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Sample records for hits gdp growth

  1. Competition and GDP Growth: The Mexican Solution

    DTIC Science & Technology

    2011-10-28

    Efficiency in Mexico, 9. 5 World Bank Group, Beyond Economic Growth Student Handbook, last modified 2004. http://www.worldbank.org/ depweb /english/beyond...www.tradingeconomics.com/brazil/gdp-growth. World Bank Group, Beyond Economic Growth Student Handbook, last modified 2004. http://www.worldbank.org/ depweb /english/beyond/global/glossary.html.

  2. Is Decoupling GDP Growth from Environmental Impact Possible?

    PubMed

    Ward, James D; Sutton, Paul C; Werner, Adrian D; Costanza, Robert; Mohr, Steve H; Simmons, Craig T

    2016-01-01

    The argument that human society can decouple economic growth-defined as growth in Gross Domestic Product (GDP)-from growth in environmental impacts is appealing. If such decoupling is possible, it means that GDP growth is a sustainable societal goal. Here we show that the decoupling concept can be interpreted using an easily understood model of economic growth and environmental impact. The simple model is compared to historical data and modelled projections to demonstrate that growth in GDP ultimately cannot be decoupled from growth in material and energy use. It is therefore misleading to develop growth-oriented policy around the expectation that decoupling is possible. We also note that GDP is increasingly seen as a poor proxy for societal wellbeing. GDP growth is therefore a questionable societal goal. Society can sustainably improve wellbeing, including the wellbeing of its natural assets, but only by discarding GDP growth as the goal in favor of more comprehensive measures of societal wellbeing.

  3. Is Decoupling GDP Growth from Environmental Impact Possible?

    PubMed Central

    Sutton, Paul C.; Werner, Adrian D.; Costanza, Robert; Mohr, Steve H.; Simmons, Craig T.

    2016-01-01

    The argument that human society can decouple economic growth—defined as growth in Gross Domestic Product (GDP)—from growth in environmental impacts is appealing. If such decoupling is possible, it means that GDP growth is a sustainable societal goal. Here we show that the decoupling concept can be interpreted using an easily understood model of economic growth and environmental impact. The simple model is compared to historical data and modelled projections to demonstrate that growth in GDP ultimately cannot be decoupled from growth in material and energy use. It is therefore misleading to develop growth-oriented policy around the expectation that decoupling is possible. We also note that GDP is increasingly seen as a poor proxy for societal wellbeing. GDP growth is therefore a questionable societal goal. Society can sustainably improve wellbeing, including the wellbeing of its natural assets, but only by discarding GDP growth as the goal in favor of more comprehensive measures of societal wellbeing. PMID:27741300

  4. Global evidence on the distribution of GDP growth rates

    NASA Astrophysics Data System (ADS)

    Williams, Michael A.; Baek, Grace; Li, Yiyang; Park, Leslie Y.; Zhao, Wei

    2017-02-01

    We study the size distribution of changes in the gross domestic product (GDP) of 167 countries for the period 1950-2011. A consensus has developed in the literature that the distribution of GDP growth rates can be approximated by the Laplace distribution in the central part and power-law distributions in the tails. Using a richer database than prior studies and testing for more theoretical distributions, we find that the distribution of GDP growth rates can be fitted using the heavy-tailed Cauchy distribution for almost all countries. Significantly, this same finding recently has been demonstrated for (1) the distribution of firm growth rates and (2) the distribution of firm economic profit rates. Together, these three findings suggest the possibility that there exist universal mechanisms that give rise to general laws governing the growth dynamics of firms and economies.

  5. [Energy consumption and GDP growth in Beijing: cointegration and causality analysis].

    PubMed

    Chen, Cao-Cao; Zhang, Yan; Liu, Chun-Lan; Wang, Hai-Hua; Li, Zheng

    2012-06-01

    In this paper, the Johansen cointegration technique and the vector error correction model (VECM) were used to examine the causal relationship between energy consumption (LEC) and gross domestic product (LGDP) for Beijing during the period of 1980 to 2008. Results indicated that LEC and LGDP for Beijing were related by one cointegrating vector and there was a long-run unidirectional causal relationship from GDP to energy consumption. The long-term and short-term elasticity from economy to energy consumption were 0.44 and 0.12 separately. Statistic analysis showed that from 1980 to 2008 every 1% growth in GDP annually would drive energy consumption increasing rate by 0.4% correspondently. And the effect imposed from economy to energy consumption was lagging. It showed that energy consumption was not a strong exogenous variable as to economy. The finding has significant implications from the point of view of energy conservation, emission reduction and economic development.

  6. A rho GDP dissociation inhibitor produced by apoptotic T-cells inhibits growth of Mycobacterium tuberculosis.

    PubMed

    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

    2015-02-01

    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(+C)D25(+)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.

  7. 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.

  8. The de novo synthesis of GDP-fucose is essential for flagellar adhesion and cell growth in Trypanosoma brucei.

    PubMed

    Turnock, Daniel C; Izquierdo, Luis; Ferguson, Michael A J

    2007-09-28

    The protozoan parasite Trypanosoma brucei causes human African sleeping sickness in sub-Saharan Africa. The parasite makes several essential glycoproteins, which has led to the investigation of the sugar nucleotides and glycosyltransferases required to synthesize these structures. Fucose is a common sugar in glycoconjugates from many organisms; however, the sugar nucleotide donor GDP-fucose was only recently detected in T. brucei, and the importance of fucose metabolism in this organism is not known. In this paper, we identified the genes encoding functional GDP-fucose biosynthesis enzymes in T. brucei and created conditional null mutants of TbGMD, the gene encoding the first enzyme in the pathway from GDP-mannose to GDP-fucose, in both bloodstream form and procyclic form parasites. Under nonpermissive conditions, both life cycle forms of the parasite became depleted in GDP-fucose and suffered growth arrest, demonstrating that fucose metabolism is essential to both life cycle stages. In procyclic form parasites, flagellar detachment from the cell body was also observed under nonpermissive conditions, suggesting that fucose plays a significant role in flagellar adhesion. Fluorescence microscopy of epitope-tagged TbGMD revealed that this enzyme is localized in glycosomes, despite the absence of PTS-1 or PTS-2 target sequences.

  9. Transforming growth factor β signaling upregulates the expression of human GDP-fucose transporter by activating transcription factor Sp1.

    PubMed

    Xu, Yu-Xin; Ma, Anna; Liu, Li

    2013-01-01

    GDP-fucose transporter plays a crucial role in fucosylation of glycoproteins by providing activated fucose donor, GDP-fucose, for fucosyltransferases in the lumen of the Golgi apparatus. Fucose-containing glycans are involved in many biological processes, which are essential for growth and development. Mutations in the GDP-fucose transporter gene cause leukocyte adhesion deficiency syndrome II, a disease characterized by slow growth, mental retardation and immunodeficiency. However, no information is available regarding its transcriptional regulation. Here, by using human cells, we show that TGF-β1 specifically induces the GDP-fucose transporter expression, but not other transporters tested such as CMP-sialic acid transporter, suggesting a diversity of regulatory pathways for the expression of these transporters. The regulatory elements that are responsive to the TGF-β1 stimulation are present in the region between bp -330 and -268 in the GDP-fucose transporter promoter. We found that this region contains two identical octamer GC-rich motifs (GGGGCGTG) that were demonstrated to be essential for the transporter expression. We also show that the transcription factor Sp1 specifically binds to the GC-rich motifs in vitro and Sp1 coupled with phospho-Smad2 is associated with the promoter region covering the Sp1-binding motifs in vivo using chromatin immunoprecipitation (ChIP) assays. In addition, we further confirmed that Sp1 is essential for the GDP-fucose transporter expression stimulated by TGF-β1 using a luciferase reporter system. These results highlight the role of TGF-β signaling in regulation of the GDP-fucose transporter expression via activating Sp1. This is the first transcriptional study for any nucleotide sugar transporters that have been identified so far. Notably, TGF-β1 receptor itself is known to be modified by fucosylation. Given the essential role of GDP-fucose transporter in fucosylation, the finding that TGF-β1 stimulates the expression of

  10. 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

  11. GDP-mannose transporter paralogues play distinct roles in polarized growth of Aspergillus nidulans.

    PubMed

    Jackson-Hayes, Loretta; Hill, Terry W; Loprete, Darlene M; Gordon, Barbara S; Groover, Chassidy J; Johnson, Laura R; Martin, Stuart A

    2010-01-01

    GDP-mannose transporters (GMT) carry GDP-mannose nucleotide sugars from the cytosol across the Golgi apparatus membrane for use as substrates in protein glycosylation in plants, animals and fungi. Genomes of some fungal species, such as the yeast Saccharomyces cerevisiae, contain only one gene encoding a GMT, while others, including Aspergillus nidulans, contain two (gmtA and gmtB). We previously showed that cell wall integrity and normal hyphal morphogenesis in A. nidulans depend upon the function of GmtA and that GmtA localizes to a Golgi-like compartment. Cells bearing the calI11 mutation in gmtA also have reduced cell surface mannosylation. Here we show that GmtB colocalizes with GmtA, suggesting that the role of GmtB is similar to that of GmtA, although the respective transcript levels differ during spore germination and early development. Transcript levels of gmtB are high in ungerminated spores and remain so throughout the first 16 h of germination. In contrast, transcript levels of gmrtA are negligible in ungerminated spores but increase to levels comparable to those of gmtB during germination. These observations suggest that although GmtA and GmtB reside within the same subcellular compartments, they nevertheless perform distinct functions at different stages of development.

  12. Identification and characterization of Arabidopsis AtNUDX9 as a GDP-d-mannose pyrophosphohydrolase: its involvement in root growth inhibition in response to ammonium

    PubMed Central

    Tanaka, Hiroyuki; Maruta, Takanori; Ogawa, Takahisa; Tanabe, Noriaki; Tamoi, Masahiro; Yoshimura, Kazuya; Shigeoka, Shigeru

    2015-01-01

    GDP-d-mannose (GDP-d-Man) is an important intermediate in ascorbic acid (AsA) synthesis, cell wall synthesis, protein N-glycosylation, and glycosylphosphatidylinositol-anchoring in plants. Thus, the modulation of intracellular levels of GDP-d-Man could be important for maintaining various cellular processes. Here an Arabidopsis GDP-d-Man pyrophosphohydrolase, AtNUDX9 (AtNUDT9; At3g46200), which hydrolysed GDP-d-Man to GMP and mannose 1-phosphate, was identified. The K m and V max values for GDP-d-Man of AtNUDX9 were 376±24 μM and 1.61±0.15 μmol min–1 mg–1 protein, respectively. Among various tissues, the expression levels of AtNUDX9 and the total activity of GDP-d-Man pyrophosphohydrolase were the highest in the roots. The GDP-d-Man pyrophosphohydrolase activity was increased in the root of plants grown in the presence of ammonium. No difference was observed in the levels of AsA in the leaf and root tissues of the wild-type and knockout-nudx9 (KO-nudx9) plants, whereas a marked increase in N-glycoprotein levels and enhanced growth were detected in the roots of KO-nudx9 plants in the presence of ammonium. These results suggest that AtNUDX9 is involved in the regulation of GDP-d-Man levels affecting ammonium sensitivity via modulation of protein N-glycosylation in the roots. PMID:26049160

  13. Identification and characterization of Arabidopsis AtNUDX9 as a GDP-d-mannose pyrophosphohydrolase: its involvement in root growth inhibition in response to ammonium.

    PubMed

    Tanaka, Hiroyuki; Maruta, Takanori; Ogawa, Takahisa; Tanabe, Noriaki; Tamoi, Masahiro; Yoshimura, Kazuya; Shigeoka, Shigeru

    2015-09-01

    GDP-d-mannose (GDP-d-Man) is an important intermediate in ascorbic acid (AsA) synthesis, cell wall synthesis, protein N-glycosylation, and glycosylphosphatidylinositol-anchoring in plants. Thus, the modulation of intracellular levels of GDP-d-Man could be important for maintaining various cellular processes. Here an Arabidopsis GDP-d-Man pyrophosphohydrolase, AtNUDX9 (AtNUDT9; At3g46200), which hydrolysed GDP-d-Man to GMP and mannose 1-phosphate, was identified. The K m and V max values for GDP-d-Man of AtNUDX9 were 376±24 μM and 1.61±0.15 μmol min(-1) mg(-1) protein, respectively. Among various tissues, the expression levels of AtNUDX9 and the total activity of GDP-d-Man pyrophosphohydrolase were the highest in the roots. The GDP-d-Man pyrophosphohydrolase activity was increased in the root of plants grown in the presence of ammonium. No difference was observed in the levels of AsA in the leaf and root tissues of the wild-type and knockout-nudx9 (KO-nudx9) plants, whereas a marked increase in N-glycoprotein levels and enhanced growth were detected in the roots of KO-nudx9 plants in the presence of ammonium. These results suggest that AtNUDX9 is involved in the regulation of GDP-d-Man levels affecting ammonium sensitivity via modulation of protein N-glycosylation in the roots.

  14. Roughness distribution of multiple hit and long surface diffusion length noise reduced discrete growth models

    NASA Astrophysics Data System (ADS)

    Disrattakit, P.; Chanphana, R.; Chatraphorn, P.

    2016-11-01

    Conventionally, the universality class of a discrete growth model is identified via the scaling of interface width. This method requires large-scale simulations to minimize finite-size effects on the results. The multiple hit noise reduction techniques (m > 1 NRT) and the long surface diffusion length noise reduction techniques (ℓ > 1 NRT) have been used to promote the asymptotic behaviors of the growth models. Lately, an alternative method involving comparison of roughness distribution in the steady state has been proposed. In this work, the roughness distribution of the (2 +1)-dimensional Das Sarma-Tamborenea (DT), Wolf-Villain (WV), and Larger Curvature (LC) models, with and without NRTs, are calculated in order to investigate effects of the NRTs on the roughness distribution. Additionally, effective growth exponents of the noise reduced (2 +1)-dimensional DT, WV and LC models are also calculated. Our results indicate that the NRTs affect the interface width both in the growth and the saturation regimes. In the steady state, the NRTs do not seem to have any impact on the roughness distribution of the DT model, but it significantly changes the roughness distribution of the WV and LC models to the normal distribution curves.

  15. Recruitment of Arf1-GDP to Golgi by Glo3p-type ArfGAPs is crucial for golgi maintenance and plant growth.

    PubMed

    Min, Myung Ki; Jang, Mihue; Lee, Myounghui; Lee, Junho; Song, Kyungyoung; Lee, Yongjik; Choi, Kwan Yong; Robinson, David G; Hwang, Inhwan

    2013-02-01

    ADP-ribosylation factor1 (Arf1), a member of the small GTP-binding proteins, plays a pivotal role in protein trafficking to multiple organelles. In its GDP-bound form, Arf1 is recruited from the cytosol to organelle membranes, where it functions in vesicle-mediated protein trafficking. However, the mechanism of Arf1-GDP recruitment remains unknown. Here, we provide evidence that two Glo3p-type Arf GTPase-activating proteins (ArfGAPs), ArfGAP domain8 (AGD8) and AGD9, are involved in the recruitment of Arf1-GDP to the Golgi apparatus in Arabidopsis (Arabidopsis thaliana). RNA interference plants expressing low levels of AGD8 and AGD9 exhibited abnormal Golgi morphology, inhibition of protein trafficking, and arrest of plant growth and development. In RNA interference plants, Arf1 was poorly recruited to the Golgi apparatus. Conversely, high levels of AGD8 and AGD9 induced Arf1 accumulation at the Golgi and suppressed Golgi disruption and inhibition of vacuolar trafficking that was caused by overexpression of AGD7. Based on these results, we propose that the Glo3p-type ArfGAPs AGD8 and AGD9 recruit Arf1-GDP from the cytosol to the Golgi for Arf1-mediated protein trafficking, which is essential for plant development and growth.

  16. Study on disparity of regional economic development based on geoinformatic Tupu and GWR model: a case of growth of GDP per capita in China from 1999 to 2003

    NASA Astrophysics Data System (ADS)

    Li, Feixue; Li, Manchun; Liang, Jian

    2007-06-01

    Regional disparity of economic development in China is always greatly concerned by investigators domestic and abroad, and sets of models have been used in the analysis. Spatial dependence, which is hidden in the data with spatial attributes, usually is not taken into account in classical statistics methods, such as ordinary linear regression(OLR) model. Along with the development of spatial statistics, more and more attentions are paid on spatial interactions between observations in the study of regional disparity. Geographically weighted regression (GWR) is a simple but effective model to recognize spatial variation and local difference, which considers the influence of the spatially non-stationarity of the variables. In this study, GWR model and Geo-Informatic Tupu were used to analyze the disparity of regional economic development in China, taking GDP per capita in 1999 and 2003 as a case, which is usually used to measure level of economic development. GDP per capita in the 338 cities in 1999 were selected to simulate GDP per capita in 2003 and to analysis non-stationarity of the growth of GDP per capita. Using Geo-Informatic Tupu, A series of maps were processed to display patterns of local parameter estimates, such as local r-squares, the residual sum of squares, local residual and so on, to gain a better understanding of the degree of spatial non-stationarity in a relationship over space. We tested for geographic heterogeneity in the parameters and compare them to estimates obtained from global regression approaches. The results suggested there was heterogeneity in the regression coefficients across broad regions of China, and a one-size fits all approach to describe growth processes appeared simplistic. The GWR model improved over the OLR model, and it was able to better explain the variation in the data and to simulate GDP per capita with smaller errors than the OLR models.

  17. The de novo and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form Trypanosoma brucei.

    PubMed

    Kuettel, Sabine; Wadum, Majken C T; Güther, Maria Lucia S; Mariño, Karina; Riemer, Carolin; Ferguson, Michael A J

    2012-04-01

    The sugar nucleotide GDP-mannose is essential for Trypanosoma brucei. Phosphomannose isomerase occupies a key position on the de novo pathway to GDP-mannose from glucose, just before intersection with the salvage pathway from free mannose. We identified the parasite phosphomannose isomerase gene, confirmed that it encodes phosphomannose isomerase activity and localized the endogenous enzyme to the glycosome. We also created a bloodstream-form conditional null mutant of phosphomannose isomerase to assess the relative roles of the de novo and salvage pathways of GDP-mannose biosynthesis. Phosphomannose isomerase was found to be essential for parasite growth. However, supplementation of the medium with low concentrations of mannose, including that found in human plasma, relieved this dependence. Therefore, we do not consider phosphomannose isomerase to be a viable drug target. We further established culture conditions where we can control glucose and mannose concentrations and perform steady-state [U-(13) C]-D-glucose labelling. Analysis of the isotopic sugar composition of the parasites variant surface glycoprotein synthesized in cells incubated in 5 mM [U-(13) C]-D-glucose in the presence and absence of unlabelled mannose showed that, under physiological conditions, about 80% of GDP-mannose synthesis comes from the de novo pathway and 20% from the salvage pathway.

  18. Spatiotemporal changes in both asset value and GDP associated with seismic exposure in China in the context of rapid economic growth from 1990 to 2010

    NASA Astrophysics Data System (ADS)

    Wu, Jidong; Wang, Cailin; He, Xin; Wang, Xu; Li, Ning

    2017-03-01

    Accurate exposure estimation is essential for seismic risk assessment. Recent rapid urbanization and economic growth in China have led to massive spatiotemporal changes in both the asset value and GDP exposed to seismic hazards. Using available GDP data, the asset value dataset produced by Wu et al (2014a) and spatial disaggregation technology, gridded maps of GDP and asset value are overlaid with the latest seismic map to investigate spatiotemporal changes in economic exposure in the most seismically hazardous areas (MSHAs) in China in 1990, 2000 and 2010. We found that 15.4% of China’s asset value and 14.1% of China’s GDP were located in MSHAs in 2010, and the asset value and GDP exposed to MSHAs reached 15.9 trillion CNY and 6.2 trillion CNY, respectively, with average annual rates of increase of 14.4% and 11.3% over the two decades. The evidence of increased exposure provides valuable information regarding whom or what risk managers should give the most attention based on the economic exposure changes in earthquake-prone areas of China. Notably, the North China seismic belt, which is associated with the largest economic exposure to earthquakes and a rapidly increasing rate of economic exposure compared to those in other seismic belts, and the Qinghai-Tibet seismic belt, which has the highest earthquake occurrence, are two seismic belts of interest. A more detailed study is required to determine the relationship between increased economic exposure and earthquake disaster losses combined with hazard level and vulnerability.

  19. Distinct roles for the two Rho GDP/GTP exchange factor domains of kalirin in regulation of neurite growth and neuronal morphology.

    PubMed

    Penzes, P; Johnson, R C; Kambampati, V; Mains, R E; Eipper, B A

    2001-11-01

    The actin cytoskeleton, essential for neuronal development, is regulated in part by small GTP binding proteins of the Rho subfamily. Kalirin-9, with two Rho subfamily-specific GDP/GTP exchange factor (GEF) domains, localizes to neurites and growth cones of primary cortical neurons. Kalirin-9 overexpression in cultured cortical neurons induces longer neurites and altered neuronal morphology. Expression of the first GEF domain alone results in drastically shortened axons and excessive growth cones, mediated by Rac1. Expression of the second GEF domain alone induces axonal over-elongation and abundant filopodial neurites, mediated by RhoA. Coordination of the actions of the individual GEF domains through their presence in Kalirin-9, with its Sec14p, spectrin, and Src homology domain 3 motifs, is essential for regulating neurite extension and neuronal morphology.

