 2} levels to the WHO guideline would have resulted in a total of 48.309 {times} 10{sup 10} and 153.38 {times} 10{sup 10} Turkish lira savings in 1990 and 1993, respectively. These correspond to 0.12% and 0.08% of 1990 and 1993 GDPs, respectively.

  4. Improvements to the stand and hit algorithm

    SciTech Connect

    Boneh, A.; Boneh, S.; Caron, R.; Jibrin, S.

    1994-12-31

    The stand and hit algorithm is a probabilistic algorithm for detecting necessary constraints. The algorithm stands at a point in the feasible region and hits constraints by moving towards the boundary along randomly generated directions. In this talk we discuss methods for choosing the standing point. As well, we present the undetected first rule for determining the hit constraints.

  5. Hitting is contagious in baseball: evidence from long hitting streaks.

    PubMed

    Bock, Joel R; Maewal, Akhilesh; Gough, David A

    2012-01-01

    Data analysis is used to test the hypothesis that "hitting is contagious". A statistical model is described to study the effect of a hot hitter upon his teammates' batting during a consecutive game hitting streak. Box score data for entire seasons comprising [Formula: see text] streaks of length [Formula: see text] games, including a total [Formula: see text] observations were compiled. Treatment and control sample groups ([Formula: see text]) were constructed from core lineups of players on the streaking batter's team. The percentile method bootstrap was used to calculate [Formula: see text] confidence intervals for statistics representing differences in the mean distributions of two batting statistics between groups. Batters in the treatment group (hot streak active) showed statistically significant improvements in hitting performance, as compared against the control. Mean [Formula: see text] for the treatment group was found to be [Formula: see text] to [Formula: see text] percentage points higher during hot streaks (mean difference increased [Formula: see text] points), while the batting heat index [Formula: see text] introduced here was observed to increase by [Formula: see text] points. For each performance statistic, the null hypothesis was rejected at the [Formula: see text] significance level. We conclude that the evidence suggests the potential existence of a "statistical contagion effect". Psychological mechanisms essential to the empirical results are suggested, as several studies from the scientific literature lend credence to contagious phenomena in sports. Causal inference from these results is difficult, but we suggest and discuss several latent variables that may contribute to the observed results, and offer possible directions for future research. PMID:23251507

  6. Distributions of region size and GDP and their relation

    NASA Astrophysics Data System (ADS)

    Sen, Hu; Chunxia, Yang; Xueshuai, Zhu; Zhilai, Zheng; Ya, Cao

    2015-07-01

    We first analyze the distribution of metropolitan (city) size, the distribution of metropolitan (city) GDP and the relation of both distributions. It is found that (1) the tails of distributions of size and GDP both obey Pareto Law with the Pareto exponent 1; (2) compared with Pareto exponent in GDP, Pareto exponent in size is bigger. Then an agent model is built to study the underlying formation mechanism of distributions of region size and GDP. Our model presents the mechanism how economic factors flow between regions to reproduce the tail behavior and the difference between the Pareto exponents of size and those of GDP. At last, the simulated results agree with the real empirical well.

  7. HITS - The Navy's new DATPG system

    NASA Astrophysics Data System (ADS)

    Hosley, L.; Modi, M.

    A new digital automatic test program generation standard called HITS (Hierarchical Integrated Test Simulator), developed by the U.S. Navy as the answer to digital LSI/VLSI circuit technology is discussed. Three major areas of the HITS program which include system flow/unique capabilities, modeling language structures, and management of HITS are preseented. HITS contains the following major software modules: the primary model processor, the secondary model processor, the test language processor, the simulator, and the tester output generator. The functions performed by the individual system modules are described. A circuit description language, which provides user flexibility when describing complex circuit models, and its components are considered. The major areas of HITS management include: (1) HITS accessibility, distribution, and availability; (2) user support; (3) advanced development; and (4) Navy/DOD coordination and standardization.

  8. Developing Health Information Technology (HIT) Programs and HIT Curriculum: The Southern Polytechnic State University Experience

    ERIC Educational Resources Information Center

    Zhang, Chi; Reichgelt, Han; Rutherfoord, Rebecca H.; Wang, Andy Ju An

    2014-01-01

    Health Information Technology (HIT) professionals are in increasing demand as healthcare providers need help in the adoption and meaningful use of Electronic Health Record (EHR) systems while the HIT industry needs workforce skilled in HIT and EHR development. To respond to this increasing demand, the School of Computing and Software Engineering…

  9. Hitting Is Contagious: Experience and Action Induction

    ERIC Educational Resources Information Center

    Gray, Rob; Beilock, Sian L.

    2011-01-01

    In baseball, it is believed that "hitting is contagious," that is, probability of success increases if the previous few batters get a hit. Could this effect be partially explained by action induction--that is, the tendency to perform an action related to one that has just been observed? A simulation was used to investigate the effect of inducing…

  10. Recognition of Hits in a Target

    NASA Astrophysics Data System (ADS)

    Semerak, Vojtech; Drahansky, Martin

    This paper describes two possible ways of hit recognition in a target. First method is based on frame differencing with use of a stabilization algorithm to eliminate movements of a target. Second method uses flood fill with random seed point definition to find hits in the target scene.

  11. Computing Principal Eigenvectors of Large Web Graphs: Algorithms and Accelerations Related to PageRank and HITS

    ERIC Educational Resources Information Center

    Nagasinghe, Iranga

    2010-01-01

    This thesis investigates and develops a few acceleration techniques for the search engine algorithms used in PageRank and HITS computations. PageRank and HITS methods are two highly successful applications of modern Linear Algebra in computer science and engineering. They constitute the essential technologies accounted for the immense growth and…

  12. Rising Blood Sugar Hitting More Obese Adults

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159853.html Rising Blood Sugar Hitting More Obese Adults To curb diabetes, researchers ... HealthDay News) -- Among obese American adults, control of blood sugar is worsening, leading to more diabetes and heart ...

  13. Credit Recovery Hits the Mainstream

    ERIC Educational Resources Information Center

    Carr, Sarah

    2014-01-01

    In communities including New Orleans, Los Angeles, and Chicago, educators are creating alternative schools for struggling students that employ online credit-recovery programs as a core portion, or all, of their curriculum. The growth in online learning generally, including blended learning, has fueled the proliferation of computer-based credit…

  14. Health Care Expenditure and GDP in Oil Exporting Countries: Evidence from OPEC Data, 1995-2012

    PubMed Central

    Fazaeli, Ali Akbar; Ghaderi, Hossein; Salehi, Masoud; Fazaeli, Ali Reza

    2016-01-01

    Background: There is a large body of literature examining income in relation to health expenditures. The share of expenditures in health sector from GDP in developed countries is often larger than in non-developed countries, suggesting that as the level of economic growth increases, health spending increase, too. Objectives: This paper estimates long-run relationships between health expenditures and GDP based on panel data of a sample of 12 countries of the Organization of the Petroleum Exporting Countries (OPEC), using data for the period 1995-2012. Patients & Methods: We use panel data unit root tests, cointegration analysis and ECM model to find long-run and short-run relation. This study examines whether health is a luxury or a necessity for OPEC countries within a unit root and cointegration framework. Results: Panel data analysis indicates that health expenditures and GDP are co-integrated and have Engle and Granger causality. In addition, in oil countries that have oil export income, the share of government expenditures in the health sector is often greater than in private health expenditures similar developed countries. Conclusions: The findings verify that health care is not a luxury good and income has a robust relationship to health expenditures in OPEC countries. PMID:26383195

  15. A Reassessment of the Relationship between GDP and Life Satisfaction

    PubMed Central

    Proto, Eugenio; Rustichini, Aldo

    2013-01-01

    The scientific debate on the relation between Gross Domestic Product (GDP) and self reported indices of life satisfaction is still open. In a well-known finding, Easterlin reported no significant relationship between happiness and aggregate income in time-series analysis. However, life satisfaction appears to be strictly monotonically increasing with income when one studies this relation at a point in time across nations. Here, we analyze the relation between per capita GDP and life satisfaction without imposing a functional form and eliminating potentially confounding country-specific factors. We show that this relation clearly increases in country with a per capita GDP below 15,000 USD (2005 in Purchasing Power Parity), then it flattens for richer countries. The probability of reporting the highest level of life satisfaction is more than 12% lower in the poor countries with a per capita GDP below 5,600 USD than in the counties with a per capita GDP of about 15,000 USD. In countries with an income above 17,000 USD the probability of reporting the highest level of life satisfaction changes within a range of 2% maximum. Interestingly enough, life satisfaction seems to peak at around 30,000 USD and then slightly but significantly decline among the richest countries. These results suggest an explanation of the Easterlin paradox: life satisfaction increases with GDP in poor country, but this relation is approximately flat in richer countries. We explain this relation with aspiration levels. We assume that a gap between aspiration and realized income is negatively perceived; and aspirations to higher income increase with income. These facts together have a negative effect on life satisfaction, opposite to the positive direct effect of the income. The net effect is ambiguous. We predict a higher negative effect in individuals with higher sensitivity to losses (measured by their neuroticism score) and provide econometric support of this explanation. PMID:24312179

  16. A reassessment of the relationship between GDP and life satisfaction.

    PubMed

    Proto, Eugenio; Rustichini, Aldo

    2013-01-01

    The scientific debate on the relation between Gross Domestic Product (GDP) and self reported indices of life satisfaction is still open. In a well-known finding, Easterlin reported no significant relationship between happiness and aggregate income in time-series analysis. However, life satisfaction appears to be strictly monotonically increasing with income when one studies this relation at a point in time across nations. Here, we analyze the relation between per capita GDP and life satisfaction without imposing a functional form and eliminating potentially confounding country-specific factors. We show that this relation clearly increases in country with a per capita GDP below 15,000 USD (2005 in Purchasing Power Parity), then it flattens for richer countries. The probability of reporting the highest level of life satisfaction is more than 12% lower in the poor countries with a per capita GDP below 5,600 USD than in the counties with a per capita GDP of about 15,000 USD. In countries with an income above 17,000 USD the probability of reporting the highest level of life satisfaction changes within a range of 2% maximum. Interestingly enough, life satisfaction seems to peak at around 30,000 USD and then slightly but significantly decline among the richest countries. These results suggest an explanation of the Easterlin paradox: life satisfaction increases with GDP in poor country, but this relation is approximately flat in richer countries. We explain this relation with aspiration levels. We assume that a gap between aspiration and realized income is negatively perceived; and aspirations to higher income increase with income. These facts together have a negative effect on life satisfaction, opposite to the positive direct effect of the income. The net effect is ambiguous. We predict a higher negative effect in individuals with higher sensitivity to losses (measured by their neuroticism score) and provide econometric support of this explanation. PMID:24312179

  17. China's post-coal growth

    NASA Astrophysics Data System (ADS)

    Qi, Ye; Stern, Nicholas; Wu, Tong; Lu, Jiaqi; Green, Fergus

    2016-08-01

    Slowing GDP growth, a structural shift away from heavy industry, and more proactive policies on air pollution and clean energy have caused China's coal use to peak. It seems that economic growth has decoupled from growth in coal consumption.

  18. HIT: time to end behavioral health discrimination.

    PubMed

    Rosenberg, Linda

    2012-10-01

    While the Health Information Technology for Economic and Clinical Health Act, enacted as part of the American Recovery and Reinvestment Act of 2009, provided $20.6 billion for incentive payments to support the adoption and meaningful use of health information technology (HIT), behavioral health organizations were not eligible to receive facility payments. The consequences of excluding behavioral health from HIT incentive payments are found in the results of the "HIT Adoption and Meaningful Use Readiness in Community Behavioral Health" survey. The survey found that only 2% of community behavioral health organizations are able to meet federal meaningful use (MU) requirements-compare this to the 27% of Federally Qualified Health Centers and 20% of hospitals that already meet some level of MU requirements. Behavioral health organizations, serving more than eight million adults, children, and families with mental illnesses and addiction disorders, are ready and eager to adopt HIT to meet the goals of better healthcare, better health, and lower costs. But reaching these goals may prove impossible unless behavioral health achieves "parity" within healthcare and receives resources for the adoption of HIT. PMID:22956203

  19. Structures of NodZ α1,6-fucosyltransferase in complex with GDP and GDP-fucose

    SciTech Connect

    Brzezinski, Krzysztof; Dauter, Zbigniew; Jaskolski, Mariusz

    2012-02-01

    Crystal structures of the bacterial α1,6-fucosyltransferase NodZ in complex with GDP and GDP-fucose are presented. Rhizobial NodZ α1,6-fucosyltransferase (α1,6-FucT) catalyzes the transfer of the fucose (Fuc) moiety from guanosine 5′-diphosphate-β-l-fucose to the reducing end of the chitin oligosaccharide core during Nod-factor (NF) biosynthesis. NF is a key signalling molecule required for successful symbiosis with a legume host for atmospheric nitrogen fixation. To date, only two α1,6-FucT structures have been determined, both without any donor or acceptor molecule that could highlight the structural background of the catalytic mechanism. Here, the first crystal structures of α1,6-FucT in complex with its substrate GDP-Fuc and with GDP, which is a byproduct of the enzymatic reaction, are presented. The crystal of the complex with GDP-Fuc was obtained through soaking of native NodZ crystals with the ligand and its structure has been determined at 2.35 Å resolution. The fucose residue is exposed to solvent and is disordered. The enzyme–product complex crystal was obtained by cocrystallization with GDP and an acceptor molecule, penta-N-acetyl-l-glucosamine (penta-NAG). The structure has been determined at 1.98 Å resolution, showing that only the GDP molecule is present in the complex. In both structures the ligands are located in a cleft formed between the two domains of NodZ and extend towards the C-terminal domain, but their conformations differ significantly. The structures revealed that residues in three regions of the C-terminal domain, which are conserved among α1,2-, α1,6- and protein O-fucosyltransferases, are involved in interactions with the sugar-donor molecule. There is also an interaction with the side chain of Tyr45 in the N-terminal domain, which is very unusual for a GT-B-type glycosyltransferase. Only minor conformational changes of the protein backbone are observed upon ligand binding. The only exception is a movement of the loop

  20. Hitting is contagious: experience and action induction.

    PubMed

    Gray, Rob; Beilock, Sian L

    2011-03-01

    In baseball, it is believed that "hitting is contagious," that is, probability of success increases if the previous few batters get a hit. Could this effect be partially explained by action induction--that is, the tendency to perform an action related to one that has just been observed? A simulation was used to investigate the effect of inducing stimuli on batting performance for more-experienced (ME) and less-experienced (LE) baseball players. Three types of inducing stimuli were compared with a no-induction condition: action (a simulated ball traveling from home plate into left, right, or center field), outcome (a ball resting in either left, right, or center field), and verbal (the word "left", "center", or "right"). For both ME and LE players, fewer pitchers were required for a successful hit in the action condition. For ME players, there was a significant relationship between the inducing stimulus direction and hit direction for both the action and outcome prompts. For LE players, the prompt only had a significant effect on batting performance in the action condition, and the magnitude of the effect was significantly smaller than for ME. The effect of the inducing stimulus decreased as the delay (i.e., no. of pitches between prompt and hit) increased, with the effect being eliminated after roughly 4 pitches for ME and 2 pitches for LE. It is proposed that the differences in the magnitude and time course of action induction as a function of experience occurred because ME have more well-developed perceptual-motor representations for directional hitting. PMID:21443380

  1. Projections of health care expenditures as a share of the GDP: actuarial and macroeconomic approaches.

    PubMed

    Warshawsky, M J

    1994-08-01

    STUDY QUESTION. Can the steady increases in health care expenditures as a share of GDP projected by widely cited actuarial models be rationalized by a macroeconomic model with sensible parameters and specification? DATA SOURCES. National Income and Product Accounts, and Social Security and Health Care Financing Administration are the data sources used in parameters estimates. STUDY DESIGN. Health care expenditures as a share of gross domestic product (GDP) are projected using two methodological approaches--actuarial and macroeconomic--and under various assumptions. The general equilibrium macroeconomic approach has the advantage of allowing an investigation of the causes of growth in the health care sector and its consequences for the overall economy. DATA COLLECTION METHODS. Simulations are used. PRINCIPAL FINDINGS. Both models unanimously project a continued increase in the ratio of health care expenditures to GDP. Under the most conservative assumptions, that is, robust economic growth, improved demographic trends, or a significant moderation in the rate of health care price inflation, the health care sector will consume more than a quarter of national output by 2065. Under other (perhaps more realistic) assumptions, including a continuation of current trends, both approaches predict that health care expenditures will comprise between a third and a half of national output. In the macroeconomic model, the increasing use of capital goods in the health care sector explains the observed rise in relative prices. Moreover, this "capital deepening" implies that a relatively modest fraction of the labor force is employed in health care and that the rest of the economy is increasingly starved for capital, resulting in a declining standard of living. PMID:8063567

  2. Projections of health care expenditures as a share of the GDP: actuarial and macroeconomic approaches.

    PubMed Central

    Warshawsky, M J

    1994-01-01

    STUDY QUESTION. Can the steady increases in health care expenditures as a share of GDP projected by widely cited actuarial models be rationalized by a macroeconomic model with sensible parameters and specification? DATA SOURCES. National Income and Product Accounts, and Social Security and Health Care Financing Administration are the data sources used in parameters estimates. STUDY DESIGN. Health care expenditures as a share of gross domestic product (GDP) are projected using two methodological approaches--actuarial and macroeconomic--and under various assumptions. The general equilibrium macroeconomic approach has the advantage of allowing an investigation of the causes of growth in the health care sector and its consequences for the overall economy. DATA COLLECTION METHODS. Simulations are used. PRINCIPAL FINDINGS. Both models unanimously project a continued increase in the ratio of health care expenditures to GDP. Under the most conservative assumptions, that is, robust economic growth, improved demographic trends, or a significant moderation in the rate of health care price inflation, the health care sector will consume more than a quarter of national output by 2065. Under other (perhaps more realistic) assumptions, including a continuation of current trends, both approaches predict that health care expenditures will comprise between a third and a half of national output. In the macroeconomic model, the increasing use of capital goods in the health care sector explains the observed rise in relative prices. Moreover, this "capital deepening" implies that a relatively modest fraction of the labor force is employed in health care and that the rest of the economy is increasingly starved for capital, resulting in a declining standard of living. PMID:8063567

  3. Statistical properties and pre-hit dynamics of price limit hits in the Chinese stock markets.

    PubMed

    Wan, Yu-Lei; Xie, Wen-Jie; Gu, Gao-Feng; Jiang, Zhi-Qiang; Chen, Wei; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

    2015-01-01

    Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders' short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners. PMID:25874716

  4. Statistical Properties and Pre-Hit Dynamics of Price Limit Hits in the Chinese Stock Markets

    PubMed Central

    Wan, Yu-Lei; Xie, Wen-Jie; Gu, Gao-Feng; Jiang, Zhi-Qiang; Chen, Wei; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

    2015-01-01

    Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders’ short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners. PMID:25874716

  5. Improvements of HITS Algorithms for Spam Links

    NASA Astrophysics Data System (ADS)

    Asano, Yasuhito; Tezuka, Yu; Nishizeki, Takao

    The HITS algorithm proposed by Kleinberg is one of the representative methods of scoring Web pages by using hyperlinks. In the days when the algorithm was proposed, most of the pages given high score by the algorithm were really related to a given topic, and hence the algorithm could be used to find related pages. However, the algorithm and the variants including Bharat's improved HITS, abbreviated to BHITS, proposed by Bharat and Henzinger cannot be used to find related pages any more on today's Web, due to an increase of spam links. In this paper, we first propose three methods to find “linkfarms,” that is, sets of spam links forming a densely connected subgraph of a Web graph. We then present an algorithm, called a trust-score algorithm, to give high scores to pages which are not spam pages with a high probability. Combining the three methods and the trust-score algorithm with BHITS, we obtain several variants of the HITS algorithm. We ascertain by experiments that one of them, named TaN+BHITS using the trust-score algorithm and the method of finding linkfarms by employing name servers, is most suitable for finding related pages on today's Web. Our algorithms take time and memory no more than those required by the original HITS algorithm, and can be executed on a PC with a small amount of main memory.

  6. Precise timing when hitting falling balls

    PubMed Central

    Brenner, Eli; Driesen, Ben; Smeets, Jeroen B. J.

    2014-01-01

    People are extremely good at hitting falling balls with a baseball bat. Despite the ball's constant acceleration, they have been reported to time hits with a standard deviation of only about 7 ms. To examine how people achieve such precision, we compared performance when there were no added restrictions, with performance when looking with one eye, when vision was blurred, and when various parts of the ball's trajectory were hidden from view. We also examined how the size of the ball and varying the height from which it was dropped influenced temporal precision. Temporal precision did not become worse when vision was blurred, when the ball was smaller, or when balls falling from different heights were randomly interleaved. The disadvantage of closing one eye did not exceed expectations from removing one of two independent estimates. Precision was higher for slower balls, but only if the ball being slower meant that one saw it longer before the hit. It was particularly important to see the ball while swinging the bat. Together, these findings suggest that people time their hits so precisely by using the changing elevation throughout the swing to adjust the bat's movement to that of the ball. PMID:24904380

  7. Precise timing when hitting falling balls.

    PubMed

    Brenner, Eli; Driesen, Ben; Smeets, Jeroen B J

    2014-01-01

    People are extremely good at hitting falling balls with a baseball bat. Despite the ball's constant acceleration, they have been reported to time hits with a standard deviation of only about 7 ms. To examine how people achieve such precision, we compared performance when there were no added restrictions, with performance when looking with one eye, when vision was blurred, and when various parts of the ball's trajectory were hidden from view. We also examined how the size of the ball and varying the height from which it was dropped influenced temporal precision. Temporal precision did not become worse when vision was blurred, when the ball was smaller, or when balls falling from different heights were randomly interleaved. The disadvantage of closing one eye did not exceed expectations from removing one of two independent estimates. Precision was higher for slower balls, but only if the ball being slower meant that one saw it longer before the hit. It was particularly important to see the ball while swinging the bat. Together, these findings suggest that people time their hits so precisely by using the changing elevation throughout the swing to adjust the bat's movement to that of the ball. PMID:24904380

  8. Science hit by US government crisis

    NASA Astrophysics Data System (ADS)

    Gwynne, Peter

    2013-11-01

    A 16-day government shutdown last month hit the US physics community hard as research projects ranging from space missions to polar geophysics were closed down after Congress failed to vote on its budget for the financial year 2014, which started on 1 October.

  9. Activation of brown adipose tissue mitochondrial GDP binding sites

    SciTech Connect

    Swick, A.G.

    1987-01-01

    The primary function of brown adipose tissue (BAT) is heat production. This ability is attributed to the existence of a unique inner mitochondrial membrane protein termed the uncoupling protein or thermogenin. This protein is permeable to H+ and thus allows respiration (and therefore thermogenesis) to proceed at a rapid rate, independent of ADP phosphorylation. Proton conductance can be inhibited by the binding of purine nucleotides to the uncoupling protein. The binding of (/sup 3/H)-GDP to BAT mitochondria is frequently used as a measure of BAT thermogenic activity. Rats fed a diet that was low but adequate in protein exhibited a decrease in feed efficiency. In addition, BAT thermogenesis was activated as indicated by an elevation in the level of GDP binding to BAT mitochondria. This phenomena occurred in older rats and persisted over time.

  10. Structures of NodZ [alpha]1,6-fucosyltransferase in complex with GDP and GDP-fucose

    SciTech Connect

    Brzezinski, Krzysztof; Dauter, Zbigniew; Jaskolski, Mariusz

    2012-03-26

    Rhizobial NodZ {alpha}1,6-fucosyltransferase ({alpha}1,6-FucT) catalyzes the transfer of the fucose (Fuc) moiety from guanosine 5'-diphosphate-{beta}-L-fucose to the reducing end of the chitin oligosaccharide core during Nod-factor (NF) biosynthesis. NF is a key signaling molecule required for successful symbiosis with a legume host for atmospheric nitrogen fixation. To date, only two {alpha}1,6-FucT structures have been determined, both without any donor or acceptor molecule that could highlight the structural background of the catalytic mechanism. Here, the first crystal structures of {alpha}1,6-FucT in complex with its substrate GDP-Fuc and with GDP, which is a byproduct of the enzymatic reaction, are presented. The crystal of the complex with GDP-Fuc was obtained through soaking of native NodZ crystals with the ligand and its structure has been determined at 2.35 {angstrom} resolution. The fucose residue is exposed to solvent and is disordered. The enzyme-product complex crystal was obtained by cocrystallization with GDP and an acceptor molecule, penta-N-acetyl-L-glucosamine (penta-NAG). The structure has been determined at 1.98 {angstrom} resolution, showing that only the GDP molecule is present in the complex. In both structures the ligands are located in a cleft formed between the two domains of NodZ and extend towards the C-terminal domain, but their conformations differ significantly. The structures revealed that residues in three regions of the C-terminal domain, which are conserved among {alpha}1,2-, {alpha}1,6- and protein O-fucosyltransferases, are involved in interactions with the sugar-donor molecule. There is also an interaction with the side chain of Tyr45 in the N-terminal domain, which is very unusual for a GT-B-type glycosyltransferase. Only minor conformational changes of the protein backbone are observed upon ligand binding. The only exception is a movement of the loop located between strand {beta}C2 and helix {alpha}C3. In addition, there is

  11. Hitting and trapping times on branched structures

    NASA Astrophysics Data System (ADS)

    Agliari, Elena; Sartori, Fabio; Cattivelli, Luca; Cassi, Davide

    2015-05-01

    In this work we consider a simple random walk embedded in a generic branched structure and we find a close-form formula to calculate the hitting time H (i ,f ) between two arbitrary nodes i and j . We then use this formula to obtain the set of hitting times {H (i,f)} for combs and their expectation values, namely, the mean first-passage time, where the average is performed over the initial node while the final node f is given, and the global mean first-passage time, where the average is performed over both the initial and the final node. Finally, we discuss applications in the context of reaction-diffusion problems.

  12. Probability of Brownian motion hitting an obstacle

    SciTech Connect

    Knessl, C.; Keller, J.B.

    2000-02-01

    The probability p(x) that Brownian motion with drift, starting at x, hits an obstacle is analyzed. The obstacle {Omega} is a compact subset of R{sup n}. It is shown that p(x) is expressible in terms of the field U(x) scattered by {Omega} when it is hit by plane wave. Therefore results for U(x), and methods for finding U(x) can be used to determine p(x). The authors illustrate this by obtaining exact and asymptotic results for p(x) when {Omega} is a slit in R{sup 2}, and asymptotic results when {Omega} is a disc in R{sup 3}.

  13. Hitting and trapping times on branched structures.

    PubMed

    Agliari, Elena; Sartori, Fabio; Cattivelli, Luca; Cassi, Davide

    2015-05-01

    In this work we consider a simple random walk embedded in a generic branched structure and we find a close-form formula to calculate the hitting time H(i,f) between two arbitrary nodes i and j. We then use this formula to obtain the set of hitting times {H(i,f)} for combs and their expectation values, namely, the mean first-passage time, where the average is performed over the initial node while the final node f is given, and the global mean first-passage time, where the average is performed over both the initial and the final node. Finally, we discuss applications in the context of reaction-diffusion problems. PMID:26066144

  14. Visual factors in hitting and catching.

    PubMed

    Regan, D

    1997-12-01

    To hit or catch an approaching ball, it is necessary to move a bat or hand to the right place at the right time. The performance of top sports players is remarkable: positional errors of less than 5 cm and temporal errors of less than 2 or 3 ms are reliably maintained. There are three schools of thought about how this is achieved. One holds that predictive visual information about where the ball will be at some future instance (when) is used to achieve the hit or catch. The second holds that the bat or hand is moved to the correct position by exploiting some relation between visual information and the required movement. The third focuses on the use of prior knowledge to supplement inadequate visual information. For a rigid spherical ball travelling at constant speed along or close to the line of sight, the retinal images contain both binocular and monocular correlates of the ball's instantaneous direction of motion in depth. Also, the retinal images contain both binocular and monocular information about time of arrival. Humans can unconfound and use this visual information, but they are unable to estimate the absolute distance of the ball or its approach speed other than crudely. In cricket, this visual inadequacy allows a slow bowler to cause the batsman to misjudge where the ball will hit the ground. Such a bowler uses a three-pronged strategy: first, to deliver the ball in such a way as to prevent the batsman from obtaining the necessary visual information until it is too late to react; secondly, to force the batsman to rely entirely on inadequate retinal image information; thirdly, to allow the batsman to learn a particular relationship between the early part of the ball's flight and the point where the ball hits the ground, and then to change the relationship with such skill that the batsman does not detect the change. PMID:9486432

  15. Boolean computation of optimum hitting sets

    SciTech Connect

    Hulme, B.L.; Baca, L.S.; Shiver, A.W.; Worrell, R.B.