  20. A mutation in GDP-mannose pyrophosphorylase causes conditional hypersensitivity to ammonium, resulting in Arabidopsis root growth inhibition, altered ammonium metabolism, and hormone homeostasis.

    PubMed

    Barth, Carina; Gouzd, Zachary A; Steele, Hilary P; Imperio, Ryan M

    2010-01-01

    Ascorbic acid (AA) is an antioxidant fulfilling a multitude of cellular functions. Given its pivotal role in maintaining the rate of cell growth and division in the quiescent centre of the root, it was hypothesized that the AA-deficient Arabidopsis thaliana mutants vtc1-1, vtc2-1, vtc3-1, and vtc4-1 have altered root growth. To test this hypothesis, root development was studied in the wild type and vtc mutants grown on Murashige and Skoog medium. It was discovered, however, that only the vtc1-1 mutant has strongly retarded root growth, while the other vtc mutants exhibit a wild-type root phenotype. It is demonstrated that the short-root phenotype in vtc1-1 is independent of AA deficiency and oxidative stress. Instead, vtc1-1 is conditionally hypersensitive to ammonium (NH(4)(+)). To provide new insights into the mechanism of NH(4)(+) sensitivity in vtc1-1, root development, NH(4)(+) content, glutamine synthetase (GS) activity, glutamate dehydrogenase activity, and glutamine content were assessed in wild-type and vtc1-1 mutant plants grown in the presence and absence of high NH(4)(+) and the GS inhibitor MSO. Since VTC1 encodes a GDP-mannose pyrophosphorylase, an enzyme generating GDP-mannose for AA biosynthesis and protein N-glycosylation, it was also tested whether protein N-glycosylation is affected in vtc1-1. Furthermore, since root development requires the action of a variety of hormones, it was investigated whether hormone homeostasis is linked to NH(4)(+) sensitivity in vtc1-1. Our data suggest that NH(4)(+) hypersensitivity in vtc1-1 is caused by disturbed N-glycosylation and that it is associated with auxin and ethylene homeostasis and/or nitric oxide signalling.

  1. A mutation in GDP-mannose pyrophosphorylase causes conditional hypersensitivity to ammonium, resulting in Arabidopsis root growth inhibition, altered ammonium metabolism, and hormone homeostasis

    PubMed Central

    Barth, Carina; Gouzd, Zachary A.; Steele, Hilary P.; Imperio, Ryan M.

    2010-01-01

    Ascorbic acid (AA) is an antioxidant fulfilling a multitude of cellular functions. Given its pivotal role in maintaining the rate of cell growth and division in the quiescent centre of the root, it was hypothesized that the AA-deficient Arabidopsis thaliana mutants vtc1-1, vtc2-1, vtc3-1, and vtc4-1 have altered root growth. To test this hypothesis, root development was studied in the wild type and vtc mutants grown on Murashige and Skoog medium. It was discovered, however, that only the vtc1-1 mutant has strongly retarded root growth, while the other vtc mutants exhibit a wild-type root phenotype. It is demonstrated that the short-root phenotype in vtc1-1 is independent of AA deficiency and oxidative stress. Instead, vtc1-1 is conditionally hypersensitive to ammonium (NH4+). To provide new insights into the mechanism of NH4+ sensitivity in vtc1-1, root development, NH4+ content, glutamine synthetase (GS) activity, glutamate dehydrogenase activity, and glutamine content were assessed in wild-type and vtc1-1 mutant plants grown in the presence and absence of high NH4+ and the GS inhibitor MSO. Since VTC1 encodes a GDP-mannose pyrophosphorylase, an enzyme generating GDP-mannose for AA biosynthesis and protein N-glycosylation, it was also tested whether protein N-glycosylation is affected in vtc1-1. Furthermore, since root development requires the action of a variety of hormones, it was investigated whether hormone homeostasis is linked to NH4+ sensitivity in vtc1-1. Our data suggest that NH4+ hypersensitivity in vtc1-1 is caused by disturbed N-glycosylation and that it is associated with auxin and ethylene homeostasis and/or nitric oxide signalling. PMID:20007685

  2. GM3 suppresses anchorage-independent growth via Rho GDP dissociation inhibitor beta in melanoma B16 cells.

    PubMed

    Wang, Pu; Xu, Su; Wang, Yinan; Wu, Peixing; Zhang, Jinghai; Sato, Toshinori; Yamagata, Sadako; Yamagata, Tatsuya

    2011-08-01

    Ly-GDI, Rho GTPase dissociation inhibitor beta, was found to be expressed parallel to the GM3 level in mouse B16 cells whose GM3 contents were modified by B4galt6 sense, B4galt6 antisense cDNA, or St3galt5 siRNA transfection. Ly-GDI expression was increased on GM3 addition to these cells and decreased with D-PDMP treatment, a glucosylceramide synthesis inhibitor. Suppression of GM3 or Ly-GDI by RNAi was concomitantly associated with an increase in anchorage-independent growth in soft agar. These results clearly indicate that GM3 suppresses anchorage-independent growth through Ly-GDI. GM3 signals regulating Ly-GDI expression was inhibited by LY294002, siRNA against Akt1 and Akt2 and rapamycin, showing that GM3 signals are transduced via the PI3K/Akt/mTOR pathway. Either siRNA towards Rictor or Raptor suppressed Ly-GDI expression. The Raptor siRNA suppressed the effects of GM3 on Ly-GDI expression and Akt phosphorylation at Thr(308) , suggesting GM3 signals to be transduced to mTOR-Raptor and Akt-Thr(308) , leading to Ly-GDI stimulation. siRNA targeting Pdpk1 reduced Akt phosphorylation at Thr(308) and rendered the cells insensitive to GM3 stimulation, indicating that Akt-Thr(308) plays a critical role in the pathway. The components aligned in this pathway showed similar effects on anchorage-independent growth as GM3 and Ly-GDI. Taken together, GM3 signals are transduced in B16 cells through PI3K, Pdpk1, Akt(Thr308) and the mTOR/Raptor pathway, leading to enhanced expression of Ly-GDI mRNA, which in turn suppresses anchorage-independent growth in melanoma B16 cells.

  3. Cdc24, the GDP-GTP exchange factor for Cdc42, is required for invasive hyphal growth of Candida albicans.

    PubMed

    Bassilana, Martine; Blyth, James; Arkowitz, Robert A

    2003-02-01

    Candida albicans, the most common human fungal pathogen, is particularly problematic for immunocompromised individuals. The reversible transition of this fungal pathogen to a filamentous form that invades host tissue is important for its virulence. Although different signaling pathways such as a mitogen-activated protein kinase and a protein kinase A cascade are critical for this morphological transition, the function of polarity establishment proteins in this process has not been determined. We examined the role of four different polarity establishment proteins in C. albicans invasive growth and virulence by using strains in which one copy of each gene was deleted and the other copy expressed behind the regulatable promoter MET3. Strikingly, mutants with ectopic expression of either the Rho G-protein Cdc42 or its exchange factor Cdc24 are unable to form invasive hyphal filaments and germ tubes in response to serum or elevated temperature and yet grow normally as a budding yeast. Furthermore, these mutants are avirulent in a mouse model for systemic infection. This function of the Cdc42 GTPase module is not simply a general feature of polarity establishment proteins. Mutants with ectopic expression of the SH3 domain containing protein Bem1 or the Ras-like G-protein Bud1 can grow in an invasive fashion and are virulent in mice, albeit with reduced efficiency. These results indicate that a specific regulation of Cdc24/Cdc42 activity is required for invasive hyphal growth and suggest that these proteins are required for pathogenicity of C. albicans.

  4. 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.

  5. 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…

  6. GDP-tubulin incorporation into growing microtubules modulates polymer stability.

    PubMed

    Valiron, Odile; Arnal, Isabelle; Caudron, Nicolas; Job, Didier

    2010-06-04

    Microtubule growth proceeds through the endwise addition of nucleotide-bound tubulin dimers. The microtubule wall is composed of GDP-tubulin subunits, which are thought to come exclusively from the incorporation of GTP-tubulin complexes at microtubule ends followed by GTP hydrolysis within the polymer. The possibility of a direct GDP-tubulin incorporation into growing polymers is regarded as hardly compatible with recent structural data. Here, we have examined GTP-tubulin and GDP-tubulin incorporation into polymerizing microtubules using a minimal assembly system comprised of nucleotide-bound tubulin dimers, in the absence of free nucleotide. We find that GDP-tubulin complexes can efficiently co-polymerize with GTP-tubulin complexes during microtubule assembly. GDP-tubulin incorporation into microtubules occurs with similar efficiency during bulk microtubule assembly as during microtubule growth from seeds or centrosomes. Microtubules formed from GTP-tubulin/GDP-tubulin mixtures display altered microtubule dynamics, in particular a decreased shrinkage rate, apparently due to intrinsic modifications of the polymer disassembly properties. Thus, although microtubules polymerized from GTP-tubulin/GDP-tubulin mixtures or from homogeneous GTP-tubulin solutions are both composed of GDP-tubulin subunits, they have different dynamic properties, and this may reveal a novel form of microtubule "structural plasticity."

  7. Two hits revisited again

    PubMed Central

    Tomlinson, I; Roylance, R; Houlston, R

    2001-01-01

    INTRODUCTION AND METHODS—Since the concept of the "two hit hypothesis" was introduced over 20 years ago, a wealth of genetic data has accumulated on the mutations found at tumour suppressor loci. Perhaps surprisingly, these data conceal large gaps in our knowledge which genetic and functional studies are beginning to uncover. The "two hit hypothesis" must be updated to take account of this new information.
RESULTS AND DISCUSSION—Here, we discuss both the results of recent studies and some of the questions that they highlight. In particular, how valid are conclusions from inherited Mendelian syndromes when applied to sporadic cancers? Why is allelic loss so common and how does it occur? Are the "two hits" random or interdependent? Is abolition of protein function always optimal for tumorigenesis? Can "third hits" occur and, if so, why? How can mismatch repair deficiency and the methylator phenotype be incorporated into the "two hit" hypothesis? We suggest that the "two hit hypothesis" is not fixed but is evolving as our knowledge expands.


Keywords: two hit model; tumour suppressor; carcinogenesis PMID:11158170

  8. 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.

  9. Silencing of the GDP-D-mannose 3,5-epimerase affects the structure and cross-linking of the pectic polysaccharide rhamnogalacturonan II and plant growth in tomato.

    PubMed

    Voxeur, Aline; Gilbert, Louise; Rihouey, Christophe; Driouich, Azeddine; Rothan, Christophe; Baldet, Pierre; Lerouge, Patrice

    2011-03-11

    L-galactose (L-Gal), a monosaccharide involved in L-ascorbate and rhamnogalacturonan II (RG-II) biosynthesis in plants, is produced in the cytosol by a GDP-D-mannose 3,5-epimerase (GME). It has been recently reported that the partial inactivation of GME induced growth defects affecting both cell division and cell expansion (Gilbert, L., Alhagdow, M., Nunes-Nesi, A., Quemener, B., Guillon, F., Bouchet, B., Faurobert, M., Gouble, B., Page, D., Garcia, V., Petit, J., Stevens, R., Causse, M., Fernie, A. R., Lahaye, M., Rothan, C., and Baldet, P. (2009) Plant J. 60, 499-508). In the present study, we show that the silencing of the two GME genes in tomato leaves resulted in approximately a 60% decrease in terminal L-Gal content in the side chain A of RG-II as well as in a lower capacity of RG-II to perform in muro cross-linking. In addition, we show that unlike supplementation with L-Gal or ascorbate, supplementation of GME-silenced lines with boric acid was able to restore both the wild-type growth phenotype of tomato seedlings and an efficient in muro boron-mediated cross-linking of RG-II. Our findings suggest that developmental phenotypes in GME-deficient lines are due to the structural alteration of RG-II and further underline the crucial role of the cross-linking of RG-II in the formation of the pectic network required for normal plant growth and development.

  10. Cyclone Chris Hits Australia

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This false-color image shows Cyclone Chris shortly after it hit Australia's northwestern coast on February 6, 2002. This scene was acquired by the Moderate-resolution Imaging Spectroradiometer (MODIS), flying aboard NASA's Terra satellite. (Please note that this scene has not been reprojected.) Cyclone Chris is one of the most powerful storms ever to hit Australia. Initially, the storm contained wind gusts of up to 200 km per hour (125 mph), but shortly after making landfall it weakened to a Category 4 storm. Meteorologists expect the cyclone to weaken quickly as it moves further inland.

  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. Nedley Depression Hit Hypothesis

    PubMed Central

    Nedley, Neil; Ramirez, Francisco E.

    2014-01-01

    Depression is often diagnosed using the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria. We propose how certain lifestyle choices and non-modifiable factors can predict the development of depression. We identified 10 cause categories (hits or “blows” to the brain) and theorize that four or more active hits could trigger a depression episode. Methods. A sample of 4271 participants from our community-based program (70% female; ages 17-94 years) was assessed at baseline and at the eighth week of the program using a custom test. Ten cause categories were examined as predictors of depression are (1) Genetic, (2)Developmental, (3)Lifestyle, (4)Circadian Rhythm, (5)Addiction, (6)Nutrition, (7)Toxic, (8)Social/Complicated Grief, (9)Medical Condition, and (10)Frontal Lobe. Results. The relationship between the DSM-5 score and a person having four hits categories in the first program week showed a sensitivity of 89.98 % (95% CI: 89.20 % - 90.73%), specificity 48.84% (CI 45.94-51.75) and Matthew Correlation Coefficient (MCC) .41 . For the eight-week test, the results showed a sensitivity 83.6% (CI 81.9-85.5), specificity 53.7% (CI 51.7-55.6) and MCC .38. Overall, the hits that improved the most from baseline after the eighth week were: Nutrition (47%), Frontal lobe (36%), Addiction (24%), Circadian rhythm (24%), Lifestyle (20%), Social (12%) and Medical (10%). Conclusions. The Nedley four-hit hypothesis seems to predict a depressive episode and correlates well with the DSM-5 criteria with good sensitivity and MCC but less specificity. Identifying these factors and applying lifestyle therapies could play an important role in the treatment of depressed individuals. PMID:27885322

  14. Computational Physics' Greatest Hits

    NASA Astrophysics Data System (ADS)

    Bug, Amy

    2011-03-01

    The digital computer, has worked its way so effectively into our profession that now, roughly 65 years after its invention, it is virtually impossible to find a field of experimental or theoretical physics unaided by computational innovation. It is tough to think of another device about which one can make that claim. In the session ``What is computational physics?'' speakers will distinguish computation within the field of computational physics from this ubiquitous importance across all subfields of physics. This talk will recap the invited session ``Great Advances...Past, Present and Future'' in which five dramatic areas of discovery (five of our ``greatest hits'') are chronicled: The physics of many-boson systems via Path Integral Monte Carlo, the thermodynamic behavior of a huge number of diverse systems via Monte Carlo Methods, the discovery of new pharmaceutical agents via molecular dynamics, predictive simulations of global climate change via detailed, cross-disciplinary earth system models, and an understanding of the formation of the first structures in our universe via galaxy formation simulations. The talk will also identify ``greatest hits'' in our field from the teaching and research perspectives of other members of DCOMP, including its Executive Committee.

  15. The relationship between health and GDP in OECD countries in the very long run.

    PubMed

    Swift, Robyn

    2011-03-01

    This paper uses Johansen multivariate cointegration analysis to examine the relationship between health and GDP for 13 OECD countries over the last two centuries, for periods ranging from 1820-2001 to 1921-2001. A similar, long run, cointegrating relationship between life expectancy and both total GDP and GDP per capita was found for all the countries estimated. The relationships have a significant influence on both total GDP and GPD per capita in most of the countries estimated, with 1% increase in life expectancy resulting in an average 6% increase in total GDP in the long run, and 5% increase in GDP per capita. Total GDP and GDP per capita also have a significant influence on life expectancy for most countries. There is no evidence of changes in the relationships for any country over the periods estimated, indicating that shifts in the major causes of illness and death over time do not appear to have influenced the link between health and economic growth.

  16. 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

  17. 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

    2016-07-06

    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.

  18. 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

  19. Spatial disparity dynamics of ecosystem service values and GDP in Shaanxi Province, China in the last 30 years.

    PubMed

    Li, Tianhong; Ding, Yao

    2017-01-01

    The regional policy in China is shifting from solely gross domestic product (GDP) orientation to development that is more balanced between economic growth and ecological protection, as well as achieving equality among regions. Using land use maps and the adjusted value coefficients to assess ecosystem service values (ESV) for the 1980s, 1995, 2000, and 2010, we estimated the ESV in Shaanxi Province for different years, and characterized the spatial and temporal distribution of ESV and GDP. The results demonstrated that the total value of ecosystem services in Shaanxi Province increased from 208.95 billion Yuan in the 1980s to 309.76 billion Yuan in 2010. Variation Coefficient (Cv) and Theil index (T) were used to reflect the disparities of GDP or ESV within the study area. The values of Cv in descending order are GDP, ESV per capita, ESV, and GDP per capita. The Theil indexes of GDP were much greater than the ones of ESV. Variations of Cv and T showed that disparity in GDP kept increasing from the 1980s to 2000, then decreased; while no significant change in regional disparity of ESV were detected in parallel. The cities with higher GDP usually contributed little to ESV, and vice versa. The variation in GDP and ESV, in terms of the prefectural totals and per capita values, increased from the 1980s to 2010. This study provides an accessible way for local decision makers to evaluate the regional balance between economic growth and ecosystem services.

  20. Spatial disparity dynamics of ecosystem service values and GDP in Shaanxi Province, China in the last 30 years

    PubMed Central

    Li, Tianhong; Ding, Yao

    2017-01-01

    The regional policy in China is shifting from solely gross domestic product (GDP) orientation to development that is more balanced between economic growth and ecological protection, as well as achieving equality among regions. Using land use maps and the adjusted value coefficients to assess ecosystem service values (ESV) for the 1980s, 1995, 2000, and 2010, we estimated the ESV in Shaanxi Province for different years, and characterized the spatial and temporal distribution of ESV and GDP. The results demonstrated that the total value of ecosystem services in Shaanxi Province increased from 208.95 billion Yuan in the 1980s to 309.76 billion Yuan in 2010. Variation Coefficient (Cv) and Theil index (T) were used to reflect the disparities of GDP or ESV within the study area. The values of Cv in descending order are GDP, ESV per capita, ESV, and GDP per capita. The Theil indexes of GDP were much greater than the ones of ESV. Variations of Cv and T showed that disparity in GDP kept increasing from the 1980s to 2000, then decreased; while no significant change in regional disparity of ESV were detected in parallel. The cities with higher GDP usually contributed little to ESV, and vice versa. The variation in GDP and ESV, in terms of the prefectural totals and per capita values, increased from the 1980s to 2010. This study provides an accessible way for local decision makers to evaluate the regional balance between economic growth and ecosystem services. PMID:28358918

  1. Toward the mechanism of NH(4) (+) sensitivity mediated by Arabidopsis GDP-mannose pyrophosphorylase.

    PubMed

    Kempinski, Chase F; Haffar, Rawaa; Barth, Carina

    2011-05-01

    The ascorbic acid (AA)-deficient Arabidopsis thaliana mutant vtc1-1, which is defective in GDP-mannose pyrophosphorylase (GMPase), exhibits conditional hypersensitivity to ammonium (NH(4) (+) ), a phenomenon that is independent of AA deficiency. As GMPase is important for GDP-mannose biosynthesis, a nucleotide sugar necessary for protein N-glycosylation, it has been thought that GDP-mannose deficiency is responsible for the growth defect in vtc1-1 in the presence of NH(4) (+) . Therefore, the motivation for this work was to elucidate the growth and developmental processes that are affected in vtc1-1 in the presence of NH(4) (+) and to determine whether GDP-mannose deficiency generally causes NH(4) (+) sensitivity. Furthermore, as NH(4) (+) may alter cytosolic pH, we investigated the responses of vtc1-1 to pH changes in the presence and absence of NH(4) (+) . Using qRT-PCR and staining procedures, we demonstrate that defective N-glycosylation in vtc1-1 contributes to cell wall, membrane and cell cycle defects, resulting in root growth inhibition in the presence of NH(4) (+) . However, by using mutants acting upstream of vtc1-1 and contributing to GDP-mannose biosynthesis, we show that GDP-mannose deficiency does not generally lead to and is not the primary cause of NH(4) (+) sensitivity. Instead, our data suggest that GMPase responds to pH alterations in the presence of NH(4) (+) .

  2. 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.

  3. Enhanced HTS hit selection via a local hit rate analysis.

    PubMed

    Posner, Bruce A; Xi, Hualin; Mills, James E J

    2009-10-01

    The postprocessing of high-throughput screening (HTS) results is complicated by the occurrence of false positives (inactive compounds misidentified as active by the primary screen) and false negatives (active compounds misidentified as inactive by the primary screen). An activity cutoff is frequently used to select "active" compounds from HTS data; however, this approach is insensitive to both false positives and false negatives. An alternative method that can minimize the occurrence of these artifacts will increase the efficiency of hit selection and therefore lead discovery. In this work, rather than merely using the activity of a given compound, we look at the presence and absence of activity among all compounds in its "chemical space neighborhood" to give a degree of confidence in its activity. We demonstrate that this local hit rate (LHR) analysis method outperforms hit selection based on ranking by primary screen activity values across ten diverse high throughput screens, spanning both cell-based and biochemical assay formats of varying biology and robustness. On average, the local hit rate analysis method was approximately 2.3-fold and approximately 1.3-fold more effective in identifying active compounds and active chemical series, respectively, than selection based on primary activity alone. Moreover, when applied to finding false negatives, this method was 2.3-fold better than ranking by primary activity alone. In most cases, novel hit series were identified that would have otherwise been missed. Additional uses of and observations regarding this HTS analysis approach are also discussed.

  4. 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.

  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

    ... PAPD and update, the HIT IAPD and update, and the annual HIT IAPD. 495.344 Section 495.344 Public... and update, the HIT IAPD and update, and the annual HIT IAPD. HHS will not approve the State Medicaid HIT plan, HIT PAPD and update, HIT-IAPD and update, or annual IAPD if any of these documents do...

  6. 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…

  7. Two genes in Arabidopsis thaliana encoding GDP-L-galactose phosphorylase are required for ascorbate biosynthesis and seedling viability.

    PubMed

    Dowdle, John; Ishikawa, Takahiro; Gatzek, Stephan; Rolinski, Susanne; Smirnoff, Nicholas

    2007-11-01

    Plants synthesize ascorbate from guanosine diphosphate (GDP)-mannose via L-galactose/L-gulose, although uronic acids have also been proposed as precursors. Genes encoding all the enzymes of the GDP-mannose pathway have previously been identified, with the exception of the step that converts GDP-L-galactose to L-galactose 1-P. We show that a GDP-L-galactose phosphorylase, encoded by the Arabidopsis thaliana VTC2 gene, catalyses this step in the ascorbate biosynthetic pathway. Furthermore, a homologue of VTC2, At5g55120, encodes a second GDP-L-galactose phosphorylase with similar properties to VTC2. Two At5g55120 T-DNA insertion mutants (vtc5-1 and vtc5-2) have 80% of the wild-type ascorbate level. Double mutants were produced by crossing the loss-of-function vtc2-1 mutant with each of the two vtc5 alleles. These show growth arrest immediately upon germination and the cotyledons subsequently bleach. Normal growth was restored by supplementation with ascorbate or L-galactose, indicating that both enzymes are necessary for ascorbate generation. vtc2-1 leaves contain more mannose 6-P than wild-type. We conclude that the GDP-mannose pathway is the only significant source of ascorbate in A. thaliana seedlings, and that ascorbate is essential for seedling growth. A. thaliana leaves accumulate more ascorbate after acclimatization to high light intensity. VTC2 expression and GDP-L-galactose phosphorylase activity rapidly increase on transfer to high light, but the activity of other enzymes in the GDP-mannose pathway is little affected. VTC2 and At5g55120 (VTC5) expression also peak in at the beginning of the light cycle and are controlled by the circadian clock. The GDP-L-galactose phosphorylase step may therefore play an important role in controlling ascorbate biosynthesis.

  8. 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

  9. 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…

  10. Robust Hitting with Dynamics Shaping

    NASA Astrophysics Data System (ADS)

    Yashima, Masahito; Yamawaki, Tasuku

    The present paper proposes the trajectory planning based on “the dynamics shaping” for a redundant robotic arm to hit a target robustly toward the desired direction, of which the concept is to shape the robot dynamics appropriately by changing its posture in order to achieve the robust motion. The positional error of the end-effector caused by unknown disturbances converges onto near the singular vector corresponding to its maximum singular value of the output controllability matrix of the robotic arm. Therefore, if we can control the direction of the singular vector by applying the dynamics shaping, we will be able to control the direction of the positional error of the end-effector caused by unknown disturbances. We propose a novel trajectory planning based on the dynamics shaping and verify numerically and experimentally that the robotic arm can robustly hit the target toward the desired direction with a simple open-loop control system even though the disturbance is applied.

  11. Functional expression of Escherichia coli enzymes synthesizing GDP-L-fucose from inherent GDP-D-mannose in Saccharomyces cerevisiae.

    PubMed

    Mattila, P; Räbinä, J; Hortling, S; Helin, J; Renkonen, R

    2000-10-01

    Fucosylation of glycans on glycoproteins and -lipids requires the enzymatic activity of relevant fucosyltransferases and GDP-L-fucose as the donor. Due to the biological importance of fucosylated glycans, a readily accessible source of GDP-L-fucose would be required. Here we describe the construction of a stable recombinant S.cerevisiae strain expressing the E.coli genes gmd and wcaG encoding the two enzymes, GDP-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase/4-reductase (GMER(FX)) respectively, needed to convert GDP-mannose to GDP-fucose via the de novo pathway. Taking advantage of the rich inherent cytosolic GDP-mannose pool in S.cerevisiae cells we could easily produce 0.2 mg/l of GDP-L-fucose with this recombinant yeast strain without addition of any external GDP-mannose. The GDP-L-fucose product could be used as the fucose donor for alpha1,3fucosyltransferase to synthesize sialyl Lewis x (sLex), a glycan crucial for the selectin-dependent leukocyte traffic.

  12. The Production and Utilization of GDP-glucose in the Biosynthesis of Trehalose 6-Phosphate by Streptomyces venezuelae.

    PubMed

    Asención Diez, Matías D; Miah, Farzana; Stevenson, Clare E M; Lawson, David M; Iglesias, Alberto A; Bornemann, Stephen

    2017-01-20

    Trehalose-6-phosphate synthase OtsA from streptomycetes is unusual in that it uses GDP-glucose as the donor substrate rather than the more commonly used UDP-glucose. We now confirm that OtsA from Streptomyces venezuelae has such a preference for GDP-glucose and can utilize ADP-glucose to some extent too. A crystal structure of the enzyme shows that it shares twin Rossmann-like domains with the UDP-glucose-specific OtsA from Escherichia coli However, it is structurally more similar to Streptomyces hygroscopicus VldE, a GDP-valienol-dependent pseudoglycosyltransferase enzyme. Comparison of the donor binding sites reveals that the amino acids associated with the binding of diphosphoribose are almost all identical in these three enzymes. By contrast, the amino acids associated with binding guanine in VldE (Asn, Thr, and Val) are similar in S. venezuelae OtsA (Asp, Ser, and Phe, respectively) but not conserved in E. coli OtsA (His, Leu, and Asp, respectively), providing a rationale for the purine base specificity of S. venezuelae OtsA. To establish which donor is used in vivo, we generated an otsA null mutant in S. venezuelae The mutant had a cell density-dependent growth phenotype and accumulated galactose 1-phosphate, glucose 1-phosphate, and GDP-glucose when grown on galactose. To determine how the GDP-glucose is generated, we characterized three candidate GDP-glucose pyrophosphorylases. SVEN_3027 is a UDP-glucose pyrophosphorylase, SVEN_3972 is an unusual ITP-mannose pyrophosphorylase, and SVEN_2781 is a pyrophosphorylase that is capable of generating GDP-glucose as well as GDP-mannose. We have therefore established how S. venezuelae can make and utilize GDP-glucose in the biosynthesis of trehalose 6-phosphate.

  13. The Production and Utilization of GDP-glucose in the Biosynthesis of Trehalose 6-Phosphate by Streptomyces venezuelae*

    PubMed Central

    Asención Diez, Matías D.; Miah, Farzana; Stevenson, Clare E. M.; Lawson, David M.; Iglesias, Alberto A.; Bornemann, Stephen

    2017-01-01

    Trehalose-6-phosphate synthase OtsA from streptomycetes is unusual in that it uses GDP-glucose as the donor substrate rather than the more commonly used UDP-glucose. We now confirm that OtsA from Streptomyces venezuelae has such a preference for GDP-glucose and can utilize ADP-glucose to some extent too. A crystal structure of the enzyme shows that it shares twin Rossmann-like domains with the UDP-glucose-specific OtsA from Escherichia coli. However, it is structurally more similar to Streptomyces hygroscopicus VldE, a GDP-valienol-dependent pseudoglycosyltransferase enzyme. Comparison of the donor binding sites reveals that the amino acids associated with the binding of diphosphoribose are almost all identical in these three enzymes. By contrast, the amino acids associated with binding guanine in VldE (Asn, Thr, and Val) are similar in S. venezuelae OtsA (Asp, Ser, and Phe, respectively) but not conserved in E. coli OtsA (His, Leu, and Asp, respectively), providing a rationale for the purine base specificity of S. venezuelae OtsA. To establish which donor is used in vivo, we generated an otsA null mutant in S. venezuelae. The mutant had a cell density-dependent growth phenotype and accumulated galactose 1-phosphate, glucose 1-phosphate, and GDP-glucose when grown on galactose. To determine how the GDP-glucose is generated, we characterized three candidate GDP-glucose pyrophosphorylases. SVEN_3027 is a UDP-glucose pyrophosphorylase, SVEN_3972 is an unusual ITP-mannose pyrophosphorylase, and SVEN_2781 is a pyrophosphorylase that is capable of generating GDP-glucose as well as GDP-mannose. We have therefore established how S. venezuelae can make and utilize GDP-glucose in the biosynthesis of trehalose 6-phosphate. PMID:27903647

  14. The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in Plasmodium asexual blood stages.

    PubMed

    Sanz, Sílvia; López-Gutiérrez, Borja; Bandini, Giulia; Damerow, Sebastian; Absalon, Sabrina; Dinglasan, Rhoel R; Samuelson, John; Izquierdo, Luis

    2016-11-16

    Glycosylation is an important posttranslational protein modification in all eukaryotes. Besides glycosylphosphatidylinositol (GPI) anchors and N-glycosylation, O-fucosylation has been recently reported in key sporozoite proteins of the malaria parasite. Previous analyses showed the presence of GDP-fucose (GDP-Fuc), the precursor for all fucosylation reactions, in the blood stages of Plasmodium falciparum. The GDP-Fuc de novo pathway, which requires the action of GDP-mannose 4,6-dehydratase (GMD) and GDP-L-fucose synthase (FS), is conserved in the parasite genome, but the importance of fucose metabolism for the parasite is unknown. To functionally characterize the pathway we generated a PfGMD mutant and analyzed its phenotype. Although the labelling by the fucose-binding Ulex europaeus agglutinin I (UEA-I) was completely abrogated, GDP-Fuc was still detected in the mutant. This unexpected result suggests the presence of an alternative mechanism for maintaining GDP-Fuc in the parasite. Furthermore, PfGMD null mutant exhibited normal growth and invasion rates, revealing that the GDP-Fuc de novo metabolic pathway is not essential for the development in culture of the malaria parasite during the asexual blood stages. Nonetheless, the function of this metabolic route and the GDP-Fuc pool that is generated during this stage may be important for gametocytogenesis and sporogonic development in the mosquito.

  15. The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in Plasmodium asexual blood stages

    PubMed Central

    Sanz, Sílvia; López-Gutiérrez, Borja; Bandini, Giulia; Damerow, Sebastian; Absalon, Sabrina; Dinglasan, Rhoel R.; Samuelson, John; Izquierdo, Luis

    2016-01-01

    Glycosylation is an important posttranslational protein modification in all eukaryotes. Besides glycosylphosphatidylinositol (GPI) anchors and N-glycosylation, O-fucosylation has been recently reported in key sporozoite proteins of the malaria parasite. Previous analyses showed the presence of GDP-fucose (GDP-Fuc), the precursor for all fucosylation reactions, in the blood stages of Plasmodium falciparum. The GDP-Fuc de novo pathway, which requires the action of GDP-mannose 4,6-dehydratase (GMD) and GDP-L-fucose synthase (FS), is conserved in the parasite genome, but the importance of fucose metabolism for the parasite is unknown. To functionally characterize the pathway we generated a PfGMD mutant and analyzed its phenotype. Although the labelling by the fucose-binding Ulex europaeus agglutinin I (UEA-I) was completely abrogated, GDP-Fuc was still detected in the mutant. This unexpected result suggests the presence of an alternative mechanism for maintaining GDP-Fuc in the parasite. Furthermore, PfGMD null mutant exhibited normal growth and invasion rates, revealing that the GDP-Fuc de novo metabolic pathway is not essential for the development in culture of the malaria parasite during the asexual blood stages. Nonetheless, the function of this metabolic route and the GDP-Fuc pool that is generated during this stage may be important for gametocytogenesis and sporogonic development in the mosquito. PMID:27849032

  16. Interrelation of GDP and pension capital: Mathematical and econometrical analysis

    NASA Astrophysics Data System (ADS)

    Nepp, A. N.; Dolgodvorov, A. D.

    2016-12-01

    This article is a mathematicalanalysis of the relationship between GDP and the development of funded pension systems. For this purpose, a mathematical formula was derived from the macro-economic GDP, proportional to the level of income and consumption for the dependence of GDP on the level of pension payments, the value of pension savings and the structure of compulsory contributions to the pension fund allocated to the distribution and accumulative pension system. A derivation of the equation proves the linear relationship of GDP and the share of pension contributions channeled to the funded pension system. Thus, the macroeconomic indicator with the larger negative impact on GDP was proven to be the elimination of the compulsory funded pension system. Based on the econometric analysis, the positive effect of the distributive pension system was proven on macroeconomic parameters.

  17. Toward the equivalence of the HIT and HIT 25 in community-residing older adults.

    PubMed

    Hayslip, B; Francis, J R

    1991-06-01

    In a study by the first author wherein 102 community-residing older adults were administered the Holtzman Inkblot Technique (HIT), data collected were analyzed regarding the equivalence of the HIT and the HIT 25. Although alpha coefficients and split-half correlations were low when single-response-per-card data were analyzed, corrected Spearman-Brown coefficients were more supportive of the use of the HIT 25 with older adults. These data suggest that although a shortened form of the HIT may be useful with aged persons, research exploring the substantive bases for creating a shortened version of the HIT is nevertheless necessary.

  18. 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…

  19. 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.

  20. 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…

  1. 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

    ... 42 Public Health 5 2010-10-01 2010-10-01 false As-needed HIT PAPD update and as-needed HIT IAPD update requirements. 495.340 Section 495.340 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES...-needed HIT PAPD update and as-needed HIT IAPD update requirements. Each State must submit a HIT...

  2. Optical spectrosopy of HiTS supernovae

    NASA Astrophysics Data System (ADS)

    Anderson, J.; Forster, F.; Smith, C.; Vivas, K.; Pignata, G.; Olivares, F.; Hamuy, M.; Martin, J. San; Maureira, J. C.; Cabrera, G.; Gonzalez-Gaitan, S.; Galbany, L.; Bufano, F.; de Jaeger, T.; Hsiao, E.; Munoz, R.; Vera, E.

    2015-04-01

    We report optical wavelength spectroscopy obtained using the Goodman instrument mounted on the SOAR at CTIO on UT 2015-03-30, for two supernovae discovered by HiTS, the High Cadence Transient Survey (see ATELs #7289, #7290).

  3. Mining Preferred Traversal Paths with HITS

    NASA Astrophysics Data System (ADS)

    Yeh, Jieh-Shan; Lin, Ying-Lin; Chen, Yu-Cheng

    Web usage mining can discover useful information hidden in web logs data. However, many previous algorithms do not consider the structure of web pages, but regard all web pages with the same importance. This paper utilizes HITS values and PNT preferences as measures to mine users' preferred traversal paths. Wë structure mining uses HITS (hypertext induced topic selection) to rank web pages. PNT (preferred navigation tree) is an algorithm that finds users' preferred navigation paths. This paper introduces the Preferred Navigation Tree with HITS (PNTH) algorithm, which is an extension of PNT. This algorithm uses the concept of PNT and takes into account the relationships among web pages using HITS algorithm. This algorithm is suitable for E-commerce applications such as improving web site design and web server performance.

  4. More Older Women Hitting the Bottle Hard

    MedlinePlus

    ... medlineplus.gov/news/fullstory_164321.html More Older Women Hitting the Bottle Hard Study found dramatic jump ... March 28, 2017 (HealthDay News) -- More older American women than ever are drinking -- and drinking hard, a ...

  5. A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the Transcreener GDP Assay.

    PubMed

    Reichman, Melvin; Schabdach, Amanda; Kumar, Meera; Zielinski, Tom; Donover, Preston S; Laury-Kleintop, Lisa D; Lowery, Robert G

    2015-12-01

    Ras homologous (Rho) family GTPases act as molecular switches controlling cell growth, movement, and gene expression by cycling between inactive guanosine diphosphate (GDP)- and active guanosine triphosphate (GTP)-bound conformations. Guanine nucleotide exchange factors (GEFs) positively regulate Rho GTPases by accelerating GDP dissociation to allow formation of the active, GTP-bound complex. Rho proteins are directly involved in cancer pathways, especially cell migration and invasion, and inhibiting GEFs holds potential as a therapeutic strategy to diminish Rho-dependent oncogenesis. Methods for measuring GEF activity suitable for high-throughput screening (HTS) are limited. We developed a simple, generic biochemical assay method for measuring GEF activity based on the fact that GDP dissociation is generally the rate-limiting step in the Rho GTPase catalytic cycle, and thus addition of a GEF causes an increase in steady-state GTPase activity. We used the Transcreener GDP Assay, which relies on selective immunodetection of GDP, to measure the GEF-dependent stimulation of steady-state GTP hydrolysis by small GTPases using Dbs (Dbl's big sister) as a GEF for Cdc42, RhoA, and RhoB. The assay is well suited for HTS, with a homogenous format and far red fluorescence polarization (FP) readout, and it should be broadly applicable to diverse Rho GEF/GTPase pairs.

  6. 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…

  7. 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…

  8. 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

  9. Differential dynamics of RAS isoforms in GDP- and GTP-bound states.

    PubMed

    Kapoor, Abhijeet; Travesset, Alex

    2015-06-01

    RAS subfamily proteins regulates cell growth promoting signaling processes by cycling between active (GTP-bound) and inactive (GDP-bound) states. Different RAS isoforms, though structurally similar, exhibit functional specificity and are associated with different types of cancers and developmental disorders. Understanding the dynamical differences between the isoforms is crucial for the design of inhibitors that can selectively target a particular malfunctioning isoform. In this study, we provide a comprehensive comparison of the dynamics of all the three RAS isoforms (HRAS, KRAS, and NRAS) using extensive molecular dynamics simulations in both the GDP- (total of 3.06 μs) and GTP-bound (total of 2.4 μs) states. We observed significant differences in the dynamics of the isoforms, which rather interestingly, varied depending on the type of the nucleotide bound and the simulation temperature. Both SwitchI (Residues 25-40) and SwitchII (Residues 59-75) differ significantly in their flexibility in the three isoforms. Furthermore, Principal Component Analysis showed that there are differences in the conformational space sampled by the GTP-bound RAS isoforms. We also identified a previously unreported pocket, which opens transiently during MD simulations, and can be targeted to regulate nucleotide exchange reaction or possibly interfere with membrane localization. Further, we present the first simulation study showing GDP destabilization in the wild-type RAS protein. The destabilization of GDP/GTP occurred only in 1/50 simulations, emphasizing the need of guanine nucleotide exchange factors (GEFs) to accelerate such an extremely unfavorable process. This observation along with the other results presented in this article further support our previously hypothesized mechanism of GEF-assisted nucleotide exchange.

  10. 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

  11. 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.

  12. Loss of HITS (FAM107B) expression in cancers of multiple organs: tissue microarray analysis.

    PubMed

    Nakajima, Hideo; Koizumi, Keita; Tanaka, Takuji; Ishigaki, Yasuhito; Yoshitake, Yoshino; Yonekura, Hideto; Sakuma, Tsutomu; Fukushima, Toshihiro; Umehara, Hisanori; Ueno, Soichiro; Minamoto, Toshinari; Motoo, Yoshiharu

    2012-10-01

    Family with sequence similarity 107 (FAM107) proteins consist of two subtypes, FAM107A and FAM107B in mammals, possessing a conserved N-terminal domain of unknown function. Recently we found that FAM107B, an 18 kDa nuclear protein, is expressed in a broad range of tissues and is downregulated in gastrointestinal cancer. Because FAM107B expression is amplified by heat-shock stimulation, we designated it heat shock-inducible tumor small protein (HITS). Although data related to FAM107A as a candidate tumor suppressor have been accumulated, little biological information is available for HITS. In the present study, we examined HITS expression using immunohistochemistry with tissue microarrays and performed detailed statistical analyses. By screening a high-density multiple organ tumor and normal tissue microarray, HITS expression was decreased in tumor tissues of the breast, thyroid, testis and uterine cervix as well as the stomach and colon. Further analysis of tissue microarrays of individual organs showed that loss of HITS expression in cancer tissues was statistically significant and commonly observed in distinct organs in a histological type-specific manner. The HITS expression intensity was inversely correlated with the primary tumor size in breast and thyroid cancers. In addition, effects of tetracycline-inducible HITS expression on tumor growth were investigated in vivo. Forced expression of HITS inhibited tumor xenograft proliferation, compared with the mock-treated tumor xenograft model. These results show that loss of HITS expression is a common phenomenon observed in cancers of distinct organs and involved in tumor development and proliferation.

  13. 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.