    1984-04-01

    This report presents the results of computational experience in solving weighted hitting set problems by Boolean algebraic methods. The feasible solutions are obtained by Boolean formula manipulations, and the optimum solutions are obtained by comparing the weight sums of the feasible solutions. Both the algebra and the optimization can be accomplished using the SETS language. One application is to physical protection problems. 8 references, 2 tables.

  16. Hitting a baseball: a biomechanical description.

    PubMed

    Welch, C M; Banks, S A; Cook, F F; Draovitch, P

    1995-11-01

    A tremendous amount of time and energy has been dedicated to the development of conditioning programs, mechanics drills, and rehabilitation protocols for the throwing athlete. In comparison, a significantly smaller amount has been spent on the needs of the hitting athlete. Before these needs can be addressed, an understanding of mechanics and the demands placed on the body during the swing must be developed. This study uses three-dimensional kinematic and kinetic data to define and quantify biomechanics during the baseball swing. The results show that a hitter starts the swing with a weight shift toward the rear foot and the generation of trunk coil. As the hitter strides forward, force applied by the front foot equal to 123% of body weight promotes segment acceleration around the axis of the trunk. The hip segment rotates to a maximum speed of 714 degrees/sec followed by a maximum shoulder segment velocity of 937 degrees/sec. The product of this kinetic link is a maximum linear bat velocity of 31 m/sec. By quantifying the hitting motion, a more educated approach can be made in developing rehabilitation, strength, and conditioning programs for the hitting athlete. PMID:8580946

  17. Paramecium bursaria Chlorella virus 1 encodes two enzymes involved in the biosynthesis of GDP-L-fucose and GDP-D-rhamnose.

    PubMed

    Tonetti, Michela; Zanardi, Davide; Gurnon, James R; Fruscione, Floriana; Armirotti, Andrea; Damonte, Gianluca; Sturla, Laura; De Flora, Antonio; Van Etten, James L

    2003-06-13

    At least three structural proteins in Paramecium bursaria Chlorella virus (PBCV-1) are glycosylated, including the major capsid protein Vp54. However, unlike other glycoprotein-containing viruses that use host-encoded enzymes in the endoplasmic reticulum-Golgi to glycosylate their proteins, PBCV-1 encodes at least many, if not all, of the glycosyltransferases used to glycosylate its structural proteins. As described here, PBCV-1 also encodes two open reading frames that resemble bacterial and mammalian enzymes involved in de novo GDP-L-fucose biosynthesis. This pathway, starting from GDP-D-mannose, consists of two sequential steps catalyzed by GDP-D-mannose 4,6 dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose epimerase/reductase, respectively. The two PBCV-1-encoded genes were expressed in Escherichia coli, and the recombinant proteins had the predicted enzyme activity. However, in addition to the dehydratase activity, PBCV-1 GMD also had a reductase activity, producing GDP-D-rhamnose. In vivo studies established that PBCV-1 GMD and GDP-4-keto-6-deoxy-D-mannose epimerase/reductase are expressed after virus infection and that both GDP-L-fucose and GDP-D-rhamnose are produced in virus-infected cells. Thus, PBCV-1 is the first virus known to encode enzymes involved in nucleotide sugar metabolism. Because fucose and rhamnose are components of the glycans attached to Vp54, the pathway could circumvent a limited supply of GDP sugars by the algal host. PMID:12679342

  18. Cryptococcus neoformans Dual GDP-Mannose Transporters and Their Role in Biology and Virulence

    PubMed Central

    Wang, Zhuo A.; Griffith, Cara L.; Skowyra, Michael L.; Salinas, Nichole; Williams, Matthew; Maier, Ezekiel J.; Gish, Stacey R.; Liu, Hong; Brent, Michael R.

    2014-01-01

    Cryptococcus neoformans is an opportunistic yeast responsible for lethal meningoencephalitis in humans. This pathogen elaborates a polysaccharide capsule, which is its major virulence factor. Mannose constitutes over one-half of the capsule mass and is also extensively utilized in cell wall synthesis and in glycosylation of proteins and lipids. The activated mannose donor for most biosynthetic reactions, GDP-mannose, is made in the cytosol, although it is primarily consumed in secretory organelles. This compartmentalization necessitates specific transmembrane transporters to make the donor available for glycan synthesis. We previously identified two cryptococcal GDP-mannose transporters, Gmt1 and Gmt2. Biochemical studies of each protein expressed in Saccharomyces cerevisiae showed that both are functional, with similar kinetics and substrate specificities in vitro. We have now examined these proteins in vivo and demonstrate that cells lacking Gmt1 show significant phenotypic differences from those lacking Gmt2 in terms of growth, colony morphology, protein glycosylation, and capsule phenotypes. Some of these observations may be explained by differential expression of the two genes, but others suggest that the two proteins play overlapping but nonidentical roles in cryptococcal biology. Furthermore, gmt1 gmt2 double mutant cells, which are unexpectedly viable, exhibit severe defects in capsule synthesis and protein glycosylation and are avirulent in mouse models of cryptococcosis. PMID:24747214

  19. Health Information Technology Knowledge and Skills Needed by HIT Employers

    PubMed Central

    Fenton, S.H.; Gongora-Ferraez, M.J.; Joost, E.

    2012-01-01

    Objective To evaluate the health information technology (HIT) workforce knowledge and skills needed by HIT employers. Methods Statewide face-to-face and online focus groups of identified HIT employer groups in Austin, Brownsville, College Station, Dallas, El Paso, Houston, Lubbock, San Antonio, and webinars for rural health and nursing informatics. Results HIT employers reported needing an HIT workforce with diverse knowledge and skills ranging from basic to advanced, while covering information technology, privacy and security, clinical practice, needs assessment, contract negotiation, and many other areas. Consistent themes were that employees needed to be able to learn on the job and must possess the ability to think critically and problem solve. Many employers wanted persons with technical skills, yet also the knowledge and understanding of healthcare operations. Conclusion The HIT employer focus groups provided valuable insight into employee skills needed in this fast-growing field. Additionally, this information will be utilized to develop a statewide HIT workforce needs assessment survey. PMID:23646090

  20. Democracy, GDP, and the Impact of Natural Disasters

    NASA Astrophysics Data System (ADS)

    van der Vink, G.; Brett, A. P.; Burgess, E.; Cecil-Cockwell, D.; Chicoine, A.; Difiore, P.; Harding, J.; Millian, C.; Olivi, E.; Piaskowy, S.; Sproat, J.; van der Hoop, H.; Walsh, P.; Warren, A.; West, L.; Wright, G.

    2007-05-01

    In 1998 Amartya Sen won the Nobel Prize in economics for the observation that there has never been a famine in a nation with a democratic form of government and a free press. We find that a similar relationship can be demonstrated for all natural disasters. Data from the United Nations Food Programme and the United States Office of Foreign Disaster Assistance is used to display strong correlations between the democracy index, GDP, and the humanitarian impact of natural disasters. We find that nations in which disasters have high humanitarian impact, approximated by lives lost, are also nations which are below the median per capita GDP and the median democracy level. While the response to natural disasters varies from country to country, several additional global trends are observed. Since 1964, the number of recorded natural disasters has increased by a factor of five. During this same time period the number of deaths has decreased significantly. In particular, the humanitarian impact of the 'typical' natural disaster has decreased by a factor of five. Post-disaster foreign aid is the common response from the international community when a natural disaster strikes. Our study also compares the history of foreign aid grants distributed by the US Office of Foreign Disaster Aid (OFDA) with the number of deaths worldwide from natural disasters. We find that the amount of aid given is responsive to the degree of global humanitarian impact.

  1. Exploring Patterns of Soil Organic Matter Decomposition with Students through the Global Decomposition Project (GDP) and the Interactive Model of Leaf Decomposition (IMOLD)

    NASA Astrophysics Data System (ADS)

    Steiner, S. M.; Wood, J. H.

    2015-12-01

    As decomposition rates are affected by climate change, understanding crucial soil interactions that affect plant growth and decomposition becomes a vital part of contributing to the students' knowledge base. The Global Decomposition Project (GDP) is designed to introduce and educate students about soil organic matter and decomposition through a standardized protocol for collecting, reporting, and sharing data. The Interactive Model of Leaf Decomposition (IMOLD) utilizes animations and modeling to learn about the carbon cycle, leaf anatomy, and the role of microbes in decomposition. Paired together, IMOLD teaches the background information and allows simulation of numerous scenarios, and the GDP is a data collection protocol that allows students to gather usable measurements of decomposition in the field. Our presentation will detail how the GDP protocol works, how to obtain or make the materials needed, and how results will be shared. We will also highlight learning objectives from the three animations of IMOLD, and demonstrate how students can experiment with different climates and litter types using the interactive model to explore a variety of decomposition scenarios. The GDP demonstrates how scientific methods can be extended to educate broader audiences, and data collected by students can provide new insight into global patterns of soil decomposition. Using IMOLD, students will gain a better understanding of carbon cycling in the context of litter decomposition, as well as learn to pose questions they can answer with an authentic computer model. Using the GDP protocols and IMOLD provide a pathway for scientists and educators to interact and reach meaningful education and research goals.

  2. Defect in cell wall integrity of the yeast saccharomyces cerevisiae caused by a mutation of the GDP-mannose pyrophosphorylase gene VIG9.

    PubMed

    Yoda, K; Kawada, T; Kaibara, C; Fujie, A; Abe, M; Hitoshi; Hashimoto; Shimizu, J; Tomishige, N; Noda, Y; Yamasaki, M

    2000-09-01

    The Saccharomyces cerevisiae VIG9 gene encodes GDP-mannose pyrophosphorylase, which synthesizes GDP-mannose from GTP and mannose-1-phosphate. Although the null mutant was lethal, the vig9 mutants so far obtained showed no growth defect but immature protein glycosylation and drug hypersensitivity. During our search for cell-wall mutants, we found a novel temperature-sensitive mutant, JS30, which required an osmotic stabilizer for viability. JS30 excreted cell surface proteins in the medium without any indication of cell lysis. Although conventional genetic analysis using mating was impossible, by detailed characterization of JS30 including an in vitro enzyme assay and nucleotide sequencing, we found the defect of JS30 was due to a mutation in the VIG9 gene. These results indicated a critical role of GDP-mannose in maintenance of cell-wall integrity. PMID:11055399

  3. Cutaneous presentation of Double Hit Lymphoma

    PubMed Central

    Khelfa, Yousef; Lebowicz, Yehuda

    2016-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), representing approximately 25% of diagnosed NHL. DLBCL is heterogeneous disease both clinically and genetically. The 3 most common chromosomal translocations in DLBCL involve the oncogenes BCL2, BCL6, and MYC. Double hit (DH) DLBCL is an aggressive form in which MYC rearrangement is associated with either BCL2 or BCL6 rearrangement. Patients typically present with a rapidly growing mass, often with B symptoms. Extranodal disease is often present. Though there is a paucity of prospective trials in this subtype, double hit lymphoma (DHL) has been linked to very poor outcomes when patients are treated with standard R-CHOP. There is, therefore, a lack of consensus regarding the standard treatment for DHL. Several retrospective analyses have been conducted to help guide treatment of this disease. These suggest that DA EPOCH-R may be the most promising regimen and that achievement of complete resolution predicts better long-term outcomes. PMID:27115017

  4. 77 FR 32639 - HIT Standards Committee and HIT Policy Committee; Call for Nominations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-01

    ... Committee was established under the American Recovery and Reinvestment ] Act 2009 (ARRA)(Pub. L. 111-5... participating in payment reform initiatives, accountable care organizations, pharmacists, behavioral health.... The HIT Policy Committee was established under the American Recovery and Reinvestment Act 2009...

  5. 77 FR 23250 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

    ... timeline, which may also account for NIST testing, where appropriate, and include dates when the HIT... timeline provided by the subcommittee, and, if necessary, revise it; and (2) Assign subcommittee(s) to... in a timely manner. (C) Advise the National Coordinator, consistent with the accepted timeline in...

  6. 76 FR 25355 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    ... gaps; and (3) A timeline, which may also account for NIST testing, where appropriate, and include dates...) Upon receipt of a subcommittee report, the HIT Standards Committee will: (1) Accept the timeline... timely manner. (C) Advise the National Coordinator, consistent with the accepted timeline in (B)(1)...

  7. HitKeeper, a generic software package for hit list management

    PubMed Central

    Hau, Jörg; Muller, Michael; Pagni, Marco

    2007-01-01

    Background The automated annotation of biological sequences (protein, DNA) relies on the computation of hits (predicted features) on the sequences using various algorithms. Public databases of biological sequences provide a wealth of biological "knowledge", for example manually validated annotations (features) that are located on the sequences, but mining the sequence annotations and especially the predicted and curated features requires dedicated tools. Due to the heterogeneity and diversity of the biological information, it is difficult to handle redundancy, frequent updates, taxonomic information and "private" data together with computational algorithms in a common workflow. Results We present HitKeeper, a software package that controls the fully automatic handling of multiple biological databases and of hit list calculations on a large scale. The software implements an asynchronous update system that introduces updates and computes hits as soon as new data become available. A query interface enables the user to search sequences by specifying constraints, such as retrieving sequences that contain specific motifs, or a defined arrangement of motifs ("metamotifs"), or filtering based on the taxonomic classification of a sequence. Conclusion The software provides a generic and modular framework to handle the redundancy and incremental updates of biological databases, and an original query language. It is published under the terms and conditions of version 2 of the GNU Public License and available at . PMID:17391514

  8. Formulation of the Multi-Hit Model With a Non-Poisson Distribution of Hits

    SciTech Connect

    Vassiliev, Oleg N.

    2012-07-15

    Purpose: We proposed a formulation of the multi-hit single-target model in which the Poisson distribution of hits was replaced by a combination of two distributions: one for the number of particles entering the target and one for the number of hits a particle entering the target produces. Such an approach reflects the fact that radiation damage is a result of two different random processes: particle emission by a radiation source and interaction of particles with matter inside the target. Methods and Materials: Poisson distribution is well justified for the first of the two processes. The second distribution depends on how a hit is defined. To test our approach, we assumed that the second distribution was also a Poisson distribution. The two distributions combined resulted in a non-Poisson distribution. We tested the proposed model by comparing it with previously reported data for DNA single- and double-strand breaks induced by protons and electrons, for survival of a range of cell lines, and variation of the initial slopes of survival curves with radiation quality for heavy-ion beams. Results: Analysis of cell survival equations for this new model showed that they had realistic properties overall, such as the initial and high-dose slopes of survival curves, the shoulder, and relative biological effectiveness (RBE) In most cases tested, a better fit of survival curves was achieved with the new model than with the linear-quadratic model. The results also suggested that the proposed approach may extend the multi-hit model beyond its traditional role in analysis of survival curves to predicting effects of radiation quality and analysis of DNA strand breaks. Conclusions: Our model, although conceptually simple, performed well in all tests. The model was able to consistently fit data for both cell survival and DNA single- and double-strand breaks. It correctly predicted the dependence of radiation effects on parameters of radiation quality.

  9. Macro determinants of cause-specific injury mortality in the OECD countries: an exploration of the importance of GDP and unemployment.

    PubMed

    Muazzam, Sana; Nasrullah, Muazzam

    2011-08-01

    Gross Domestic Product (GDP) and unemployment has a strong documented impact on injury mortality. The aim of our study is to investigate the relationship of GDP per capita and unemployment with gender- and cause-specific injury mortalities in the member nations of Organization for Economic Cooperation and Development (OECD). Country-based data on injury mortality per 100,000 population, including males and females aged 1-74, for the 4 year period 1996-1999, were gathered from the World Health Organization's Statistical Information System. We selected fourteen cause-specific injury mortalities. Data on GDP, unemployment rate and population growth were taken from World Development Indicators. GDP and unemployment rate per 100 separately were regressed on total and cause-specific injury mortality rate per 100,000 for males and females. Overall in the OECD countries, GDP per capita increased 12.5% during 1996-1999 (P = 0.03) where as unemployment rate decreased by 12.3% (P = 0.05). Among males, most cause-specific injury mortality rates decreased with increasing GDP except motor vehicle traffic crashes (MTC) that increased with increasing GDP (coefficient = 0.75; P < 0.001). Similar trend was found in females, except suicidal injury mortalities that also increased with increasing GDP (coefficient = 0.31; P = 0.04). When we modeled cause-specific injury mortality rates with unemployment, injuries due to firearm missiles (coefficient = 0.53; P < 0.001), homicide (coefficient = 0.36; P < 0.001), and other violence (coefficient = 0.41; P < 0.001) increased with increase in unemployment rate among males. However, among females only accidental falls (coefficient = 0.36; P = 0.01) were found significantly associated with increasing unemployment rate. GDP is more related to cause-specific injury mortality than unemployment. Injury mortality does not relate similarly to each diagnosis-specific cause among males and females. Further research on

  10. Changes in GDP binding to brown adipose tissue mitochondria and the uncoupling protein

    SciTech Connect

    Swick, A.G.; Swick, R.W. )

    1988-12-01

    Incubation in vitro of brown adipose tissue (BAT) mitochondria with divalent cations, spermine, or alkaline phosphatase led to a marked increase in the binding of ({sup 3}H)GDP. The effect of Mg{sup 2+} appeared to be the most specific and led to the largest increase in GDP binding. A simplified method was developed for measuring GDP binding to purified uncoupling protein from rat BAT mitochondria. Application of this method indicates that uncoupling protein from cold-acclimated rats binds twice as much GDP as uncoupling protein from cold-acclimated rats that were briefly returned to thermoneutrality, paralleling changes in GDP binding to the mitochondria. Incubation of BAT mitochondria with Mg{sup 2+} led to a smaller increase in GDP binding to the subsequently purified uncoupling protein, suggesting that divalent cations may somehow participate in the regulation of the activity of the uncoupling protein.

  11. Roughness Optimization at High Modes for GDP CHx Microshells

    SciTech Connect

    Theobald, M.; Dumay, B.; Chicanne, C.; Barnouin, J.; Legaie, O.; Baclet, P.

    2004-03-15

    For the ''Megajoule'' Laser (LMJ) facility of the CEA, amorphous hydrogenated carbon (a-C:H) is the nominal ablator to be used for inertial confinement fusion (ICF) experiments. These capsules contain the fusible deuterium-tritium mixture to achieve ignition. Coatings are prepared by glow discharge polymerization (GDP) with trans-2-butene and hydrogen. The films properties have been investigated. Laser fusion targets must have optimized characteristics: a diameter of about 2.4 mm for LMJ targets, a thickness up to 175 {mu}m, a sphericity and a thickness concentricity better than 99% and an outer and an inner roughness lower than 20 nm at high modes. The surface finish of these laser fusion targets must be extremely smooth to minimize hydrodynamic instabilities.Movchan and Demchishin, and later Thornton introduced a structure zone model (SZM) based on both evaporated and sputtered metals. They investigated the influence of base temperature and the sputtering gas pressure on structure and properties of thick polycrystalline coatings of nickel, titanium, tungsten, aluminum oxide. An original cross-sectional analysis by atomic force microscopy (AFM) allows amorphous materials characterization and permits to make an analogy between the amorphous GDP material and the existing model (SZM). The purpose of this work is to understand the relationship between the deposition parameters, the growing structures and the surface roughness.The coating structure as a function of deposition parameters was first studied on plane silicon substrates and then optimized on PAMS shells. By adjusting the coating parameters, the structures are modified, and in some case, the high modes roughness decreases dramatically.

  12. Characterization of the GDP-D-mannose biosynthesis pathway in Coxiella burnetii: the initial steps for GDP-β-D-virenose biosynthesis.

    PubMed

    Narasaki, Craig T; Mertens, Katja; Samuel, James E

    2011-01-01

    Coxiella burnetii, the etiologic agent of human Q fever, is a gram-negative and naturally obligate intracellular bacterium. The O-specific polysaccharide chain (O-PS) of the lipopolysaccharide (LPS) of C. burnetii is considered a heteropolymer of the two unusual sugars β-D-virenose and dihydrohydroxystreptose and mannose. We hypothesize that GDP-D-mannose is a metabolic intermediate to GDP-β-D-virenose. GDP-D-mannose is synthesized from fructose-6-phosphate in 3 successive reactions; Isomerization to mannose-6-phosphate catalyzed by a phosphomannose isomerase (PMI), followed by conversion to mannose-1-phosphate mediated by a phosphomannomutase (PMM) and addition of GDP by a GDP-mannose pyrophosphorylase (GMP). GDP-D-mannose is then likely converted to GDP-6-deoxy-D-lyxo-hex-4-ulopyranose (GDP-Sug), a virenose intermediate, by a GDP-mannose-4,6-dehydratase (GMD). To test the validity of this pathway in C. burnetii, three open reading frames (CBU0671, CBU0294 and CBU0689) annotated as bifunctional type II PMI, as PMM or GMD were functionally characterized by complementation of corresponding E. coli mutant strains and in enzymatic assays. CBU0671, failed to complement an Escherichia coli manA (PMM) mutant strain. However, complementation of an E. coli manC (GMP) mutant strain restored capsular polysaccharide biosynthesis. CBU0294 complemented a Pseudomonas aeruginosa algC (GMP) mutant strain and showed phosphoglucomutase activity (PGM) in a pgm E. coli mutant strain. Despite the inability to complement a manA mutant, recombinant C. burnetii PMI protein showed PMM enzymatic activity in biochemical assays. CBU0689 showed dehydratase activity and determined kinetic parameters were consistent with previously reported data from other organisms. These results show the biological function of three C. burnetii LPS biosynthesis enzymes required for the formation of GDP-D-mannose and GDP-Sug. A fundamental understanding of C. burnetii genes that encode PMI, PMM and GMP is

  13. Vanadium Nitrogenase: A Two-Hit Wonder?

    PubMed Central

    Hu, Yilin; Lee, Chi Chung; Ribbe, Markus W.

    2013-01-01

    Nitrogenase catalyzes the biological conversion of atmospheric dinitrogen to bioavailable ammonia. The molybdenum (Mo)- and vanadium (V)-dependent nitrogenases are two homologous members of this metalloenzyme family. However, despite their similarities in structure and function, the characterization of V-nitrogenase has taken a much longer and more winding path than that of its Mo-counterpart. From the initial discovery of this nitrogen-fixing system, to the recent finding of its CO-reducing capacity, V-nitrogenase has proven to be a two-hit wonder in the over-a-century-long research of nitrogen fixation. This perspective provides a brief account of the catalytic function and structural basis of V-nitrogenase, as well as a short discussion of the theoretical and practical potentials of this unique metalloenzyme. PMID:22101422

  14. Vanadium nitrogenase: a two-hit wonder?

    PubMed

    Hu, Yilin; Lee, Chi Chung; Ribbe, Markus W

    2012-01-28

    Nitrogenase catalyzes the biological conversion of atmospheric dinitrogen to bioavailable ammonia. The molybdenum (Mo)- and vanadium (V)-dependent nitrogenases are two homologous members of this metalloenzyme family. However, despite their similarities in structure and function, the characterization of V-nitrogenase has taken a much longer and more winding path than that of its Mo-counterpart. From the initial discovery of this nitrogen-fixing system, to the recent finding of its CO-reducing capacity, V-nitrogenase has proven to be a two-hit wonder in the over-a-century-long research of nitrogen fixation. This perspective provides a brief account of the catalytic function and structural basis of V-nitrogenase, as well as a short discussion of the theoretical and practical potentials of this unique metalloenzyme. PMID:22101422

  15. A Two-Hit Model of Autism: Adolescence as the Second Hit

    PubMed Central

    Picci, Giorgia; Scherf, K. Suzanne

    2015-01-01

    Adolescence brings dramatic changes in behavior and neural organization. Unfortunately, for some 30% of individuals with autism, there is marked decline in adaptive functioning during adolescence. We propose a two-hit model of autism. First, early perturbations in neural development function as a “first hit” that sets up a neural system that is “built to fail” in the face of a second hit. Second, the confluence of pubertal hormones, neural reorganization, and increasing social demands during adolescence provides the “second hit” that interferes with the ability to transition into adult social roles and levels of adaptive functioning. In support of this model, we review evidence about adolescent-specific neural and behavioral development in autism. We conclude with predictions and recommendations for empirical investigation about several domains in which developmental trajectories for individuals with autism may be uniquely deterred in adolescence. PMID:26609500

  16. External validation of the HIT Expert Probability (HEP) score.

    PubMed

    Joseph, Lee; Gomes, Marcelo P V; Al Solaiman, Firas; St John, Julie; Ozaki, Asuka; Raju, Manjunath; Dhariwal, Manoj; Kim, Esther S H

    2015-03-01

    The diagnosis of heparin-induced thrombocytopenia (HIT) can be challenging. The HIT Expert Probability (HEP) Score has recently been proposed to aid in the diagnosis of HIT. We sought to externally and prospectively validate the HEP score. We prospectively assessed pre-test probability of HIT for 51 consecutive patients referred to our Consultative Service for evaluation of possible HIT between August 1, 2012 and February 1, 2013. Two Vascular Medicine fellows independently applied the 4T and HEP scores for each patient. Two independent HIT expert adjudicators rendered a diagnosis of HIT likely or unlikely. The median (interquartile range) of 4T and HEP scores were 4.5 (3.0, 6.0) and 5 (3.0, 8.5), respectively. There were no significant differences between area under receiver-operating characteristic curves of 4T and HEP scores against the gold standard, confirmed HIT [defined as positive serotonin release assay and positive anti-PF4/heparin ELISA] (0.74 vs 0.73, p = 0.97). HEP score ≥ 2 was 100 % sensitive and 16 % specific for determining the presence of confirmed HIT while a 4T score > 3 was 93 % sensitive and 35 % specific. In conclusion, the HEP and 4T scores are excellent screening pre-test probability models for HIT, however, in this prospective validation study, test characteristics for the diagnosis of HIT based on confirmatory laboratory testing and expert opinion are similar. Given the complexity of the HEP scoring model compared to that of the 4T score, further validation of the HEP score is warranted prior to widespread clinical acceptance. PMID:25588983

  17. Improved Curveball Hitting through the Enhancement of Visual Cues.

    ERIC Educational Resources Information Center

    Osborne, Kurt; And Others

    1990-01-01

    The study investigated the effectiveness of using visual cues to highlight the seams of baseballs, to improve the hitting of curveballs by five undergraduate varsity baseball team candidates. Results indicated that subjects hit a greater percentage of marked than unmarked balls. (Author/DB)

  18. Infants' Reactions to Object Collision on Hit and Miss Trajectories

    ERIC Educational Resources Information Center

    Schmuckler, Mark A.; Collimore, Lisa M.; Dannemiller, James L.

    2007-01-01

    This experiment investigated the impact of the path of approach of an object, from head on versus from the side, and the type of imminent contact with that object, a hit versus a miss, on young infants' perceptions of object looming. Consistent with earlier studies, we found that 4- to 5-month-old infants do indeed discriminate hits versus misses.…

  19. Object Rotation Effects on the Timing of a Hitting Action

    ERIC Educational Resources Information Center

    Scott, Mark A.; van der Kamp, John; Savelsbergh, Geert J. P.; Oudejans, Raoul R. D.; Davids, Keith

    2004-01-01

    In this article, the authors investigated how perturbing optical information affects the guidance of an unfolding hitting action. Using monocular and binocular vision, six participants were required to hit a rectangular foam object, released from two different heights, under four different approach conditions, two with object rotation (to perturb…

  20. Optoelectronic hit/miss transform for screening cervical smear slides

    NASA Astrophysics Data System (ADS)

    Narayanswamy, R.; Turner, R. M.; McKnight, D. J.; Johnson, K. M.; Sharpe, J. P.

    1995-06-01

    An optoelectronic morphological processor for detecting regions of interest (abnormal cells) on a cervical smear slide using the hit/miss transform is presented. Computer simulation of the algorithm tested on 184 Pap-smear images provided 95% detection and 5% false alarm. An optoelectronic implementation of the hit/miss transform is presented, along with preliminary experimental results.