  14. Optical Diagnostics on HIT-SI3

    NASA Astrophysics Data System (ADS)

    Everson, Christopher; Jarboe, Thomas; Morgan, Kyle

    2016-10-01

    Interferometry and Thomson Scattering are implemented on the HIT-SI3 (Helicity Injected Torus - Steady Inductive 3) device to provide time resolved measurements of electron density and spatially resolved measurements of electron temperature, respectively. HIT-SI3 is a modification of the original HIT-SI apparatus that uses three injectors instead of two. The scientific aim of HIT-SI3 is to develop a deeper understanding of how injector behavior and interactions influence current drive and spheromak stability. The interferometer system makes use of an intermediate frequency between two parallel 184.3 μm Far-Infrared (FIR) laser cavities which are optically pumped by a CO2 laser. The phase shift in this beat frequency due to the plasma index of refraction is used to calculate the line-integrated electron density. To measure the electron temperature, Thomson Scattered light from a 20 J (1 GW pulse) Ruby laser off of free electrons in the HIT-SI3 plasma is measured simultaneously at four locations across the spheromak (nominally 23 cm minor radius). Polychromators bin the collected light into 3 spectral bands to detect the relative level of scattering. Work supported by the D.O.E.

  15. Hitting America’s Soft Underbelly. The Potential Threat of Deliberate Biological Attacks Against the U.S. Agricultural and Food Industry

    DTIC Science & Technology

    2004-01-01

    constituencies. 17 Under the HACCP rule, all facilities that slaughter and process meat and poultry are re- quired to identify critical control points...xviii Hitting America’s Soft Underbelly GAO General Accounting Office GDP gross domestic product HACCP Hazard Analysis and Critical Control Points LSD...and dairy farm- ers alone earn between $50 billion and $54 billion a year through meat and milk sales,7 while roughly $50 billion in revenues are gener

  16. 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

  17. Two pathways for importing GDP-fucose into the endoplasmic reticulum lumen function redundantly in the O-fucosylation of Notch in Drosophila.

    PubMed

    Ishikawa, Hiroyuki O; Ayukawa, Tomonori; Nakayama, Minoru; Higashi, Shunsuke; Kamiyama, Shin; Nishihara, Shoko; Aoki, Kazuhisa; Ishida, Nobuhiro; Sanai, Yutaka; Matsuno, Kenji

    2010-02-05

    Notch is a transmembrane receptor that shares homology with proteins containing epidermal growth factor-like repeats and mediates the cell-cell interactions necessary for many cell fate decisions. In Drosophila, O-fucosyltransferase 1 catalyzes the O-fucosylation of these epidermal growth factor-like repeats. This O-fucose elongates, resulting in an O-linked tetrasaccharide that regulates the signaling activities of Notch. Fucosyltransferases utilize GDP-fucose, which is synthesized in the cytosol, but fucosylation occurs in the lumen of the endoplasmic reticulum (ER) and Golgi. Therefore, GDP-fucose uptake into the ER and Golgi is essential for fucosylation. However, although GDP-fucose biosynthesis is well understood, the mechanisms and intracellular routes of GDP-fucose transportation remain unclear. Our previous study on the Drosophila Golgi GDP-fucose transporter (Gfr), which specifically localizes to the Golgi, suggested that another GDP-fucose transporter(s) exists in Drosophila. Here, we identified Efr (ER GDP-fucose transporter), a GDP-fucose transporter that localizes specifically to the ER. Efr is a multifunctional nucleotide sugar transporter involved in the biosynthesis of heparan sulfate-glycosaminoglycan chains and the O-fucosylation of Notch. Comparison of the fucosylation defects in the N-glycans in Gfr and Efr mutants revealed that Gfr and Efr made distinct contributions to this modification; Gfr but not Efr was crucial for the fucosylation of N-glycans. We also found that Gfr and Efr function redundantly in the O-fucosylation of Notch, although they had different localizations and nucleotide sugar transportation specificities. These results indicate that two pathways for the nucleotide sugar supply, involving two nucleotide sugar transporters with distinct characteristics and distributions, contribute to the O-fucosylation of Notch.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Hydrodynamic response from oxygen non-uniformities in glow-discharge polymer (GDP) plastic in OMEGA OHRV experiments

    NASA Astrophysics Data System (ADS)

    Ali, Suzanne; Celliers, Peter; Haan, Steve; Baxamusa, Salman; Johnson, Michael; Hughes, Jim; Reynolds, Hannah; Watson, Brian

    2016-10-01

    Simulations and target characterization indicated that inhomogeneity in oxygen content could be a significant seed for Rayleigh-Taylor growth in GDP-ablator NIF implosions. This has been indirectly supported by observation of larger than expected in-flight modulations during NIF GDP capsule implosions, and the realization that such inhomogeneities can result from photo-induced oxygen uptake. In order to investigate the magnitude of the effect of these oxygen heterogeneities on the hydrodynamic response of GDP ablators, oxygen modulations were photo-induced in GDP foils by illuminating the foils with blue light through a periodic mask pattern. The foils were then used as ablators driven on OMEGA by a halfraum to replicate foot conditions on NIF. The resulting optically reflective shock wave was observed using the OMEGA High Resolution Velocimeter (OHRV). Two-dimensional velocity maps were obtained for both oxygen-modulated and unmodulated samples, with the modulated samples showing clear evidence of the propagation of a rippled shock wave as a result of the photo-induced oxygen heterogeneity. This work was supported by Department of Energy Contract #DE-NA0001808. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  4. 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

    ... Recommendations AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice..., clinical operations, implementation, and privacy and security. HIT Standards Committee's Schedule for the... information technology standards, implementation specifications, and/or certification criteria. Once the...

  5. 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.

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

    PubMed

    Brzezinski, Krzysztof; Dauter, Zbigniew; Jaskolski, Mariusz

    2012-02-01

    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 located between strand βC2 and helix αC3. In addition, there is a shift of the αC3 helix itself upon GDP

  7. 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

  8. Post-hit dynamics of price limit hits in the Chinese stock markets

    NASA Astrophysics Data System (ADS)

    Wu, Ting; Wang, Yue; Li, Ming-Xia

    2017-01-01

    Price limit trading rules are useful to cool off traders short-term trading mania on individual stocks. The price dynamics approaching the limit boards are known as the magnet effect. However, the price dynamics after opening price limit hits are not well investigated. Here, we provide a detailed analysis on the price dynamics after the hits of up-limit or down-limit is open based on all A-share stocks traded in the Chinese stock markets. A "W" shape is found in the expected return, which reveals high probability of a continuous price limit hit on the following day. We also find that price dynamics after opening limit hits are dependent on the market trends. The time span of continuously hitting the price limit is found to an influence factor of the expected profit after the limit hit is open. Our analysis provides a better understanding of the price dynamics around the limit boards and contributes potential practical values for investors.

  9. Mumps Cases Hit 10-Year High in U.S.

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_162676.html Mumps Cases Hit 10-Year High in U.S. Contagious ... 21, 2016 WEDNESDAY, Dec. 21, 2016 (HealthDay News) -- Mumps cases have hit a 10-year high in ...

  10. Universal Hitting Time Statistics for Integrable Flows

    NASA Astrophysics Data System (ADS)

    Dettmann, Carl P.; Marklof, Jens; Strömbergsson, Andreas

    2017-02-01

    The perceived randomness in the time evolution of "chaotic" dynamical systems can be characterized by universal probabilistic limit laws, which do not depend on the fine features of the individual system. One important example is the Poisson law for the times at which a particle with random initial data hits a small set. This was proved in various settings for dynamical systems with strong mixing properties. The key result of the present study is that, despite the absence of mixing, the hitting times of integrable flows also satisfy universal limit laws which are, however, not Poisson. We describe the limit distributions for "generic" integrable flows and a natural class of target sets, and illustrate our findings with two examples: the dynamics in central force fields and ellipse billiards. The convergence of the hitting time process follows from a new equidistribution theorem in the space of lattices, which is of independent interest. Its proof exploits Ratner's measure classification theorem for unipotent flows, and extends earlier work of Elkies and McMullen.

  11. Rescue of Notch signaling in cells incapable of GDP-L-fucose synthesis by gap junction transfer of GDP-L-fucose in Drosophila.

    PubMed

    Ayukawa, Tomonori; Matsumoto, Kenjiroo; Ishikawa, Hiroyuki O; Ishio, Akira; Yamakawa, Tomoko; Aoyama, Naoki; Suzuki, Takuya; Matsuno, Kenji

    2012-09-18

    Notch (N) is a transmembrane receptor that mediates cell-cell interactions to determine many cell-fate decisions. N contains EGF-like repeats, many of which have an O-fucose glycan modification that regulates N-ligand binding. This modification requires GDP-L-fucose as a donor of fucose. The GDP-L-fucose biosynthetic pathways are well understood, including the de novo pathway, which depends on GDP-mannose 4,6 dehydratase (Gmd) and GDP-4-keto-6-deoxy-D-mannose 3,5-epimerase/4-reductase (Gmer). However, the potential for intercellularly supplied GDP-L-fucose and the molecular basis of such transportation have not been explored in depth. To address these points, we studied the genetic effects of mutating Gmd and Gmer on fucose modifications in Drosophila. We found that these mutants functioned cell-nonautonomously, and that GDP-L-fucose was supplied intercellularly through gap junctions composed of Innexin-2. GDP-L-fucose was not supplied through body fluids from different isolated organs, indicating that the intercellular distribution of GDP-L-fucose is restricted within a given organ. Moreover, the gap junction-mediated supply of GDP-L-fucose was sufficient to support the fucosylation of N-glycans and the O-fucosylation of the N EGF-like repeats. Our results indicate that intercellular delivery is a metabolic pathway for nucleotide sugars in live animals under certain circumstances.

  12. Cryptococcus neoformans dual GDP-mannose transporters and their role in biology and virulence.

    PubMed

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

    2014-06-01

    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.

  13. GDP-mannose pyrophosphorylase is essential for cell wall integrity, morphogenesis and viability of Aspergillus fumigatus.

    PubMed

    Jiang, Hechun; Ouyang, Haomiao; Zhou, Hui; Jin, Cheng

    2008-09-01

    GDP-mannose pyrophosphorylase (GMPP) catalyses the synthesis of GDP-mannose, which is the precursor for the mannose residues in glycoconjugates, using mannose 1-phosphate and GTP as substrates. Repression of GMPP in yeast leads to phenotypes including cell lysis, defective cell wall, and failure of polarized growth and cell separation. Although several GMPPs have been isolated and characterized in filamentous fungi, the physiological consequences of their actions are not clear. In this study, Afsrb1, which is a homologue of yeast SRB1/PSA1/VIG9, was identified in the Aspergillus fumigatus genome. The Afsrb1 gene was expressed in Escherichia coli, and recombinant AfSrb1 was functionally confirmed as a GMPP. By the replacement of the native Afsrb1 promoter with an inducible Aspergillus nidulans alcA promoter, the conditional inactivation mutant strain YJ-gmpp was constructed. The presence of 3 % glucose completely blocked transcription of P(alcA)-Afsrb1, and was lethal to strain YJ-gmpp. Repression of Afsrb1 expression in strain YJ-gmpp led to phenotypes including hyphal lysis, defective cell wall, impaired polarity maintenance, and branching site selection. Also, rapid germination and reduced conidiation were documented. However, in contrast to yeast, strain YJ-gmpp retained the ability to direct polarity establishment and septation. Our results showed that the Afsrb1 gene is essential for cell wall integrity, morphogenesis and viability of Aspergillus fumigatus.

  14. Fragment-Based Whole Cell Screen Delivers Hits against M. tuberculosis and Non-tuberculous Mycobacteria.

    PubMed

    Moreira, Wilfried; Lim, Jia Jie; Yeo, Si Ying; Ramanujulu, Pondy M; Dymock, Brian W; Dick, Thomas

    2016-01-01

    Reactive multi-target 'fragment drugs' represent critical components of current tuberculosis regimens. These compounds, such as pyrazinamide, are old synthetic antimycobacterials that are activated inside Mycobacterium tuberculosis bacilli and are smaller than the usual drug-like, single-target molecules. Based on the success of small 'dirty' drugs in the chemotherapy of tuberculosis, we suggested previously that fragment-based whole cell screens should be introduced in our current antimycobacterial drug discovery efforts. Here, we carried out such a screen and characterized bactericidal activity, selectivity and spectrum of hits we obtained. A library of 1725 fragments was tested at a single concentration for growth inhibitory activity against M. bovis BCG as screening strain and 38 of 116 primary hits were confirmed in dose response analyses to be active against virulent M. tuberculosis. Bacterial kill experiments showed that most hits displayed bactericidal activity at their minimal inhibitory concentration. Cytotoxicity assays established that a large proportion of hits displayed a favorable selectivity index for mammalian cells. Importantly, one third of M. tuberculosis active fragments were also active against M. abscessus and M. avium, two emerging non-tuberculous mycobacterial (NTM) pathogens, opening the opportunity to develop broad spectrum antimycobacterials. Activity determination against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa) bacteria, as well as fungi (Candida albicans, Cryptococcus neoformans) showed only a small overlap indicating a generally narrow spectrum of these novel antimicrobial hits for mycobacteria. In conclusion, we carried out the first fragment-based whole cell screen against bacteria and identified a substantial number of hits with excellent physicochemical properties and dual activity against M. tuberculosis and NTM pathogens

  15. Multivariate time series analysis on the dynamic relationship between Class B notifiable diseases and gross domestic product (GDP) in China.

    PubMed

    Zhang, Tao; Yin, Fei; Zhou, Ting; Zhang, Xing-Yu; Li, Xiao-Song

    2016-12-01

    The surveillance of infectious diseases is of great importance for disease control and prevention, and more attention should be paid to the Class B notifiable diseases in China. Meanwhile, according to the International Monetary Fund (IMF), the annual growth of Chinese gross domestic product (GDP) would decelerate below 7% after many years of soaring. Under such circumstances, this study aimed to answer what will happen to the incidence rates of infectious diseases in China if Chinese GDP growth remained below 7% in the next five years. Firstly, time plots and cross-correlation matrices were presented to illustrate the characteristics of data. Then, the multivariate time series (MTS) models were proposed to explore the dynamic relationship between incidence rates and GDP. Three kinds of MTS models, i.e., vector auto-regressive (VAR) model for original series, VAR model for differenced series and error-correction model (ECM), were considered in this study. The rank of error-correction term was taken as an indicator for model selection. Finally, our results suggested that four kinds of infectious diseases (epidemic hemorrhagic fever, pertussis, scarlet fever and syphilis) might need attention in China because their incidence rates have increased since the year 2010.

  16. Stochastic dynamics and the predictability of big hits in online videos

    NASA Astrophysics Data System (ADS)

    Miotto, José M.; Kantz, Holger; Altmann, Eduardo G.

    2017-03-01

    The competition for the attention of users is a central element of the Internet. Crucial issues are the origin and predictability of big hits, the few items that capture a big portion of the total attention. We address these issues analyzing 106 time series of videos' views from YouTube. We find that the average gain of views is linearly proportional to the number of views a video already has, in agreement with usual rich-get-richer mechanisms and Gibrat's law, but this fails to explain the prevalence of big hits. The reason is that the fluctuations around the average views are themselves heavy tailed. Based on these empirical observations, we propose a stochastic differential equation with Lévy noise as a model of the dynamics of videos. We show how this model is substantially better in estimating the probability of an ordinary item becoming a big hit, which is considerably underestimated in the traditional proportional-growth models.

  17. Multiple-hit parameter estimation in monolithic detectors

    PubMed Central

    Hunter, William C. J.; Barrett, Harrison H.; Miyaoka, Robert S.; Lewellen, Tom K.

    2012-01-01

    We examine a maximum-a-priori (MAP) method for estimating the primary interaction position of gamma rays with multiple-interaction sites (hits) in a monolithic detector. In assessing the performance of a multiple-hit estimator over that of a conventional one-hit estimator, we consider a few different detector and readout configurations of a 50-mm-wide square LSO block. For this study, we use simulated data from SCOUT, a Monte-Carlo tool for photon tracking and modeling scintillation-camera output. With this tool, we determine estimate bias and variance for a multiple-hit estimator and compare these with similar metrics for a conventional ML estimator, which assumes full energy deposition in one hit. We also examine the effect of event filtering on these metrics; for this purpose, we use a likelihood threshold to reject signals that are not likely to have been produced under the assumed likelihood model. Depending on detector design, we observe a 1–12% improvement of intrinsic resolution for a 1-or-2-hit estimator as compared with a 1-hit estimator. We also observe improved differentiation of photopeak events using a 1-or-2-hit estimator as compared with the 1-hit estimator; more than 6% of photopeak events that were rejected by likelihood filtering for the 1-hit estimator were accurately identified as photo peak events and positioned without loss of resolution by a 1-or-2-hit estimator. PMID:23238325

  18. 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.

  19. The relationships between electricity consumption and GDP in Asian countries, using hierarchical structure methods

    NASA Astrophysics Data System (ADS)

    Kantar, Ersin; Keskin, Mustafa

    2013-11-01

    This study uses hierarchical structure methods (minimal spanning tree (MST) and hierarchical tree (HT)) to examine the relationship between energy consumption and economic growth in a sample of 30 Asian countries covering the period 1971-2008. These countries are categorized into four panels based on the World Bank income classification, namely high, upper middle, lower middle, and low income. In particular, we use the data of electricity consumption and real gross domestic product (GDP) per capita to detect the topological properties of the countries. We show a relationship between electricity consumption and economic growth by using the MST and HT. We also use the bootstrap technique to investigate a value of the statistical reliability to the links of the MST. Finally, we use a clustering linkage procedure in order to observe the cluster structure. The results of the structural topologies of these trees are as follows: (i) we identified different clusters of countries according to their geographical location and economic growth, (ii) we found a strong relationship between energy consumption and economic growth for all income groups considered in this study and (iii) the results are in good agreement with the causal relationship between electricity consumption and economic growth.

  20. 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.

  1. The Rock that Hit New York

    SciTech Connect

    Meade, Roger Allen; Keksis, August Lawrence

    2016-10-03

    On January 12, 1975, a rock seemed to fall from the sky over New York State’s Schoharie County hitting the tractor of a local farmer, who was “preparing his fields for spring planting.” As the farmer later described the event to a reporter from the UFO INVESTIGATOR, the object glanced off the tractor, fell to the ground, and melted its way through a patch of ice that was two and one half inches thick. The farmer, Leonard Tillapaugh, called the county sheriff, Harvey Stoddard, who recovered the rock, noting that it “was still warm.” Why and how a sample of the rock came to Los Alamos is not known. However, it captivated a wide Laboratory audience, was subjected to rigorous testing and evaluation. Los Alamos used the scientific method in the manner promoted by Hynek. Did Los Alamos solve the mystery of the rock’s origin? Not definitively. Although the exact origin could not be determined, it was shown conclusively that the rock was not from outer space. With that said, the saga of Rock that hit New York came to an end. Nothing more was said or written about it. The principals involved have long since passed from the scene. The NICAP ceased operations in 1980. And, the rock, itself, has disappeared.

  2. 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

  3. 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

    ... Recommendations AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice..., and privacy and security. Other groups are convened to address specific issues as needed, such as the... recommendations received from the HIT Policy Committee regarding health information technology...

  4. 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

  5. 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.

  6. Multiple-Hit Parameter Estimation in Monolithic Detectors

    PubMed Central

    Barrett, Harrison H.; Lewellen, Tom K.; Miyaoka, Robert S.

    2014-01-01

    We examine a maximum-a-posteriori method for estimating the primary interaction position of gamma rays with multiple interaction sites (hits) in a monolithic detector. In assessing the performance of a multiple-hit estimator over that of a conventional one-hit estimator, we consider a few different detector and readout configurations of a 50-mm-wide square cerium-doped lutetium oxyorthosilicate block. For this study, we use simulated data from SCOUT, a Monte-Carlo tool for photon tracking and modeling scintillation- camera output. With this tool, we determine estimate bias and variance for a multiple-hit estimator and compare these with similar metrics for a one-hit maximum-likelihood estimator, which assumes full energy deposition in one hit. We also examine the effect of event filtering on these metrics; for this purpose, we use a likelihood threshold to reject signals that are not likely to have been produced under the assumed likelihood model. Depending on detector design, we observe a 1%–12% improvement of intrinsic resolution for a 1-or-2-hit estimator as compared with a 1-hit estimator. We also observe improved differentiation of photopeak events using a 1-or-2-hit estimator as compared with the 1-hit estimator; more than 6% of photopeak events that were rejected by likelihood filtering for the 1-hit estimator were accurately identified as photopeak events and positioned without loss of resolution by a 1-or-2-hit estimator; for PET, this equates to at least a 12% improvement in coincidence-detection efficiency with likelihood filtering applied. PMID:23193231

  7. Hit-and-run planetary collisions.

    PubMed

    Asphaug, Erik; Agnor, Craig B; Williams, Quentin

    2006-01-12

    Terrestrial planet formation is believed to have concluded in our Solar System with about 10 million to 100 million years of giant impacts, where hundreds of Moon- to Mars-sized planetary embryos acquired random velocities through gravitational encounters and resonances with one another and with Jupiter. This led to planet-crossing orbits and collisions that produced the four terrestrial planets, the Moon and asteroids. But here we show that colliding planets do not simply merge, as is commonly assumed. In many cases, the smaller planet escapes from the collision highly deformed, spun up, depressurized from equilibrium, stripped of its outer layers, and sometimes pulled apart into a chain of diverse objects. Remnants of these 'hit-and-run' collisions are predicted to be common among remnant planet-forming populations, and thus to be relevant to asteroid formation and meteorite petrogenesis.