  1. Effects of maternal mortality on gross domestic product (GDP) in the WHO African region.

    PubMed

    Kirigia, Joses M; Oluwole, Doyin; Mwabu, Germano M; Gatwiri, Doris; Kainyu, Lenity H

    2006-01-01

    WHO African region has got the highest maternal mortality rate compared to the other five regions. Maternal mortality is hypothesized to have significantly negative effect on the gross domestic product (GDP). The objective of the current study was to estimate the loss in GDP attributable to maternal mortality in the WHO African Region. The burden of maternal mortality on GDP was estimated using a double-log econometric model. The analysis is based on cross-sectional data for 45 of the 46 Member States in the WHO African Region. Data were obtained from UNDP and the World Bank publications. All the explanatory variables included in the double-log model were found to have statistically significant effect on per capita gross domestic product (GDP) at 5 % level in a t-distribution test. The coefficients for land (D), capital (K), educational enrollment (EN) and exports (X) had a positive sign; while labor (L), imports (M) and maternal mortality rate (MMR) were found to impact negatively on GDP. Maternal mortality of a single person was found to reduce per capita GDP by US $ 0.36 per year. The study has demonstrated that maternal mortality has a statistically significant negative effect on GDP. Thus, as policy-makers strive to increase GDP through land reform programs, capital investments, export promotion and increase in educational enrollment, they should always remember that investment in maternal mortality-reducing interventions promises significant economic returns. PMID:17348747

  2. Antarctic ozone hole hits record depth

    SciTech Connect

    Not Available

    1991-10-18

    A bad year for the ozone over Antarctica looked like a good bet this year. For the past 2 years, stratospheric ozone destruction has equaled the record set in 1987. Now things look even worse, with a record-setting ozone hole. In 1987, 1989, and 1990, the minimum amount of ozone over Antarctica early each October was 120 to 125 Dobson units compared to the typical level of 220 that prevailed before manmade Chlorofluorocarbons (CFCs) began eating into the ozone layer. The depletion allowed as much as twice the usual amount of biologically damaging ultraviolet light to reach the earth's surface. But researchers took some comfort in the fact that the hole seemed to have hit a barrier to further losses. Now that barrier may have been breached. On 6 October, the satellite-borne Total Ozone Mapping Spectrometer detected an ozone minimum of 110 Dobson units. The region of the lower stratosphere where icy cloud particles and the chlorine of CFCs combine to destroy ozone - between 14 and 24 kilometers - looks much the same as it did in 1987.

  3. MECHANICAL PROPERTIES OF THIN GDP SHELLS USED AS CRYOGENIC DIRECT DRIVE TARGETS AT OMEGA

    SciTech Connect

    NIKROO,A; CZECHOWICZ,D; CHEN,K.C; DICKEN,M; MORRIS,C; ANDREWS,R; GREENWOOD,A.L; CASTILLO,E

    2003-06-01

    OAK-B135 Thin glow discharge polymer (GDP) shells are currently used as the targets for cryogenic direct drive laser fusion experiments. These shells need to be filled with nearly 1000 atm of D{sub 2} and cooled to cryogenic temperatures without failing due to buckling and bursting pressures they experience in this process. Therefore, the mechanical and permeation properties of these shells are of utmost importance in successful and rapid filling with D{sub 2}. In this paper, they present an overview of buckle and burst pressures of several different types of GDP shells. These include those made using traditional GDP deposition parameters (standard GDP) using a high deposition pressure and using modified parameters (strong GDP) of low deposition pressure that leads to more robust shells.

  4. 42 CFR 495.340 - As-needed HIT PAPD update and as-needed HIT IAPD update requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... update or a HIT IAPD no later than 60 days after the occurrence of project changes including but not... document or the HIT implementation advance planning document. (d) A change in implementation concept or a change to the scope of the project. (e) A change to the approved cost allocation methodology....

  5. Biochemical characterization of GDP-L-fucose de novo synthesis pathway in fungus Mortierella alpina

    SciTech Connect

    Ren, Yan; Perepelov, Andrei V.; Wang, Haiyan; Zhang, Hao; Knirel, Yuriy A.; Wang, Lei; Chen, Wei

    2010-01-22

    Mortierella alpina is a filamentous fungus commonly found in soil, which is able to produce large amount of polyunsaturated fatty acids. L-Fucose is an important sugar found in a diverse range of organisms, playing a variety of biological roles. In this study, we characterized the de novo biosynthetic pathway of GDP-L-fucose (the nucleotide-activated form of L-fucose) in M. alpina. Genes encoding GDP-D-mannose 4,6-dehydratase (GMD) and GDP-keto-6-deoxymannose 3,5-epimerase/4-reductase (GMER) were expressed heterologously in Escherichia coli. The recombinant enzymes were produced as His-tagged fusion proteins. Conversion of GDP-mannose to GDP-4-keto-6-deoxy mannose by GMD and GDP-4-keto-6-deoxy mannose to GDP-L-fucose by GMER were analyzed by capillary electrophoresis, electro-spray ionization-mass spectrometry, and nuclear magnetic resonance spectroscopy. The k{sub m} values of GMD for GDP-mannose and GMER for GDP-4-keto-6-deoxy mannose were determined to be 0.77 mM and 1.047 mM, respectively. Both NADH and NADPH may be used by GMER as the coenzyme. The optimum temperature and pH were determined to be 37 {sup o}C and pH 9.0 (GMD) or pH 7.0 (GMER). Divalent cations are not required for GMD and GMER activity, and the activities of both enzymes may be enhanced by DTT. To our knowledge this is the first report on the characterization of GDP-L-fucose biosynthetic pathway in fungi.

  6. Biosynthesis of GDP-fucose and other sugar nucleotides in the blood stages of Plasmodium falciparum.

    PubMed

    Sanz, Sílvia; Bandini, Giulia; Ospina, Diego; Bernabeu, Maria; Mariño, Karina; Fernández-Becerra, Carmen; Izquierdo, Luis

    2013-06-01

    Carbohydrate structures play important roles in many biological processes, including cell adhesion, cell-cell communication, and host-pathogen interactions. Sugar nucleotides are activated forms of sugars used by the cell as donors for most glycosylation reactions. Using a liquid chromatography-tandem mass spectrometry-based method, we identified and quantified the pools of UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine, GDP-mannose, and GDP-fucose in Plasmodium falciparum intraerythrocytic life stages. We assembled these data with the in silico functional reconstruction of the parasite metabolic pathways obtained from the P. falciparum annotated genome, exposing new active biosynthetic routes crucial for further glycosylation reactions. Fucose is a sugar present in glycoconjugates often associated with recognition and adhesion events. Thus, the GDP-fucose precursor is essential in a wide variety of organisms. P. falciparum presents homologues of GDP-mannose 4,6-dehydratase and GDP-L-fucose synthase enzymes that are active in vitro, indicating that most GDP-fucose is formed by a de novo pathway that involves the bioconversion of GDP-mannose. Homologues for enzymes involved in a fucose salvage pathway are apparently absent in the P. falciparum genome. This is in agreement with in vivo metabolic labeling experiments showing that fucose is not significantly incorporated by the parasite. Fluorescence microscopy of epitope-tagged versions of P. falciparum GDP-mannose 4,6-dehydratase and GDP-L-fucose synthase expressed in transgenic 3D7 parasites shows that these enzymes localize in the cytoplasm of P. falciparum during the intraerythrocytic developmental cycle. Although the function of fucose in the parasite is not known, the presence of GDP-fucose suggests that the metabolite may be used for further fucosylation reactions. PMID:23615908

  7. Biosynthesis of GDP-fucose and Other Sugar Nucleotides in the Blood Stages of Plasmodium falciparum*

    PubMed Central

    Sanz, Sílvia; Bandini, Giulia; Ospina, Diego; Bernabeu, Maria; Mariño, Karina; Fernández-Becerra, Carmen; Izquierdo, Luis

    2013-01-01

    Carbohydrate structures play important roles in many biological processes, including cell adhesion, cell-cell communication, and host-pathogen interactions. Sugar nucleotides are activated forms of sugars used by the cell as donors for most glycosylation reactions. Using a liquid chromatography-tandem mass spectrometry-based method, we identified and quantified the pools of UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine, GDP-mannose, and GDP-fucose in Plasmodium falciparum intraerythrocytic life stages. We assembled these data with the in silico functional reconstruction of the parasite metabolic pathways obtained from the P. falciparum annotated genome, exposing new active biosynthetic routes crucial for further glycosylation reactions. Fucose is a sugar present in glycoconjugates often associated with recognition and adhesion events. Thus, the GDP-fucose precursor is essential in a wide variety of organisms. P. falciparum presents homologues of GDP-mannose 4,6-dehydratase and GDP-l-fucose synthase enzymes that are active in vitro, indicating that most GDP-fucose is formed by a de novo pathway that involves the bioconversion of GDP-mannose. Homologues for enzymes involved in a fucose salvage pathway are apparently absent in the P. falciparum genome. This is in agreement with in vivo metabolic labeling experiments showing that fucose is not significantly incorporated by the parasite. Fluorescence microscopy of epitope-tagged versions of P. falciparum GDP-mannose 4,6-dehydratase and GDP-l-fucose synthase expressed in transgenic 3D7 parasites shows that these enzymes localize in the cytoplasm of P. falciparum during the intraerythrocytic developmental cycle. Although the function of fucose in the parasite is not known, the presence of GDP-fucose suggests that the metabolite may be used for further fucosylation reactions. PMID:23615908

  8. Cloning and expression of murine enzymes involved in the salvage pathway of GDP-L-fucose.

    PubMed

    Niittymäki, Jaana; Mattila, Pirkko; Roos, Christophe; Huopaniemi, Laura; Sjöblom, Solveig; Renkonen, Risto

    2004-01-01

    In the salvage pathway of GDP-L-fucose, free cytosolic fucose is phosphorylated by L-fucokinase to form L-fucose-L-phosphate, which is then further converted to GDP-L-fucose in the reaction catalyzed by GDP-L-fucose pyrophosphorylase. We report here the cloning and expression of murine L-fucokinase and GDP-L-fucose pyrophosphorylase. Murine L-fucokinase is expressed as two transcripts of 3057 and 3270 base pairs, encoding proteins of 1019 and 1090 amino acids with predicted molecular masses of 111 kDa and 120 kDa respectively. Only the longer splice variant of L-fucokinase was enzymatically active when expressed in COS-7 cells. Murine GDP-L-fucose pyrophosphorylase has an open reading frame of 1773 base pairs encoding a protein of 591 amino acids with a predicted molecular mass of 65.5 kDa. GDP-L-fucose, the reaction product of GDP-L-pyrophosphorylase, was identified by HPLC and MALDI-TOF MS analysis. The tissue distribution of murine L-fucokinase and GDP-L-fucose pyrophosphorylase was investigated by quantitative real time PCR, which revealed high expression of L-fucokinase and GDP-L-fucose pyrophosphorylase in various tissues. The wide expression of both enzymes can also be observed from the large amount of data collected from a number of expressed sequence tag libraries, which indicate that not only the de novo pathway alone, but also the salvage pathway, could have a significant role in the synthesis of GDP-L-fucose in the cytosol. PMID:14686921

  9. Ozone loss hits us where we live

    SciTech Connect

    Appenzeller, T.

    1991-11-01

    The news about Earth's ozone layer just keeps getting worse. Three weeks ago, NASA researchers reported that the ozone hole over the Antarctic hit a record depth this year. Now comes the United Nations Environment Program, together with the World Meteorological Organization, with an even more distressing assessment of the state of the ozone layer. For the first time, the 80-member UN panel said, measurements show the ozone shield is eroding over temperate latitudes in summer, exposing crops and people to a larger dose of ultraviolet light just when they are most vulnerable. For a small group of atmospheric modelers, though, the bad news is bittersweet. Four months ago researchers predicted summertime ozone losses of just the magnitude the UN panel has now reported: about 3% over the past decade for northern temperate latitudes. Ozone modelers are encouraged by the agreement, particularly because other models are now yielding the same result. The modeling effort was spurred by earlier measurements showing a serious erosion of ozone at midlatitudes, mainly in winter. In 1988, an analysis of data collected from the ground showed that ozone levels at the latitude of the US were dropping by about 1% to 3% per decade; last April, an analysis of measurements from the satellite-borne Total Ozone Mapping Spectrometer boosted that figure to between 4% and 5%. Those findings raised the question: What mechanisms could be driving the midlatitude losses The fact that the losses seemed to be concentrated in winter suggested one possibility. The winter ozone losses at the poles are driven by chemical reactions taking place on the surface of ice crystals in polar stratospheric clouds. Such clouds don't form at temperate latitudes. But some researchers suggested that masses of air already depleted in ozone or enriched in reactive chlorine by the chemistry in the polar clouds might be escaping to temperate latitudes during the winter.

  10. Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum

    PubMed Central

    2014-01-01

    Background In view of the need to continuously feed the pipeline with new anti-malarial agents adapted to differentiated and more stringent target product profiles (e.g., new modes of action, transmission-blocking activity or long-duration chemo-protection), a chemical library consisting of more than 250,000 compounds has been evaluated in a blood-stage Plasmodium falciparum growth inhibition assay and further assessed for chemical diversity and novelty. Methods The selection cascade used for the triaging of hits from the chemical library started with a robust three-step in vitro assay followed by an in silico analysis of the resulting confirmed hits. Upon reaching the predefined requirements for selectivity and potency, the set of hits was subjected to computational analysis to assess chemical properties and diversity. Furthermore, known marketed anti-malarial drugs were co-clustered acting as ‘signposts’ in the chemical space defined by the hits. Then, in cerebro evaluation of the chemical structures was performed to identify scaffolds that currently are or have been the focus of anti-malarial medicinal chemistry programmes. Next, prioritization according to relaxed physicochemical parameters took place, along with the search for structural analogues. Ultimately, synthesis of novel chemotypes with desired properties was performed and the resulting compounds were subsequently retested in a P. falciparum growth inhibition assay. Results This screening campaign led to a 1.25% primary hit rate, which decreased to 0.77% upon confirmatory repeat screening. With the predefined potency (EC50 < 1 μM) and selectivity (SI > 10) criteria, 178 compounds progressed to the next steps where chemical diversity, physicochemical properties and novelty assessment were taken into account. This resulted in the selection of 15 distinct chemical series. Conclusion A selection cascade was applied to prioritize hits resulting from the screening of a medium-sized chemical

  11. Rapid changes in number of GDP binding sites on brown adipose tissue mitochondria

    SciTech Connect

    Swick, A.G.; Swick, R.W.

    1986-08-01

    (TH)GDP binding to brown adipose tissue (BAT) mitochondria increased more than twofold in 20 min when rats were moved from 27 to 4C. When animals housed at 4C for 2 h were returned to 27C, GDP binding decreased sharply in 20 min and returned to control levels in 2 h. These results are consistent with a rapid unmasking and remasking of GDP bindings sites. GDP binding to mitochondria from warm and acutely cold treated rats was not modified by prior swelling, by freeze-thawing, nor by sonication of the mitochondria before assay. GDP-inhibitable proton conductance, as measured by passive swelling, was unaffected by this brief exposure to cold but more than doubled in rats kept at 4C for 10 days. The authors hypothesize that the rate of GDP-inhibitable swelling may be a reflection of uncoupling protein concentration in the BAT mitochondria, whereas physiological thermogenic activity is more appropriately indicated by GDP binding. The alterations in binding activity appear not to be due to changes in the mitochondrial membrane integrity.

  12. Mothers with Serious Mental Illness: Their Experience of “Hitting Bottom”

    PubMed Central

    Montgomery, Phyllis; Mossey, Sharolyn; Bailey, Patricia; Forchuk, Cheryl

    2011-01-01

    This study sought to understand the experience of “hitting bottom” from the perspective of 32 mothers with serious mental illness. Secondary narrative analysis of 173 stories about experiences related to hitting bottom were identified. Enactment of their perceived mothering roles and responsibilities was compromised when confronted by the worst of illness. Subsequent to women's descent to bottom was their need for a timely and safe exit from bottom. An intense experience in bottom further jeopardized their parenting and treatment self-determination and, for some, their potential for survival. The results suggest that prevention of bottom is feasible with early assessment of the diverse issues contributing to mothers' vulnerabilities. Interventions to lessen their pain may circumvent bottom experiences. Healing necessitates purposeful approaches to minimize the private and public trauma of bottom experiences, nurture growth towards a future, and establish resources to actualize such a life. PMID:22007325

  13. Does Human Capital Contribute to Economic Growth in Mauritius?

    ERIC Educational Resources Information Center

    Neeliah, Harris; Seetanah, Boopen

    2016-01-01

    Purpose: Real gross domestic product (GDP) growth for Mauritius has averaged more than 5 per cent since 1970 and GDP per capita has increased more than tenfold between 1970 and 2012, from less than $500 to more than $9,000. It has often been reported that human capital, along with other growth enablers, has played an important role in this…

  14. Identification and characterization of GDP-d-mannose 4,6-dehydratase and GDP-l-fucose snthetase in a GDP-l-fucose biosynthetic gene cluster from Helicobacter pylori.

    PubMed

    Wu, B; Zhang, Y; Wang, P G

    2001-07-13

    In this study two open reading frames, namely HP0044 and HP0045 from H. pylori, were cloned and overexpressed in E. coli. The two recombinant proteins were demonstrated to have GDP-d-mannose 4,6-dehydratase (GMD) and GDP-l-fucose synthetase (GFS) activities, respectively. The recombinant GMD was a tetramer and had an optimum pH of 6.5. Exogenous NADP(+) was essential for its activity. The K(m) and K(cat) for GDP-d-mannose were 117.3 microM and 0.27 s(-1), respectively. The recombinant GFS was a homodimer with an optimum pH of 8.0. The K(m) and K(cat) for GDP-4-keto-6-deoxy-d-mannose were 64.08 microM and 0.75 s(-1), respectively. It can use both NADPH and NADH, but less efficient with the latter. Amino acid sequence alignment and phylogenetic analysis showed that H. pylori GFS was highly homologous to the GFS of E. coli O111 and both of them were located on a separate phylogenetic branch from other GFS. The unique clustering and origin of the two genes were also discussed. PMID:11444851

  15. Even Mild Football Head Hits Can Harm Vision

    MedlinePlus

    ... www.nlm.nih.gov/medlineplus/news/fullstory_158807.html Even Mild Football Head Hits Can Harm Vision Study of college players raises concerns about repetitive non-concussive impacts To use the sharing features on ...

  16. Concussion Study Shows Player-To-Player Hits Most Damaging

    MedlinePlus

    ... Study Shows Player-to-Player Hits Most Damaging Running longer before the contact happens also spells more ... the University of Georgia. "We also found that running a long distance before colliding with an opponent ...

  17. People with learning disabilities are hit hard by funding cutbacks.

    PubMed

    Hughes, Charlie

    Thank you for publishing Ken Mack's letter (March 5) drawing attention to the suffering and distress caused by welfare reforms and cutbacks, and how people with disabilities and their families are being hit particularly hard. PMID:24617400

  18. Even Mild Football Head Hits Can Harm Vision

    MedlinePlus

    ... html Even Mild Football Head Hits Can Harm Vision Study of college players raises concerns about repetitive ... Repeated blows to the head can cause near vision to blur slightly, even if the individual impacts ...

  19. The Chelyabinsk Meteorite Hits an Anomalous Zone in the Urals

    NASA Astrophysics Data System (ADS)

    Kochemasov, G. G.

    2013-09-01

    The Chelyabinsk meteorite is "strange" because it hits an area in the Urals where anomalous events are observed: shining skies, light balls, UFOs, electrphonic bolids. The area tectonically occurs at the intersection of two fold belts: Urals and Timan.

  20. Combined hit theory-microdosimetric explanation of cellular radiobiological action

    SciTech Connect

    Bond, V.P.; Varma, M.N.

    1983-01-01

    Hit theory is combined with microdosimetry in a stochastic approach that explains the observed responses of cell populations exposed in radiation fields of different qualities. The central thesis is that to expose a population of cells in a low-level radiation field is to subject the cells to the potential for interaction with charged particles in the vicinity of the cells, quantifiable in terms of the charged particle fluence theta. When such an interaction occurs there is a resulting stochastic transfer of energy to a critical volume (CV) of cross section sigma, within the cell(s). The severity of cell injury is dependent on the amount of energy thus imparted, or the hit size. If the severity is above some minimal level, there is a non-zero probability that the injury will result in a quantal effect (e.g., a mutational or carcinogenic initial event, cell transformation). A microdosimetric proportional counter, viewed here as a phantom cell CV that permits measurements not possible in the living cell, is used to determine the incidence of hit cells and the spectrum of hit sizes. Each hit is then weighted on the basis of an empirically-determined function that provides the fraction of cells responding quantally, as a function of hit size. The sum of the hits so weighted provides the incidence of quantally-responding cells, for any amount of exposure theta in a radiation field of any quality or mixture qualities. The hit size weighting function for pink mutations in Tradescantia is discussed, as are its implications in terms of a replacement for RBE and dose equivalent. 14 references, 9 figures.

  1. Do pigeons prefer alternatives that include near-hit outcomes?

    PubMed

    Stagner, Jessica P; Case, Jacob P; Sticklen, Mary F; Duncan, Amanda K; Zentall, Thomas R

    2015-07-01

    Pigeons show suboptimal choice on a gambling-like task similar to that shown by humans. Humans also show a preference for gambles in which there are near hits (losses that come close to winning). In the present research, we asked if pigeons would show a preference for alternatives with near-hit-like trials. In Experiment 1, we included an alternative that presented a near hit, in which a stimulus associated with reinforcement (a presumed conditioned reinforcer) changed to a stimulus associated with the absence of reinforcement (a presumed conditioned inhibitor). The pigeons tended to avoid this alternative. In Experiment 2, we varied the duration of the presumed conditioned reinforcer (2 vs. 8 s) that changed to a presumed conditioned inhibitor (8 vs. 2 s) and found that the longer the conditioned reinforcer was presented, the more the pigeons avoided it. In Experiment 3, the near-hit alternative involved an ambiguous stimulus for 8 s that changed to a presumed conditioned reinforcer (or a presumed conditioned inhibitor) for 2 s, but the pigeons still avoided it. In Experiment 4, we controlled for the duration of the conditioned reinforcer by presenting it first for 2 s followed by the ambiguous stimulus for 8 s. Once again, the pigeons avoided the alternative with the near-hit trials. In all 4 experiments, the pigeons tended to avoid alternatives that provided near-hit-like trials. We concluded that humans may be attracted to near-hit trials because near-hit trials give them the illusion of control, whereas this does not appear to be a factor for pigeons. PMID:26167775

  2. Superfast Cosmic Jet "Hits the Wall"

    NASA Astrophysics Data System (ADS)

    1999-01-01

    -288. The jet travelled quickly until its advance suddenly was stopped and the endpoint of the jet became brighter than the core. "This fast-moving material obviously hit something," Hjellming said. What did it it hit? "Probably a mixture of external material plus material from a previous jet ejection." Further studies of the collision could yield new information about the physics of cosmic jets. Such jets are believed to be powered by black holes into which material is being drawn. The exact mechanism by which the black hole's gravitational energy accelerates particles to nearly the speed of light is not well understood. There is even dispute about the types of particles ejected. Competing models call for either a mixture of electrons and protons or a mixture of electrons and positrons. Because protons are more than 1,800 times more massive than electrons or positrons (the positively-charged antiparticle of the electron), the electron-proton mixture would be much more massive than the electron-positron pair. Thus, an electron-proton jet is called a heavy jet and an electron-positron jet is called a light jet. A light jet would be much more easily slowed or stopped by tenuous interstellar material than a heavy jet, so the collision of XTE J1748-288's jet may indicate that it is a light jet. "There's still a lot more work to do before anyone can conclude that, but the collision offers the possibility of answering the light-heavy jet question," Hjellming said. A 1998 VLA study by John Wardle of Brandeis University and his colleagues indicated that the jet of a distant quasar is a light, electron-positron jet. Though the black holes in quasars are supermassive, usually millions of times more massive than the Sun, the physics of jet production in them is thought to be similar to the physics of jet production by smaller black holes, only a few times more massive than the sun, such as the one possibly in XTE J1748-288. The VLA is an instrument of the National Radio Astronomy

  3. Modeling the effects of health on economic growth.

    PubMed

    Bhargava, A; Jamison, D T; Lau, L J; Murray, C J

    2001-05-01

    This paper investigates the effects of health indicators such as adult survival rates (ASR) on GDP growth rates at 5-year intervals in several countries. Panel data were analyzed on GDP series based on purchasing power adjustments and on exchange rates. First, we developed a framework for modeling the inter-relationships between GDP growth rates and explanatory variables by re-examining the life expectancy-income relationship. Second, models for growth rates were estimated taking into account the interaction between ASR and lagged GDP level; issues of endogeneity and reverse causality were addressed. Lastly, we computed confidence intervals for the effect of ASR on growth rate and applied a test for parameter stability. The results showed positive effects of ASR on GDP growth rates in low-income countries. PMID:11373839

  4. Thomson Scattering Measurements on HIT-SI3

    NASA Astrophysics Data System (ADS)

    Everson, C. J.; Morgan, K. D.; Jarboe, T. R.

    2015-11-01

    A multi-point Thomson Scattering diagnostic has been implemented on HIT-SI3 (Helicity Injected Torus - Steady Inductive 3) to measure electron temperature. The HIT-SI3 experiment is a modification of the original HIT-SI apparatus that uses three injectors instead of two. This modification alters the configuration of magnetic fields and thus the plasma behavior in the device. The scientific aim of HIT-SI3 is to develop a deeper understanding of how injector behavior and interactions influence current drive and plasma performance in the spheromak. The Thomson Scattering system includes a 20 J (1 GW pulse) Ruby laser that provides the incident beam, and collection optics that are installed such that measurements can be taken at four spatial locations in HIT-SI3 plasmas. For each measurement point, a 3-channel polychromator is used to detect the relative level of scattering. These measurements allow for the presence of temperature gradients in the spheromak to be investigated. Preliminary HIT-SI3 temperature data are presented and can be compared to predictions from computational models. Work supported by the D.O.E.

  5. 42 CFR 495.344 - Approval of the State Medicaid HIT plan, the HIT PAPD and update, the HIT IAPD and update, and...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) STANDARDS AND CERTIFICATION STANDARDS FOR THE ELECTRONIC HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM... include all of the information required under this subpart. ... 42 Public Health 5 2010-10-01 2010-10-01 false Approval of the State Medicaid HIT plan, the...

  6. Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models.

    PubMed

    Baeder, Desiree Y; Yu, Guozhi; Hozé, Nathanaël; Rolff, Jens; Regoes, Roland R

    2016-05-26

    Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'. PMID:27160596

  7. Crystal structure of a tetrameric GDP-D-mannose 4,6-dehydratase from a bacterial GDP-D-rhamnose biosynthetic pathway

    SciTech Connect

    Webb, N.A.; Mulichak, A.M.; Lam, J.S.; Rocchetta, H.L.; Garavito, R.M.

    2010-03-08

    D-Rhamnose is a rare 6-deoxy monosaccharide primarily found in the lipopolysaccharide of pathogenic bacteria, where it is involved in host-bacterium interactions and the establishment of infection. The biosynthesis of D-rhamnose proceeds through the conversion of GDP-D-mannose by GDP-D-mannose 4,6-dehydratase (GMD) to GDP-4-keto-6-deoxymannose, which is subsequently reduced to GDP-D-rhamnose by a reductase. We have determined the crystal structure of GMD from Pseudomonas aeruginosa in complex with NADPH and GDP. GMD belongs to the NDP-sugar modifying subfamily of the short-chain dehydrogenase/reductase (SDR) enzymes, all of which exhibit bidomain structures and a conserved catalytic triad (Tyr-XXX-Lys and Ser/Thr). Although most members of this enzyme subfamily display homodimeric structures, this bacterial GMD forms a tetramer in the same fashion as the plant MUR1 from Arabidopsis thaliana. The cofactor binding sites are adjoined across the tetramer interface, which brings the adenosyl phosphate moieties of the adjacent NADPH molecules to within 7 {angstrom} of each other. A short peptide segment (Arg35-Arg43) stretches into the neighboring monomer, making not only protein-protein interactions but also hydrogen bonding interactions with the neighboring cofactor. The interface hydrogen bonds made by the Arg35-Arg43 segment are generally conserved in GMD and MUR1, and the interacting residues are highly conserved among the sequences of bacterial and eukaryotic GMDs. Outside of the Arg35-Arg43 segment, residues involved in tetrameric contacts are also quite conserved across different species. These observations suggest that a tetramer is the preferred, and perhaps functionally relevant, oligomeric state for most bacterial and eukaryotic GMDs.

  8. Different Effects of Guanine Nucleotides (GDP and GTP) on Protein-Mediated Mitochondrial Proton Leak

    PubMed Central

    Woyda-Ploszczyca, Andrzej M.; Jarmuszkiewicz, Wieslawa

    2014-01-01

    In this study, we compared the influence of GDP and GTP on isolated mitochondria respiring under conditions favoring oxidative phosphorylation (OXPHOS) and under conditions excluding this process, i.e., in the presence of carboxyatractyloside, an adenine nucleotide translocase inhibitor, and/or oligomycin, an FOF1-ATP synthase inhibitor. Using mitochondria isolated from rat kidney and human endothelial cells, we found that the action of GDP and GTP can differ diametrically depending on the conditions. Namely, under conditions favoring OXPHOS, both in the absence and presence of linoleic acid, an activator of uncoupling proteins (UCPs), the addition of 1 mM GDP resulted in the state 4 (non-phosphorylating respiration)-state 3 (phosphorylating respiration) transition, which is characteristic of ADP oxidative phosphorylation. In contrast, the addition of 1 mM GTP resulted in a decrease in the respiratory rate and an increase in the membrane potential, which is characteristic of UCP inhibition. The stimulatory effect of GDP, but not GTP, was also observed in inside-out submitochondrial particles prepared from rat kidney mitochondria. However, the effects of GDP and GTP were more similar in the presence of OXPHOS inhibitors. The importance of these observations in connection with the action of UCPs, adenine nucleotide translocase (or other carboxyatractyloside-sensitive carriers), carboxyatractyloside- and purine nucleotide-insensitive carriers, as well as nucleoside-diphosphate kinase (NDPK) are considered. Because the measurements favoring oxidative phosphorylation better reflect in vivo conditions, our study strongly supports the idea that GDP cannot be considered a significant physiological inhibitor of UCP. Moreover, it appears that, under native conditions, GTP functions as a more efficient UCP inhibitor than GDP and ATP. PMID:24904988

  9. Improved curveball hitting through the enhancement of visual cues.

    PubMed

    Osborne, K; Rudrud, E; Zezoney, F

    1990-01-01

    This study investigated the effectiveness of using visual cues to highlight the seams of baseballs to improve the hitting of curveballs. Five undergraduate varsity baseball team candidates served as subjects. Behavior change was assessed through an alternating treatments design involving unmarked balls and two treatment conditions that included baseballs with 1/4-in. and 1/8-in. orange stripes marking the seams of the baseballs. Results indicated that subjects hit a greater percentage of marked than unmarked balls. These results suggest that the addition of visual cues may be a significant and beneficial technique to enhance hitting performance. Further research is suggested regarding the training procedures, effect of feedback, rate of fading cues, generalization to live pitching, and generalization to other types of pitches. PMID:2249972

  10. Influence of Running on Pistol Shot Hit Patterns.

    PubMed

    Kerkhoff, Wim; Bolck, Annabel; Mattijssen, Erwin J A T

    2016-01-01

    In shooting scene reconstructions, risk assessment of the situation can be important for the legal system. Shooting accuracy and precision, and thus risk assessment, might be correlated with the shooter's physical movement and experience. The hit patterns of inexperienced and experienced shooters, while shooting stationary (10 shots) and in running motion (10 shots) with a semi-automatic pistol, were compared visually (with confidence ellipses) and statistically. The results show a significant difference in precision (circumference of the hit patterns) between stationary shots and shots fired in motion for both inexperienced and experienced shooters. The decrease in precision for all shooters was significantly larger in the y-direction than in the x-direction. The precision of the experienced shooters is overall better than that of the inexperienced shooters. No significant change in accuracy (shift in the hit pattern center) between stationary shots and shots fired in motion can be seen for all shooters. PMID:26331462

  11. Interval Throwing and Hitting Programs in Baseball: Biomechanics and Rehabilitation.

    PubMed

    Chang, Edward S; Bishop, Meghan E; Baker, Dylan; West, Robin V

    2016-01-01

    Baseball injuries from throwing and hitting generally occur as a consequence of the repetitive and high-energy motions inherent to the sport. Biomechanical studies have contributed to understanding the pathomechanics leading to injury and to the development of rehabilitation programs. Interval-based throwing and hitting programs are designed to return an athlete to competition through a gradual progression of sport-specific exercises. Proper warm-up and strict adherence to the program allows the athlete to return as quickly and safely as possible. PMID:26991569

  12. Direct determination of the hit locations from experimental HPGe pulses

    NASA Astrophysics Data System (ADS)

    Désesquelles, P.; Boston, A. J.; Boston, H. C.; Cresswell, J. R.; Dimmock, M. R.; Lazarus, I. H.; Ljungvall, J.; Nelson, L.; Nga, D.-T.; Nolan, P. J.; Rigby, S. V.; Simpson, J.; Van-Oanh, N.-T.

    2013-11-01

    The gamma-tracking technique optimises the determination of the energy and emission angle of gamma-rays detected by modern segmented HPGe detectors. This entails the determination, using the delivered pulse shapes, of the interaction points of the gamma-ray within the crystal. The direct method presented here allows the localisation of the hits using only a large sample of pulses detected in the actual operating conditions. No external crystal scanning system or pulse shape simulation code is needed. In order to validate this method, it is applied to sets of pulses obtained using the University of Liverpool scanning system. The hit locations are determined by the method with good precision.

  13. Multi-hit time-to-amplitude CAMAC module (MTAC)

    SciTech Connect

    Kang, H.

    1980-10-01

    A Multi-Hit Time-to-Amplitude Module (MTAC) for the SLAC Mark III drift chamber system has been designed to measure drift time by converting time-proportional chamber signals into analog levels, and converting the analog data by slow readout via a semi-autonomous controller in a CAMAC crate. The single width CAMAC module has 16 wire channels, each with a 4-hit capacity. An externally generated common start initiates an internal precision ramp voltage which is then sampled using a novel shift register gating scheme and CMOS sampling switches. The detailed design and performance specifications are described.

  14. Design of Thomson Scattering Diagnostic for HIT-SI

    NASA Astrophysics Data System (ADS)

    Morgan, Kyle; Fryett, Taylor; Golingo, Raymond; Jarboe, Tom; Victor, Brian

    2012-10-01

    Steady Inductive Helicity Injection (SIHI) is used to create a spheromak inside the HIT-SI machine. A multi-point Thomson scattering diagnostic has been designed and is under construction for the HIT-SI experiment. The system uses a 20J Ruby Laser with 20ns pulse length. The collection system allows for eight spatial measurement locations, with four being active at any time. Four polychromators are being used to spectrally resolve the scattered light. Present Langmuir probe measurements show an electron temperature of about 12eV, within the range the polychromators can resolve. Properties of system and expected measurement are given.

  15. Integrated Dataset of Screening Hits against Multiple Neglected Disease Pathogens

    PubMed Central

    Nwaka, Solomon; Besson, Dominique; Ramirez, Bernadette; Maes, Louis; Matheeussen, An; Bickle, Quentin; Mansour, Nuha R.; Yousif, Fouad; Townson, Simon; Gokool, Suzanne; Cho-Ngwa, Fidelis; Samje, Moses; Misra-Bhattacharya, Shailja; Murthy, P. K.; Fakorede, Foluke; Paris, Jean-Marc; Yeates, Clive; Ridley, Robert; Van Voorhis, Wesley C.; Geary, Timothy

    2011-01-01

    New chemical entities are desperately needed that overcome the limitations of existing drugs for neglected diseases. Screening a diverse library of 10,000 drug-like compounds against 7 neglected disease pathogens resulted in an integrated dataset of 744 hits. We discuss the prioritization of these hits for each pathogen and the strong correlation observed between compounds active against more than two pathogens and mammalian cell toxicity. Our work suggests that the efficiency of early drug discovery for neglected diseases can be enhanced through a collaborative, multi-pathogen approach. PMID:22247786

  16. GDP-D-mannose pyrophosphorylase from Pogonatherum paniceum enhances salinity and drought tolerance of transgenic tobacco.

    PubMed

    Ai, Taobo; Liao, Xuehong; Li, Rui; Fan, Linhong; Luo, Fengxue; Xu, Ying; Wang, Shenghua

    2016-01-01

    Pogonatherum paniceum is a highly drought- and salt-tolerant plant species that is typically used for ecological restoration and the conservation of soil and water in many countries. Understanding the molecular mechanisms underlying plant abiotic stress responses, especially to salinity and drought stresses, in species such as P. paniceum could be important to broader crop improvement efforts. GDP-D-mannose pyrophosphorylase (GMPase) is the limiting enzyme in the synthesis of L-ascorbic acid (AsA), which plays a crucial role in the detoxification of reactive oxygen species (ROS). We have cloned and characterized the cDNA of the PpGMP gene of P. paniceum encoding a GMPase. The full-length cDNA sequence contains 1411 nucleotides encoding a putative protein with 361 amino acid residues and an approximate molecular mass of 39.68 kDa. The GMPase transcript was up-regulated in P. paniceum plants subjected to salinity and drought stress, respectively. Transgenic tobacco expressing PpGMPase exhibited enhanced salinity and drought resistance, a higher seed germination rate, better growth performance, a higher AsA content, a more stable redox state, higher superoxide dismutase (SOD) activity, and lower levels of malonaldehyde (MDA) and H2O2 under drought and salinity stress. Taken together, expression of PpGMPase in tobacco conferred salinity and drought stress tolerance by increasing the content of AsA, thereby enhancing ROS-detoxifying functions. Thus, PpGMP is a potential candidate gene for crop improvement. PMID:27442366

  17. Systems GMM estimates of the health care spending and GDP relationship: a note.

    PubMed

    Kumar, Saten

    2013-06-01

    This paper utilizes the systems generalized method of moments (GMM) [Arellano and Bover (1995) J Econometrics 68:29-51; Blundell and Bond (1998) J Econometrics 87:115-143], and panel Granger causality [Hurlin and Venet (2001) Granger Causality tests in panel data models with fixed coefficients. Mime'o, University Paris IX], to investigate the health care spending and gross domestic product (GDP) relationship for organisation for economic co-operation and development countries over the period 1960-2007. The system GMM estimates confirm that the contribution of real GDP to health spending is significant and positive. The panel Granger causality tests imply that a bi-directional causality exists between health spending and GDP. To this end, policies aimed at raising health spending will eventually improve the well-being of the population in the long run. PMID:22581267

  18. [Strategy of molecular drug design: hits, leads and drug candidates].

    PubMed

    Guo, Zong-ru

    2008-09-01

    Hits, leads and drug candidates constitute three millstones in the course of drug discovery and development. The definition of drug candidates is a critical point in the value chain of drug innovation, which not only differentiates the research and development stages, but more importantly, determines the perspective and destiny of the pre-clinical and clinical studies. All outcomes from the development stage are actually attributed to the chemical structure of candidates. The quality of candidates, however, is restricted by the drug-likeness of lead compounds, which in turn is decided by the characteristics of hits. The hit-to-lead is to provide a promising and druggable structure for further development, whereas the optimization of lead compounds is a process to transform an active compound into a drug, which in essence is molecular manipulation in multi-dimensional space related to pharmacodynamic, pharmacokinetic, physico-chemical, and safety properties. This review discusses the strategic principles in hit discovery, lead identification and optimization, as well as drug candidate definition with practical examples. PMID:19048779

  19. 42 CFR 495.342 - Annual HIT IAPD requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (CONTINUED) STANDARDS AND CERTIFICATION STANDARDS FOR THE ELECTRONIC HEALTH RECORD TECHNOLOGY INCENTIVE... delays in meeting target dates in the approved HIT technology PAPD/IAPD and approved changes to it. (c) A... status which consists of a detailed accounting of all expenditures for project development over the...

  20. 42 CFR 495.342 - Annual HIT IAPD requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Annual HIT IAPD requirements. 495.342 Section 495.342 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... status which consists of a detailed accounting of all expenditures for project development over the...

  1. Plans for Federal Reading Panel Hit a New Roadblock

    ERIC Educational Resources Information Center

    Manzo, Kathleen Kennedy

    2007-01-01

    After several years of planning and a series of false starts, a new federal venture to review reading research has hit another bureaucratic hurdle--one that could keep it from ever getting off the ground. A planned announcement last week of the membership of the Commission on Reading Research was put on hold by the National Institute for Literacy…

  2. Assessing the lipophilicity of fragments and early hits.

    PubMed

    Mortenson, Paul N; Murray, Christopher W

    2011-07-01

    A key challenge in many drug discovery programs is to accurately assess the potential value of screening hits. This is particularly true in fragment-based drug design (FBDD), where the hits often bind relatively weakly, but are correspondingly small. Ligand efficiency (LE) considers both the potency and the size of the molecule, and enables us to estimate whether or not an initial hit is likely to be optimisable to a potent, druglike lead. While size is a key property that needs to be controlled in a small molecule drug, there are a number of additional properties that should also be considered. Lipophilicity is amongst the most important of these additional properties, and here we present a new efficiency index (LLE(AT)) that combines lipophilicity, size and potency. The index is intuitively defined, and has been designed to have the same target value and dynamic range as LE, making it easily interpretable by medicinal chemists. Monitoring both LE and LLE(AT) should help both in the selection of more promising fragment hits, and controlling molecular weight and lipophilicity during optimisation. PMID:21614595

  3. Hit Identification and Optimization in Virtual Screening: Practical Recommendations Based Upon a Critical Literature Analysis

    PubMed Central

    Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B.; Szukala, Richard; Johnson, Michael E.; Hevener, Kirk E.

    2013-01-01

    A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, drug-like, and ADMET filters were applied to the reported hits to assess the quality of compounds reported and a careful analysis of a subset of the studies which presented hit optimization was performed. This data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, defining hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria. PMID:23688234

  4. A comparison of age level on baseball hitting kinematics.

    PubMed

    Escamilla, Rafael F; Fleisig, Glenn S; DeRenne, Coop; Taylor, Marcus K; Moorman, Claude T; Imamura, Rodney; Barakatt, Edward; Andrews, James R

    2009-08-01

    We propose that learning proper hitting kinematics should be encouraged at a young age during youth baseball because this may help reinforce proper hitting kinematics as a player progresses to higher levels of baseball in their adult years. To enhance our understanding between youth and adult baseball hitting, kinematic and temporal analyses of baseball hitting were evaluated with a high-speed motion analysis system between 12 skilled youth and 12 skilled adult baseball players. There were only a small number of temporal differences between youth and adult hitters, with adult hitters taking significantly greater time than youth hitters during the stride phase and during the swing. Compared with youth hitters, adult hitters a) had significantly greater (p < .01) lead knee flexion when the hands started to move forward; b) flexed the lead knee over a greater range of motion during the transition phase (31 degrees versus 13 degrees); c) extended the lead knee over a greater range of motion during the bat acceleration phase (59 degrees versus 32 degrees); d) maintained a more open pelvis position at lead foot off ground; and e) maintained a more open upper torso position when the hands started to move forward and a more closed upper torso position at bat-ball contact. Moreover, adult hitters had greater peak upper torso angular velocity (857 degrees/s versus 717 degrees/s), peak left elbow extension angular velocity (752 degrees/s versus 598 degrees/s), peak left knee extension angular velocity (386 degrees/s versus 303 degrees/s), and bat linear velocity at bat-ball contact (30 m/s versus 25 m/s). The numerous differences in kinematic and temporal parameters between youth and adult hitters suggest that hitting mechanics are different between these two groups. PMID:19827470

  5. One-hit models of carcinogenesis: conservative or not

    SciTech Connect

    Bailar, J.C. III; Crouch, E.A.C.; Shaikh, R.; Spiegelman, D.

    1988-12-01

    One-hit formulas are widely believed to be conservative when used to analyze carcinogenesis bioassays, in the sense that they will rarely underestimate risks of cancer at low exposures. Such formulas are generally applied to the lifetime incidence of cancer at a specific site, with risks estimated from animal data at zero dose (control), and two or more additional doses that are appreciable fractions of a maximum tolerated dose. No empirical study has demonstrated that the one-hit formula is conservative in the sense described. The Carcinogenesis Bioassay Database System contains data on 1212 separate bioassays of 308 chemical substances tested at exactly three evaluable doses. These provided sufficient data to examine 8432 specific combination of cancer site with sex, species, and chemical. For each of these they fitted a one-hit formula to the zero and maximum dose data points, then examined the relation of the fitted curve to the incidence rate observed at the mid-dose, with and without adjustment for intercurrent mortality. Both underestimates and overestimates of risk at mid-dose occurred substantially more often than expected by chance. They cannot tell whether such underestimates would occur at lower doses, but offer six biological reasons why underestimates might be expected. In a high percentage of animal bioassays, the one-hit formula is not conservative when applied in the usual way to animal data. It remains possible that the one-hit formula may indeed be conservative at sufficiently low doses (below the observational range), but the usual procedure, applied to the usual dose range, can be nonconservative in estimating the slope of the formula at such low doses. Risk assessments for regulation of carcinogens should incorporate some measure of additional uncertainty.

  6. Identification of a GDP-mannose pyrophosphorylase gene from Sulfolobus solfataricus.

    PubMed

    Sacchetti, Silvana; Bartolucci, Simonetta; Rossi, Mosè; Cannio, Raffaele

    2004-05-12

    An open reading frame (ORF) encoding a putative GDP-mannose pyrophosphorylase (SsoGMPP) was identified on the genome sequence of Sulfolobus solfataricus P2, the predicted gene product showing high amino acid sequence homology to several archaeal, bacterial, and eukaryal GDP-mannose pyrophosphorylases such as guanidine diphosphomannose pyrophosphorylases (GMPPs) from Saccharomyces cerevisiae and Arabidopsis thaliana. The sequence was PCR amplified from genomic DNA of S. solfataricus P2 and heterologous gene expression obtained as a fusion to glutathione S-transferase in Escherichia coli, under conditions suitable to reduce the formation of inclusion bodies. Specific assays performed at 60 degrees C revealed the presence of the archaeal synthesizing GDP-mannose enzyme activity in the cell extracts of the transformed E. coli. As a positive control, the same assays were performed at the mesophilic enzyme optimum temperature on the already characterized yeast recombinant GMPP. The recombinant protein was purified to homogeneity by glutathione sepharose affinity chromatography and its thermophilic nature could be verified. The enzyme was definitively identified by demonstrating its capability to catalyze also the reverse reaction of pyrophosphorolysis and, most interestingly, its high specificity for synthesizing GDP-mannose. PMID:15145064

  7. Hydrogen bonding in the mechanism of GDP-mannose mannosyl hydrolase

    NASA Astrophysics Data System (ADS)

    Mildvan, A. S.; Xia, Z.; Azurmendi, H. F.; Legler, P. M.; Balfour, M. R.; Lairson, L. L.; Withers, S. G.; Gabelli, S. B.; Bianchet, M. A.; Amzel, L. M.

    2006-06-01

    GDP-mannose mannosyl hydrolase (GDPMH) from E. coli catalyzes the hydrolysis of GDP-α- D-sugars to GDP and β- D-sugars by nucleophilic substitution with inversion at the anomeric C1 of the sugar, with general base catalysis by His-124. The 1.3 Å X-ray structure of the GDPMH-Mg 2+-GDP complex was used to model the complete substrate, GDP-mannose into the active site. The substrate is linked to the enzyme by 12 hydrogen bonds, as well as by the essential Mg 2+. In addition, His-124 was found to participate in a hydrogen bonded triad: His-124-NδH⋯Tyr-127-OH⋯Pro-120(C dbnd6 O). The contributions of these hydrogen bonds to substrate binding and to catalysis were investigated by site-directed mutagenesis. The hydrogen bonded triad detected in the X-ray structure was found to contribute little to catalysis since the Y127F mutation of the central residue shows only 2-fold decreases in both kcat and Km. The GDP leaving group is activated by the essential Mg 2+ which contributes at least 10 5-fold to kcat, and by nine hydrogen bonds, including those from Tyr-103, Arg-37, Arg-52, and Arg-65 (via an intervening water), each of which contribute factors to kcat ranging from 24- to 309-fold. Both Arg-37 and Tyr-103 bind the β-phosphate of the leaving GDP and are only 5.0 Å apart. Accordingly, the R37Q/Y103F double mutant shows partially additive effects of the two single mutants on kcat, indicating cooperativity of Arg-37 and Tyr-103 in promoting catalysis. The extensive activation of the GDP leaving group suggests a mechanism with dissociative character with a cationic oxocarbenium-like transition state and a half-chair conformation of the sugar ring, as found with glycosidase enzymes. Accordingly, Asp-22 which contributes 10 2.1- to 10 2.6-fold to kcat, is positioned to both stabilize a developing cationic center at C1 and to accept a hydrogen bond from the C2-OH of the mannosyl group, and His-88, which contributes 10 2.3-fold to kcat, is positioned to accept

  8. A Second GDP-l-galactose Phosphorylase in Arabidopsis en Route to Vitamin C

    PubMed Central

    Linster, Carole L.; Adler, Lital N.; Webb, Kristofor; Christensen, Kathryn C.; Brenner, Charles; Clarke, Steven G.

    2008-01-01

    The Arabidopsis thaliana VTC2 gene encodes an enzyme that catalyzes the conversion of GDP-l-galactose to l-galactose 1-phosphate in the first committed step of the Smirnoff-Wheeler pathway to plant vitamin C synthesis. Mutations in VTC2 had previously been found to lead to only partial vitamin C deficiency. Here we show that the Arabidopsis gene At5g55120 encodes an enzyme with high sequence identity to VTC2. Designated VTC5, this enzyme displays substrate specificity and enzymatic properties that are remarkably similar to those of VTC2, suggesting that it may be responsible for residual vitamin C synthesis in vtc2 mutants. The exact nature of the reaction catalyzed by VTC2/VTC5 is controversial because of reports that kiwifruit and Arabidopsis VTC2 utilize hexose 1-phosphates as phosphorolytic acceptor substrates. Using liquid chromatography-mass spectroscopy and a VTC2-H238N mutant, we provide evidence that the reaction proceeds through a covalent guanylylated histidine residue within the histidine triad motif. Moreover, we show that both the Arabidopsis VTC2 and VTC5 enzymes catalyze simple phosphorolysis of the guanylylated enzyme, forming GDP and l-galactose 1-phosphate from GDP-l-galactose and phosphate, with poor reactivity of hexose 1-phosphates as phosphorolytic acceptors. Indeed, the endogenous activities from Japanese mustard spinach, lemon, and spinach have the same substrate requirements. These results show that Arabidopsis VTC2 and VTC5 proteins and their homologs in other plants are enzymes that guanylylate a conserved active site His residue with GDP-l-galactose, forming l-galactose 1-phosphate for vitamin C synthesis, and regenerate the enzyme with phosphate to form GDP. PMID:18463094

  9. 77 FR 66617 - HIT Policy and Standards Committees; Workgroup Application Database

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-06

    ... HUMAN SERVICES HIT Policy and Standards Committees; Workgroup Application Database AGENCY: Office of the... Application Database. The Office of the National Coordinator (ONC) has launched a new Health Information Technology Federal Advisory Committee Workgroup Application Database. Name of Committees: HIT...

  10. 75 FR 32472 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Standards... Information Technology AGENCY: Office of the National Coordinator for Health Information Technology, HHS... Information Technology (ONC). Name of Committee: HIT Standards Committee. General Function of the...

  11. Manual laterality and hitting performance in major league baseball.

    PubMed

    Grondin, S; Guiard, Y; Ivry, R B; Koren, S

    1999-06-01

    Asymmetrical hand function was examined in the context of expert sports performance: hitting in professional baseball. An archival study was conducted to examine the batting performance of all Major League Baseball players from 1871 to 1992, focusing on those who batted left (n = 1,059) to neutralize the game asymmetry. Among them, left-handers (n = 421) were more likely to hit with power and to strike out than right-handers (n = 638). One possible account, based on the idea of hand dominance and an analogy to tennis, is that batting left involves a double-handed forehand for left-handers and a weaker and more reliable double-handed backhand for right-handers. The results are also interpretable in the light of Y. Guiard's (1987) kinematic chain model of a between-hands asymmetrical division of labor, which provides a detailed account of why left batting is optimal for left-handers. PMID:10385985

  12. A memory model for internet hits after media exposure

    NASA Astrophysics Data System (ADS)

    Chessa, Antonio G.; Murre, Jaap M. J.

    2004-02-01

    We present a cognitive model, based on the mathematical theory of point processes, which extends the results of two studies by Johansen (Physica A 276 (2000) 338; Physica A 296 (2001) 539) on download relaxation dynamics. Responses from subjects are considered as single events, which are received from original listeners or readers and from a network of social contacts, through which a message may propagate further. We collected data on the number of daily visits at our web site after a radio interview with the second author, in which the name of the web site was mentioned. A model based on an exponential hit time distribution and a homogeneous point process for regular visitors fits our data and Johansen's very well and is superior to both the power law and the logarithmic function. The fits suggest that hit data from different sources share the same cognitive mechanism, which are controlled merely by the encoding and retrieval of the target information memorised.

  13. A Quantum Algorithm for Estimating Hitting Times of Markov Chains

    NASA Astrophysics Data System (ADS)

    Narayan Chowdhury, Anirban; Somma, Rolando

    We present a quantum algorithm to estimate the hitting time of a reversible Markov chain faster than classically possible. To this end, we show that the hitting time is given by an expected value of the inverse of a Hermitian matrix. To obtain this expected value, our algorithm combines three important techniques developed in the literature. One such a technique is called spectral gap amplification and we use it to amplify the gap of the Hermitian matrix or reduce its condition number. We then use a new algorithm by Childs, Kothari, and Somma to implement the inverse of a matrix, and finally use methods developed in the context of quantum metrology to reduce the complexity of expected-value estimation for a given precision. The authors acknowledge support from AFOSR Grant Number FA9550-12-1-0057 and the Google Research Award.

  14. A hit-and-run giant impact scenario

    NASA Astrophysics Data System (ADS)

    Reufer, Andreas; Meier, Matthias M. M.; Benz, Willy; Wieler, Rainer

    2012-09-01

    The formation of the Moon from the debris of a slow and grazing giant impact of a Mars-sized impactor on the proto-Earth (Cameron and Ward [1976]. Lunar Planet. Sci. Conf.; Canup and Asphaug [2001]. Nature 412, 708) is widely accepted today. We present an alternative scenario with a hit-and-run collision (Asphaug [2010]. Chem. Erde 70, 199) with a fractionally increased impact velocity and a steeper impact angle.

  15. Hitting moving targets with a continuously changing temporal window.

    PubMed

    de la Malla, Cristina; López-Moliner, Joan

    2015-09-01

    Hitting a moving target requires that we do not miss the target when it is around the aimed position. The time available for us not to miss the target when it is at the position of interest is usually called the time window and depends on target's speed and size. These variables, among others, have been manipulated in previous studies but kept constant within the same trial or session. Here, we present results of a hitting task in which targets underwent simple harmonic motion, which is defined by a sinusoidal function. Target velocity changes continuously in this motion and so does the time window which is shorter in the centre (peak velocity) and longer at the turning points (lowest velocity) within a single trial. We studied two different conditions in which the target moved with a reliable (across trials) amplitude displacement or reliable peak velocity, respectively, and subjects were free to decide where and when to hit it. Results show that subjects made a compromise between maximum and minimum target's speed, so that they did hit the target at intermediate speed values. Interestingly, the reliability of target peak velocity (or displacement) modulated the point of interception. When target's peak velocity was more reliable, subjects intercepted the target at positions with smaller temporal windows and the reverse was true when displacement was reliable. Subjects adapted the interceptive behaviour to the underlying statistical structure of the targets. Finally, in a control condition in which the temporal window also depended on the instant size and not only on speed, subjects intercepted the target when it moved at similar speeds than when the size was constant. This finding suggests that velocity rather than the temporal window contributed more to controlling the interceptive movements. PMID:26003129

  16. The burden of natural and technological disaster-related mortality on gross domestic product (GDP) in the WHO African region.

    PubMed

    Kirigia, Joses M; Sambo, Luis G; Aldis, W; Mwabu, Germano M

    2002-01-01

    The WHO Africa region has the highest disaster mortality rate compared to the other five regions of the organization. Those deaths are hypothesized to have significantly negative effect on per capita gross domestic product (GDP). The objective of this study was to estimate the loss in GDP attributable to natural and technological disaster-related mortality in the WHO African Region. We estimated the impact of disaster-related mortality on GDP using double-log econometric model and cross-sectional data (from the UNDP and the World Bank publications) on 45 out of 46 countries in the WHO African Region. The coefficients for capital (K), educational enrolment (EN), life expectancy (LE) and exports (X) had a positive sign; while imports (M) and disaster mortality (DS) were found to impact negatively on GDP. The abovementioned explanatory variables were found to have statistically significant effect on GDP at 5% level in a t-distribution test. Disaster mortality of a single person was found to reduce GDP by US$0.018. We have demonstrated that disaster mortality has a significant negative effect on GDP. Thus, as policy-makers strive to increase GDP through capital investment, export promotion and increase in educational enrolment, they should always recall that investments in strengthening national capacity to mitigate the effects of national disasters expeditiously and effectively shall yield significant economic returns. PMID:17298162

  17. Dimensions of Well-Being in EU Regions: Do GDP and Unemployment Tell Us All We Need to Know?

    ERIC Educational Resources Information Center

    Stewart, Kitty

    2005-01-01

    Unemployment and GDP are widely used as proxies for a broader concept of well-being in the European Union, especially at regional level. This paper asks whether such an approach is reasonable. Using data from a range of sources, it examines the association between unemployment, GDP and a number of alternative well-being indicators in five…

  18. Progress on the HIT-SI3 Experiment

    NASA Astrophysics Data System (ADS)

    Golingo, R. P.; Rogers, J. A.; Ennis, D. A.; Hansen, C. J.; Hossack, A. C.; Jarboe, T. R.; Nelson, B. A.; Marklin, G. J.; Victor, B. S.