  8. 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

  9. Cloning and characterization of GDP-perosamine synthetase (Per) from Escherichia coli O157:H7 and synthesis of GDP-perosamine in vitro

    SciTech Connect

    Zhao Guohui; Liu Jun; Liu Xiang; Chen Min; Zhang Houcheng Wang, Peng George

    2007-11-23

    GDP-perosamine synthetase (Per, E.C. not yet classified) is important to the synthesis of Escherichia coli O157:H7 O-antigen. The mutant in per gene can disrupt the synthesis of O157 O-antigen. In this study, GDP-perosamine synthetase was cloned from E. coli O157:H7 and over-expressed in E. coli BL21 (DE3). The recombinant His-tagged Per fusion protein was a decamer with molecular weight of 431 kDa. The optimal pH value of this recombinant protein was 7.5. The divalent ions had no significant effect on Per-catalyzed reaction. The K{sub m} and K{sub cat}/K{sub m} for GDP-4-keto-6-deoxy-D-mannose were 0.09 mM and 2.1 x 10{sup 5} M{sup -1} S{sup -1}, and those for L-glutamate were 2 mM and 0.52 x 10{sup 5} M{sup -1}S{sup -1}, respectively. Per was used to synthesize GDP-perosamine from GDP-mannose together with recombinant GDP-mannose dehydratase (GMD, E.C. 4.2.1.47). The purified GDP-perosamine was identified by MS and NMR. In summary, this work provided a feasible approach for the synthesis of GDP-perosamine which can lead to the study of LPS biosynthesis of pathogenic E. coli O157:H7.

  10. New approaches for efficient solution of hitting set problem

    NASA Technical Reports Server (NTRS)

    Fijany, Amir; Vatan, Farrokh

    2004-01-01

    A new method for solving the hitting set problem is proposed. This method is based on the mapping of the problem onto an integer programming optimization problem. this new approach provides an algorithm with much better performance compare to the algorithms for the hitting set problem that currently are used for solving the diagnosis problem.

  11. First Plasma Results from the HIT-SI Spheromak

    NASA Astrophysics Data System (ADS)

    Sieck, P. E.; Hamp, W. T.; Izzo, V. A.; Jarboe, T. R.; Nelson, B. A.; O'Neill, R. G.; Redd, A. J.; Smith, R. J.

    2003-10-01

    HIT-SI is the newest device in the Helicity Injected Torus (HIT) program. HIT-SI is a ``bow tie'' spheromak formed and sustained by Steady Inductive Helicity Injection (SIHI) current drive. SIHI injects helicity at a nearly constant rate with no open field lines intersecting the boundary. (T. R. Jarboe, Fusion Technology 36) (1), p. 85, 1999 HIT-SI has been designed with a bow tie geometry to achieve stable high-β (>10%) spheromak equilibria. (U. Shumlak and T. R. Jarboe, Phys. Plasmas 7) (7), p. 2959, 2000 Diagnostics currently include surface magnetic probes and flux loops, visible light imaging, H-alpha line radiation monitors, voltage measurements across insulating breaks, injector current Rogowski coils, and injector flux loops. HIT-SI is currently operating in parallel with experiments on HIT-II. At the conclusion of HIT-II operations, HIT-SI will inherit a multi-point Thomson Scattering system, a scanning two-chord FIR interferometer, and other advanced diagnostics, as well as more power supplies to extend the discharge duration. Results are presented which characterize injector operation and possible evidence for spheromak formation.

  12. 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)

  13. 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.

  14. 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…

  15. 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.

  16. 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.

  17. KONJAC1 and 2 Are Key Factors for GDP-Mannose Generation and Affect l-Ascorbic Acid and Glucomannan Biosynthesis in Arabidopsis.

    PubMed

    Sawake, Shota; Tajima, Noriaki; Mortimer, Jenny C; Lao, Jeemeng; Ishikawa, Toshiki; Yu, Xiaolan; Yamanashi, Yukiko; Yoshimi, Yoshihisa; Kawai-Yamada, Maki; Dupree, Paul; Tsumuraya, Yoichi; Kotake, Toshihisa

    2015-12-01

    Humans are unable to synthesize l-ascorbic acid (AsA), yet it is required as a cofactor in many critical biochemical reactions. The majority of human dietary AsA is obtained from plants. In Arabidopsis thaliana, a GDP-mannose pyrophosphorylase (GMPP), VITAMIN C DEFECTIVE1 (VTC1), catalyzes a rate-limiting step in AsA synthesis: the formation of GDP-Man. In this study, we identified two nucleotide sugar pyrophosphorylase-like proteins, KONJAC1 (KJC1) and KJC2, which stimulate the activity of VTC1. The kjc1kjc2 double mutant exhibited severe dwarfism, indicating that KJC proteins are important for growth and development. The kjc1 mutation reduced GMPP activity to 10% of wild-type levels, leading to a 60% reduction in AsA levels. On the contrary, overexpression of KJC1 significantly increased GMPP activity. The kjc1 and kjc1kjc2 mutants also exhibited significantly reduced levels of glucomannan, which is also synthesized from GDP-Man. Recombinant KJC1 and KJC2 enhanced the GMPP activity of recombinant VTC1 in vitro, while KJCs did not show GMPP activity. Yeast two-hybrid assays suggested that the stimulation of GMPP activity occurs via interaction of KJCs with VTC1. These results suggest that KJCs are key factors for the generation of GDP-Man and affect AsA level and glucomannan accumulation through the stimulation of VTC1 GMPP activity.

  18. Implicit Hitting Set Problems and Multi-genome Alignment

    NASA Astrophysics Data System (ADS)

    Karp, Richard M.

    Let U be a finite set and S a family of subsets of U. Define a hitting set as a subset of U that intersects every element of S. The optimal hitting set problem is: given a positive weight for each element of U, find a hitting set of minimum total weight. This problem is equivalent to the classic weighted set cover problem.We consider the optimal hitting set problem in the case where the set system S is not explicitly given, but there is an oracle that will supply members of S satisfying certain conditions; for example, we might ask the oracle for a minimum-cardinality set in S that is disjoint from a given set Q. The problems of finding a minimum feedback arc set or minimum feedback vertex set in a digraph are examples of implicit hitting set problems. Our interest is in the number of oracle queries required to find an optimal hitting set. After presenting some generic algorithms for this problem we focus on our computational experience with an implicit hitting set problem related to multi-genome alignment in genomics. This is joint work with Erick Moreno Centeno.

  19. Geometric Hitting Set for Segments of Few Orientations

    SciTech Connect

    Fekete, Sandor P.; Huang, Kan; Mitchell, Joseph S. B.; Parekh, Ojas D.; Phillips, Cynthia A.

    2016-01-13

    Here we study several natural instances of the geometric hitting set problem for input consisting of sets of line segments (and rays, lines) having a small number of distinct slopes. These problems model path monitoring (e.g., on road networks) using the fewest sensors (the \\hitting points"). We give approximation algorithms for cases including (i) lines of 3 slopes in the plane, (ii) vertical lines and horizontal segments, (iii) pairs of horizontal/vertical segments. Lastly, we give hardness and hardness of approximation results for these problems. We prove that the hitting set problem for vertical lines and horizontal rays is polynomially solvable.

  20. Enhancing GDP-fucose production in recombinant Escherichia coli by metabolic pathway engineering.

    PubMed

    Zhai, Yafei; Han, Donglei; Pan, Ying; Wang, Shuaishuai; Fang, Junqiang; Wang, Peng; Liu, Xian-wei

    2015-02-01

    Guanosine 5'-diphosphate (GDP)-fucose is the indispensible donor substrate for fucosyltransferase-catalyzed synthesis of fucose-containing biomolecules, which have been found involving in various biological functions. In this work, the salvage pathway for GDP-fucose biosynthesis from Bacterioides fragilis was introduced into Escherichia coli. Besides, the biosynthesis of guanosine 5'-triphosphate (GTP), an essential substrate for GDP-fucose biosynthesis, was enhanced via overexpression of enzymes involved in the salvage pathway of GTP biosynthesis. The production capacities of metabolically engineered strains bearing different combinations of recombinant enzymes were compared. The shake flask fermentation of the strain expressing Fkp, Gpt, Gmk and Ndk obtained the maximum GDP-fucose content of 4.6 ± 0.22 μmol/g (dry cell mass), which is 4.2 fold that of the strain only expressing Fkp. Through fed-batch fermentation, the GDP-fucose content further rose to 6.6 ± 0.14 μmol/g (dry cell mass). In addition to a better productivity than previous fermentation processes based on the de novo pathway for GDP-fucose biosynthesis, the established schemes in this work also have the advantage to be a potential avenue to GDP-fucose analogs encompassing chemical modification on the fucose residue.

  1. 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.

  2. Isolation and characterization of the Arabidopsis heat-intolerant 2 (hit2) mutant reveal the essential role of the nuclear export receptor EXPORTIN1A (XPO1A) in plant heat tolerance.

    PubMed

    Wu, Shin-Jye; Wang, Lian-Chin; Yeh, Ching-Hui; Lu, Chun-An; Wu, Shaw-Jye

    2010-06-01

    *The Arabidopsis heat-intolerant 2 (hit2) mutant was isolated on the basis of its impaired ability to withstand moderate heat stress (37 degrees C). Determination of the genetic mutation that underlies the hit2 thermosensitive phenotype allowed better understanding of the mechanisms by which plants cope with heat stress. *Genetic analysis revealed that hit2 is a single recessive mutation. Map-based cloning was used to identify the hit2 locus. The response of hit2 to other types of heat stress was also investigated to characterize the protective role of HIT2. *hit2 was defective in basal but not in acquired thermotolerance. hit2 was sensitive to methyl viologen-induced oxidative stress, and the survival of hit2 seedlings in response to heat stress was affected by light conditions. The mutated locus was located at the EXPORTIN1A (XPO1A) gene, which encodes a nuclear transport receptor. Two T-DNA insertion lines, xpo1a-1 and xpo1a-3, exhibited the same phenotypes as hit2. *The results provide evidence that Arabidopsis XPO1A is dispensable for normal plant growth and development but is essential for thermotolerance, in part by mediating the protection of plants against heat-induced oxidative stress.

  3. Hitting Time Asymptotics for Hard-Core Interactions on Grids

    NASA Astrophysics Data System (ADS)

    Nardi, F. R.; Zocca, A.; Borst, S. C.

    2016-01-01

    We consider the hard-core model with Metropolis transition probabilities on finite grid graphs and investigate the asymptotic behavior of the first hitting time between its two maximum-occupancy configurations in the low-temperature regime. In particular, we show how the order-of-magnitude of this first hitting time depends on the grid sizes and on the boundary conditions by means of a novel combinatorial method. Our analysis also proves the asymptotic exponentiality of the scaled hitting time and yields the mixing time of the process in the low-temperature limit as side-result. In order to derive these results, we extended the model-independent framework in Manzo et al. (J Stat Phys 115(1/2):591-642, 2004) for first hitting times to allow for a more general initial state and target subset.

  4. 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.

  5. Pregnant Women Should Avoid Zika-Hit Texas Town: CDC

    MedlinePlus

    ... news/fullstory_162573.html Pregnant Women Should Avoid Zika-Hit Texas Town: CDC Advisory follows reports of ... border with Mexico, because five cases of local Zika infection have been reported there, U.S. health officials ...

  6. 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

  7. 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

    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.

  8. 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.

  9. 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…

  10. A GDP fluctuation model based on interacting firms

    NASA Astrophysics Data System (ADS)

    Li, Honggang; Gao, Yan

    2008-09-01

    A distinctive feature of the market economies is the short-run fluctuations in output around the trend of long-run growth over time, and we regard this feature is internal to complex economic systems composed of interacting heterogeneous units. To explore such internal mechanisms of macroeconomic fluctuations, we present a multi-agent Keynesian theory-based model, which can provide a good approximation to the key empirical features of the western business cycles in the 20th Century, such as the structure of the autocorrelation function of overall output growth, correlations between the output growth of individual agents over time, the distribution of recessions, etc.

  11. The GDP-bound form of Arf6 is located at the plasma membrane.

    PubMed

    Macia, Eric; Luton, Frédéric; Partisani, Mariagrazia; Cherfils, Jacqueline; Chardin, Pierre; Franco, Michel

    2004-05-01

    The function of Arf6 has been investigated largely by using the T27N and the Q67L mutants, which are thought to be blocked in GDP- and GTP-bound states, respectively. However, these mutants have been poorly characterized biochemically. Here, we found that Arf6(T27N) is not an appropriate marker of the inactive GDP-bound form because it has a high tendency to lose its nucleotide in vitro and to denature. As a consequence, most of the protein is aggregated in vivo and localizes to detergent-insoluble structures. However, a small proportion of Arf6(T27N) is able to form a stable complex with its exchange factor EFA6 at the plasma membrane, accounting for its dominant-negative phenotype. To define the cellular localization of Arf6-GDP, we designed a new mutant, Arf6(T44N). In vitro, this mutant has a 30-fold decreased affinity for GTP. In vivo, it is mostly GDP bound and, in contrast to the wild type, does not switch to the active conformation when expressed with EFA6. This GDP-locked mutant is found at the plasma membrane, where it localizes with EFA6 and Ezrin in actin- and phosphatidylinositol (4,5)-bisphosphate-enriched domains. From these results, we conclude that the Arf6 GDP-GTP cycle takes place at the plasma membrane.

  12. 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.

  13. MSHAM: a multi-hit sample and hold multiplexer

    SciTech Connect

    Bernstein, D.

    1980-10-01

    The MSHAM is a single-width CAMAC module intended to be used for dE/dx or Z-position measurements, with a density of 16 analog channels. It is designed to record up to four hits/event per channel but the design can be easily adapted to eight hits. The charge collection time interval allowed per hit is externally controlled in the range of 50 to 500 ns, according to the requirements of the experiment. Besides the electrical performance of the MSHAM, i.e., linearity, noise, cross-talk, etc., the goal was to design mutli-function circuits and high density packaging in order to achieve low cost per channel.

  14. 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.

  15. Applications of Biophysics in High-Throughput Screening Hit Validation.

    PubMed

    Genick, Christine Clougherty; Barlier, Danielle; Monna, Dominique; Brunner, Reto; Bé, Céline; Scheufler, Clemens; Ottl, Johannes

    2014-06-01

    For approximately a decade, biophysical methods have been used to validate positive hits selected from high-throughput screening (HTS) campaigns with the goal to verify binding interactions using label-free assays. By applying label-free readouts, screen artifacts created by compound interference and fluorescence are discovered, enabling further characterization of the hits for their target specificity and selectivity. The use of several biophysical methods to extract this type of high-content information is required to prevent the promotion of false positives to the next level of hit validation and to select the best candidates for further chemical optimization. The typical technologies applied in this arena include dynamic light scattering, turbidometry, resonance waveguide, surface plasmon resonance, differential scanning fluorimetry, mass spectrometry, and others. Each technology can provide different types of information to enable the characterization of the binding interaction. Thus, these technologies can be incorporated in a hit-validation strategy not only according to the profile of chemical matter that is desired by the medicinal chemists, but also in a manner that is in agreement with the target protein's amenability to the screening format. Here, we present the results of screening strategies using biophysics with the objective to evaluate the approaches, discuss the advantages and challenges, and summarize the benefits in reference to lead discovery. In summary, the biophysics screens presented here demonstrated various hit rates from a list of ~2000 preselected, IC50-validated hits from HTS (an IC50 is the inhibitor concentration at which 50% inhibition of activity is observed). There are several lessons learned from these biophysical screens, which will be discussed in this article.

  16. 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.

  17. Tolosa-Hunt Syndrome in Double-Hit Lymphoma

    PubMed Central

    Peddi, Prakash; Gallagher, Kevin M.; Chandrasekharan, Chandrikha; Wang, Qi; Gonzalez-Toledo, Eduardo; Nair, Binu S.; Munker, Reinhold; Mills, Glenn M.; Koshy, Nebu V.

    2015-01-01

    Tolosa-Hunt syndrome (THS) is a painful condition characterized by hemicranial pain, retroorbital pain, loss of vision, oculomotor nerve paralysis, and sensory loss in distribution of ophthalmic and maxillary division of trigeminal nerve. Lymphomas rarely involve cavernous sinus and simulate Tolosa-Hunt syndrome. Here we present a first case of double-hit B cell lymphoma (DHL) relapsing and masquerading as Tolosa-Hunt syndrome. The neurological findings were explained by a lymphomatous infiltration of the right Gasserian ganglion which preceded systemic relapse. As part of this report, the diagnostic criteria for Tolosa-Hunt syndrome and double-hit lymphoma are reviewed and updated treatment recommendations are presented. PMID:25918657

  18. A cross-section test of Cobb-Douglass production function between market capitalization and GDP

    NASA Astrophysics Data System (ADS)

    Avakian, Adam; Podobnik, Boris; Stanley, H. Eugene

    2012-02-01

    Most classical economic theories imply that both (a) economies with lower output (GDP) per person tend to grow faster in per capita terms and (b) economies with lower capital per person tend to grow faster in per capita terms. It is well-known that the former was found to be wrong. Taking market capitalization as a proxy for physical capital, we analyze a cohort of countries over a 17-year period (1994-2010) and we find the latter statement in agreement with empirical data implying a contradictive result that while capital data worldwide tend to converge, GDP data tend to diverge. However, for the countries analyzed, for which we have both market capitalization and GDP data, we find that even economies with lower output (GDP) per person tend to grow faster in per capita terms. The result that for all countries one obtains divergence while for a group of countries having both market capitalization and GDP data we have convergence is in contrast with the refutation of (a) but our results only apply to countries that have an exchange market, and are thus participating in globalization, indicating the convergent effect of globalization.

  19. GDP-D-mannose 3,5-epimerase (GME) plays a key role at the intersection of ascorbate and non-cellulosic cell-wall biosynthesis in tomato.

    PubMed

    Gilbert, Louise; Alhagdow, Moftah; Nunes-Nesi, Adriano; Quemener, Bernard; Guillon, Fabienne; Bouchet, Brigitte; Faurobert, Mireille; Gouble, Barbara; Page, David; Garcia, Virginie; Petit, Johann; Stevens, Rebecca; Causse, Mathilde; Fernie, Alisdair R; Lahaye, Marc; Rothan, Christophe; Baldet, Pierre

    2009-11-01

    The GDP-D-mannose 3,5-epimerase (GME, EC 5.1.3.18), which converts GDP-d-mannose to GDP-l-galactose, is generally considered to be a central enzyme of the major ascorbate biosynthesis pathway in higher plants, but experimental evidence for its role in planta is lacking. Using transgenic tomato lines that were RNAi-silenced for GME, we confirmed that GME does indeed play a key role in the regulation of ascorbate biosynthesis in plants. In addition, the transgenic tomato lines exhibited growth defects affecting both cell division and cell expansion. A further remarkable feature of the transgenic plants was their fragility and loss of fruit firmness. Analysis of the cell-wall composition of leaves and developing fruit revealed that the cell-wall monosaccharide content was altered in the transgenic lines, especially those directly linked to GME activity, such as mannose and galactose. In agreement with this, immunocytochemical analyses showed an increase of mannan labelling in stem and fruit walls and of rhamnogalacturonan labelling in the stem alone. The results of MALDI-TOF fingerprinting of mannanase cleavage products of the cell wall suggested synthesis of specific mannan structures with modified degrees of substitution by acetate in the transgenic lines. When considered together, these findings indicate an intimate linkage between ascorbate and non-cellulosic cell-wall polysaccharide biosynthesis in plants, a fact that helps to explain the common factors in seemingly unrelated traits such as fruit firmness and ascorbate content.

  20. 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.

  1. eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control.

    PubMed

    Jennings, Martin D; Kershaw, Christopher J; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P; Costello, Joseph L; Donaldson, Ian J; Zhou, Yu; Pavitt, Graham D

    2016-11-16

    In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation.

  2. Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses

    PubMed Central

    Toyama, Yuki; Kano, Hanaho; Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

    2017-01-01

    Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation. PMID:28223697

  3. 42 CFR 495.342 - Annual HIT IAPD requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Annual HIT IAPD requirements. 495.342 Section 495.342 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION STANDARDS FOR THE ELECTRONIC HEALTH RECORD TECHNOLOGY...

  4. Dealing with Hitting and Aggression in the Classroom.

    ERIC Educational Resources Information Center

    Saifer, Steffen

    1996-01-01

    Notes that while hitting-aggressive behavior is probably the greatest single behavior concern of teachers, children can be taught appropriate behavior for the classroom. Offers tips for dealing with: roughhousing; existing problems; grabbing toys; and war games, guns, or violent play. Suggests allowing children the choice of an alternative…

  5. Appreciating an Old Favorite: Sousa's All-Time Hit

    ERIC Educational Resources Information Center

    Van Outryve, Karen

    2006-01-01

    In this article, the author presents John Philip Sousa's all time hit, "The Stars and Stripes Forever". It is one of the most recognizable pieces of American music. Wherever John Philip Sousa and his band appeared, this march was likely to be played. According to American poet and educator Eli Siegel (1902-78), who first articulated the…

  6. Madoff Debacle Hits Colleges and Raises Questions about Trustee Conflicts

    ERIC Educational Resources Information Center

    Fain, Paul

    2009-01-01

    Several colleges and universities lost millions in the alleged $50-billion Ponzi scheme run by the Wall Street trader Bernard L. Madoff. The losses include institutions' endowment holdings in hedge funds that were invested with Madoff as well as hits taken by supporting foundations and donors. Several foundations that have been active in higher…

  7. Hit identification and optimization in virtual screening: practical recommendations based on a critical literature analysis.