    2012-10-01

    The HIT-SI program at the University of Washington is investigating the formation and sustainment of toroidal current using steady inductive helicity injection (SIHI). The HIT-SI experiment consists of a bow tie shaped flux conserver with two helicity injectors on opposite sides of the machine. All plasma facing surfaces are coated with an insulting material to prevent arcing. The injectors are driven 90 degrees out of phase leading to a constant rate of helicity injection. Presently toroidal currents up to three times the injector current are created in the device. Discoveries made during the operation have guided the design of an improved injection geometry. Three injectors, which will operate with 120 degree phase differences, are presently being assembled to be mounted on one side of the device. These injectors will have the same preferred direction and produce a rotating structure with less n=1 than presently used. The injectors will operate at a higher frequency. The IDCD model predicts this will lead to a further reduction of the perturbations in the confinement volume. Additional diagnostic access has been gained by placing the injectors on one of the device. The present assembly status of the injectors and additional diagnostics for HIT-SI3 will be presented.

  19. Cognitive orientations in marathon running and "hitting the wall"

    PubMed Central

    Stevinson, C. D.; Biddle, S. J.

    1998-01-01

    OBJECTIVES: To investigate whether runners' cognitions during a marathon are related to "hitting the wall". To test a new and more comprehensive system for classifying cognition of marathon runners. METHODS: Non-elite runners (n = 66) completed a questionnaire after finishing the 1996 London marathon. The runners were recruited through the charity SPARKS for whom they were raising money by running in the race. RESULTS: Most runners reported that during the race their thoughts were internally associative, with internally dissociative thoughts being the least prevalent. Runners who "hit the wall" used more internal dissociation than other runners, indicating that it is a hazardous strategy, probably because sensory feedback is blocked. However, internal association was related to an earlier onset of "the wall", suggesting that too much attention on physical symptoms may magnify them, thereby exaggerating any discomfort. External dissociation was related to a later onset, probably because it may provide a degree of distraction but keeps attention on the race. CONCLUSIONS: "Hitting the wall" for recreational non-elite marathon runners is associated with their thought patterns during the race. In particular, "the wall" is associated with internal dissociation. 




 PMID:9773172

  20. Effective progression of nuclear magnetic resonance-detected fragment hits.

    PubMed

    Eaton, Hugh L; Wyss, Daniel F

    2011-01-01

    Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade as an alternate lead generation tool to HTS approaches. Several compounds have now progressed into the clinic which originated from a fragment-based approach, demonstrating the utility of this emerging field. While fragment hit identification has become much more routine and may involve different screening approaches, the efficient progression of fragment hits into quality lead series may still present a major bottleneck for the broadly successful application of FBDD. In our laboratory, we have extensive experience in fragment-based NMR screening (SbN) and the subsequent iterative progression of fragment hits using structure-assisted chemistry. To maximize impact, we have applied this approach strategically to early- and high-priority targets, and those struggling for leads. Its application has yielded a clinical candidate for BACE1 and lead series in about one third of the SbN/FBDD projects. In this chapter, we will give an overview of our strategy and focus our discussion on NMR-based FBDD approaches. PMID:21371601

  1. Hubs and Authorities in the World Trade Network Using a Weighted HITS Algorithm

    PubMed Central

    Deguchi, Tsuyoshi; Takahashi, Katsuhide; Takayasu, Hideki; Takayasu, Misako

    2014-01-01

    We investigate the economic hubs and authorities of the world trade network (WTN) from to , an era of rapid economic globalization. Using a well-defined weighted hyperlink-induced topic search (HITS) algorithm, we can calculate the values of the weighted HITS hub and authority for each country in a conjugate way. In the context of the WTN, authority values are large for countries with significant imports from large hub countries, and hub values are large for countries with significant exports to high-authority countries. The United States was the largest economic authority in the WTN from to . The authority value of the United States has declined since , and China has now become the largest hub in the WTN. At the same time, China's authority value has grown as China is transforming itself from the “factory of the world” to the “market of the world.” European countries show a tendency to trade mostly within the European Union, which has decreased Europe's hub and authority values. Japan's authority value has increased slowly, while its hub value has declined. These changes are consistent with Japan's transition from being an export-driven economy in its high economic growth era in the latter half of the twentieth century to being a more mature, economically balanced nation. PMID:25050940

  2. 42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false State Medicaid health information technology (HIT... Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include... Medicaid Information Technology Architecture (MITA) principles as described in the Medicaid...

  3. Teachers' Perspectives on Hitting Back in School: Between Inexcusable Violence and Self-Defense

    ERIC Educational Resources Information Center

    Fleischmann, Amos

    2015-01-01

    Israeli schools expressly forbid a student to hit back after being attacked. In semistructured interviews, 71 Israeli educators were asked for their views on the hitting-back tactic. The interviews compared their attitude toward hitting back as teachers with their take on the matter as parents. The results, analyzed using grounded theory, show…

  4. 42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false State Medicaid health information technology (HIT... Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include... Medicaid Information Technology Architecture (MITA) principles as described in the Medicaid...

  5. 42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false State Medicaid health information technology (HIT... Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include... Medicaid Information Technology Architecture (MITA) principles as described in the Medicaid...

  6. 42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false State Medicaid health information technology (HIT... Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include... Medicaid Information Technology Architecture (MITA) principles as described in the Medicaid...

  7. 42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false State Medicaid health information technology (HIT... Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include... Medicaid Information Technology Architecture (MITA) principles as described in the Medicaid...

  8. 77 FR 2448 - Special Local Regulation; HITS Triathlon; Corpus Christi Bayfront, Corpus Christi, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-18

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulation; HITS Triathlon; Corpus Christi... from portions of the Corpus Christi Bayfront area during the HITS Triathlon on February 18th and 19th, 2012. This Special Local Regulation is necessary to ensure the safety of HITS Triathlon...

  9. The impact of the GDP and population on trade of COMESA using panel data approach

    NASA Astrophysics Data System (ADS)

    Hamzalouh, Lubna; Ismail, Mohd. Tahir; Rahman, Rosmanjawati Abd.

    2016-06-01

    The general consensus from a plethora of literature is that the estimates of variability for analyzing panel data models are precise and achieve accurate inferences. Panel data can also be used to control for heterogeneity through several models, such as the fixed effect model (FEM), the random effects model (REM), and the pooled regression model(PM). This study aims to uncover the increases in trade volume among the member countries of Common Market for Eastern and Southern Africa (COMESA) and identify the important factors that affect COMESA trade using panel data models. In addition, this study intends to investigate the independent variables and their effect on the export and import of COMESA member countries. Results show that in FEM, an increase in GDP leads to a 65% increase in imports, and in REM, an increase in GDP leads to an 86% increase in exports. These findings suggest that FEM and REM are appropriate for explaining the imports and exports of COMESA, respectively.

  10. A hybrid group method of data handling with discrete wavelet transform for GDP forecasting

    NASA Astrophysics Data System (ADS)

    Isa, Nadira Mohamed; Shabri, Ani

    2013-09-01

    This study is proposed the application of hybridization model using Group Method of Data Handling (GMDH) and Discrete Wavelet Transform (DWT) in time series forecasting. The objective of this paper is to examine the flexibility of the hybridization GMDH in time series forecasting by using Gross Domestic Product (GDP). A time series data set is used in this study to demonstrate the effectiveness of the forecasting model. This data are utilized to forecast through an application aimed to handle real life time series. This experiment compares the performances of a hybrid model and a single model of Wavelet-Linear Regression (WR), Artificial Neural Network (ANN), and conventional GMDH. It is shown that the proposed model can provide a promising alternative technique in GDP forecasting.

  11. National GDP, Science Interest and Science Achievement: A Person-by-Nation Interaction

    PubMed Central

    Drob, Elliot M. Tucker; Cheung, Amanda K.; Briley, Daniel A.

    2014-01-01

    Maximizing science achievement is a critical target of educational policy, with important implications for national and international economic and technological competitiveness. Previous research has identified both science interest and socioeconomic status (SES) as robust predictors of science achievement, but little research has examined their joint effects. In a dataset drawn from approximately 400,000 high school students from 57 countries, we document large interest by SES and interest by per capita gross domestic product (GDP) interactions in the prediction of science achievement. Student interest in science is a substantially stronger predictor of science achievement in higher socioeconomic contexts and in higher GDP nations. Our results are consistent with the hypothesis that, in higher opportunity contexts, motivational factors play larger roles in learning and achievement. They add to the growing body of evidence indicating that substantial cross national differences in psychological effect sizes are not simply a logical possibility, but in many cases, an empirical reality. PMID:25304883

  12. Identification and Characterization of GONST1, a Golgi-Localized GDP-Mannose Transporter in Arabidopsis

    PubMed Central

    Baldwin, Timothy C.; Handford, Michael G.; Yuseff, Maria-Isabel; Orellana, Ariel; Dupree, Paul

    2001-01-01

    Transport of nucleotide sugars across the Golgi apparatus membrane is required for the luminal synthesis of a variety of plant cell surface components. We identified an Arabidopsis gene encoding a nucleotide sugar transporter (designated GONST1) that we have shown by transient gene expression to be localized to the Golgi. GONST1 complemented a GDP-mannose transport–defective yeast mutant (vrg4-2), and Golgi-rich vesicles from the complemented strain displayed increased GDP-mannose transport activity. GONST1 promoter::β-glucuronidase studies suggested that this gene is expressed ubiquitously. The identification of a Golgi-localized nucleotide sugar transporter from plants will allow the study of the importance of this class of proteins in the synthesis of plant cell surface components such as cell wall polysaccharides. PMID:11595802

  13. Growth

    NASA Astrophysics Data System (ADS)

    Waag, Andreas

    This chapter is devoted to the growth of ZnO. It starts with various techniques to grow bulk samples and presents in some detail the growth of epitaxial layers by metal organic chemical vapor deposition (MOCVD), molecular beam epitaxy (MBE), and pulsed laser deposition (PLD). The last section is devoted to the growth of nanorods. Some properties of the resulting samples are also presented. If a comparison between GaN and ZnO is made, very often the huge variety of different growth techniques available to fabricate ZnO is said to be an advantage of this material system. Indeed, growth techniques range from low cost wet chemical growth at almost room temperature to high quality MOCVD growth at temperatures above 1, 000∘C. In most cases, there is a very strong tendency of c-axis oriented growth, with a much higher growth rate in c-direction as compared to other crystal directions. This often leads to columnar structures, even at relatively low temperatures. However, it is, in general, not straight forward to fabricate smooth ZnO thin films with flat surfaces. Another advantage of a potential ZnO technology is said to be the possibility to grow thin films homoepitaxially on ZnO substrates. ZnO substrates are mostly fabricated by vapor phase transport (VPT) or hydrothermal growth. These techniques are enabling high volume manufacturing at reasonable cost, at least in principle. The availability of homoepitaxial substrates should be beneficial to the development of ZnO technology and devices and is in contrast to the situation of GaN. However, even though a number of companies are developing ZnO substrates, only recently good quality substrates have been demonstrated. However, these substrates are not yet widely available. Still, the situation concerning ZnO substrates seems to be far from low-cost, high-volume production. The fabrication of dense, single crystal thin films is, in general, surprisingly difficult, even when ZnO is grown on a ZnO substrate. However

  14. The Rabies Virus L Protein Catalyzes mRNA Capping with GDP Polyribonucleotidyltransferase Activity.

    PubMed

    Ogino, Minako; Ito, Naoto; Sugiyama, Makoto; Ogino, Tomoaki

    2016-01-01

    The large (L) protein of rabies virus (RABV) plays multiple enzymatic roles in viral RNA synthesis and processing. However, none of its putative enzymatic activities have been directly demonstrated in vitro. In this study, we expressed and purified a recombinant form of the RABV L protein and verified its guanosine 5'-triphosphatase and GDP polyribonucleotidyltransferase (PRNTase) activities, which are essential for viral mRNA cap formation by the unconventional mechanism. The RABV L protein capped 5'-triphosphorylated but not 5'-diphosphorylated RABV mRNA-start sequences, 5'-AACA(C/U), with GDP to generate the 5'-terminal cap structure G(5')ppp(5')A. The 5'-AAC sequence in the substrate RNAs was found to be strictly essential for RNA capping with the RABV L protein. Furthermore, site-directed mutagenesis showed that some conserved amino acid residues (G1112, T1170, W1201, H1241, R1242, F1285, and Q1286) in the PRNTase motifs A to E of the RABV L protein are required for cap formation. These findings suggest that the putative PRNTase domain in the RABV L protein catalyzes the rhabdovirus-specific capping reaction involving covalent catalysis of the pRNA transfer to GDP, thus offering this domain as a target for developing anti-viral agents. PMID:27213429

  15. The Rabies Virus L Protein Catalyzes mRNA Capping with GDP Polyribonucleotidyltransferase Activity

    PubMed Central

    Ogino, Minako; Ito, Naoto; Sugiyama, Makoto; Ogino, Tomoaki

    2016-01-01

    The large (L) protein of rabies virus (RABV) plays multiple enzymatic roles in viral RNA synthesis and processing. However, none of its putative enzymatic activities have been directly demonstrated in vitro. In this study, we expressed and purified a recombinant form of the RABV L protein and verified its guanosine 5′-triphosphatase and GDP polyribonucleotidyltransferase (PRNTase) activities, which are essential for viral mRNA cap formation by the unconventional mechanism. The RABV L protein capped 5′-triphosphorylated but not 5′-diphosphorylated RABV mRNA-start sequences, 5′-AACA(C/U), with GDP to generate the 5′-terminal cap structure G(5′)ppp(5′)A. The 5′-AAC sequence in the substrate RNAs was found to be strictly essential for RNA capping with the RABV L protein. Furthermore, site-directed mutagenesis showed that some conserved amino acid residues (G1112, T1170, W1201, H1241, R1242, F1285, and Q1286) in the PRNTase motifs A to E of the RABV L protein are required for cap formation. These findings suggest that the putative PRNTase domain in the RABV L protein catalyzes the rhabdovirus-specific capping reaction involving covalent catalysis of the pRNA transfer to GDP, thus offering this domain as a target for developing anti-viral agents. PMID:27213429

  16. Estimated Radiation on Mars, Hits per Cell Nucleus

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This global map of Mars shows estimates for amounts of high-energy-particle cosmic radiation reaching the surface, a serious health concern for any future human exploration of the planet.

    The estimates are based on cosmic-radiation measurements made on the way to Mars by the Mars radiation environment experiment, an instrument on NASA's 2001 Mars Odyssey spacecraft, plus information about Mars' surface elevations from the laser altimeter instrument on NASA's Mars Global Surveyor. The areas of Mars expected to have least radiation are where elevation is lowest, because those areas have more atmosphere above them to block out some of the radiation. Earth's thick atmosphere shields us from most cosmic radiation, but Mars has a much thinner atmosphere than Earth does.

    Colors in the map refer to the estimated average number of times per year each cell nucleus in a human there would be hit by a high-energy cosmic ray particle. The range is generally from two hits (color-coded green), a moderate risk level, to eight hits (coded red), a high risk level.

    NASA's Jet Propulsion Laboratory, Pasadena, Calif. manages the 2001 Mars Odyssey and Mars Global Surveyor missions for NASA's Office of Space Science, Washington D.C. The Mars radiation environment experiment was developed by NASA's Johnson Space Center. Lockheed Martin Astronautics, Denver, is the prime contractor for Odyssey, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  17. Dynamic stereoacuity: a test for hitting a baseball?

    PubMed

    Solomon, H; Zinn, W J; Vacroux, A

    1988-07-01

    Vision is a critical ingredient in professional sports such as baseball. It would, therefore, be logical to assume that vision testing should be able to discriminate between good and bad performance. Past attempts to establish this vision/performance relationship have not been successful. We believe the fault is anchored in the fact that all routine vision testing is static and unable to measure motion parameters. Using an instrument of our design to test dynamic stereoacuity, we have been able to detect subtle differences among individuals. The data show a segregation between major league hitters and pitchers. Such information could be used as one clue to predict hitting performance. PMID:3403900

  18. Hit efficiency study of CMS prototype forward pixel detectors

    SciTech Connect

    Kim, Dongwook; /Johns Hopkins U.

    2006-01-01

    In this paper the author describes the measurement of the hit efficiency of a prototype pixel device for the CMS forward pixel detector. These pixel detectors were FM type sensors with PSI46V1 chip readout. The data were taken with the 120 GeV proton beam at Fermilab during the period of December 2004 to February 2005. The detectors proved to be highly efficient (99.27 {+-} 0.02%). The inefficiency was primarily located near the corners of the individual pixels.

  19. The groin hit: complications of intravenous drug abuse.

    PubMed

    Roszler, M H; McCarroll, K A; Donovan, K R; Rashid, T; Kling, G A

    1989-05-01

    We are seeing an increased number of complications in intravenous drug abusers who resort to injecting the groin for vascular access (the "groin hit"). Vascular complications include venous thrombosis, arteriovenous fistula, mycotic aneurysm, ruptured pseudoaneurysm, and dissecting hematoma. Soft tissue complications include cellulitis and abscess. The latter may dissect into the extraperitoneal space. Skeletal complications include osteomyelitis and septic arthritis. This paper illustrates the radiographic spectrum of these complications. An algorithm will illustrate the radiographic evaluation of a groin mass in a drug addict. PMID:2727357

  20. Two tomato GDP-D-mannose epimerase isoforms involved in ascorbate biosynthesis play specific roles in cell wall biosynthesis and development.

    PubMed

    Mounet-Gilbert, Louise; Dumont, Marie; Ferrand, Carine; Bournonville, Céline; Monier, Antoine; Jorly, Joana; Lemaire-Chamley, Martine; Mori, Kentaro; Atienza, Isabelle; Hernould, Michel; Stevens, Rebecca; Lehner, Arnaud; Mollet, Jean Claude; Rothan, Christophe; Lerouge, Patrice; Baldet, Pierre

    2016-08-01

    GDP-D-mannose epimerase (GME, EC 5.1.3.18) converts GDP-D-mannose to GDP-L-galactose, and is considered to be a central enzyme connecting the major ascorbate biosynthesis pathway to primary cell wall metabolism in higher plants. Our previous work demonstrated that GME is crucial for both ascorbate and cell wall biosynthesis in tomato. The aim of the present study was to investigate the respective role in ascorbate and cell wall biosynthesis of the two SlGME genes present in tomato by targeting each of them through an RNAi-silencing approach. Taken individually SlGME1 and SlGME2 allowed normal ascorbate accumulation in the leaf and fruits, thus suggesting the same function regarding ascorbate. However, SlGME1 and SlGME2 were shown to play distinct roles in cell wall biosynthesis, depending on the tissue considered. The RNAi-SlGME1 plants harbored small and poorly seeded fruits resulting from alterations of pollen development and of pollination process. In contrast, the RNAi-SlGME2 plants exhibited vegetative growth delay while fruits remained unaffected. Analysis of SlGME1- and SlGME2-silenced seeds and seedlings further showed that the dimerization state of pectin rhamnogalacturonan-II (RG-II) was altered only in the RNAi-SlGME2 lines. Taken together with the preferential expression of each SlGME gene in different tomato tissues, these results suggest sub-functionalization of SlGME1 and SlGME2 and their specialization for cell wall biosynthesis in specific tomato tissues. PMID:27382114

  1. Two tomato GDP-D-mannose epimerase isoforms involved in ascorbate biosynthesis play specific roles in cell wall biosynthesis and development

    PubMed Central

    Mounet-Gilbert, Louise; Dumont, Marie; Ferrand, Carine; Bournonville, Céline; Monier, Antoine; Jorly, Joana; Lemaire-Chamley, Martine; Mori, Kentaro; Atienza, Isabelle; Hernould, Michel; Stevens, Rebecca; Lehner, Arnaud; Mollet, Jean Claude; Rothan, Christophe; Lerouge, Patrice; Baldet, Pierre

    2016-01-01

    GDP-D-mannose epimerase (GME, EC 5.1.3.18) converts GDP-D-mannose to GDP-L-galactose, and is considered to be a central enzyme connecting the major ascorbate biosynthesis pathway to primary cell wall metabolism in higher plants. Our previous work demonstrated that GME is crucial for both ascorbate and cell wall biosynthesis in tomato. The aim of the present study was to investigate the respective role in ascorbate and cell wall biosynthesis of the two SlGME genes present in tomato by targeting each of them through an RNAi-silencing approach. Taken individually SlGME1 and SlGME2 allowed normal ascorbate accumulation in the leaf and fruits, thus suggesting the same function regarding ascorbate. However, SlGME1 and SlGME2 were shown to play distinct roles in cell wall biosynthesis, depending on the tissue considered. The RNAi-SlGME1 plants harbored small and poorly seeded fruits resulting from alterations of pollen development and of pollination process. In contrast, the RNAi-SlGME2 plants exhibited vegetative growth delay while fruits remained unaffected. Analysis of SlGME1- and SlGME2-silenced seeds and seedlings further showed that the dimerization state of pectin rhamnogalacturonan-II (RG-II) was altered only in the RNAi-SlGME2 lines. Taken together with the preferential expression of each SlGME gene in different tomato tissues, these results suggest sub-functionalization of SlGME1 and SlGME2 and their specialization for cell wall biosynthesis in specific tomato tissues. PMID:27382114

  2. Multiple cell hits by particle tracks in solid tissues.

    PubMed

    Todd, P

    1992-01-01

    Relative Biological Effectiveness (RBE) and Quality Factor (Q) at extreme values of Linear Energy Transfer (LET) have been determined on the basis of experiments with single-cell systems and specific tissue responses. In typical single cell systems, each heavy particle (Ar or Fe) passes through a single cell or no cell. In tissue end-point experiments each heavy particle passes through several cells, and the LET can exceed 200 keV/micrometer in every cell. In most laboratory animal tissue systems, however, only a small portion of the hit cells are capable of expressing the end-point of interest to the investigator, such as cell killing, mutation or carcinogenesis. The following question must therefore be addressed: Do RBE's and Q factors derived from single-cell experiments properly account for the increased probability of multiple-cell damage by HZE tracks? A model is offered in which measured radiation effects and known tissue properties are combined to estimate the value of a multiplier of damage effectiveness on the basis of number of cells at risk, p3n, per track containing a hit cell, where n is the number of cells per track, based on tissue and organ geometry, and P3 is the probability that a cell in the track is capable of expressing the experimental end-point. PMID:11537036

  3. Overview of the HIT-II Program and Diagnostic Development

    NASA Astrophysics Data System (ADS)

    Smith, R. J.; Redd, A. J.; Nelson, B. A.; Jarboe, T. R.; Gu, P.; Hamp, W. T.; Jewell, P. D.

    2001-10-01

    The HIT-II device is a low-aspect ratio (Ro = 0.3m, a = 0.2m) torus with a 0.5T field on axis. The machine configuration allows both inductive current drive and coaxial helicity injection (CHI) current drive operations and is capable of producing plasma currents of 200 kA in either mode. The device has active feedback control of the equilibrium and is capable of combining both current drive techniques during the same discharge. The plasma demonstrates a variety of phenomena including IREs and an n=1 rotating instability in both modes of operation (believed to be the mechanism for current drive in CHI plasmas). Details of the operation of the HIT-II device are presented along with data from several new diagnostics: a novel two chord scanning interferometer using a Martin-Puplett configuration, a multi-point Thomson scattering system, an internal magnetic probe, and a Zeff detector. These diagnostics are designed to give information on density and temperature profiles and the localization of internal magnetic fluctuations in the plasma.

  4. A Hit or Miss History of Statistics at Sandia

    SciTech Connect

    Diegert, Kathleen V.

    1999-08-04

    The Statistics and Human Factors Department at SNL has evolved as the Labs' mission has evolved from engineering designs for the non-nuclear parts of nuclear weapons, including the safety and security components, to a multi-program lab focusing on national security. Twenty years ago their client base was the engineers, scientists, and managers of the nuclear weapon stockpile program, at Sandia and other facilities within the DOE complex. Client relationships developed over years of association. Components and systems were assigned to statisticians so that they could develop a knowledge base in that area. Because of the many different component types and system designs in the stockpile, they typically juggled five or six statistical projects at a time. project participation other than statistical consulting was limited. They rarely had the time to lead project teams, and any skills or inclinations in that direction were often undeveloped. This paper describes a (hit-or-miss) selection of some early and recent efforts. This paper also presents their self-assessment metrics and their external assessment metrics. These metrics were selected to track the business aspects of the department; they are systematic (not hit-or-miss). These two types of histories should allow them to judge whether we're doing the right things, and also doing things right.

  5. Adiabatic condition and the quantum hitting time of Markov chains

    SciTech Connect

    Krovi, Hari; Ozols, Maris; Roland, Jeremie

    2010-08-15

    We present an adiabatic quantum algorithm for the abstract problem of searching marked vertices in a graph, or spatial search. Given a random walk (or Markov chain) P on a graph with a set of unknown marked vertices, one can define a related absorbing walk P{sup '} where outgoing transitions from marked vertices are replaced by self-loops. We build a Hamiltonian H(s) from the interpolated Markov chain P(s)=(1-s)P+sP{sup '} and use it in an adiabatic quantum algorithm to drive an initial superposition over all vertices to a superposition over marked vertices. The adiabatic condition implies that, for any reversible Markov chain and any set of marked vertices, the running time of the adiabatic algorithm is given by the square root of the classical hitting time. This algorithm therefore demonstrates a novel connection between the adiabatic condition and the classical notion of hitting time of a random walk. It also significantly extends the scope of previous quantum algorithms for this problem, which could only obtain a full quadratic speedup for state-transitive reversible Markov chains with a unique marked vertex.

  6. Promiscuous 2-aminothiazoles (PrATs): a frequent hitting scaffold.

    PubMed

    Devine, Shane M; Mulcair, Mark D; Debono, Cael O; Leung, Eleanor W W; Nissink, J Willem M; Lim, San Sui; Chandrashekaran, Indu R; Vazirani, Mansha; Mohanty, Biswaranjan; Simpson, Jamie S; Baell, Jonathan B; Scammells, Peter J; Norton, Raymond S; Scanlon, Martin J

    2015-02-12

    We have identified a class of molecules, known as 2-aminothiazoles (2-ATs), as frequent-hitting fragments in biophysical binding assays. This was exemplified by 4-phenylthiazol-2-amine being identified as a hit in 14/14 screens against a diverse range of protein targets, suggesting that this scaffold is a poor starting point for fragment-based drug discovery. This prompted us to analyze this scaffold in the context of an academic fragment library used for fragment-based drug discovery (FBDD) and two larger compound libraries used for high-throughput screening (HTS). This analysis revealed that such "promiscuous 2-aminothiazoles" (PrATs) behaved as frequent hitters under both FBDD and HTS settings, although the problem was more pronounced in the fragment-based studies. As 2-ATs are present in known drugs, they cannot necessarily be deemed undesirable, but the combination of their promiscuity and difficulties associated with optimizing them into a lead compound makes them, in our opinion, poor scaffolds for fragment libraries. PMID:25559643

  7. Heparin-induced thrombocytopenia (HIT II) - a drug-associated autoimmune disease.

    PubMed

    Nowak, Götz

    2009-11-01

    Autoimmune thrombocytopenia (ITP) is an acquired autoimmune disease characterised by isolated persistent thrombocytopenia and normal megakaryopoiesis. This definition also applies to heparin-induced thrombocytopenia (HIT II), a frequent side effect of heparin treatment. In HIT II, the immunogen is a coagulation active complex of heparin and platelet factor 4 (PF4). By now, diagnostics of HIT II is often material and time consuming. Three groups of patients were investigated for HIT II antibodies (HIT II-AB): 54 hospitalised stroke patients, 87 hospitalised cardiac patients, and 71 patients on chronic haemodialysis, all treated with heparin. Furthermore, 100 healthy volunteers were investigated. For detection of HIT II-AB the innovative whole blood test PADA-HIT (PADA: platelet adhesion assay) was used. PADA-HIT quantifies the interaction of IgG antibodies with FcgammaIIA receptors by comparing the activation state of platelets in citrated and heparinised whole blood. The occurrence of HIT II-AB in blood was very high with 44 % of stroke patients, 69% of cardiac patients and 38% of haemodialysis patients compared to only 15% of healthy volunteers. This demonstrates a high incidence and a rapid onset of HIT II-AB in patients being acutely treated with heparin. HIT II is one of the most frequent and severe autoimmune diseases bearing a great thrombosis risk. PADA-HIT represents an innovative diagnostic method for detection of autoimmune antibodies of IgG type that are directed against platelet factor 4 (PF4)-heparin-complex. By early and fast diagnostics and appropriate treatment severe complications of HIT II can be prevented. PMID:19888524

  8. Influence of corruption on economic growth rate and foreign investment

    NASA Astrophysics Data System (ADS)

    Podobnik, Boris; Shao, Jia; Njavro, Djuro; Ivanov, Plamen Ch.; Stanley, H. E.