    PubMed

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

    2013-09-12

    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, druglike, 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 that presented hit optimization was performed. These data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, definition of 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.

  8. 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

  9. EFFECTS OF CONVERSION TO A BICARBONATE/LACTATE-BUFFERED, NEUTRAL-PH, LOW-GDP PD REGIMEN IN PREVALENT PD: A 2-YEAR RANDOMIZED CLINICAL TRIAL.

    PubMed

    Farhat, Karima; Douma, Caroline; Ferrantelli, Evelina; Ter Wee, Pieter M; Beelen, Robert H; van Ittersum, Frans J

    2017-03-27

    inflammation (cancer antigen [CA]125, hyaluronan [HA], vascular endothelial growth factor [VEGF], macrophage chemo-attractant protein [MCP]-1, HA and transforming growth factor [TGF]β-1). ♦ Conclusion: In prevalent PD patients, our study did not find a difference in RRF after conversion from conventional to neutral-pH, low-GDP PD fluids, although there is a possibility that the study was underpowered to detect a difference. Decline in UF during standardized PET was lower after 2 years in the Physioneal group.

  10. Developing a comprehensive time series of GDP per capita for 210 countries from 1950 to 2015

    PubMed Central

    2012-01-01

    Background Income has been extensively studied and utilized as a determinant of health. There are several sources of income expressed as gross domestic product (GDP) per capita, but there are no time series that are complete for the years between 1950 and 2015 for the 210 countries for which data exist. It is in the interest of population health research to establish a global time series that is complete from 1950 to 2015. Methods We collected GDP per capita estimates expressed in either constant US dollar terms or international dollar terms (corrected for purchasing power parity) from seven sources. We applied several stages of models, including ordinary least-squares regressions and mixed effects models, to complete each of the seven source series from 1950 to 2015. The three US dollar and four international dollar series were each averaged to produce two new GDP per capita series. Results and discussion Nine complete series from 1950 to 2015 for 210 countries are available for use. These series can serve various analytical purposes and can illustrate myriad economic trends and features. The derivation of the two new series allows for researchers to avoid any series-specific biases that may exist. The modeling approach used is flexible and will allow for yearly updating as new estimates are produced by the source series. Conclusion GDP per capita is a necessary tool in population health research, and our development and implementation of a new method has allowed for the most comprehensive known time series to date. PMID:22846561

  11. GDP-to-GTP exchange on the microtubule end can contribute to the frequency of catastrophe

    PubMed Central

    Piedra, Felipe-Andrés; Kim, Tae; Garza, Emily S.; Geyer, Elisabeth A.; Burns, Alexander; Ye, Xuecheng; Rice, Luke M.

    2016-01-01

    Microtubules are dynamic polymers of αβ-tubulin that have essential roles in chromosome segregation and organization of the cytoplasm. Catastrophe—the switch from growing to shrinking—occurs when a microtubule loses its stabilizing GTP cap. Recent evidence indicates that the nucleotide on the microtubule end controls how tightly an incoming subunit will be bound (trans-acting GTP), but most current models do not incorporate this information. We implemented trans-acting GTP into a computational model for microtubule dynamics. In simulations, growing microtubules often exposed terminal GDP-bound subunits without undergoing catastrophe. Transient GDP exposure on the growing plus end slowed elongation by reducing the number of favorable binding sites on the microtubule end. Slower elongation led to erosion of the GTP cap and an increase in the frequency of catastrophe. Allowing GDP-to-GTP exchange on terminal subunits in simulations mitigated these effects. Using mutant αβ-tubulin or modified GTP, we showed experimentally that a more readily exchangeable nucleotide led to less frequent catastrophe. Current models for microtubule dynamics do not account for GDP-to-GTP exchange on the growing microtubule end, so our findings provide a new way of thinking about the molecular events that initiate catastrophe. PMID:27146111

  12. GDP-to-GTP exchange on the microtubule end can contribute to the frequency of catastrophe.

    PubMed

    Piedra, Felipe-Andrés; Kim, Tae; Garza, Emily S; Geyer, Elisabeth A; Burns, Alexander; Ye, Xuecheng; Rice, Luke M

    2016-11-07

    Microtubules are dynamic polymers of αβ-tubulin that have essential roles in chromosome segregation and organization of the cytoplasm. Catastrophe-the switch from growing to shrinking-occurs when a microtubule loses its stabilizing GTP cap. Recent evidence indicates that the nucleotide on the microtubule end controls how tightly an incoming subunit will be bound (trans-acting GTP), but most current models do not incorporate this information. We implemented trans-acting GTP into a computational model for microtubule dynamics. In simulations, growing microtubules often exposed terminal GDP-bound subunits without undergoing catastrophe. Transient GDP exposure on the growing plus end slowed elongation by reducing the number of favorable binding sites on the microtubule end. Slower elongation led to erosion of the GTP cap and an increase in the frequency of catastrophe. Allowing GDP-to-GTP exchange on terminal subunits in simulations mitigated these effects. Using mutant αβ-tubulin or modified GTP, we showed experimentally that a more readily exchangeable nucleotide led to less frequent catastrophe. Current models for microtubule dynamics do not account for GDP-to-GTP exchange on the growing microtubule end, so our findings provide a new way of thinking about the molecular events that initiate catastrophe.

  13. Carbon emissions, logistics volume and GDP in China: empirical analysis based on panel data model.

    PubMed

    Guo, Xiaopeng; Ren, Dongfang; Shi, Jiaxing

    2016-12-01

    This paper studies the relationship among carbon emissions, GDP, and logistics by using a panel data model and a combination of statistics and econometrics theory. The model is based on the historical data of 10 typical provinces and cities in China during 2005-2014. The model in this paper adds the variability of logistics on the basis of previous studies, and this variable is replaced by the freight turnover of the provinces. Carbon emissions are calculated by using the annual consumption of coal, oil, and natural gas. GDP is the gross domestic product. The results showed that the amount of logistics and GDP have a contribution to carbon emissions and the long-term relationships are different between different cities in China, mainly influenced by the difference among development mode, economic structure, and level of logistic development. After the testing of panel model setting, this paper established a variable coefficient model of the panel. The influence of GDP and logistics on carbon emissions is obtained according to the influence factors among the variables. The paper concludes with main findings and provides recommendations toward rational planning of urban sustainable development and environmental protection for China.

  14. 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

  15. UN study reports Asian economic crisis has hit women's health.

    PubMed

    Ciment, J

    1999-02-13

    A UN Population Fund report, "Southeast Asian Populations in Crisis," revealed that the economic crisis in Southeastern Asia has had a disproportionately adverse effect on the health of women and girls. This has occurred because the industries employing women have been hardest hit and because governments have reduced spending on health care and female education. Thailand, for example, has reduced its AIDS budget by 25% even as increasing numbers of women are pushed into the sex trade by economic necessity. Reproductive health services for adolescents have been hit just as shrinking family budgets are forcing adolescents to drop out of school. The report's authors are calling for a more detailed look at the situation.

  16. 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...

  17. Repeat Head Hits May Not Put NFL Players at Risk of Motor Problems

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_163670.html Repeat Head Hits May Not Put NFL Players at Risk ... 19, 2017 (HealthDay News) -- Repeated hits to the head may not doom NFL players to suffer movement ...

  18. Gemcitabine induced cardiomyopathy: a case of multiple hit cardiotoxicity.

    PubMed

    Mohebali, Donya; Matos, Jason; Chang, James Ducksoon

    2017-02-01

    Gemcitabine is a commonly used antineoplastic agent used to treat a variety of cancers with rarely reported cardiac side effects. We describe a case of a 67-year-old woman with follicular lymphoma who experienced a rarely reported side effect of gemcitabine: cardiomyopathy. This case highlights a multiple hit mechanism of myocyte damage that may occur following the use of multiple cardio-toxic agents despite their administration in doses not associated with cardiotoxicity.

  19. Improved Low-Cost Multi-Hit Transparent Armor

    DTIC Science & Technology

    2006-11-01

    MD Aberdeen Proving Ground , MD 21005-5069 ABSTRACT Operation Iraqi Freedom has clearly demonstrated the criticality of transparent armor in...Motyka at ARL) A polymer backing acts as a spall shield and holds fractured armor in place. Interlayer between polycarbonate and ceramics is...Hsieh, Gary A. Gilde U.S. Army Research Laboratory Aberdeen Proving Ground , MD IMPROVED LOW-COST MULTI-HIT TRANSPARENT ARMOR Distribution A

  20. 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.

  1. COPD: A stepwise or a hit hard approach?

    PubMed

    Ferreira, A J; Reis, A; Marçal, N; Pinto, P; Bárbara, C

    2016-01-01

    Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD) patients, and although there are some undisputed recommendations, there is still debate regarding the management of COPD. One of the hindrances to deciding which therapeutic approach to choose is late diagnosis or misdiagnosis of COPD. After a proper diagnosis is achieved and severity assessed, the choice between a stepwise or "hit hard" approach has to be made. For GOLD A patients the stepwise approach is recommended, whilst for B, C and D patients this remains debatable. Moreover, in patients for whom inhaled corticosteroids (ICS) are recommended, a step-up or "hit hard" approach with triple therapy will depend on the patient's characteristics and, for patients who are being over-treated with ICS, ICS withdrawal should be performed, in order to optimize therapy and reduce excessive medications. This paper discusses and proposes stepwise, "hit hard", step-up and ICS withdrawal therapeutic approaches for COPD patients based on their GOLD group. We conclude that all approaches have benefits, and only a careful patient selection will determine which approach is better, and which patients will benefit the most from each approach.

  2. 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

  3. 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.

  4. 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…

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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

  11. Hubs and authorities in the world trade network using a weighted HITS algorithm.

    PubMed

    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 1992 to 2012, 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 1992 to 2012. The authority value of the United States has declined since 2001, 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.

  12. Free energy simulations of a GTPase: GTP and GDP binding to archaeal initiation factor 2.

    PubMed

    Satpati, Priyadarshi; Clavaguéra, Carine; Ohanessian, Gilles; Simonson, Thomas

    2011-05-26

    Archaeal initiation factor 2 (aIF2) is a protein involved in the initiation of protein biosynthesis. In its GTP-bound, "ON" conformation, aIF2 binds an initiator tRNA and carries it to the ribosome. In its GDP-bound, "OFF" conformation, it dissociates from tRNA. To understand the specific binding of GTP and GDP and its dependence on the ON or OFF conformational state of aIF2, molecular dynamics free energy simulations (MDFE) are a tool of choice. However, the validity of the computed free energies depends on the simulation model, including the force field and the boundary conditions, and on the extent of conformational sampling in the simulations. aIF2 and other GTPases present specific difficulties; in particular, the nucleotide ligand coordinates a divalent Mg(2+) ion, which can polarize the electronic distribution of its environment. Thus, a force field with an explicit treatment of electronic polarizability could be necessary, rather than a simpler, fixed charge force field. Here, we begin by comparing a fixed charge force field to quantum chemical calculations and experiment for Mg(2+):phosphate binding in solution, with the force field giving large errors. Next, we consider GTP and GDP bound to aIF2 and we compare two fixed charge force fields to the recent, polarizable, AMOEBA force field, extended here in a simple, approximate manner to include GTP. We focus on a quantity that approximates the free energy to change GTP into GDP. Despite the errors seen for Mg(2+):phosphate binding in solution, we observe a substantial cancellation of errors when we compare the free energy change in the protein to that in solution, or when we compare the protein ON and OFF states. Finally, we have used the fixed charge force field to perform MDFE simulations and alchemically transform GTP into GDP in the protein and in solution. With a total of about 200 ns of molecular dynamics, we obtain good convergence and a reasonable statistical uncertainty, comparable to the force

  13. 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.

  14. 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.

  15. 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

  16. Health Care Expenditure and GDP in African Countries: Evidence from Semiparametric Estimation with Panel Data

    PubMed Central

    Lv, Zhike; Zhu, Huiming

    2014-01-01

    A large body of literature studies on the relationship between health care expenditure (HCE) and GDP have been analyzed using data intensively from developed countries, but little is known for other regions. This paper considers a semiparametric panel data analysis for the study of the relationship between per capita HCE and per capita GDP for 42 African countries over the period 1995–2009. We found that infant mortality rate per 1,000 live births has a negative effect on per capita HCE, while the proportion of the population aged 65 is statistically insignificant in African countries. Furthermore, we found that the income elasticity is not constant but varies with income level, and health care is a necessity rather than a luxury for African countries. PMID:24741366

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

    PubMed

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

    2016-05-21

    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.

  18. 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

  19. Chemoenzymatic synthesis of GDP-L-fucose and the Lewis X glycan derivatives.

    PubMed

    Wang, Wei; Hu, Tianshun; Frantom, Patrick A; Zheng, Tianqing; Gerwe, Brian; Del Amo, David Soriano; Garret, Sarah; Seidel, Ronald D; Wu, Peng

    2009-09-22

    Lewis X (Le(x))-containing glycans play important roles in numerous cellular processes. However, the absence of robust, facile, and cost-effective methods for the synthesis of Le(x) and its structurally related analogs has severely hampered the elucidation of the specific functions of these glycan epitopes. Here we demonstrate that chemically defined guanidine 5'-diphosphate-beta-l-fucose (GDP-fucose), the universal fucosyl donor, the Le(x) trisaccharide, and their C-5 substituted derivatives can be synthesized on preparative scales, using a chemoenzymatic approach. This method exploits l-fucokinase/GDP-fucose pyrophosphorylase (FKP), a bifunctional enzyme isolated from Bacteroides fragilis 9343, which converts l-fucose into GDP-fucose via a fucose-1-phosphate (Fuc-1-P) intermediate. Combining the activities of FKP and a Helicobacter pylori alpha1,3 fucosyltransferase, we prepared a library of Le(x) trisaccharide glycans bearing a wide variety of functional groups at the fucose C-5 position. These neoglycoconjugates will be invaluable tools for studying Le(x)-mediated biological processes.

  20. Chemoenzymatic synthesis of GDP-l-fucose and the Lewis X glycan derivatives

    PubMed Central

    Wang, Wei; Hu, Tianshun; Frantom, Patrick A.; Zheng, Tianqing; Gerwe, Brian; del Amo, David Soriano; Garret, Sarah; Seidel, Ronald D.; Wu, Peng

    2009-01-01

    Lewis X (Lex)-containing glycans play important roles in numerous cellular processes. However, the absence of robust, facile, and cost-effective methods for the synthesis of Lex and its structurally related analogs has severely hampered the elucidation of the specific functions of these glycan epitopes. Here we demonstrate that chemically defined guanidine 5′-diphosphate-β-l-fucose (GDP-fucose), the universal fucosyl donor, the Lex trisaccharide, and their C-5 substituted derivatives can be synthesized on preparative scales, using a chemoenzymatic approach. This method exploits l-fucokinase/GDP-fucose pyrophosphorylase (FKP), a bifunctional enzyme isolated from Bacteroides fragilis 9343, which converts l-fucose into GDP-fucose via a fucose-1-phosphate (Fuc-1-P) intermediate. Combining the activities of FKP and a Helicobacter pylori α1,3 fucosyltransferase, we prepared a library of Lex trisaccharide glycans bearing a wide variety of functional groups at the fucose C-5 position. These neoglycoconjugates will be invaluable tools for studying Lex-mediated biological processes. PMID:19805264

  1. Cloning, purification and preliminary crystallographic analysis of the Bacillus subtilis GTPase YphC–GDP complex

    SciTech Connect

    Xu, Ling; Muench, Stephen P.; Roujeinikova, Anna; Sedelnikova, Svetlana E.; Rice, David W.

    2006-05-01

    Crystals of a selenomethionine-incorporated YphC–GDP complex have been grown using the hanging-drop vapour-diffusion method and polyethylene glycol as a precipitating agent. The Bacillus subtilis YphC gene encodes an essential GTPase thought to be involved in ribosome binding and whose protein product may represent a target for the development of a novel antibacterial agent. Sequence analysis reveals that YphC belongs to the EngA family of GTPases, which uniquely contain two adjacent GTP-binding domains. Crystals of a selenomethionine-incorporated YphC–GDP complex have been grown using the hanging-drop vapour-diffusion method and polyethylene glycol as a precipitating agent. The crystals belong to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 62.71, b = 65.05, c = 110.61 Å, and have one molecule in the asymmetric unit. Data sets at three different wavelengths were collected on a single crystal to 2.5 Å resolution at the Daresbury SRS in order to solve the structure by MAD. Ultimately, analysis of YphC in complex with GDP may allow a greater understanding of the EngA family of essential GTPases.

  2. Impact of HIV/AIDS on Gross Domestic Product (GDP) in the WHO Africa Region.

    PubMed

    Kirigia, Joses M; Sambo, Luis G; Okorosobo, Tuoyo; Mwabu, Germano M

    2002-01-01

    HIV/AIDS is hypothesized to have substantive negative impact on health status and economic development of individuals, households, communities and nations. The objective of this study was to estimate the burden of HIV/AIDS on GDP in the WHO African Region using a production function approach. The economic burden analysis was done using a double-log econometric model and a cross-sectional data on 45 to 46 countries in the WHO African Region. The data were obtained from WHO, UNAIDS, ECA, UNDP and the World Bank publications. The coefficient for Capital (K), Education (EN), Export (X) and Imports (M) were found to be statistically significant determinants of per capita Gross Domestic Product (GDP) at 5% level of significance (using a one-sided t-distribution test). Unfortunately, HIV/AIDS morbidity (V) and HIV/AIDS deaths (VD), at the same level of significance, were found to have statistically insignificant impact on GDP. However, the coefficients of these variables had negative signs as expected. In all African countries, there is need for more detailed research on the total economic cost of HIV/AIDS (probably estimated using micro-level costing and willingness-to-pay methods) and for economic evaluations of treatment, prevention and promotion programmes.

  3. 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.

  4. Hit-and-Run” Transformation by Adenovirus Oncogenes

    PubMed Central

    Nevels, Michael; Täuber, Birgitt; Spruss, Thilo; Wolf, Hans; Dobner, Thomas

    2001-01-01

    According to classical concepts of viral oncogenesis, the persistence of virus-specific oncogenes is required to maintain the transformed cellular phenotype. In contrast, the “hit-and-run” hypothesis claims that viruses can mediate cellular transformation through an initial “hit,” while maintenance of the transformed state is compatible with the loss (“run”) of viral molecules. It is well established that the adenovirus E1A and E1B gene products can cooperatively transform primary human and rodent cells to a tumorigenic phenotype and that these cells permanently express the viral oncogenes. Additionally, recent studies have shown that the adenovirus E4 region encodes two novel oncoproteins, the products of E4orf6 and E4orf3, which cooperate with the viral E1A proteins to transform primary rat cells in an E1B-like fashion. Unexpectedly, however, cells transformed by E1A and either E4orf6 or E4orf3 fail to express the viral E4 gene products, and only a subset contain E1A proteins. In fact, the majority of these cells lack E4- and E1A-specific DNA sequences, indicating that transformation occurred through a hit-and-run mechanism. We provide evidence that the unusual transforming activities of the adenoviral oncoproteins may be due to their mutagenic potential. Our results strongly support the possibility that even tumors that lack any detectable virus-specific molecules can be of viral origin, which could have a significant impact on the use of adenoviral vectors for gene therapy. PMID:11238835

  5. 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.

  6. 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

  7. 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.

  8. Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits.

    PubMed

    Wunberg, Tobias; Hendrix, Martin; Hillisch, Alexander; Lobell, Mario; Meier, Heinrich; Schmeck, Carsten; Wild, Hanno; Hinzen, Berthold

    2006-02-01

    Drug-like and lead-like hits derived from HTS campaigns provide good starting points for lead optimization. However, too strong emphasis on potency as hit-selection parameter might hamper the success of such projects. A detailed absorption, distribution, metabolism, excretion and toxicology (ADME-Tox) profiling is needed to help identify hits with a minimum number of (known) liabilities. This is particularly true for drug-like hits. Herein, we describe how to break down large numbers of screening hits and we provide a comprehensive overview of the strengths and weaknesses for each structural class. The overall profile (e.g. ligand efficiency, selectivity and ADME-Tox) is the distinctive feature that will define the priority for follow-up.

  9. Applying the new HIT results to tokamak and solar plasmas

    NASA Astrophysics Data System (ADS)

    Jarboe, Thomas; Sutherland, Derek; Hossack, Aaron; Nelson, Brian; Morgan, Kyle; Chris, Hansen; Benedett, Thomas; Everson, Chris; Penna, James

    2016-10-01

    Understanding sustainment of stable equilibria with helicity injection in HIT-SI has led to a simple picture of several tokamak features. Perturbations cause a viscous-like force on the current that flattens the λ profile, which sustains and stabilizes the equilibrium. An explanation of the mechanism is based on two properties of stable, ideal, two-fluid, magnetized plasma. First, the electron fluid is frozen to magnetic fields and, therefore, current flow is also magnetic field flow. Second, for a stable equilibrium the structure perpendicular to the flux surface resists deformation. Thus toroidal current is from electrons frozen in nested, rotating resilient flux surfaces. Only symmetric flux surfaces allow free differential current flow. Perturbations cause interference of the flux surfaces. Thus, perturbations cause forces that oppose differential electron rotation and forced differential flow produces a symmetrizing force against perturbations and instability. This mechanism can explain the level of field error that spoils tokamak performance and the rate of poloidal flux loss in argon-induced disruptions in DIII-D. This new understanding has led to an explanation of the source of the solar magnetic fields and the power source for the chromosphere, solar wind and corona. Please place in spheromak and FRC section with other HIT posters.

  10. A novel inhibitor of Rho GDP-dissociation inhibitor α improves the therapeutic efficacy of paclitaxel in Lewis lung carcinoma.

    PubMed

    Peng, Xing Chen; Chen, Xu Xia; Zhang, Y U; Wang, Hai Jun; Feng, You

    2015-07-01

    Molecular-targeted therapies are considered a promising strategy for the treatment of most types of human cancer. Rho GDP-dissociation inhibitor α (RhoGDIα), which functions mainly by controlling the cellular distribution and activity of Rho GTPases and is associated with tumor progression and poor prognosis of cancer patients, has become a new promising target for anticancer treatment. Recently, a specific RhoGDIα inhibitor (no. SKLB-163) was developed via computer-aided drug design and de novo synthesis. Previous studies have shown that SKLB-163 had extremely good antitumor activities against diverse cancer cell lines. In the present study, SKLB-163 was used in combination with paclitaxel in order to determine the synergistic effect of the antitumor activity. The findings showed that the combination therapy clearly inhibited cell proliferation and induced apoptosis of LL/2 in vitro. The LL/2 mice model also showed that the combination therapy inhibited tumor growth in vivo. Proliferative cell nuclear antigen (PCNA) immunohistochmeistry and terminal deoxynucleotidyl transferase dUTP nick end-labeling showed that combination therapy inhibited cell proliferation and increased apoptosis compared to the treatment with SKLB-163 or paclitaxel alone. The data suggests that the combination therapy exerted synergistic antitumor effects, providing a novel way to augment the antitumor efficacy of cytotoxic chemotherapy.

  11. [Diagnosis and treatment of heparin-induced thrombocytopenia (HIT) based on its atypical immunological features].

    PubMed

    Miyata, Shigeki; Maeda, Takuma

    2016-03-01

    Heparin-induced thrombocytopenia (HIT) is a prothrombotic side effect of heparin therapy caused by HIT antibodies, i.e., anti-platelet factor 4 (PF4)/heparin IgG with platelet-activating properties. For serological diagnosis, antigen immunoassays are commonly used worldwide. However, such assays do not indicate their platelet-activating properties, leading to low specificity for the HIT diagnosis. Therefore, over-diagnosis is currently the most serious problem associated with HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for appropriate HIT diagnosis. Recent advances in our understanding of the pathogenesis of HIT include it having several clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response on heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. These lines of evidence suggest that the mechanisms underlying HIT antibody formation may be compatible with a non-T cell-dependent immune reaction. These atypical clinical and serological features should be carefully considered while endeavoring to accurately diagnose HIT, which leads to appropriate therapies such as immediate administration of an alternative anticoagulant to prevent thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

  12. 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.

  13. 5'-Phospho-RNA Acceptor Specificity of GDP Polyribonucleotidyltransferase of Vesicular Stomatitis Virus in mRNA Capping.

    PubMed

    Ogino, Minako; Ogino, Tomoaki

    2017-03-15

    The GDP polyribonucleotidyltransferase (PRNTase) domain of the multifunctional L protein of rhabdoviruses, such as vesicular stomatitis virus (VSV) and rabies virus, catalyzes the transfer of 5'-phospho-RNA (pRNA) from 5'-triphospho-RNA (pppRNA) to GDP via a covalent enzyme-pRNA intermediate to generate a 5'-cap structure (GpppA). Here, using an improved oligo-RNA capping assay with the VSV L protein, we showed that the Michaelis constants for GDP and pppAACAG (VSV mRNA-start sequence) are 0.03 and 0.4 μM, respectively. A competition assay between GDP and GDP analogues in the GpppA formation and pRNA transfer assay using GDP analogues as pRNA acceptors indicated that the PRNTase domain recognizes the C-2-amino group, but not the C-6-oxo group, N-1-hydrogen, or N-7-nitrogen, of GDP for the cap formation. 2,6-Diaminopurine-riboside (DAP), 7-deazaguanosine (7-deaza-G), and 7-methylguanosine (m(7)G) diphosphates efficiently accepted pRNA, resulting in the formation of DAPpppA, 7-deaza-GpppA, and m(7)GpppA (cap 0), respectively. Furthermore, either the 2'- or 3'-hydroxyl group of GDP was found to be required for efficient pRNA transfer. A 5'-diphosphate form of antiviral ribavirin weakly inhibited the GpppA formation but did not act as a pRNA acceptor. These results indicate that the PRNTase domain has a unique guanosine-binding mode different from that of eukaryotic mRNA capping enzyme, guanylyltransferase. IMPORTANCE mRNAs of nonsegmented negative-strand (NNS) RNA viruses, such as VSV, possess a fully methylated cap structure, which is required for mRNA stability, efficient translation, and evasion of antiviral innate immunity in host cells. GDP polyribonucleotidyltransferase (PRNTase) is an unconventional mRNA capping enzyme of NNS RNA viruses that is distinct from the eukaryotic mRNA capping enzyme, guanylyltransferase. In this study, we studied the pRNA acceptor specificity of VSV PRNTase using various GDP analogues and identified chemical groups of GDP as

  14. Antibodies associated with heparin-induced thrombocytopenia (HIT) inhibit activated protein C generation: new insights into the prothrombotic nature of HIT

    PubMed Central

    Krishnaswamy, Sriram; Rauova, Lubica; Zhai, Li; Hayes, Vincent; Amirikian, Karine; Esko, Jeffrey D.; Bougie, Daniel W.; Aster, Richard H.; Cines, Douglas B.; Poncz, Mortimer

    2011-01-01

    Heparin-induced thrombocytopenia (HIT) is caused by antibodies that recognize complexes between platelet factor 4 (PF4) and heparin or glycosaminoglycan side chains. These antibodies can lead to a limb- and life-threatening prothrombotic state. We now show that HIT antibodies are able to inhibit generation of activated protein C (aPC) by thrombin/thrombomodulin (IIa/TM) in the presence of PF4. Tetrameric PF4 potentiates aPC generation by formation of complexes with chondroitin sulfate (CS) on TM. Formation of these complexes occurs at a specific molar ratio of PF4 to glycosaminoglycan. This observation and the finding that the effect of heparin on aPC generation depends on the concentration of PF4 suggest similarity between PF4/CS complexes and those that bind HIT antibodies. HIT antibodies reduced the ability of PF4 to augment aPC formation. Cationic protamine sulfate, which forms similar complexes with heparin, also enhanced aPC generation, but its activity was not blocked by HIT antibodies. Our studies provide evidence that complexes formed between PF4 and TM's CS may play a physiologic role in potentiating aPC generation. Recognition of these complexes by HIT antibodies reverses the PF4-dependent enhancement in aPC generation and may contribute to the prothrombotic nature of HIT. PMID:21772054

  15. Anti-diabetic potential of the essential oil of Pinus koraiensis leaves toward streptozotocin-treated mice and HIT-T15 pancreatic β cells.

    PubMed

    Joo, Hye-Eun; Lee, Hyo-Jung; Sohn, Eun Jung; Lee, Min-Ho; Ko, Hyun-Suk; Jeong, Soo-Jin; Lee, Hyo-Jeong; Kim, Sung-Hoon

    2013-01-01

    The metabolic syndrome creates risk factors for coronary heart disease, diabetes, fatty liver, obesity and several cancers. Our group has already reported that the essential oil from leaves of Pinus koraiensis SIEB (EOPK) exerted antihyperlipidemic effects by upregulating the low-density lipoprotein receptor and inhibiting acyl-coenzyme A, cholesterol acyltransferases. We evaluated in the current study the anti-diabetic effects of EOPK on mice with streptozotocin (STZ)-induced type I diabetes and on HIT-T15 pancreatic β cells. EOPK significantly protected HIT-T15 cells from STZ-induced cytotoxicity and reduced the blood glucose level in STZ-induced diabetic mice when compared with the untreated control. EOPK consistently and significantly suppressed the α-amylase activity in a dose-dependent manner and enhanced the expression of insulin at the mRNA level in STZ-treated HIT-T15 cells, while the expression of insulin was attenuated. EOPK also significantly abrogated the population of reactive oxygen species when compared to the untreated control in STZ-treated HIT-T15 cells. Furthermore, EOPK significantly reduce nitric oxide production, suppressed the phosphorylation of endothelial nitric oxide (NO) synthase and suppressed the production of vascular endothelial growth factor (VEGF) in STZ-treated HIT-T15 cells, implying its potential application to diabetic retinopathy. Overall, our findings suggest that EOPK had hypoglycemic potential by inhibiting reactive oxygene species (ROS), endothelial NO synthase (eNOS) and VEGF in STZ-treated mice and HIT-T15 pancreatic β cells as a potent anti-diabetic agent.

  16. 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.

  17. Rho GDP dissociation inhibitor beta promotes cell proliferation and invasion by modulating the AKT pathway in hepatocellular carcinoma.

    PubMed

    Fang, Yang; Yi, Jiang; Lizhi, Lv; Qiucheng, Cai

    2014-11-01

    Rho GDP dissociation inhibitor (GDI) beta, (RhoGDI2), has been identified as a proto-oncogene that is upregulated in human cancers, but the role of RhoGDI2 in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the RhoGDI2 expression level in HCC tissues and the function of RhoGDI2 in HCC cell growth and metastasis. We examined the RhoGDI2 mRNA expression level in 64 sets of HCC tissue and their adjacent nontumor tissue counterparts using quantitative real-time polymerase chain reaction. In vitro proliferation and invasion assays were conducted to determine the effect of RhoGDI2 on the ability of HCC cells to proliferate and invade, respectively. Western blot analysis was conducted to examine expression levels of RhoGDI2p-AKT, MMP-2, and MMP-9 in HCC cells. RhoGDI2 mRNA was significantly overexpressed in the HCC specimens compared with the nonneoplastic liver specimens, and the RhoGDI2 mRNA and protein levels were higher in the HCC cell lines, especially the highly metastatic cell lines 97L and 97H. To further investigate the role that RhoGDI2 plays in HCC, we overexpressed RhoGDI2 using a lentivirus-mediated overexpression technique in two HCC cell lines (Huh7 and 7721) that endogenously express a low level of RhoGDI2. Stable cells overexpressing RhoGDI2 demonstrated a significant increase in cell proliferation and invasion. Furthermore, our additional findings indicated that RhoGDI2-mediated cellular invasion requires the PI3K/Akt signaling-dependent expression of matrix metalloproteinases (MMPs). Our findings suggest that RhoGDI2 plays an important role in HCC growth and invasion and should be considered a novel HCC therapeutic target candidate.

  18. 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.

  19. 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.

  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.

  1. Building markets: Most recycling markets hit bottom in 1993

    SciTech Connect

    Not Available

    1994-04-01

    For most recycling markets, 1993 was the year prices hit bottom. However, in the final weeks of 1993, recyclers saw slight, but much appreciated, price increases for most commodities. Overall in 1993, glass, plastics, and steel markets remained relatively stable, with some price fluctuations, while markets for paper and aluminum weakened. The paper recycling industry suffered from weak but volatile markets for all grades of secondary fiber, despite and explosion of new deinking facilities, and a host of voluntary recycled-content purchasing agreements. In a move that some recyclers say may be a needed shot in the arm for paper markets, Clinton signed an Executive Order in October 1993 requiring federal agencies to purchase printing and writing paper containing 20% post-consumer material by the end of 1994 and 30% post-consumer content by the end of 1998. Many recyclers are hoping that this will serve as a model for state and local governments.

  2. 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

  3. The data of GDP and exchange rate used in the Balassa-Samuelson hypothesis.

    PubMed

    Wang, Weiguo; Xue, Jing; Du, Chonghua

    2016-12-01

    This article introduces the data of the log real GDP per capita ratio and the log real exchange rate which are used to revisit the Balassa-Samuelson Hypothesis. We acquired the data from IMF and World Bank database, and provide the name and source of the data. All data are openly accessible. Besides, we describe the value of data as well as the method to process the data which can also be found in "The Balassa-Samuelson Hypothesis in the developed and developing countries revisited" (Weiguo Wang, Jing Xue, Chonghua Du, 2016) [1].

  4. 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

  5. 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.

  6. Validation of the Impact of Health Information Technology (I-HIT) Scale: an international collaborative.

    PubMed

    Dykes, Patricia C; Hurley, Ann C; Brown, Suzanne; Carr, Robyn; Cashen, Margaret; Collins, Rita; Cook, Robyn; Currie, Leanne; Docherty, Charles; Ensio, Anneli; Foster, Joanne; Hardiker, Nicholas R; Honey, Michelle L L; Killalea, Rosaleen; Murphy, Judy; Saranto, Kaija; Sensmeier, Joyce; Weaver, Charlotte

    2009-01-01

    In 2005, the Healthcare Information Management Systems Society (HIMSS) Nursing Informatics Community developed a survey to measure the impact of health information technology (HIT), the I-HIT Scale, on the role of nurses and interdisciplinary communication in hospital settings. In 2007, nursing informatics colleagues from Australia, England, Finland, Ireland, New Zealand, Scotland and the United States formed a research collaborative to validate the I-HIT across countries. All teams have completed construct and face validation in their countries. Five out of six teams have initiated reliability testing by practicing nurses. This paper reports the international collaborative's validation of the I-HIT Scale completed to date.

  7. 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,...

  8. 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,...

  9. Economic growth rate management by soft computing approach

    NASA Astrophysics Data System (ADS)

    Maksimović, Goran; Jović, Srđan; Jovanović, Radomir

    2017-01-01

    Economic growth rate management is very important process in order to improve the economic stability of any country. The main goal of the study was to manage the impact of agriculture, manufacturing, industry and services on the economic growth rate prediction. Soft computing methodology was used in order to select the inputs influence on the economic growth rate prediction. It is known that the economic growth may be developed on the basis of combination of different factors. Gross domestic product (GDP) was used as economic growth indicator. It was found services have the highest impact on the GDP growth rate. On the contrary, the manufacturing has the smallest impact on the GDP growth rate.

  10. 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.

  11. Antisense-mediated depletion of tomato GDP-L-galactose phosphorylase increases susceptibility to chilling stress.

    PubMed

    Wang, Li-Yan; Li, Dong; Deng, Yong-Sheng; Lv, Wei; Meng, Qing-Wei

    2013-02-15

    The GDP-L-galactose phosphorylase (GGP), which converts GDP-l-galactose to l-Gal-1-phosphate, is generally considered to be a key enzyme of the major ascorbate biosynthesis pathways in higher plants, but experimental evidence for its role in tomato is lacking. In the present study, the GGP gene was isolated from tomato (Solanum lycopersicum) and transient expression of SlGGP-GFP (green fluorescent protein) fusion protein in onion cells revealed the cytoplasmic and nucleus localization of the protein. Antisense transgenic tomato lines with only 50-75% ascorbate level of the wild type (WT) were obtained. Chilling treatment induced lower increase in AsA levels and redox ratio of ascorbate in antisense transgenic plants compared with WT plants. Under chilling stress, transgenic plants accumulated more malendialdehyde (MDA) and more O(2)(·-), leaked more electrolytes and showed lower maximal photochemical efficiency of PSII (Fv/Fm), net photosynthetic rate (Pn), and oxidizable P700 compared with WT plants. Furthermore, the antisense transgenic plants exhibited significantly higher H(2)O(2) level and lower ascorbate peroxidase (APX) activity. Our results suggested that GGP plays an important role in protecting plants against chilling stress by maintaining ascorbate pool and ascorbate redox state.

  12. Ecological economics and economic growth.

    PubMed

    Victor, Peter A

    2010-01-01

    Boulding's 1966 paper on the economics of spaceship Earth established the framework for ecological economics and an understanding of economic growth. In ecological economics, economies are conceptualized as open subsystems of the closed biosphere and are subject to biophysical laws and constraints. Economic growth measured as an increase in real gross domestic product (GDP) has generally been associated with increases in the use of energy and materials and the generation of wastes. Scale, composition, and technology are the proximate determinants of environmental impacts. They are often reduced to two: scale (GDP) and intensity (impact per unit GDP). New work described in this paper defines "green" growth as intensity that declines faster than scale increases. Similarly, "brown" growth occurs when intensity declines more slowly than increases in scale, and "black" growth happens when both scale and intensity increase. These concepts are then related to the environmental Kuznets curve, which can be understood as a transition from brown to green growth. Ecological economics provides a macroperspective on economic growth. It offers broad policy principles, and it challenges the primacy of economic growth as a policy objective, but many important questions remain.

  13. Influence of Bicarbonate/Low-GDP Peritoneal Dialysis Fluid (Bicavera) on In Vitro and Ex Vivo Epithelial-to-Mesenchymal Transition of Mesothelial Cells

    PubMed Central

    Fernández–Perpén, Antonio; Pérez–Lozano, María Luisa; Bajo, María–Auxiliadora; Albar–Vizcaino, Patricia; Correa, Pilar Sandoval; del Peso, Gloria; Castro, María–José; Aguilera, Abelardo; Ossorio, Marta; Peter, Mirjam E.; Passlick–Deetjen, Jutta; Aroeira, Luiz S.; Selgas, Rafael; López–Cabrera, Manuel; Sánchez–Tomero, J. Antonio

    2012-01-01

    ♦ Background: Peritoneal membrane damage induced by peritoneal dialysis (PD) is largely associated with epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs), which is believed to be a result mainly of the glucose degradation products (GDPs) present in PD solutions. ♦ Objectives: This study investigated the impact of bicarbonate-buffered, low-GDP PD solution (BicaVera: Fresenius Medical Care, Bad Homburg, Germany) on EMT of MCs in vitro and ex vivo. ♦ Methods: In vitro studies: Omentum-derived MCs were incubated with lactate-buffered standard PD fluid or BicaVera fluid diluted 1:1 with culture medium. Ex vivo studies: From 31 patients randomly distributed to either standard or BicaVera solution and followed for 24 months, effluents were collected every 6 months for determination of EMT markers in effluent MCs. ♦ Results: Culturing of MCs with standard fluid in vitro resulted in morphology change to a non-epithelioid shape, with downregulation of E-cadherin (indicative of EMT) and strong induction of vascular endothelial growth factor (VEGF) expression. By contrast, in vitro exposure of MCs to bicarbonate/low-GDP solution had less impact on both EMT parameters. Ex vivo studies partially confirmed the foregoing results. The BicaVera group, with a higher prevalence of the non-epithelioid MC phenotype at baseline (for unknown reasons), showed a clear and significant trend to gain and maintain an epithelioid phenotype at medium- and longer-term and to show fewer fibrogenic characteristics. By contrast, the standard solution group demonstrated a progressive and significantly higher presence of the non-epithelioid phenotype. Compared with effluent MCs having an epithelioid phenotype, MCs with non-epithelioid morphology showed significantly lower levels of E-cadherin and greater levels of fibronectin and VEGF. In comparing the BicaVera and standard solution groups, MCs from the standard solution group showed significantly higher secretion of

  14. 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…

  15. Optimal morphological hit-or-miss filtering of gray-level images

    NASA Astrophysics Data System (ADS)

    Dougherty, Edward R.

    1993-05-01

    The binary hit-or-miss transform is applied to filter digital gray-scale signals. This is accomplished by applying a union of hit-or-miss transforms to an observed signal's umbra and then taking the surface of the filtered umbra as the estimate of the ideal signal. The hit-or-miss union is constructed to provide the optimal mean-absolute-error filter for both the ideal signal and its umbra. The method is developed in detail for thinning hit-or-miss filters and applies at once to the dual thickening filters. It requires the output of the umbra filter to be an umbra, which in general is not true. A key aspect of the paper is the complete characterization of umbra-preserving union-of-hit-or-miss thinning and thickening filters. Taken together, the mean-absolute-error theory and the umbra-preservation characterization provide a full characterization of binary hit-or-miss filtering as applied to digital gray-scale signals. The theory is at once applicable to hit-or-miss filtering of digital gray-scale signals via the three- dimensional binary hit-or-miss transform.

  16. 77 FR 15760 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-16

    ... National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice... Health Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy...

  17. 76 FR 22396 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-21

    ... National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice... Health Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy...

  18. 76 FR 70455 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

    ... National Coordinator for Health Information Technology, HHS ACTION: Notice of meeting. This notice... Health Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy...

  19. 76 FR 50734 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-16

    ... National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice... Health Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy...

  20. 78 FR 66267 - Safety Zone; HITS Triathlon Series; Colorado River; Lake Havasu, AZ

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-05

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; HITS Triathlon Series; Colorado River; Lake... establishing a safety zone upon the navigable waters of the Colorado River in support of the HITS Triathlon... Series; Colorado River, Lake Havasu City, AZ. (a) Location. The safety zone includes the waters in...