    2008-06-01

    We analyze the dependence of the Gross Domestic Product ( GDP) per capita growth rates on changes in the Corruption Perceptions Index ( CPI). For the period 1999 2004 for all countries in the world, we find on average that an increase of CPI by one unit leads to an increase of the annual GDP per capita growth rate by 1.7%. By regressing only the European countries with transition economies, we find that an increase of CPI by one unit generates an increase of the annual GDP per capita growth rate by 2.4%. We also analyze the relation between foreign direct investments received by different countries and CPI, and we find a statistically significant power-law functional dependence between foreign direct investment per capita and the country corruption level measured by the CPI. We introduce a new measure to quantify the relative corruption between countries based on their respective wealth as measured by GDP per capita.

  9. Radial junction solar cells based on heterojunction with intrinsic thin layer (HIT) structure

    NASA Astrophysics Data System (ADS)

    Shen, Haoting

    The radial junction wire array structure was previously proposed as a solar cell geometry to separate the direction of carrier collection from the direction of light absorption, thereby circumventing the need to use high quality but expensive single crystal silicon (c-Si) material that has long minority carrier diffusion lengths. The Si radial junction structure can be realized by forming radial p-n junctions on Si pillar/wire arrays that have a diameter comparable to the minority carrier diffusion length. With proper design, the Si pillar arrays are also able to enhance light trapping and thereby increase the light absorption. However, the larger junction area and surface area on the pillar arrays compared to traditional planar junction Si solar cells makes it challenging to fabricate high performance devices due an in increase in surface defects. Therefore, effective surface passivation strategies are essential for radial junction devices. Hydrogenated amorphous silicon (a-Si:H) deposited by plasma-enhanced chemical vapor deposition (PECVD) using a heterojunction with intrinsic thin layer (HIT) structure has previously been demonstrated as a very effective surface passivation layer for planar c-Si solar cells. It is therefore of interest to use a-Si:H in a HIT layer structure for radial p-n junction c-Si pillar array solar cells. This poses several challenges, however, including the need to fabricate ultra-thin a-Si:H layers conformally on high aspect ratio Si pillars, control the crystallinity at the a-Si:H/c-Si interface to yield a low interface state density and optimize the layer thicknesses, doping and contacts to yield high performance devices. This research in this thesis was aimed at developing the processing technology required to apply the HIT structure to radial junction Si pillar array solar cell devices and to evaluate the device characteristics. Initial studies focused on understanding the effects of process conditions on the growth rate and

  10. Overview of the HIT-SI3 Experiment and Ion Doppler Spectroscopy Results from HIT-SI

    NASA Astrophysics Data System (ADS)

    Hossack, A. C.; Morgan, K. D.; Hansen, C. J.; Everson, C. J.; Sutherland, D. A.; Summers, A. W.; Chandra, R. N.; Nguyen, N. H.; Nelson, B. A.; Jarboe, T. R.; Elliott, D. B.; Victor, B. S.

    2015-11-01

    HIT-SI3 is a one-meter diameter spheromak current drive experiment. The plasma is formed and sustained by three inductive helicity injectors. The loop voltage and magnetic flux in each injector are oscillated in phase. The three injectors can be phased 120 or 60 degrees apart giving constant helicity injection. Operating frequencies include 14.5 kHz, 47.5 kHz, and higher. Toroidal current 3 times greater than the quadrature sum of injector currents has been achieved. Results are presented from a new, internal magnetic probe which spans the entire major radius of the flux conserver. Initial results will also be presented from the multi-point Thomson scattering diagnostic, ion Doppler spectrometer (IDS), and laser-induced fluorescence neutral density diagnostic. IDS results from the previous experiment, HIT-SI, are also presented. The spheromak plasma exhibits coherent motion driven by the injector currents and higher injector driving frequencies yielded higher betas than low frequency. Measurements are also compared with NIMROD and PSI-TET simulations and show qualitative agreement with temperature and velocity profiles. Work supported by USDoE.

  11. Influence of GDP on interaction of transducin with cyclic nucleotide phosphodiesterase and rhodopsin from bovine retinal rods

    SciTech Connect

    Rybin, V.O.

    1986-12-20

    In the presence of guanine nucleotides and rhodopsin-containing membranes from bovine retinal rod outer segments transducin stimulates light-sensitive cyclic nucleotide phosphodiesterase 5.5- to 7-fold. The activation constant (K/sub act/) for GTP and Gpp(NH)p is equal to 0.25 ..mu..M, while that for GDP and GDP..beta..S is 14 and 110 ..mu..M, respectively. GDP free of admixtures of other nucleotides does not activate phosphodiesterase at concentrations up to 1 mM, but is bound to transducin and inhibits the Gpp(NH)p-dependent activation of phosphodiesterase. The nature of the interaction of transducin with depolarized rhodopsin also depends on the type of guanine nucleotide bound: in the presence of GDP rhodopsin-containing membranes bind 70-100% of the transducin, whereas in the presence of Gpp(NH)p only 13% of the protein is bound. The data obtained indicate that GDP and GTP convert transducin to two different functional states: the transducin-GTP complex is bound to phosphodiesterase and activates it, while the transducin-GDP complex is bound primarily to rhodopsin.

  12. On the statistical dependence of hits in frequency-hop multiple access

    NASA Astrophysics Data System (ADS)

    Frank, Colin D.; Pursley, Michael B.

    1990-09-01

    The statistical dependence of hits due to multiple-access interference in an asynchronous slow-frequency-hop packet radio network in which the radios employ memoryless hopping patterns is described. Models in which hits are conditionally independent given the number of interfering packets are investigated. It is shown that, if the conditional probability of a hit is chosen appropriately, the distribution function for the number of hits in a packet for these models can be used to compute upper and lower bounds on the true distribution function for the number of hits. Conditions are described for which these models can be used to compute upper and lower bounds on the codeword and packet error probabilities. If the ratio of the number of interfering packets to the number of frequency slots is held constant, hits in the asynchronous frequency-hop network are asymptotically independent in the limit as the number of frequency slots increases.

  13. A GDP-driven model for the binary and weighted structure of the International Trade Network

    NASA Astrophysics Data System (ADS)

    Almog, Assaf; Squartini, Tiziano; Garlaschelli, Diego

    2015-01-01

    Recent events such as the global financial crisis have renewed the interest in the topic of economic networks. One of the main channels of shock propagation among countries is the International Trade Network (ITN). Two important models for the ITN structure, the classical gravity model of trade (more popular among economists) and the fitness model (more popular among networks scientists), are both limited to the characterization of only one representation of the ITN. The gravity model satisfactorily predicts the volume of trade between connected countries, but cannot reproduce the missing links (i.e. the topology). On the other hand, the fitness model can successfully replicate the topology of the ITN, but cannot predict the volumes. This paper tries to make an important step forward in the unification of those two frameworks, by proposing a new gross domestic product (GDP) driven model which can simultaneously reproduce the binary and the weighted properties of the ITN. Specifically, we adopt a maximum-entropy approach where both the degree and the strength of each node are preserved. We then identify strong nonlinear relationships between the GDP and the parameters of the model. This ultimately results in a weighted generalization of the fitness model of trade, where the GDP plays the role of a ‘macroeconomic fitness’ shaping the binary and the weighted structure of the ITN simultaneously. Our model mathematically explains an important asymmetry in the role of binary and weighted network properties, namely the fact that binary properties can be inferred without the knowledge of weighted ones, while the opposite is not true.

  14. Brown adipose tissue mitochondria: modulation by GDP and fatty acids depends on the respiratory substrates

    PubMed Central

    De Meis, Leopoldo; Ketzer, Luisa A.; Camacho-Pereira, Juliana; Galina, Antonio

    2011-01-01

    The UCP1 [first UCP (uncoupling protein)] that is found in the mitochondria of brown adipocytes [BAT (brown adipose tissue)] regulates the heat production, a process linked to non-shivering thermogenesis. The activity of UCP1 is modulated by GDP and fatty acids. In this report, we demonstrate that respiration and heat released by BAT mitochondria vary depending on the respiratory substrate utilized and the coupling state of the mitochondria. It has already been established that, in the presence of pyruvate/malate, BAT mitochondria are coupled by faf-BSA (fatty-acid-free BSA) and GDP, leading to an increase in ATP synthesis and mitochondrial membrane potential along with simultaneous decreases in both the rates of respiration and heat production. Oleate restores the uncoupled state, inhibiting ATP synthesis and increasing the rates of both respiration and heat production. We now show that in the presence of succinate: (i) the rates of uncoupled mitochondria respiration and heat production are five times slower than in the presence of pyruvate/malate; (ii) faf-BSA and GDP accelerate heat and respiration as a result and, in coupled mitochondria, these two rates are accelerated compared with pyruvate/malate; (iii) in spite of the differences in respiration and heat production noted with the two substrates, the membrane potential and the ATP synthesized were the same; and (iv) oleate promoted a decrease in heat production and respiration in coupled mitochondria, an effect different from that observed using pyruvate/malate. These effects are not related to the production of ROS (reactive oxygen species). We suggest that succinate could stimulate a new route to heat production in BAT mitochondria. PMID:21561434

  15. Permanent Ocular Injury Following Paintball Pellet Hit: A Medicolegal Case.

    PubMed

    Ghazanfari-Nasrabad, Mahdi; Amrollahi-Sharifabadi, Mohammad; Kargar-Bideh, Omidreza; Azizi-Sharifabad, Saeed

    2016-01-01

    Paintball is a ubiquitous recreation, with severe and occasionally irreversible injuries. In this study, a rare medicolegal case of paintball-related closed globe blunt ocular injury was described. An 18-year-old boy who was hit in his right eye by a paintball pellet presented with severe eye pain and blurred vision. Ophthalmologic examinations showed lid edema, conjunctival hyperemia, conjunctival laceration, subconjunctival hemorrhage, corneal edema, anterior vitreous hemorrhage, congested sclera, commotio retinae, vitreous hemorrhage, retinal hemorrhage, macular edema, and macular hole. After maximum medical improvement, the patient who sustained incurable maculopathy and decreased visual acuity was referred to the legal medicine center for appraisal of the impairment. AMA Guides was used to assess the impairment of the functional vision. Despite his monocular visual defect, the patient was rated in the range of mild vision loss namely AMA class 1 with 22 percentage visual system impairment. PMID:26211673

  16. Inflammation and the Two-Hit Hypothesis of Schizophrenia

    PubMed Central

    Feigenson, Keith A.; Kusnecov, Alex W.; Silverstein, Steven M.

    2014-01-01

    The high societal and individual cost of schizophrenia necessitates finding better, more effective treatment, diagnosis, and prevention strategies. One of the obstacles in this endeavor is the diverse set of etiologies that comprises schizophrenia. A substantial body of evidence has grown over the last few decades to suggest that schizophrenia is a heterogeneous syndrome with overlapping symptoms and etiologies. At the same time, an increasing number of clinical, epidemiological, and experimental studies have shown links between schizophrenia and inflammatory conditions. In this review, we analyze the literature on inflammation and schizophrenia, with a particular focus on comorbidity, biomarkers, and environmental insults. We then identify several mechanisms by which inflammation could influence the development of schizophrenia via the two-hit hypothesis. Lastly, we note the relevance of these findings to clinical applications in the diagnosis, prevention, and treatment of schizophrenia. PMID:24247023

  17. Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides.

    PubMed

    Floyd, David M; Stein, Philip; Wang, Zheng; Liu, Jian; Castro, Steve; Clark, Julie A; Connelly, Michele; Zhu, Fangyi; Holbrook, Gloria; Matheny, Amy; Sigal, Martina S; Min, Jaeki; Dhinakaran, Rajkumar; Krishnan, Senthil; Bashyum, Sridevi; Knapp, Spencer; Guy, R Kiplin

    2016-09-01

    Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent antimalarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity studies revealed relationships between potency and modifications at N-2, C-3, and C-4. Careful structure-property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicological effects, inherent in the more potent primary screening hits such as 10b. Analogues 13h and 13i, with structural modifications at each site, were shown to possess excellent antimalarial activity in vivo. The (+)-(3S,4S) enantiomer of 13i and similar analogues were identified as the more potent. On the basis of these studies, we have selected (+)-13i for further study as a preclinical candidate. PMID:27505686

  18. Ozone hits low levels over Antarctica, U. S

    SciTech Connect

    Zurer, P.

    1993-10-04

    This year's Antarctic ozone hole is as deep as any ever observed and is approaching the record geographical extent of 1992, according to preliminary satellite data. In addition, both groundbased and satellite observations indicate that ozone concentrations over the U.S. hit record lows earlier this year. For more than a decade, almost all the ozone at certain altitudes over Antarctica has been destroyed as the Sun returns to the polar region in September. This dramatic photochemical depletion, catalyzed by chlorine and bromine from man-made compounds, reaches its nadir in early October. Ozone levels return to near normal later in the season, when the circular pattern of winds that isolates air over Antarctica breaks down, and ozone-rich air pours in from the north.

  19. Rational Prediction with Molecular Dynamics for Hit Identification

    PubMed Central

    Nichols, Sara E; Swift, Robert V; Amaro, Rommie E

    2012-01-01

    Although the motions of proteins are fundamental for their function, for pragmatic reasons, the consideration of protein elasticity has traditionally been neglected in drug discovery and design. This review details protein motion, its relevance to biomolecular interactions and how it can be sampled using molecular dynamics simulations. Within this context, two major areas of research in structure-based prediction that can benefit from considering protein flexibility, binding site detection and molecular docking, are discussed. Basic classification metrics and statistical analysis techniques, which can facilitate performance analysis, are also reviewed. With hardware and software advances, molecular dynamics in combination with traditional structure-based prediction methods can potentially reduce the time and costs involved in the hit identification pipeline. PMID:23110535

  20. Imidazolopiperazines: hit to lead optimization of new antimalarial agents.

    PubMed

    Wu, Tao; Nagle, Advait; Kuhen, Kelli; Gagaring, Kerstin; Borboa, Rachel; Francek, Caroline; Chen, Zhong; Plouffe, David; Goh, Anne; Lakshminarayana, Suresh B; Wu, Jeanette; Ang, Hui Qing; Zeng, Peiting; Kang, Min Low; Tan, William; Tan, Maria; Ye, Nicole; Lin, Xuena; Caldwell, Christopher; Ek, Jared; Skolnik, Suzanne; Liu, Fenghua; Wang, Jianling; Chang, Jonathan; Li, Chun; Hollenbeck, Thomas; Tuntland, Tove; Isbell, John; Fischli, Christoph; Brun, Reto; Rottmann, Matthias; Dartois, Veronique; Keller, Thomas; Diagana, Thierry; Winzeler, Elizabeth; Glynne, Richard; Tully, David C; Chatterjee, Arnab K

    2011-07-28

    Starting from a hit series from a GNF compound library collection and based on a cell-based proliferation assay of Plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. SAR for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant parasites and improvement of physiochemical and pharmacokinetic properties. The lead compounds in this series showed good potencies in vitro and decent oral exposure levels in vivo. In a Plasmodium berghei mouse infection model, one lead compound lowered the parasitemia level by 99.4% after administration of 100 mg/kg single oral dose and prolonged mice survival by an average of 17.0 days. The lead compounds were also well-tolerated in the preliminary in vitro toxicity studies and represents an interesting lead for drug development. PMID:21644570

  1. 76 FR 46297 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-02

    ... access only. Name of Committees: HIT Standards Committee's Workgroups: Clinical Operations, Vocabulary... issues related to their specific subject matter, e.g., clinical operations vocabulary standards,...

  2. 76 FR 14975 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ... access only. Name of Committees: HIT Standards Committee's Workgroups: Clinical Operations, Vocabulary... specific subject matter, e.g., clinical operations vocabulary standards, clinical quality,...

  3. Anxiety vulnerability in women: a two-hit hypothesis.

    PubMed

    Catuzzi, Jennifer E; Beck, Kevin D

    2014-09-01

    Females are twice as likely to develop an anxiety disorder compared to males, and thus, are believed to possess an innate vulnerability that increases their susceptibility to develop an anxiety disorder. However, studies using aversive learning paradigms to model anxiety disorders in humans and animals have revealed contradictory results. While females exhibit the ability to rapidly acquire stimulus-response associations, which may result from a greater attentional bias towards threat, females are also capable to readily extinguish these associations. Thus, there is little evidence to suggest that the female sex represents a vulnerability factor of anxiety, per se. However, if females are to possess a second vulnerability factor that increases the inflexibility of stimulus-response associations, then an anxiety disorder may be more likely to develop. Behavioral inhibition (BI) is a vulnerability factor associated with the formation of inflexible stimulus-response associations. In this "two hit" model of anxiety vulnerability, females possessing a BI temperament will rapidly acquire stimulus-response associations that are resistant to extinction, resulting in the development of an anxiety disorder. In this review we explore evidence for a "two-hit" hypothesis underlying anxiety vulnerability in females. We explore the literature for evidence of a sex difference in attentional bias towards threat that may lead to the facilitated acquisition of stimulus-response associations in females. We also provide evidence that BI is associated with inflexible stimulus-response association formation. We conclude with data generated from our laboratory that highlights the additive effect of the female sex and behavioral inhibition vulnerabilities using a model behavior for anxiety disorder-susceptibility, active avoidance. PMID:24518489

  4. Improving health and well-being independently of GDP: dividends of greener and prosocial economies.

    PubMed

    Pretty, Jules; Barton, Jo; Bharucha, Zareen Pervez; Bragg, Rachel; Pencheon, David; Wood, Carly; Depledge, Michael H

    2016-01-01

    Increases in gross domestic product (GDP) beyond a threshold of basic needs do not lead to further increases in well-being. An explanation is that material consumption (MC) also results in negative health externalities. We assess how these externalities influence six factors critical for well-being: (i) healthy food; (ii) active body; (iii) healthy mind; (iv) community links; (v) contact with nature; and (vi) attachment to possessions. If environmentally sustainable consumption (ESC) were increasingly substituted for MC, thus improving well-being and stocks of natural and social capital, and sustainable behaviours involving non-material consumption (SBs-NMC) became more prevalent, then well-being would increase regardless of levels of GDP. In the UK, the individualised annual health costs of negative consumption externalities (NCEs) currently amount to £62 billion for the National Health Service, and £184 billion for the economy (for mental ill-health, dementia, obesity, physical inactivity, diabetes, loneliness and cardiovascular disease). A dividend is available if substitution by ESC and SBs-NMC could limit the prevalence of these conditions. PMID:25670173

  5. Lead generation and examples opinion regarding how to follow up hits.

    PubMed

    Orita, Masaya; Ohno, Kazuki; Warizaya, Masaichi; Amano, Yasushi; Niimi, Tatsuya

    2011-01-01

    In fragment-based drug discovery (FBDD), not only identifying the starting fragment hit to be developed but also generating a drug lead from that starting fragment hit is important. Converting fragment hits to leads is generally similar to a high-throughput screening (HTS) hits-to-leads approach in that properties associated with activity for a target protein, such as selectivity against other targets and absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox), and physicochemical properties should be taken into account. However, enhancing the potency of the fragment hit is a key requirement in FBDD, unlike HTS, because initial fragment hits are generally weak. This enhancement is presently achieved by adding additional chemical groups which bind to additional parts of the target protein or by joining or combining two or more hit fragments; however, strategies for effecting greater improvements in effective activity are needed. X-ray analysis is a key technology attractive for converting fragments to drug leads. This method makes it clear whether a fragment hit can act as an anchor and provides insight regarding introduction of functional groups to improve fragment activity. Data on follow-up chemical synthesis of fragment hits has allowed for the differentiation of four different strategies: fragment optimization, fragment linking, fragment self-assembly, and fragment evolution. Here, we discuss our opinion regarding how to follow up on fragment hits, with a focus on the importance of fragment hits as an anchor moiety to so-called hot spots in the target protein using crystallographic data. PMID:21371599

  6. Radial junction solar cells based on heterojunction with intrinsic thin layer (HIT) structure

    NASA Astrophysics Data System (ADS)

    Shen, Haoting

    The radial junction wire array structure was previously proposed as a solar cell geometry to separate the direction of carrier collection from the direction of light absorption, thereby circumventing the need to use high quality but expensive single crystal silicon (c-Si) material that has long minority carrier diffusion lengths. The Si radial junction structure can be realized by forming radial p-n junctions on Si pillar/wire arrays that have a diameter comparable to the minority carrier diffusion length. With proper design, the Si pillar arrays are also able to enhance light trapping and thereby increase the light absorption. However, the larger junction area and surface area on the pillar arrays compared to traditional planar junction Si solar cells makes it challenging to fabricate high performance devices due an in increase in surface defects. Therefore, effective surface passivation strategies are essential for radial junction devices. Hydrogenated amorphous silicon (a-Si:H) deposited by plasma-enhanced chemical vapor deposition (PECVD) using a heterojunction with intrinsic thin layer (HIT) structure has previously been demonstrated as a very effective surface passivation layer for planar c-Si solar cells. It is therefore of interest to use a-Si:H in a HIT layer structure for radial p-n junction c-Si pillar array solar cells. This poses several challenges, however, including the need to fabricate ultra-thin a-Si:H layers conformally on high aspect ratio Si pillars, control the crystallinity at the a-Si:H/c-Si interface to yield a low interface state density and optimize the layer thicknesses, doping and contacts to yield high performance devices. This research in this thesis was aimed at developing the processing technology required to apply the HIT structure to radial junction Si pillar array solar cell devices and to evaluate the device characteristics. Initial studies focused on understanding the effects of process conditions on the growth rate and

  7. Development of a potent and selective FLT3 kinase inhibitor by systematic expansion of a non-selective fragment-screening hit.

    PubMed

    Nakano, Hirofumi; Hasegawa, Tsukasa; Imamura, Riyo; Saito, Nae; Kojima, Hirotatsu; Okabe, Takayoshi; Nagano, Tetsuo

    2016-05-01

    A non-selective inhibitor (1) of FMS-like tyrosine kinase-3 (FLT3) was identified by fragment screening and systematically modified to afford a potent and selective inhibitor 26. We confirmed that 26 inhibited the growth of FLT-3-activated human acute myeloid leukemia cell line MV4-11. Our design strategy enabled rapid development of a novel type of FLT3 inhibitor from the hit fragment in the absence of target-structural information. PMID:26995531

  8. 75 FR 62399 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-08

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Standards Committee Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice. SUMMARY: Section 3003(b)(3) of...

  9. 75 FR 369 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-05

    .... Date and Time: The HIT Policy Committee Workgroups will hold the following public meetings during the... Technology (ONC). The meetings will be open to the public via dial-in access only. Name of Committees: HIT... accommodated during the scheduled open public session, ONC will take written comments after the meeting...

  10. Factors associated with hit-and-run pedestrian fatalities and driver identification.

    PubMed

    MacLeod, Kara E; Griswold, Julia B; Arnold, Lindsay S; Ragland, David R

    2012-03-01

    As hit-and-run crashes account for a significant proportion of pedestrian fatalities, a better understanding of these crash types will assist efforts to reduce these fatalities. Of the more than 48,000 pedestrian deaths that were recorded in the United States between 1998 and 2007, 18.1% of them were caused by hit-and-run drivers. Using national data on single pedestrian-motor vehicle fatal crashes (1998-2007), logistic regression analyses were conducted to identify factors related to hit-and-run and to identify factors related to the identification of the hit-and-run driver. Results indicate an increased risk of hit-and-run in the early morning, poor light conditions, and on the weekend. There may also be an association between the type of victim and the likelihood of the driver leaving and being identified. Results also indicate that certain driver characteristics, behavior, and driving history are associated with hit-and-run. Alcohol use and invalid license were among the leading driver factor associated with an increased risk of hit-and-run. Prevention efforts that address such issues could substantially reduce pedestrian fatalities as a result of hit-and-run. However, more information about this driver population may be necessary. PMID:22269520

  11. Visual Illusions and the Control of Ball Placement in Goal-Directed Hitting

    ERIC Educational Resources Information Center

    Caljouw, Simone R.; Van der Kamp, John; Savelsbergh, Geert J. P.

    2010-01-01

    When hitting, kicking, or throwing balls at targets, online control in the target area is impossible. We assumed this lack of late corrections in the target area would induce an effect of a single-winged Muller-Lyer illusion on ball placement. After extensive practice in hitting balls to different landing locations, participants (N = 9) had to hit…

  12. Inhibition of GDP/GTP exchange on G alpha subunits by proteins containing G-protein regulatory motifs.

    PubMed

    Natochin, M; Gasimov, K G; Artemyev, N O

    2001-05-01

    A novel Galpha binding consensus sequence, termed G-protein regulatory (GPR) or GoLoco motif, has been identified in a growing number of proteins, which are thought to modulate G-protein signaling. Alternative roles of GPR proteins as nucleotide exchange factors or as GDP dissociation inhibitors for Galpha have been proposed. We investigated the modulation of the GDP/GTP exchange of Gialpha(1), Goalpha, and Gsalpha by three proteins containing GPR motifs (GPR proteins), LGN-585-642, Pcp2, and RapIGAPII-23-131, to elucidate the mechanisms of GPR protein function. The GPR proteins displayed similar patterns of interaction with Gialpha(1) with the following order of affinities: Gialpha(1)GDP > Gialpha(1)GDPAlF(4)(-) > or = Gialpha(1)GTPgammaS. No detectable binding of the GPR proteins to Gsalpha was observed. LGN-585-642, Pcp2, and RapIGAPII-23-131 inhibited the rates of spontaneous GTPgammaS binding and blocked GDP release from Gialpha(1) and Goalpha. The inhibitory effects of the GPR proteins on Gialpha(1) were significantly more potent, indicating that Gi might be a preferred target for these modulators. Our results suggest that GPR proteins are potent GDP dissociation inhibitors for Gialpha-like Galpha subunits in vitro, and in this capacity they may inhibit GPCR/Gi protein signaling in vivo. PMID:11318657

  13. The Missing Mantle Paradox, and the Statistical Argument for Repeated Hit and Run Collisions

    NASA Astrophysics Data System (ADS)

    Asphaug, E.; Reufer, A.

    2015-10-01

    Mercury's formation can be explained by a giant impact. However, a direct hit blasting off the mantle [1] leaves debris stranded in orbitabout the Sun,to be re-accumulated back onto Mercury. A hit and run collision [2] provides a cleaner solution, and in most cases,much lower levels of shock and potentially greater retention of volatiles. However, hit and run is usually followed by subsequent re-collision, and ultimate accretion; an embryo's survival after being a hit and run projectile is unlikely in any single instance. Most of the original planetary embryoshave been accreted by Earth and Venus; unaccreted planets are lucky. Here we show that the surviving terrestrial planet population is likely to have about as many hit and run survivors, as it is to have untouched survivors. That is, the differences between Mercury and Mars can be explained in a statistical manner as a consequence of accretionary attrition. We consider applications to asteroids, meteorites and exoplanets.

  14. PageRank, HITS and a unified framework for link analysis

    SciTech Connect

    Ding, Chris; He, Xiaofeng; Husbands, Parry; Zha, Hongyuan; Simon, Horst

    2001-10-01

    Two popular webpage ranking algorithms are HITS and PageRank. HITS emphasizes mutual reinforcement between authority and hub webpages, while PageRank emphasizes hyperlink weight normalization and web surfing based on random walk models. We systematically generalize/combine these concepts into a unified framework. The ranking framework contains a large algorithm space; HITS and PageRank are two extreme ends in this space. We study several normalized ranking algorithms which are intermediate between HITS and PageRank, and obtain closed-form solutions. We show that, to first order approximation, all ranking algorithms in this framework, including PageRank and HITS, lead to same ranking which is highly correlated with ranking by indegree. These results support the notion that in web resource ranking indegree and outdegree are of fundamental importance. Rankings of webgraphs of different sizes and queries are presented to illustrate our analysis.

  15. A New Neutral-pH Low-GDP Peritoneal Dialysis Fluid

    PubMed Central

    Himmele, Rainer; Jensen, Lynn; Fenn, Dominik; Ho, Chih-Hu; Sawin, Dixie-Ann; Diaz-Buxo, Jose A.

    2012-01-01

    ♦ Background: Conventional peritoneal dialysis fluids (PDFs) consist of ready-to-use solutions with an acidic pH. Sterilization of these fluids is known to generate high levels of glucose degradation products (GDPs). Although several neutral-pH, low-GDP PD solutions have been developed, none are commercially available in the United States. We analyzed pH and GDPs in Delflex Neutral pH (Fresenius Medical Care North America, Waltham, MA, USA), the first neutral-pH PDF to be approved by the US Food and Drug Administration. ♦ Methods: We evaluated whether patients (n = 26; age range: 18 - 78 years) could properly mix the Delflex Neutral pH PDF after standardized initial training. We further analyzed the concentrations of 10 different glucose degradation products in Delflex Neutral pH PDF and compared the results with similar analyses in other commercially available biocompatible PDFs. ♦ Results: All pH measurements (n = 288) in the delivered Delflex Neutral pH solution consistently fell within the labeled range of 7.0 ± 0.4. Analysis of mixing errors showed no significant impact on the pH results. Delflex Neutral pH, Balance (Fresenius Medical Care, Bad Homburg, Germany), BicaVera (Fresenius Medical Care), and Gambrosol Trio (Gambro Lundia AB, Lund, Sweden) exhibited similar low total GDP concentrations, with maximums in the 4.25% solutions of 88 μmol/L, 74 μmol/L, 74 μmol/L, and 79 μmol/L respectively; the concentration in Physioneal (Baxter Healthcare Corporation, Deerfield, IL, USA) was considerably higher at 263.26 μmol/L. The total GDP concentration in Extraneal (Baxter Healthcare Corporation) was 63 μmol/L, being thus slightly lower than the concentrations in the 4.25% glucose solutions, but higher than the concentrations in the 1.5% and 2.5% glucose solutions. ♦ Conclusions: The new Delflex Neutral pH PDF consistently delivers neutral pH with minimal GDPs. PMID:22383632

  16. Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual-hit hypothesis of neurodegeneration.

    PubMed

    Heinemann, Scott D; Posimo, Jessica M; Mason, Daniel M; Hutchison, Daniel F; Leak, Rehana K

    2016-08-01

    The dual-hit hypothesis of neurodegeneration states that severe stress sensitizes vulnerable cells to subsequent challenges so that the two hits are synergistic in their toxic effects. Although the hippocampus is vulnerable to a number of neurodegenerative disorders, there are no models of synergistic cell death in hippocampal neurons in response to combined proteotoxic and oxidative stressors, the two major characteristics of these diseases. Therefore, a relatively high-throughput dual-hit model of stress synergy was developed in primary hippocampal neurons. In order to increase the rigor of the study and strengthen the interpretations, three independent, unbiased viability assays were employed at multiple timepoints. Stress synergy was elicited when hippocampal neurons were treated with the proteasome inhibitor MG132 followed by exposure to the oxidative toxicant paraquat, but only after 48 h. MG132 and paraquat only elicited additive effects 24 h after the final hit and even loss of heat shock protein 70 activity and glutathione did not promote stress synergy at this early timepoint. Dual hits of MG132 elicited modest glutathione loss and slightly synergistic toxic effects 48 h after the second hit, but only at some concentrations and only according to two viability assays (metabolic fitness and cytoskeletal integrity). The thiol N-acetyl cysteine protected hippocampal neurons against dual MG132/MG132 hits but not dual MG132/paraquat hits. These findings support the view that proteotoxic and oxidative stress propel and propagate each other in hippocampal neurons, leading to synergistically toxic effects, but not as the default response and only after a delay. The neuronal stress synergy observed here lies in contrast to astrocytic responses to dual hits, because astrocytes that survive severe proteotoxic stress resist additional cell loss following second hits. In conclusion, a new model of hippocampal vulnerability was developed for the testing of therapies

  17. The effect of fastball backspin rate on baseball hitting accuracy.

    PubMed

    Higuchi, Takatoshi; Morohoshi, Jun; Nagami, Tomoyuki; Nakata, Hiroki; Kanosue, Kazuyuki

    2013-06-01

    The effectiveness of fastballs of equivalent speed can differ; for example, one element of this difference could be due to the effect of rate and orientation of ball spin on launched ball trajectory. In the present experiment, baseball batters' accuracy in hitting fastballs with different backspin rates at a constant ball velocity of 36 m/s was examined. Thirteen skilled baseball players (professionals, semiprofessionals, and college varsity players) participated in the study. The movements of bat and ball were recorded using two synchronized high-speed video cameras. The Pearson product-moment correlation coefficient (r) was calculated and used to analyze the relationship between ball backspin rate and the vertical distance between ball center and sweet spot at the moment of ball-bat impact. Ball backspin rate was positively correlated with increases in the distance from the optimal contact point of the swung bat (sweet spot) to the actual point of contact (r = .38, P < .001). Batters were most effective at the usual backspin rate for the ball velocity used. The decrease in accuracy of the batter's swing that was observed when the fastball's backspin deviated from the usual rate likely occurred because experienced batters predict ball trajectory from perceived ball speed. PMID:22923374

  18. Hitting Matrix and Domino Tiling with Diagonal Impurities

    NASA Astrophysics Data System (ADS)

    Nakano, Fumihiko; Sadahiro, Taizo

    2013-06-01

    As a continuation to our previous work (Nakano and Sadahiro in Fundam. Inform. 117:249-264, 2012; Nakano and Sadahiro in J. Stat. Phys. 139(4):565-597, 2010), we consider the domino tiling problem with impurities. (1) If we have more than two impurities on the boundary, we can compute the number of corresponding perfect matchings by using the hitting matrix method (Fomin in Trans. Am. Math. Soc. 353(9):3563-3583, 2001). (2) We have an alternative proof of the main result in Nakano and Sadahiro (Fundam. Inform. 117:249-264, 2012) and result in (1) above using the formula by Kenyon and Wilson (Trans. Am. Math. Soc. 363(3):1325-1364, 2011; Electron. J. Comb. 16(1):112, 2009) of counting the number of groves on circular planar graphs. (3) We study the behavior of the probability of finding the impurity at a given site when the size of the graph tends to infinity, as well as the scaling limit of those.

  19. Equilibrium and Stability Calculations in HIT-SI

    NASA Astrophysics Data System (ADS)

    Hansen, Chris; Marklin, George; Jarboe, Thomas

    2012-10-01

    The PSI-TET equilibrium code solves for solutions to the Ideal MHD equilibrium equation μ0j = λB in arbitrary 3D geometry. A mimetic discretization on a tetrahedral mesh is employed, with up to 3rd order spatial representation. Geometric and polynomial multigrid along with a hybrid MPI/OpenMP parallelism model is used to provide solver scalability. Lambda is allowed to vary across flux surfaces but must be constant in stochastic regions. A scalar flux surface variable is computed by solving an artificial diffusion problem with a large ratio of parallel to perpendicular thermal conductivity. A fixed lambda profile, specified as a function of this flux surface variable, is defined. Equilibria in HIT-SI have been computed for the homogenous (spheromak) and inhomogeneous (injector) fields separately. Combined equilibria of interest with injector driving have also been computed for various lambda profiles. A linearized Ideal MHD module has been developed to evaluate the stability properties of computed equilbria. Equilibrium states and stability analysis will be presented for a range of lambda profiles. Results will also be presented comparing linear to high order Mimetic representations and Mimetic to standard nodal finite element representations. Work supported by DOE.

  20. Scientific impact: the story of your big hit

    NASA Astrophysics Data System (ADS)

    Sinatra, Roberta; Wang, Dashun; Deville, Pierre; Song, Chaoming; Barabasi, Albert-Laszlo

    2014-03-01

    A gradual increase in performance through learning and practice characterize most trades, from sport to music or engineering, and common sense suggests this to be true in science as well. This prompts us to ask: what are the precise patterns that lead to scientific excellence? Does performance indeed improve throughout a scientific career? Are there quantifiable signs of an impending scientific hit? Using citation-based measures as a proxy of impact, we show that (i) major discoveries are not preceded by works of increasing impact, nor are followed by work of higher impact, (ii) the precise time ranking of the highest impact work in a scientist's career is uniformly random, with the higher probability to have a major discovery in the middle of scientific careers being due only to changes in productivity, (iii) there is a strong correlation between the highest impact work and average impact of a scientist's work. These findings suggest that the impact of a paper is drawn randomly from an impact distribution that is unique for each scientist. We present a model which allows to reconstruct the individual impact distribution, making possible to create synthetic careers that exhibit the same properties of the real data and to define a ranking based on the overall impact of a scientist. RS acknowledges support from the James McDonnell Foundation.

  1. Crystal structure of the GTPase domain and the bundle signalling element of dynamin in the GDP state.

    PubMed

    Anand, Roopsee; Eschenburg, Susanne; Reubold, Thomas F

    2016-01-01

    Dynamin is the prototype of a family of large multi-domain GTPases. The 100 kDa protein is a key player in clathrin-mediated endocytosis, where it cleaves off vesicles from membranes using the energy from GTP hydrolysis. We have solved the high resolution crystal structure of a fusion protein of the GTPase domain and the bundle signalling element (BSE) of dynamin 1 liganded with GDP. The structure provides a hitherto missing snapshot of the GDP state of the hydrolytic cycle of dynamin and reveals how the switch I region moves away from the active site after GTP hydrolysis and release of inorganic phosphate. Comparing our structure of the GDP state with the known structures of the GTP state, the transition state and the nucleotide-free state of dynamin 1 we describe the structural changes through the hydrolytic cycle. PMID:26612256

  2. Relating traffic fatalities to GDP in Europe on the long term.

    PubMed

    Antoniou, Constantinos; Yannis, George; Papadimitriou, Eleonora; Lassarre, Sylvain

    2016-07-01

    Modeling road safety development can provide important insight into policies for the reduction of traffic fatalities. In order to achieve this goal, both the quantifiable impact of specific parameters, as well as the underlying trends that cannot always be measured or observed, need to be considered. One of the key relationships in road safety links fatalities with risk and exposure, where exposure reflects the amount of travel, which in turn translates to how much travelers are exposed to risk. In general two economic variables: GDP and unemployment rate are selected to analyse the statistical relationships with some indicators of road accident fatality risk. The objective of this research is to provide an overview of relevant literature on the topic and outline some recent developments in macro-panel data analysis that have resulted in ongoing research that has the potential to improve our ability to forecast traffic fatality trends, especially under turbulent financial situations. For this analysis, time series of the number of fatalities and GDP in 30 European countries for a period of 38 years (1975-2012) are used. This process relies on estimating long-term models (as captured by long term time-series models, which model each country separately). Based on these developments, utilizing state-of-the-art modelling and analysis techniques such as the Common Correlated Effects Mean Group estimator (Pesaran), the long-term elasticity mean value equals 0.63, and is significantly different from zero for 10 countries only. When we take away the countries, where the number of fatalities is stationary, the average elasticity takes a higher value of nearly 1. This shows the strong sensitivity of the estimate of the average elasticity over a panel of European countries and underlines the necessity to be aware of the underlying nature of the time series, to get a suitable regression model. PMID:27042989

  3. Interaction of Anesthetics with the Rho GTPase Regulator Rho GDP Dissociation Inhibitor†

    PubMed Central

    Ho, Cojen; Shanmugasundararaj, Sivananthaperumal; Miller, Keith W.; Malinowski, Steve A.; Cook, Anthony C.; Slater, Simon J.

    2015-01-01

    The physiological effects of anesthetics have been ascribed to their interaction with hydrophobic sites within functionally relevant CNS proteins. Studies have shown that volatile anesthetics compete for luciferin binding to the hydrophobic substrate binding site within firefly luciferase and inhibit its activity (Franks, N. P., and Lieb, W. R. (1984) Nature 310, 599–601). To assess whether anesthetics also compete for ligand binding to a mammalian signal transduction protein, we investigated the interaction of the volatile anesthetic, halothane, with the Rho GDP dissociation inhibitor (RhoGDIα), which binds the geranylgeranyl moiety of GDP-bound Rho GTPases. Consistent with the existence of a discrete halothane binding site, the intrinsic tryptophan fluorescence of RhoGDIα was quenched by halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) in a saturable, concentration-dependent manner. Bromine quenching of tryptophan fluorescence is short range and W192 and W194 of the RhoGDIα are located within the geranylgeranyl binding pocket, suggesting that halothane binds within this region. Supporting this, N-acetyl-geranylgeranyl cysteine reversed tryptophan quenching by halothane. Short chain n-alcohols (n<6) also reversed tryptophan quenching, suggesting that RhoGDIα may also bind n-alkanols. Consistent with this, E193 was photo-labeled by 3-azibutanol. This residue is located in the vicinity of, but outside, the geranylgeranyl chain binding pocket, suggesting that the alcohol binding site is distinct from that occupied by halothane. Supporting this, N-acetyl-geranylgeranyl cysteine enhanced E193 photo-labeling by 3-azibutanol. Overall, the results suggest that halothane binds to a site within the geranylgeranyl chain binding pocket of RhoGDIα, whereas alcohols bind to a distal site that interacts allosterically with this pocket. PMID:18702520

  4. An interactive environmental model for economic growth: evidence from a panel of countries.

    PubMed

    Ramakrishnan, Suresh; Hishan, Sanil S; Nabi, Agha Amad; Arshad, Zeeshan; Kanjanapathy, Malini; Zaman, Khalid; Khan, Faisal

    2016-07-01

    This study aims to determine an interactive environmental model for economic growth that would be supported by the "sustainability principles" across the globe. The study examines the relationship between environmental pollutants (i.e., carbon dioxide emission, sulfur dioxide emission, mono-nitrogen oxide, and nitrous oxide emission); population growth; energy use; trade openness; per capita food production; and it's resulting impact on the real per capita GDP and sectoral growth (i.e., share of agriculture, industry, and services in GDP) in a panel of 34 high-income OECD, high-income non-OECD, and Europe and Central Asian countries, for the period of 1995-2014. The results of the panel fixed effect regression show that per capita GDP are influenced by sulfur dioxide emission, population growth, and per capita food production variability, while energy and trade openness significantly increases per capita income of the region. The results of the panel Seemingly Unrelated Regression (SUR) show that carbon dioxide emission significantly decreases the share of agriculture and industry in GDP, while it further supports the share of services sector to GDP. Both the sulfur dioxide and mono-nitrogen oxide emission decreases the share of services in GDP; nitrous oxide decreases the share of industry in GDP; while mono-nitrogen oxide supports the industrial activities. The following key growth-specific results has been obtained from the panel SUR estimation, i.e., (i) Both the food production per capita and trade openness significantly associated with the increasing share of agriculture, (ii) food production and energy use significantly increases the service sectors' productivity; (iii) food production decreases the industrial activities; (iv) trade openness decreases the share of services to GDP while it supports the industrial share to GDP; and finally, (v) energy demand decreases along with the increase agricultural share in the region. The results emphasize the need for

  5. Helicopter In-Flight Tracking System (HITS) for the Gulf of Mexico

    NASA Technical Reports Server (NTRS)

    Martone, Patrick; Tucker, George; Aiken, Edwin W. (Technical Monitor)

    2001-01-01

    The National Aeronautics and Space Administration (NASA) Ames Research Center (ARC) is sponsoring deployment and testing of the Helicopter In-flight Tracking System (HITS) in a portion of the Gulf of Mexico offshore area. Using multilateration principles, HITS determines the location and altitude of all transponder-equipped aircraft without requiring changes to current Mode A, C or S avionics. HITS tracks both rotary and fixed-wing aircraft operating in the 8,500 sq. mi. coverage region. The minimum coverage altitude of 100 ft. is beneficial for petroleum industry, allowing helicopters to be tracked onto the pad of most derricks. In addition to multilateration, HITS provides surveillance reports for aircraft equipped for Automatic Dependent Surveillance - Broadcast (ADS-B), a new surveillance system under development by the Federal Aviation Administration (FAA). The U.S. Department of Transportation (DOT) Volpe National Transportation Systems Center (Volpe Center) is supporting NASA in managing HITS installation and operation, and in evaluating the system's effectiveness. Senses Corporation is supplying, installing and maintaining the HITS ground system. Project activities are being coordinated with the FAA and local helicopter operators. Flight-testing in the Gulf will begin in early 2002. This paper describes the HITS project - specifically, the system equipment (architecture, remote sensors, central processing system at Intracoastal City, LA, and communications) and its performance (accuracy, coverage, and reliability). The paper also presents preliminary results of flight tests.

  6. Acute hormonal responses before and after 2 weeks of HIT in well trained junior triathletes.

    PubMed

    Zinner, C; Wahl, P; Achtzehn, S; Reed, J L; Mester, J

    2014-04-01

    The aim was to compare the acute hormonal response to a single HIT session at the beginning and end of a HIT shock microcycle. 13 male junior triathletes (15.8±1.8 yrs.) performed 16 HIT sessions within a 2 week period. Venous blood samples were collected before and after the first and last HIT session. Significant increases in cortisol (first session +89.7%; last session +70.3%) and hGH (first session +435.1%; last session +314.6%) concentrations were observed after both training sessions (P<0.05). The acute responses of cortisol, hGH, T3, and fT3 were not different between the first and last HIT sessions (P=1.00). Although no acute changes in testosterone were detected after the training sessions, testosterone concentrations were significantly higher at all time points (62.6-80.1%) during the last compared to first training session (P≤0.001). Findings from the present study reveal that 16 sessions of HIT led to significant increases in baseline concentrations of serum testosterone. This might indicate a heightened anabolic state even in junior triathletes. Based on the hormonal data, we conclude that at the end of this 2 week microcycle no familiarization effect was evident and that the training stimulus produced by HIT was still great enough to "stress" the athletes and induce positive training adaptations. PMID:24081622

  7. Current challenges and novel treatment strategies in double hit lymphomas

    PubMed Central

    Anderson, Mary Ann; Tsui, Alpha; Wall, Meaghan; Huang, David C. S.; Roberts, Andrew W.

    2016-01-01

    High-grade B-cell lymphomas with recurrent chromosomal break points have been termed ‘double hit lymphoma’ (DHL). The most commonly seen DHL is diffuse large B-cell lymphoma (DLBCL) with t(14;18) and t(8;14) or t(8;22) resulting in overexpression of BCL2 and MYC, respectively. The increased proliferation due to MYC overexpression, without the ability for an apoptotic brake as a result of BCL2 overexpression, results in ‘the perfect storm of oncogenesis’. Thus this disease presents a number of diagnostic and therapeutic challenges for the hematologist. The first and foremost challenge is to recognize the DHL. As different morphological entities can be affected it is incumbent on pathologists and clinicians to maintain a high index of suspicion especially in disease that appears unusually aggressive or refractory to therapy. Diagnosis by fluorescence in situ hybridization (FISH) is a sensitive and specific method for detection of the disease but is time-consuming and expensive. While detection by immunohistochemistry (IHC) is sensitive and correlates with survival, standardized methods for this are not widely agreed upon. The second and equally important challenge in DHL is optimizing clinical outcome in a group of patients for whom the prognosis is widely regarded as poor. While improvements have been achieved by dose escalating standard chemotherapeutic regimens, many patients continue to do badly. Furthermore as a disease of aging many patients are unsuitable for dose-intensive chemotherapy regimens. There are now multiple novel targeted agents in various stages of clinical development that offer hope for better outcomes without undue toxicity. Among the most exciting of these developments include specific inhibitors of both BCL2 and MYC. PMID:26834954

  8. Hit-and-run trophallaxis of small hive beetles.

    PubMed

    Neumann, Peter; Naef, Jan; Crailsheim, Karl; Crewe, Robin M; Pirk, Christian W W

    2015-12-01

    Some parasites of social insects are able to exploit the exchange of food between nestmates via trophallaxis, because they are chemically disguised as nestmates. However, a few parasites succeed in trophallactic solicitation although they are attacked by workers. The underlying mechanisms are not well understood. The small hive beetle (=SHB), Aethina tumida, is such a parasite of honey bee, Apis mellifera, colonies and is able to induce trophallaxis. Here, we investigate whether SHB trophallactic solicitation is innate and affected by sex and experience. We quantified characteristics of the trophallactic solicitation in SHBs from laboratory-reared individuals that were either bee-naïve or had 5 days experience. The data clearly show that SHB trophallactic solicitation is innate and further suggest that it can be influenced by both experience and sex. Inexperienced SHB males begged more often than any of the other groups had longer breaks than their experienced counterparts and a longer soliciting duration than both experienced SHB males and females, suggesting that they start rather slowly and gain more from experience. Successful experienced females and males were not significantly different from each other in relation to successful trophallactic interactions, but had a significantly shorter soliciting duration compared to all other groups, except successful inexperienced females. Trophallactic solicitation success, feeding duration and begging duration were not significantly affected by either SHB sex or experience, supporting the notion that these behaviors are important for survival in host colonies. Overall, success seems to be governed by quality rather than quantity of interactions, thereby probably limiting both SHB energy investment and chance of injury (<1%). Trophallactic solicitation by SHBs is a singular example for an alternative strategy to exploit insect societies without requiring chemical disguise. Hit-and-run trophallaxis is an attractive test

  9. Testing the relationships between energy consumption, CO2 emissions, and economic growth in 24 African countries: a panel ARDL approach.

    PubMed

    Asongu, Simplice; El Montasser, Ghassen; Toumi, Hassen

    2016-04-01

    This study complements existing literature by examining the nexus between energy consumption (EC), CO2 emissions (CE), and economic growth (GDP; gross domestic product) in 24 African countries using a panel autoregressive distributed lag (ARDL) approach. The following findings are established. First, there is a long-run relationship between EC, CE, and GDP. Second, a long-term effect from CE to GDP and EC is apparent, with reciprocal paths. Third, the error correction mechanisms are consistently stable. However, in cases of disequilibrium, only EC can be significantly adjusted to its long-run relationship. Fourth, there is a long-run causality running from GDP and CE to EC. Fifth, we find causality running from either CE or both CE and EC to GDP, and inverse causal paths are observable. Causality from EC to GDP is not strong, which supports the conservative hypothesis. Sixth, the causal direction from EC to GDP remains unobservable in the short term. By contrast, the opposite path is observable. There are also no short-run causalities from GDP, or EC, or EC, and GDP to EC. Policy implications are discussed. PMID:26635224

  10. Throat hit in users of the electronic cigarette: An exploratory study.

    PubMed

    Etter, Jean-François

    2016-02-01

    A cross-sectional survey on the Internet in 2012-2014 was used to study the "throat hit," the specific sensation in the throat felt by users of e-cigarettes. Participants were 1672 current users of e-cigarettes, visitors of Websites dedicated to e-cigarettes and to smoking cessation. It was assessed whether the strength of the throat hit was associated with the characteristics of e-cigarettes and e-liquids, modifications of the devices, patterns of use, reasons for use, satisfaction with e-cigarettes, dependence on e-cigarettes, smoking behavior, and perceived effects on smoking. The strongest throat hit was obtained by using better-quality models and liquids with high nicotine content. Those who reported a "very strong" throat hit used liquids with 17.3 mg/mL nicotine, versus 7.1 mg/mL for those reporting a "very weak" hit (p < .001). The strength of the throat hit was also associated with ratings of dependence on e-cigarettes, and with the perceived efficacy of e-cigarettes to relieve craving for tobacco and to facilitate smoking cessation. All the variables assessing satisfaction with e-cigarettes were associated with a stronger throat hit. From a public health perspective, there is a trade-off between e-cigarette models that provide high levels of nicotine, a strong throat hit, high satisfaction, and more effects on smoking, but may also be addictive, and models than contain less nicotine and are less addictive, but produce a weaker throat hit, are less satisfactory, and are possibly less efficient at helping people quit smoking. This trade-off must be kept in mind when regulating e-cigarettes. (PsycINFO Database Record PMID:26653150

  11. Performance of bifacial HIT solar cells on n-type silicon substrates

    NASA Astrophysics Data System (ADS)

    Liu, Qin; Ye, Xiao-Jun; Liu, Cheng; Chen, Ming-Bo

    2010-03-01

    The performance of amorphous silicon (a-Si:H) / crystalline silicon (c-Si) heterojunction is studied, and the effects of the emitter layer thickness, doping concentration, intrinsic layer thickness, back heavily-doped n layer, interface state and band offset on the optical and electrical performance of bifacial heterojunction with intrinsic thin-layer (HIT) solar cells on ntype silicon substrates are discussed. It is found that the HIT solar cells on n-type substrates can obtain a higher conversion efficiency than those on p-type substrates by calculating the band diagrams and parameters of HIT solar cells.

  12. Concentration of rat brown adipose tissue uncoupling protein may not be correlated with /sup 3/H-GDP binding

    SciTech Connect

    Henningfield, M.F.; Swick, A.G.; Swick, R.W.

    1986-03-01

    Rats fed diets low in protein or exposed to cold show an increase in brown adipose tissue (BAT) mitochondrial /sup 3/H-GDP binding. To investigate this phenomenon further, the uncoupling protein associated with BAT function was measured immunochemically on nitrocellulose blots. Quantitation of uncoupling protein was achieved by densitometer scanning with a BioRad densitometer. Peaks were integrated with Chromatochart software and an Apple IIe computer. A standard curve of purified uncoupling protein (50 to 500 ng) was used to calculate uncoupling protein concentration. There is a 1.5-fold increase in uncoupling protein per mg of protein in BAT mitochondria from rats exposed to cold for 15 days. There was no decrease in uncoupling protein from rats exposed to the cold followed by 24 h at 27/sup 0/C although /sup 3/H-GDP binding had decreased by half. Rats fed diets containing either 5 or 15% lactalbumin for 3 weeks did not show differences in uncoupling protein concentration although /sup 3/H-GDP binding was 1.5-fold greater in BAT mitochondria from the low protein group. These results indicate that GDP binding does not necessarily reflect the concentration of uncoupling protein in BAT mitochondria.

  13. Book Review: "The Road to Sustainability, GDP and Future Generations" Pulselli et al, WIT Press, Southhampton, UK 197p 2008

    EPA Science Inventory

    “The Road to Sustainability, GDP and future generations” by Pulselli, F.M., Bastianoni, S., Marchettini, N. Tiezzi, E. was reviewed upon request by the journal’s editor. Briefly, this book presents the authors’ perspective on the complex and important topic of sustainability. Su...

  14. Structure of Gαi1 bound to a GDP-selective peptide provides insight into guanine nucleotide exchange

    PubMed Central

    Johnston, Christopher A.; Willard, Francis S.; Jezyk, Mark R.; Fredericks, Zoey; Bodor, Erik T.; Jones, Miller B.; Blaesius, Rainer; Watts, Val J.; Harden, T. Kendall; Sondek, John; Ramer, J. Kevin; Siderovski, David P.

    2005-01-01

    Heterotrimeric G-proteins are molecular switches that regulate numerous signaling pathways involved in cellular physiology. This characteristic is achieved by the adoption of two principal states: an inactive, GDP-bound and an active, GTP-bound state. Under basal conditions G-proteins exist in the inactive GDP-bound state, thus nucleotide exchange is crucial to the onset of signaling. Despite our understanding of G-protein signaling pathways, the mechanism of nucleotide exchange remains elusive. We employed phage display technology to identify nucleotide-state-dependent Gα binding peptides. Herein, we report a GDP-selective Gα-binding peptide, KB-752, that enhances spontaneous nucleotide exchange of Gαi subunits. Structural determination of the Gαi1/peptide complex reveals unique changes in the Gα switch regions predicted to enhance nucleotide exchange by creating a GDP dissociation route. Our results cast light onto a potential mechanism by which Gα subunits adopt a conformation suitable for nucleotide exchange. PMID:16004878

  15. A Novel GDP-d-glucose Phosphorylase Involved in Quality Control of the Nucleoside Diphosphate Sugar Pool in Caenorhabditis elegans and Mammals*

    PubMed Central

    Adler, Lital N.; Gomez, Tara A.; Clarke, Steven G.; Linster, Carole L.

    2011-01-01

    The plant VTC2 gene encodes GDP-l-galactose phosphorylase, a rate-limiting enzyme in plant vitamin C biosynthesis. Genes encoding apparent orthologs of VTC2 exist in both mammals, which produce vitamin C by a distinct metabolic pathway, and in the nematode worm Caenorhabditis elegans where vitamin C biosynthesis has not been demonstrated. We have now expressed cDNAs of the human and worm VTC2 homolog genes (C15orf58 and C10F3.4, respectively) and found that the purified proteins also display GDP-hexose phosphorylase activity. However, as opposed to the plant enzyme, the major reaction catalyzed by these enzymes is the phosphorolysis of GDP-d-glucose to GDP and d-glucose 1-phosphate. We detected activities with similar substrate specificity in worm and mouse tissue extracts. The highest expression of GDP-d-glucose phosphorylase was found in the nervous and male reproductive systems. A C. elegans C10F3.4 deletion strain was found to totally lack GDP-d-glucose phosphorylase activity; this activity was also found to be decreased in human HEK293T cells transfected with siRNAs against the human C15orf58 gene. These observations confirm the identification of the worm C10F3.4 and the human C15orf58 gene expression products as the GDP-d-glucose phosphorylases of these organisms. Significantly, we found an accumulation of GDP-d-glucose in the C10F3.4 mutant worms, suggesting that the GDP-d-glucose phosphorylase may function to remove GDP-d-glucose formed by GDP-d-mannose pyrophosphorylase, an enzyme that has previously been shown to lack specificity for its physiological d-mannose 1-phosphate substrate. We propose that such removal may prevent the misincorporation of glucosyl residues for mannosyl residues into the glycoconjugates of worms and mammals. PMID:21507950

  16. Economic growth and obesity: an interesting relationship with world-wide implications.

    PubMed

    Egger, Garry; Swinburn, Boyd; Islam, F M Amirul

    2012-03-01

    The prosperity of a country, commonly measured in terms of its annual per capita Gross Domestic Product (GDP), has different relationships with population levels of body weight and happiness, as well as environmental impacts such as carbon emissions. The aim of this study was to examine these relationships and to try to find a level of GDP, which provides for sustainable economic activity, optimal happiness and healthy levels of mean body mass index (BMI). Spline regression analyses were conducted using national indices from 175 countries: GDP, adult BMI, mean happiness scores, and carbon footprint per capita for the year 2007. Results showed that GDP was positively related to BMI and happiness up to ∼$US3000 and ∼$5000 per capita respectively, with no significant relationships beyond these levels. GDP was also positively related to CO(2) emissions with a recognised sustainable carbon footprint of less than 5 tonnes per capita occurring at a GDP of <$US15,000. These findings show that a GDP between $US5 and $15,000 is associated with greater population happiness and environmental stability. A mean BMI of 21-23 kg/m(2), which minimises the prevalence of underweight and overweight in the population then helps to define an ideal position in relation to growth, which few countries appear to have obtained. Within a group of wealthy countries (GDP>$US30,000), those with lower income inequalities and more regulated (less liberal) market systems had lower mean BMIs. PMID:22305524

  17. Labelled drug-related public expenditure in relation to gross domestic product (GDP) in Europe: a luxury good?

    PubMed

    Prieto, Luis

    2010-01-01

    "Labelled drug-related public expenditure" is the direct expenditure explicitly labelled as related to illicit drugs by the general government of the state. As part of the reporting exercise corresponding to 2005, the European Monitoring Centre for Drugs and Drug Addiction's network of national focal points set up in the 27 European Union (EU) Member States, Norway, and the candidates countries to the EU, were requested to identify labelled drug-related public expenditure, at the country level. This was reported by 10 countries categorised according to the functions of government, amounting to a total of EUR 2.17 billion. Overall, the highest proportion of this total came within the government functions of Health (66%), and Public Order and Safety (POS) (20%). By country, the average share of GDP was 0.023% for Health, and 0.013% for POS. However, these shares varied considerably across countries, ranging from 0.00033% in Slovakia, up to 0.053% of GDP in Ireland in the case of Health, and from 0.003% in Portugal, to 0.02% in the UK, in the case of POS; almost a 161-fold difference between the highest and the lowest countries for Health, and a 6-fold difference for POS. Why do Ireland and the UK spend so much in Health and POS, or Slovakia and Portugal so little, in GDP terms? To respond to this question and to make a comprehensive assessment of drug-related public expenditure across countries, this study compared Health and POS spending and GDP in the 10 reporting countries. Results found suggest GDP to be a major determinant of the Health and POS drug-related public expenditures of a country. Labelled drug-related public expenditure showed a positive association with the GDP across the countries considered: r = 0.81 in the case of Health, and r = 0.91 for POS. The percentage change in Health and POS expenditures due to a one percent increase in GDP (the income elasticity of demand) was estimated to be 1.78% and 1.23% respectively. Being highly income elastic

  18. 76 FR 28784 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ... access only. Name of Committees: HIT Standards Committee's Workgroups: Clinical Operations, Vocabulary... Standards Committee Workgroups will hold the following public meetings during June 2011: June 1st Vocabulary... specific subject matter, e.g., clinical operations vocabulary standards, clinical quality,...

  19. 76 FR 39107 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-05

    ... access only. Name of Committees: HIT Standards Committee's Workgroups: Clinical Operations, Vocabulary... Standards Committee Workgroups will hold the following public meetings during July 2011: July 8th Vocabulary... specific subject matter, e.g., clinical operations vocabulary standards, clinical quality,...

  20. 76 FR 22398 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-21

    ... access only. Name of Committees: HIT Standards Committee's Workgroups: Clinical Operations, Vocabulary... Standards Committee Workgroups will hold the following public meetings during May 2011: May 5th Vocabulary... specific subject matter, e.g., clinical operations vocabulary standards, clinical quality,...

  1. A functional modulation for timing a movement: a coordinative structure in baseball hitting.

    PubMed

    Katsumata, Hiromu

    2007-02-01

    In baseball hitting, a powerful bat-swing needs to be produced by utilizing ground reaction force (GRF) and it should also be temporally coordinated relative to the flight of the pitch. The temporal organization of hitting movements associated with these task requirements was investigated by analyzing GRF during hitting slow and fast pitches. The timing of stepping with a front foot and shifting weight forward was modulated relative to the pitch's speed. The temporal relation between successive motion phases was compensatory and timing variability progressively reduced up to ball-bat contact. These results demonstrated the coordinative structure of the hitting movement for timing the bat-swing relative to the pitch's flight. PMID:17204344

  2. 75 FR 33811 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Privacy & Security Tiger Team Meeting; Notice of Meeting AGENCY: Office of the National... Policy Committee's Privacy & Security Tiger Team. General Function of the Committee: To...

  3. U.S. Teen Birth Rate Continues to Fall, Hits New Record Low

    MedlinePlus

    ... U.S. Teen Birth Rate Continues to Fall, Hits New Record Low CDC statistics for 2015 show another ... fell another 8 percent in 2015, reaching a new record low. According to the report from the ...

  4. High-Throughput Screening and Hit Validation of Extracellular-Related Kinase 5 (ERK5) Inhibitors.

    PubMed

    Myers, Stephanie M; Bawn, Ruth H; Bisset, Louise C; Blackburn, Timothy J; Cottyn, Betty; Molyneux, Lauren; Wong, Ai-Ching; Cano, Celine; Clegg, William; Harrington, Ross W; Leung, Hing; Rigoreau, Laurent; Vidot, Sandrine; Golding, Bernard T; Griffin, Roger J; Hammonds, Tim; Newell, David R; Hardcastle, Ian R

    2016-08-01

    The extracellular-related kinase 5 (ERK5) is a promising target for cancer therapy. A high-throughput screen was developed for ERK5, based on the IMAP FP progressive binding system, and used to identify hits from a library of 57 617 compounds. Four distinct chemical series were evident within the screening hits. Resynthesis and reassay of the hits demonstrated that one series did not return active compounds, whereas three series returned active hits. Structure-activity studies demonstrated that the 4-benzoylpyrrole-2-carboxamide pharmacophore had excellent potential for further development. The minimum kinase binding pharmacophore was identified, and key examples demonstrated good selectivity for ERK5 over p38α kinase. PMID:27400250

  5. Multi-point Thomson Scattering First Results on the HIT-II Plasma

    NASA Astrophysics Data System (ADS)

    Smith, R. J.; Liptac, J. E.; Jarboe, T. R.; Nelson, B. A.; Leblanc, B. P.; Phillips, P.

    1999-11-01

    A multi-point Thomson scattering diagnostic has recently been implemented on the HIT/>Helicity Injected Torus--II (HIT--II). The HIT--II device is a low-aspect ratio (Ro = 0.3 m, a = 0.2 m) torus with a 0.5 Tesla field on axis. The machine configuration allows both inductive current drive and Coaxial Helicity Injection (CHI) current drive operations and is capable of producing plasma currents on the order of 200 kA in either mode. Electron temperature and density profile measurements for both inductive and CHI current driven plasmas are presented and discussed along with results from complimentary diagnostics on the HIT--II device --- a two chord FIR interferometer, a 16 channel ion doppler spectrometer and two symmetrically viewing VUV spectrometers.

  6. Temporal scales for nearshore hits of current-driven pollution in the Gulf of Finland.

    PubMed

    Viikmäe, Bert; Soomere, Tarmo

    2016-05-15

    Lagrangian trajectories of water parcels reconstructed using the TRACMASS model from three-dimensional velocity fields by the RCO model for 1965-2004 are used to analyse the temporal scales and the probability for the hits to the nearshore by pollution originating from a major fairway in the Gulf of Finland and transported by surface currents. Increasing the simulation length from 10 to 20days induces a linear increase in particle age, but the pattern of nearshore hits remains the same. A reasonable benefit can be reached by relatively small shifts of certain parts of the present fairway in a few locations. The overall probabilities do not reveal any trend for 1965-2004. The largest changes in the nearshore hits are revealed for the proportion of hits to the opposite nearshore areas. This feature probably reflects an abrupt turn of the geostrophic air-flow over the southern Baltic Sea by ~40° since 1987. PMID:27004999

  7. Knee Replacement Patients May Be Able to Hit the Shower Sooner

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159055.html Knee Replacement Patients May Be Able to Hit the Shower ... effect on surgical-site wound infection risk for [knee replacement surgery]," the researchers wrote. The findings were published ...

  8. Scientists Pick U.S. Cities Where Zika Might Hit This Summer

    MedlinePlus

    ... U.S. Cities Where Zika Might Hit This Summer Weather and travel patterns could expose people as far ... the southern and eastern United States as the weather warms, according to experts at the National Center ...

  9. 75 FR 65486 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-25

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Standards... Information Technology, HHS. ACTION: Notice of meetings. This notice announces forthcoming subcommittee... National Coordinator for Health Information Technology. BILLING CODE 4150-45-P...

  10. 75 FR 51818 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-23

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Standards... Information Technology, HHS. ACTION: Notice of meetings. This notice announces forthcoming subcommittee... Information Technology. BILLING CODE 4150-45-P...

  11. 75 FR 3905 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-25

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Standards... Information Technology, HHS. ACTION: Notice of meetings. This notice announces forthcoming subcommittee... Information Technology. BILLING CODE 4150-45-P...

  12. 76 FR 9782 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-22

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Standards... Information Technology, HHS ] ACTION: Notice of meetings. This notice announces forthcoming subcommittee... and Coordination, Office of the National Coordinator for Health Information Technology. BILLING...

  13. 75 FR 3906 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-25

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Information Technology, HHS. ACTION: Notice of meetings. This notice announces forthcoming subcommittee... and adoption of a nationwide health information technology infrastructure that permits the...

  14. 75 FR 29762 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology HIT Policy Committee... Information Technology, HHS. ACTION: Notice of meetings. This notice announces forthcoming subcommittee... health information technology infrastructure that permits the electronic exchange and use of...

  15. 75 FR 51819 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-23

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Information Technology, HHS. ACTION: Notice of meetings. This notice announces forthcoming subcommittee... health information technology infrastructure that permits the electronic exchange and use of...

  16. 75 FR 57025 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-17

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Standards... Information Technology, HHS. ACTION: Notice of meetings. This notice announces forthcoming subcommittee... National Coordinator for Health Information Technology. BILLING CODE 4150-45-P...

  17. U.S. Teen Birth Rate Continues to Fall, Hits New Record Low

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159170.html U.S. Teen Birth Rate Continues to Fall, Hits New ... record low. According to the report from the U.S. Centers for Disease Control and Prevention, moms aged ...

  18. A σD-dependent antisense transcript modulates expression of the cyclic-di-AMP hydrolase GdpP in Bacillus subtilis.

    PubMed

    Luo, Yun; Helmann, John D

    2012-11-01

    Cyclic-di-AMP (c-di-AMP) is an essential second messenger in Bacillus subtilis, and depletion leads to defects in the integrity of the cell wall. Levels of c-di-AMP are regulated by both the rates of synthesis (by diadenylate cyclases) and the rates of degradation (by the GdpP phosphodiesterase, formerly YybT). Little is known about the regulation of gdpP expression or GdpP activity, but mutations that inactivate GdpP lead to high-level resistance to β-lactam antibiotics. Here we demonstrate that expression of gdpP is regulated by a cis-acting antisense RNA (gdpP(as)) in vivo. Transcription of this antisense RNA is initiated in the middle of the gdp gene and is dependent on an alternative sigma factor, σ(D), previously associated with the expression of late flagellar genes, chemotaxis proteins and cell wall autolytic enzymes. Changes in σ(D) activity can modulate GdpP protein levels by ~2.5-fold, which may provide a mechanism for the cell to upregulate c-di-AMP levels in coordination with the activation of autolytic enzymes. PMID:22956758

  19. A σD-dependent antisense transcript modulates expression of the cyclic-di-AMP hydrolase GdpP in Bacillus subtilis

    PubMed Central

    Luo, Yun

    2012-01-01

    Cyclic-di-AMP (c-di-AMP) is an essential second messenger in Bacillus subtilis, and depletion leads to defects in the integrity of the cell wall. Levels of c-di-AMP are regulated by both the rates of synthesis (by diadenylate cyclases) and the rates of degradation (by the GdpP phosphodiesterase, formerly YybT). Little is known about the regulation of gdpP expression or GdpP activity, but mutations that inactivate GdpP lead to high-level resistance to β-lactam antibiotics. Here we demonstrate that expression of gdpP is regulated by a cis-acting antisense RNA (gdpPas) in vivo. Transcription of this antisense RNA is initiated in the middle of the gdp gene and is dependent on an alternative sigma factor, σD, previously associated with the expression of late flagellar genes, chemotaxis proteins and cell wall autolytic enzymes. Changes in σD activity can modulate GdpP protein levels by ~2.5-fold, which may provide a mechanism for the cell to upregulate c-di-AMP levels in coordination with the activation of autolytic enzymes. PMID:22956758

  20. Nuclear microbeam analysis of ICF target material made by GDP technique

    NASA Astrophysics Data System (ADS)

    Rong, C.; He, X.; Meng, J.; Gao, D.; Zhang, Y.; Li, X.; Lyu, H.; Zhu, Y.; Zheng, Y.; Wang, X.; Shen, H.

    2015-04-01

    Germanium doped carbon-hydrogen polymer (CH) by Glow Discharge Polymer (GDP) technique has become the preferred Inertial Confinement Fusion (ICF) target material. The nondestructive measurement of elements content in the ICF target has become a significant work in recent years. This paper presents the compositional and distributional results of the Germanium doped CH analysis. The Ge doped CH materials as thin film and as hollow sphere were investigated by the Rutherford Backscattering Spectroscopy (RBS) combined with the particle induced X-ray emission (PIXE) and the Elastic Recoil Detection Analysis (ERDA). The samples are thin film with 36 μm thickness and ICF target with 500-2000 μm diameter. The calibration and geometrical arrangement in the analysis of spherical target should be carefully considered in order to acquire accurate results. In the work, the uniformity of the sphere is shown and the ratio of carbon, hydrogen and germanium has been measured. The ratio values are in good agreement with the results obtained by the combustion method. In addition, the difference of the composition from thin film to hollow sphere is also discussed. This work demonstrates that nuclear microbeam analysis is an ideal method to evaluate the ICF target quality.

  1. Characterization of the gene coding for GDP-mannose dehydrogenase (algD) from Azotobacter vinelandii.

    PubMed Central

    Campos, M; Martínez-Salazar, J M; Lloret, L; Moreno, S; Núñez, C; Espín, G; Soberón-Chávez, G

    1996-01-01

    Azotobacter vinelandii presents a differentiation process leading to the formation of desiccation-resistant cysts. Alginate, the exopolysaccharide produced by this bacterium, has been postulated to have a role in cyst formation. Here, we report the cloning and characterization of the A. vinelandii gene coding for the enzyme GDP-mannose dehydrogenase (algD), which is the key enzyme for alginate synthesis in Pseudomonas aeruginosa. This gene has a high degree of similarity with the algD gene from P. aeruginosa, and similar proteins seem to be involved in algD regulation in both bacteria. We show the existence of two mRNA start sites; one of these sites corresponds to a promoter transcribed by RNA polymerase containing a sigma E subunit. An A. vinelandii algD mutant which is completely impaired in alginate production and which is unable to form desiccation-resistant cells was constructed. The effects of NH4, NO3, and NaCl concentrations on algD transcription for three A. vinelandii strains producing different alginate levels were evaluated. We found a strict correlation between alginate production and algD transcription for the three strains studied; however, the effects on algD transcription under the conditions studied were different for each strain. The nitrogen source regulates algD expression in the wild-type strain. PMID:8606150

  2. Efficient hit-finding approaches for histone methyltransferases: the key parameters.

    PubMed

    Ahrens, Thomas; Bergner, Andreas; Sheppard, David; Hafenbradl, Doris

    2012-01-01

    For many novel epigenetics targets the chemical ligand space and structural information were limited until recently and are still largely unknown for some targets. Hit-finding campaigns are therefore dependent on large and chemically diverse libraries. In the specific case of the histone methyltransferase G9a, the authors have been able to apply an efficient process of intelligent selection of compounds for primary screening, rather than screening the full diverse deck of 900 000 compounds to identify hit compounds. A number of different virtual screening methods have been applied for the compound selection, and the results have been analyzed in the context of their individual success rates. For the primary screening of 2112 compounds, a FlashPlate assay format and full-length histone H3.1 substrate were employed. Validation of hit compounds was performed using the orthogonal fluorescence lifetime technology. Rated by purity and IC(50) value, 18 compounds (0.9% of compound screening deck) were finally considered validated primary G9a hits. The hit-finding approach has led to novel chemotypes being identified, which can facilitate hit-to-lead projects. This study demonstrates the power of virtual screening technologies for novel, therapeutically relevant epigenetics protein targets. PMID:21990582

  3. USER FRUSTRATION IN HIT INTERFACES: EXPLORING PAST HCI RESEARCH FOR A BETTER UNDERSTANDING OF CLINICIANS’ EXPERIENCES

    PubMed Central

    Opoku-Boateng, Gloria A.

    2015-01-01

    User frustration research has been one way of looking into clinicians’ experience with health information technology use and interaction. In order to understand how clinician frustration with Health Information Technology (HIT) use occurs, there is the need to explore Human-Computer Interaction (HCI) literature that addresses both frustration and HIT use. In the past three decades, HCI frustration research has increased and expanded. Researchers have done a lot of work to understand emotions, end-user frustration and affect. This paper uses a historical literature review approach to review the origins of emotion and frustration research and explore the research question; Does HCI research on frustration provide insights on clinicians’ frustration with HIT interfaces? From the literature review HCI research on emotion and frustration provides additional insights that can indeed help explain user frustration in HIT. Different approaches and HCI perspectives also help frame HIT user frustration research as well as inform HIT system design. The paper concludes with a suggested directions on how future design and research may take. PMID:26958238

  4. Arabidopsis VTC2 Encodes a GDP-l-Galactose Phosphorylase, the Last Unknown Enzyme in the Smirnoff-Wheeler Pathway to Ascorbic Acid in Plants*

    PubMed Central

    Linster, Carole L.; Gomez, Tara A.; Christensen, Kathryn C.; Adler, Lital N.; Young, Brian D.; Brenner, Charles; Clarke, Steven G.

    2008-01-01

    The first committed step in the biosynthesis of l-ascorbate from d-glucose in plants requires conversion of GDP-l-galactose to l-galactose 1-phosphate by a previously unidentified enzyme. Here we show that the protein encoded by VTC2, a gene mutated in vitamin C-deficient Arabidopsis thaliana strains, is a member of the GalT/Apa1 branch of the histidine triad protein superfamily that catalyzes the conversion of GDP-l-galactose to l-galactose 1-phosphate in a reaction that consumes inorganic phosphate and produces GDP. In characterizing recombinant VTC2 from Arabidopsis thaliana as a specific GDP-l-galactose/GDP-d-glucose phosphorylase, we conclude that enzymes catalyzing each of the ten steps of the Smirnoff-Wheeler pathway from glucose to ascorbate have been identified. Finally, we identify VTC2 homologs in plants, invertebrates, and vertebrates, suggesting that a similar reaction is used widely in nature. PMID:17462988

  5. The Discovery of in Vivo Active Mitochondrial Branched-Chain Aminotransferase (BCATm) Inhibitors by Hybridizing Fragment and HTS Hits.

    PubMed

    Bertrand, Sophie M; Ancellin, Nicolas; Beaufils, Benjamin; Bingham, Ryan P; Borthwick, Jennifer A; Boullay, Anne-Bénédicte; Boursier, Eric; Carter, Paul S; Chung, Chun-wa; Churcher, Ian; Dodic, Nerina; Fouchet, Marie-Hélène; Fournier, Charlène; Francis, Peter L; Gummer, Laura A; Herry, Kenny; Hobbs, Andrew; Hobbs, Clare I; Homes, Paul; Jamieson, Craig; Nicodeme, Edwige; Pickett, Stephen D; Reid, Iain H; Simpson, Graham L; Sloan, Lisa A; Smith, Sarah E; Somers, Donald O'N; Spitzfaden, Claus; Suckling, Colin J; Valko, Klara; Washio, Yoshiaki; Young, Robert J

    2015-09-24

    The hybridization of hits, identified by complementary fragment and high throughput screens, enabled the discovery of the first series of potent inhibitors of mitochondrial branched-chain aminotransferase (BCATm) based on a 2-benzylamino-pyrazolo[1,5-a]pyrimidinone-3-carbonitrile template. Structure-guided growth enabled rapid optimization of potency with maintenance of ligand efficiency, while the focus on physicochemical properties delivered compounds with excellent pharmacokinetic exposure that enabled a proof of concept experiment in mice. Oral administration of 2-((4-chloro-2,6-difluorobenzyl)amino)-7-oxo-5-propyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile 61 significantly raised the circulating levels of the branched-chain amino acids leucine, isoleucine, and valine in this acute study. PMID:26090771

  6. S. Africa: ESKOM's Massive investment hits new snag

    SciTech Connect

    2008-08-15

    ESKOM, the government-owned company that generates nearly 95 percent of the power in South Africa, has been facing serious capacity shortages for some time, forcing it to resort to mandatory rationing of major industrial users and occasional outages. A combination of rapid economic growth and chronic underinvestment in infrastructure resulted in the disappearance of a once plentiful capacity surplus. Considerable rate increases and emphasis on conservation are planned.

  7. Being selective at the plate: processing dependence between perceptual variables relates to hitting goals and performance.

    PubMed

    Gray, Rob

    2013-08-01

    Performance of a skill that involves acting on a goal object (e.g., a ball to be hit) can influence one's judgment of the size and speed of that object. The present study examined how these action-specific effects are affected when the goal of the actor is varied and they are free to choose between alternative actions. In Experiment 1, expert baseball players were asked to perform three different directional hitting tasks in a batting simulation and make interleaved perceptual judgments about three ball parameters (speed, plate crossing location, and size). Perceived ball size was largest (and perceived speed was slowest) when the ball crossing location was optimal for the particular hitting task the batter was performing (e.g., an "outside" pitch for opposite-field hitting). The magnitude of processing dependency between variables (speed vs. location and size vs. location) was positively correlated with batting performance. In Experiment 2, the action-specific effects observed in Experiment 1 were mimicked by systematically changing the ball diameter in the simulation as a function of plate crossing location. The number of swing initiations was greater when ball size was larger, and batters were more successful in the hitting task for which the larger pitches were optimal (e.g., greater number of pull hits than opposite-field hits when "inside" pitches were larger). These findings suggest attentional accentuation of goal-relevant targets underlies action-related changes in perception and are consistent with an action selection role for these effects. PMID:23163787

  8. Population growth and development: the case of Bangladesh.

    PubMed

    Nakibullah, A

    1998-04-01

    In a poor, overly populated country such as Bangladesh, some believe that a high rate of population growth is a cause of poverty which impedes economic development. Population growth would therefore be exogenous to economic development. However, others believe that rapid population growth is a consequence rather than a cause of poverty. Population growth is therefore endogenous to economic development. Findings are presented from an investigation of whether population growth has been exogenous or endogenous with respect to Bangladesh's development process during the past 3 decades. The increase in per capita real gross domestic product (GDP) is used as a measure of development. Data on population, real GDP per capita, and real investment share of GDP are drawn from the Penn World Table prepared by Summers and Heston in 1991. The data are annual and cover the period 1959-90. Analysis of the data indicate that population growth is endogenous to Bangladesh's development process. These findings are reflected both in the Granger causality tests and the decompositions of variances of detrended real GDP per capita and population growth. PMID:12294506

  9. Doublecortin Is Excluded from Growing Microtubule Ends and Recognizes the GDP-Microtubule Lattice.

    PubMed

    Ettinger, Andreas; van Haren, Jeffrey; Ribeiro, Susana A; Wittmann, Torsten

    2016-06-20

    Many microtubule (MT) functions are mediated by a diverse class of proteins (+TIPs) at growing MT plus ends that control intracellular MT interactions and dynamics and depend on end-binding proteins (EBs) [1]. Cryoelectron microscopy has recently identified the EB binding site as the interface of four tubulin dimers that undergoes a conformational change in response to β-tubulin GTP hydrolysis [2, 3]. Doublecortin (DCX), a MT-associated protein (MAP) required for neuronal migration during cortical development [4, 5], binds to the same site as EBs [6], and recent in vitro studies proposed DCX localization to growing MT ends independent of EBs [7]. Because this conflicts with observations in neurons [8, 9] and the molecular function of DCX is not well understood, we revisited intracellular DCX dynamics at low expression levels. Here, we report that DCX is not a +TIP in cells but, on the contrary, is excluded from the EB1 domain. In addition, we find that DCX-MT interactions are highly sensitive to MT geometry. In cells, DCX binding was greatly reduced at MT segments with high local curvature. Remarkably, this geometry-dependent binding to MTs was completely reversed in the presence of taxanes, which reconciles incompatible observations in cells [9] and in vitro [10]. We propose a model explaining DCX specificity for different MT geometries based on structural changes induced by GTP hydrolysis that decreases the spacing between adjacent tubulin dimers [11]. Our data are consistent with a unique mode of MT interaction in which DCX specifically recognizes this compacted GDP-like MT lattice. PMID:27238282

  10. Helix dipole movement and conformational variability contribute to allosteric GDP release in Galphai subunits.

    PubMed

    Preininger, Anita M; Funk, Michael A; Oldham, William M; Meier, Scott M; Johnston, Christopher A; Adhikary, Suraj; Kimple, Adam J; Siderovski, David P; Hamm, Heidi E; Iverson, Tina M

    2009-03-31

    Heterotrimeric G proteins (Galphabetagamma) transmit signals from activated G protein-coupled receptors (GPCRs) to downstream effectors through a guanine nucleotide signaling cycle. Numerous studies indicate that the carboxy-terminal alpha5 helix of Galpha subunits participates in Galpha-receptor binding, and previous EPR studies suggest this receptor-mediated interaction induces a rotation and translation of the alpha5 helix of the Galpha subunit [Oldham, W. M., et al. (2006) Nat. Struct. Mol. Biol. 13, 772-777]. On the basis of this result, an engineered disulfide bond was designed to constrain the alpha5 helix of Galpha(i1) into its EPR-measured receptor-associated conformation through the introduction of cysteines at position 56 in the alpha1 helix and position 333 in the alpha5 helix (I56C/Q333C Galpha(i1)). A functional mimetic of the EPR-measured alpha5 helix dipole movement upon receptor association was additionally created by introduction of a positive charge at the amino terminus of this helix, D328R Galpha(i1). Both proteins exhibit a dramatically elevated level of basal nucleotide exchange. The 2.9 A resolution crystal structure of I56C/Q333C Galpha(i1) in complex with GDP-AlF(4)(-) reveals the shift of the alpha5 helix toward the guanine nucleotide binding site that is anticipated by EPR measurements. The structure of the I56C/Q333C Galpha(i1) subunit further revealed altered positions for the switch regions and throughout the Galpha(i1) subunit, accompanied by significantly elevated crystallographic temperature factors. Combined with previous evidence in the literature, the structural analysis supports the critical role of electrostatics of the alpha5 helix dipole and overall conformational variability during nucleotide release. PMID:19222191