  1. 75 FR 21630 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... Technology (ONC). The meetings will be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups: Meaningful Use, Privacy & Security Policy, Strategic Plan, Adoption... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT...

  2. 76 FR 79684 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-22

    ... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to the National Coordinator on a policy... HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the...

  3. 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.

  4. 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.

  5. Stochastic, weighted hit size theory of cellular radiobiological action

    SciTech Connect

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

    1982-01-01

    A stochastic theory that appears to account well for the observed responses of cell populations exposed in radiation fields of different qualities and for different durations of exposure is described. The theory appears to explain well most cellular radiobiological phenomena observed in at least autonomous cell systems, argues for the use of fluence rate (phi) instead of absorbed dose for quantification of the amount of radiation involved in low level radiation exposure. With or without invoking the cell sensitivity function, the conceptual improvement would be substantial. The approach suggested also shows that the absorbed dose-cell response functions currently employed do not reflect the spectrum of cell sensitivities to increasing cell doses of a single agent, nor can RBE represent the potency ratio for different agents that can produce similar quantal responses. Thus, for accurate comparison of cell sensitivities among different cells in the same individual, or between the cells in different kinds of individuals, it is necessary to quantify cell sensitivity in terms of the hit size weighting or cell sensitivity function introduced here. Similarly, this function should be employed to evaluate the relative potency of radiation and other radiomimetic chemical or physical agents.

  6. The "first hit" toward alcohol reinforcement: role of ethanol metabolites.

    PubMed

    Israel, Yedy; Quintanilla, María Elena; Karahanian, Eduardo; Rivera-Meza, Mario; Herrera-Marschitz, Mario

    2015-05-01

    This review analyzes literature that describes the behavioral effects of 2 metabolites of ethanol (EtOH): acetaldehyde and salsolinol (a condensation product of acetaldehyde and dopamine) generated in the brain. These metabolites are self-administered into specific brain areas by animals, showing strong reinforcing effects. A wealth of evidence shows that EtOH, a drug consumed to attain millimolar concentrations, generates brain metabolites that are reinforcing at micromolar and nanomolar concentrations. Salsolinol administration leads to marked increases in voluntary EtOH intake, an effect inhibited by mu-opioid receptor blockers. In animals that have ingested EtOH chronically, the maintenance of alcohol intake is no longer influenced by EtOH metabolites, as intake is taken over by other brain systems. However, after EtOH withdrawal brain acetaldehyde has a major role in promoting binge-like drinking in the condition known as the "alcohol deprivation effect"; a condition seen in animals that have ingested alcohol chronically, are deprived of EtOH for extended periods, and are allowed EtOH re-access. The review also analyzes the behavioral effects of acetate, a metabolite that enters the brain and is responsible for motor incoordination at low doses of EtOH. Also discussed are the paradoxical effects of systemic acetaldehyde. Overall, evidence strongly suggests that brain-generated EtOH metabolites play a major role in the early ("first-hit") development of alcohol reinforcement and in the generation of relapse-like drinking.

  7. Surface Magnetics on the HIT-SI Experiment

    NASA Astrophysics Data System (ADS)

    Wrobel, J. S.; Jarboe, T. R.; Nelson, B. A.; Smith, R. J.; Stewart, B. T.

    2008-11-01

    An array of 96 surface magnetic probes sensitive to the poloidal and toroidal B field are embedded in the HIT-SI spheromak equilibrium flux conserver, a 12.7mm thick chromium copper alloy shell with an L/R time of 100ms. An extensive calibration campaign has been completed to correct for the frequency dependent attenuation of the magnetic field by the shell and provide plasma edge field measurements over a 10Hz-200kHz bandwidth. The system is expected to provide several important results: 1) A measurement of the non-Taylor part of the equilibrium which may reveal details of the small scale, high frequency magnetic relaxation process. 2) A measurement of the MHD mode amplitudes and evolution in the equilibrium region. 3) Provide insight into injector effects which are important for future injector designs. Comparison of experimental vector field results to computational simulations will explore the dominant physics involved in steady inductive helicity injection current drive. Analysis, progress and methods will be presented.

  8. SHIELD-HIT12A - a Monte Carlo particle transport program for ion therapy research

    NASA Astrophysics Data System (ADS)

    Bassler, N.; Hansen, D. C.; Lühr, A.; Thomsen, B.; Petersen, J. B.; Sobolevsky, N.

    2014-03-01

    Purpose: The Monte Carlo (MC) code SHIELD-HIT simulates the transport of ions through matter. Since SHIELD-HIT08 we added numerous features that improves speed, usability and underlying physics and thereby the user experience. The "-A" fork of SHIELD-HIT also aims to attach SHIELD-HIT to a heavy ion dose optimization algorithm to provide MC-optimized treatment plans that include radiobiology. Methods: SHIELD-HIT12A is written in FORTRAN and carefully retains platform independence. A powerful scoring engine is implemented scoring relevant quantities such as dose and track-average LET. It supports native formats compatible with the heavy ion treatment planning system TRiP. Stopping power files follow ICRU standard and are generated using the libdEdx library, which allows the user to choose from a multitude of stopping power tables. Results: SHIELD-HIT12A runs on Linux and Windows platforms. We experienced that new users quickly learn to use SHIELD-HIT12A and setup new geometries. Contrary to previous versions of SHIELD-HIT, the 12A distribution comes along with easy-to-use example files and an English manual. A new implementation of Vavilov straggling resulted in a massive reduction of computation time. Scheduled for later release are CT import and photon-electron transport. Conclusions: SHIELD-HIT12A is an interesting alternative ion transport engine. Apart from being a flexible particle therapy research tool, it can also serve as a back end for a MC ion treatment planning system. More information about SHIELD-HIT12A and a demo version can be found on http://www.shieldhit.org.

  9. Parallel modulation of brown adipose tissue GDP-binding, substrate uptake and (Na(+)-K+)-ATPase activity in the rat.

    PubMed

    Zamora, F; Alemany, M; Arola, L

    1991-10-01

    Brown adipose tissue (Na(+)-K+)-ATPase activity, in vitro glucose uptake and 2-aminoisobutyric acid uptake, as well as mitochondrial GDP-binding and succinate dehydrogenase activity were determined in order to study the relationship between these parameters in control, cold acclimated and cafeteria-fed rats. GDP-binding, (Na(+)-K+)-ATPase and glucose uptake were increased in interscapular brown adipose tissue from cold-acclimated and cafeteria-fed rats, whereas 2-aminoisobutyric acid uptake was only increased in cafeteria-fed rats. GDP-binding and (Na(+)-K+)-ATPase activity showed a high correlation coefficient suggesting a parallel modulation of both systems, which would probably share a common regulation mechanism.

  10. Functional YFP-tagging of the essential GDP-mannose transporter reveals an important role for the secretion related small GTPase SrgC protein in maintenance of Golgi bodies in Aspergillus niger.

    PubMed

    Carvalho, Neuza D S P; Arentshorst, Mark; Weenink, Xavier O; Punt, Peter J; van den Hondel, Cees A M J J; Ram, Arthur F J

    2011-03-01

    The addition of mannose residues to glycoproteins and glycolipids in the Golgi is carried out by mannosyltransferases. Their activity depends on the presence of GDP-mannose in the lumen of the Golgi. The transport of GDP-mannose (mannosyl donor) into the Golgi requires a specific nucleotide sugar transport present in the Golgi membrane. Here, we report the identification and functional characterization of the putative GDP-mannose transporter in Aspergillus niger, encoded by the gmtA gene (An17g02140). The single GDP-mannose transporter was identified in the A. niger genome and deletion analysis showed that gmtA is an essential gene. The lethal phenotype of the gmtA could be fully complemented by expressing an YFP-GmtA fusion protein from the endogenous gmtA promoter. Fluorescence studies revealed that, as in other fungal species, GmtA localized as punctate dots throughout the hyphal cytoplasm, representing Golgi bodies or Golgi equivalents. SrgC encodes a member of the Rab6/Ypt6 subfamily of secretion-related GTPases and is predicted to be required for the Golgi to vacuole transport. Loss of function of the srgC gene in A. niger resulted in strongly reduced growth and the inability to form conidiospores at 37°C and higher. Furthermore, the srgC disruption in the A. niger strain expressing the functional YFP-GmtA fusion protein led to an apparent 'disappearance' of the Golgi-like structures. The analysis suggests that SrgC has an important role in maintaining the integrity of Golgi-like structures in A. niger.

  11. Structural basis of GDP release and gating in G protein coupled Fe2+ transport

    PubMed Central

    Guilfoyle, Amy; Maher, Megan J; Rapp, Mikaela; Clarke, Ronald; Harrop, Stephen; Jormakka, Mika

    2009-01-01

    G proteins are key molecular switches in the regulation of membrane protein function and signal transduction. The prokaryotic membrane protein FeoB is involved in G protein coupled Fe2+ transport, and is unique in that the G protein is directly tethered to the membrane domain. Here, we report the structure of the soluble domain of FeoB, including the G protein domain, and its assembly into an unexpected trimer. Comparisons between nucleotide free and liganded structures reveal the closed and open state of a central cytoplasmic pore, respectively. In addition, these data provide the first observation of a conformational switch in the nucleotide-binding G5 motif, defining the structural basis for GDP release. From these results, structural parallels are drawn to eukaryotic G protein coupled membrane processes. PMID:19629046

  12. 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.

  13. Single GDP-dissociation Inhibitor Protein regulates endocytic and secretory pathways in Leishmania

    PubMed Central

    Shanmugam, Senthil kumar; Kumar, Kamal; Singh, Pawan Kishor; Rastogi, Ruchir; Mukhopadhyay, Amitabha

    2016-01-01

    The role of GDP dissociation inhibitor (GDI) protein in regulation of Rab cycle in Leishmania is not known. Here, we have cloned and characterized the functions of GDI homologue in vivo in Leishmania. Our results have shown that LdGDI:WT along with GDP removes the Rab5 from purified endosomes and inhibits the homotypic fusion between early endosomes. Whereas, LdGDI:R239A, a dominant negative mutant of GDI, under the same condition neither removes the Rab5 from endosome nor inhibits fusion. To determine the role of Ld-GDI in vivo, transgenic parasites overexpressing GFP-LdGDI:WT or GFP-LdGDI:R239A, are co-expressed with RFP-LdRab5:WT, RFP-LdRab7:WT or RFP-LdRab1:WT. Our results have shown that overexpression of GFP-LdGDI:WT extracts the RFP-LdRab5, RFP-LdRab7 or RFP-LdRab1 from their discrete endomembrane predominantly into cytosol. No change in the distribution of indicated Rabs is detected with overexpression of GFP-LdGDI:R239A. To determine the functional significance, we have used hemoglobin as an endocytic marker and gp63 as a marker for secretory pathway. We have found that overexpression of GFP-LdGDI:WT enhances the lysosomal targeting of internalized hemoglobin and the secretion of gp63 in the parasites possibly by triggering Rab cycle. This is the first demonstration of a single GDI ubiquitously regulating both endocytic and secretory pathways in Leishmania. PMID:27841328

  14. 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

  15. 'Hit by the wind' and temperature-shift panic among Vietnamese refugees.

    PubMed

    Hinton, Devon; Hinton, Susan; Pham, Thang; Chau, Ha; Tran, Minh

    2003-09-01

    Surveying 60 Vietnamese patients with either current or past post-traumatic stress disorder, this article aims to phenomenologically characterize the syndrome of 'hit by the wind' in a multidimensional manner. This includes determining the patient conceptualization of the disorder, profiling 'hit by the wind' episodes suffered by patients in the previous month, and presenting case vignettes. Eighteen of the 60 patients (30%) suffered at least one episode of 'hit by the wind' in the last month; all 18 patients had at least one episode of 'hit by the wind' in the last month that met panic attack criteria. For the 18 patients, 33 episodes of'hit by the wind' that met panic attack criteria were experienced in the previous month. For these 33 episodes, the most frequently reported DSM-IV panic attack symptoms were chills (100%; 33/33) and dizziness (88%; 29/33). Flashbacks played a role in the 'hit by the wind' episodes for 5 of the 18 patients (28%). In the discussion, a model of how the syndrome of 'hit by the wind' generates panic is adduced; also, possible Chinese origins of the disorder are discussed.

  16. 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.

  17. Application of artificial neural network with extreme learning machine for economic growth estimation

    NASA Astrophysics Data System (ADS)

    Milačić, Ljubiša; Jović, Srđan; Vujović, Tanja; Miljković, Jovica

    2017-01-01

    The purpose of this research is to develop and apply the artificial neural network (ANN) with extreme learning machine (ELM) to forecast gross domestic product (GDP) growth rate. The economic growth forecasting was analyzed based on agriculture, manufacturing, industry and services value added in GDP. The results were compared with ANN with back propagation (BP) learning approach since BP could be considered as conventional learning methodology. The reliability of the computational models was accessed based on simulation results and using several statistical indicators. Based on results, it was shown that ANN with ELM learning methodology can be applied effectively in applications of GDP forecasting.

  18. 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

  19. 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.

  20. 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...

  1. 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.

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

    PubMed

    Prieto, Luis

    2010-05-17

    "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

  3. Causality links among renewable energy consumption, CO2 emissions, and economic growth in Africa: evidence from a panel ARDL-PMG approach.

    PubMed

    Attiaoui, Imed; Toumi, Hassen; Ammouri, Bilel; Gargouri, Ilhem

    2017-04-05

    This research examines the causality (For the remainder of the paper, the notion of causality refers to Granger causality.) links among renewable energy consumption (REC), CO2 emissions (CE), non-renewable energy consumption (NREC), and economic growth (GDP) using an autoregressive distributed lag model based on the pooled mean group estimation (ARDL-PMG) and applying Granger causality tests for a panel consisting of 22 African countries for the period between 1990 and 2011. There is unidirectional and irreversible short-run causality from CE to GDP. The causal direction between CE and REC is unobservable over the short-term. Moreover, we find unidirectional, short-run causality from REC to GDP. When testing per pair of variables, there are short-run bidirectional causalities among REC, CE, and GDP. However, if we add CE to the variables REC and NREC, the causality to GDP is observable, and causality from the pair REC and NREC to economic growth is neutral. Likewise, if we add NREC to the variables GDP and REC, there is causality. There are bidirectional long-run causalities among REC, CE, and GDP, which supports the feedback assumption. Causality from GDP to REC is not strong for the panel. If we test per pair of variables, the strong causality from GDP and CE to REC is neutral. The long-run PMG estimates show that NREC and gross domestic product increase CE, whereas REC decreases CE.

  4. Screening a Small Library of Xanthones for Antitumor Activity and Identification of a Hit Compound which Induces Apoptosis.

    PubMed

    Barbosa, João; Lima, Raquel T; Sousa, Diana; Gomes, Ana Sara; Palmeira, Andreia; Seca, Hugo; Choosang, Kantima; Pakkong, Pannee; Bousbaa, Hassan; Pinto, Madalena M; Sousa, Emília; Vasconcelos, M Helena; Pedro, Madalena

    2016-01-13

    Our previous work has described a library of thioxanthones designed to have dual activity as P-glycoprotein modulators and antitumor agents. Some of these compounds had shown a significant cell growth inhibitory activity towards leukemia cell lines, without affecting the growth of non-tumor human fibroblasts. However, their effect in cell lines derived from solid tumors has not been previously studied. The present work aimed at: (i) screening this small series of compounds from an in-house library, for their in vitro cell growth inhibitory activity in human tumor cell lines derived from solid tumors; and (ii) initiate a study of the effect of the most potent compound on apoptosis. The tumor cell growth inhibitory effect of 27 compounds was first analysed in different human tumor cell lines, allowing the identification of a hit compound, TXA1. Its hydrochloride salt TXA1·HCl was then synthesized, to improve solubility and bioavailability. Both TXA1 and TXA1·HCl inhibited the growth of MCF-7, NCI-H460, A375-C5, HeLa, 786-O, Caki-2 and AGS cell lines. The effect of TXA1·HCl in MCF-7 cells was found to be irreversible and was associated, at least in part, with an increase in cellular apoptosis.

  5. 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 Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces...

  6. 75 FR 21629 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  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. Indoor Tanning: a Big Financial Hit to U.S. Health Care

    MedlinePlus

    ... Indoor Tanning: A Big Financial Hit to U.S. Health Care Skin cancers from UV light in devices totalled $ ... tanning are estimated to have cost the U.S. health care system hundreds of millions of dollars in 2015, ...

  14. 7 in 10 U.S. Workplaces Hit by Opioid Abuse: Survey

    MedlinePlus

    ... medlineplus.gov/news/fullstory_164032.html 7 in 10 U.S. Workplaces Hit by Opioid Abuse: Survey Poll ... 06/08/2017) By Robert Preidt Friday, March 10, 2017 FRIDAY, March 10, 2017 (HealthDay News) -- Prescription ...

  15. 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,...

  16. 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,...

  17. 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,...

  18. 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.

  19. On the accuracy of the Head Impact Telemetry (HIT) System used in football helmets.

    PubMed

    Jadischke, Ron; Viano, David C; Dau, Nathan; King, Albert I; McCarthy, Joe

    2013-09-03

    On-field measurement of head impacts has relied on the Head Impact Telemetry (HIT) System, which uses helmet mounted accelerometers to determine linear and angular head accelerations. HIT is used in youth and collegiate football to assess the frequency and severity of helmet impacts. This paper evaluates the accuracy of HIT for individual head impacts. Most HIT validations used a medium helmet on a Hybrid III head. However, the appropriate helmet is large based on the Hybrid III head circumference (58 cm) and manufacturer's fitting instructions. An instrumented skull cap was used to measure the pressure between the head of football players (n=63) and their helmet. The average pressure with a large helmet on the Hybrid III was comparable to the average pressure from helmets used by players. A medium helmet on the Hybrid III produced average pressures greater than the 99th percentile volunteer pressure level. Linear impactor tests were conducted using a large and medium helmet on the Hybrid III. Testing was conducted by two independent laboratories. HIT data were compared to data from the Hybrid III equipped with a 3-2-2-2 accelerometer array. The absolute and root mean square error (RMSE) for HIT were computed for each impact (n=90). Fifty-five percent (n=49) had an absolute error greater than 15% while the RMSE was 59.1% for peak linear acceleration.

  20. The impact of Health Information Technology (I-HIT) Scale: the Australian results.

    PubMed

    Cook, Robyn; Foster, Joanne

    2009-01-01

    One of role of the nurse in the clinical setting is that of co-ordinating communication across the healthcare team. On a daily basis nurses interact with the person receiving care, their family members, and multiple care providers thus placing the nurse in the central position with access to a vast array of information on the person. Through this nurses have historically functioned as "information repositories". With the advent of Health Information Technology (HIT) tools there is a potential that HIT could impact interdisciplinary communication, practice efficiency and effectiveness, relationships and workflow in acute care settings [1][3]. In 2005, the HIMSS Nursing Informatics Community developed the I-HIT Scale to measure the impact of HIT on the nursing role and interdisciplinary communication in USA hospitals. In 2007, nursing informatics colleagues from Australia, Finland, Ireland, New Zealand, Scotland and the USA formed a research collaborative to validate the I-HIT in six additional countries. This paper will discuss the background, methodology, results and implications from the Australian I-HIT survey of over 1,100 nurses. The results are currently being analyzed and will be presented at the conference.

  1. Are Stripes Beneficial? Dazzle Camouflage Influences Perceived Speed and Hit Rates

    PubMed Central

    von Helversen, Bettina; Schooler, Lael J.; Czienskowski, Uwe

    2013-01-01

    In the animal kingdom, camouflage refers to patterns that help potential prey avoid detection. Mostly camouflage is thought of as helping prey blend in with their background. In contrast, disruptive or dazzle patterns protect moving targets and have been suggested as an evolutionary force in shaping the dorsal patterns of animals. Dazzle patterns, such as stripes and zigzags, are thought to reduce the probability with which moving prey will be captured by impairing predators' perception of speed. We investigated how different patterns of stripes (longitudinal—i.e., parallel to movement direction–and vertical–i.e., perpendicular to movement direction) affect the probability with which humans can hit moving objects and if differences in hitting probability are caused by a misperception of speed. A first experiment showed that longitudinally striped objects were hit more often than unicolored objects. However, vertically striped objects did not differ from unicolored objects. A second study examining the link between perceived speed and hitting probability showed that longitudinally and vertically striped objects were both perceived as moving faster and were hit more often than unicolored objects. In sum, our results provide evidence that striped patterns disrupt the perception of speed, which in turn influences how often objects are hit. However, the magnitude and the direction of the effects depend on additional factors such as speed and the task setup. PMID:23637795

  2. "Biocompatible" Neutral pH Low-GDP Peritoneal Dialysis Solutions: Much Ado About Nothing?

    PubMed

    Misra, Paraish S; Nessim, Sharon J; Perl, Jeffrey

    2017-03-01

    Adverse outcomes in peritoneal dialysis (PD), including PD related infections, the loss of residual kidney function (RKF), and longitudinal, deleterious changes in peritoneal membrane function continue to limit the long-term success of PD therapy. The observation that these deleterious changes occur upon exposure to conventional glucose-based PD solutions fuels the search for a more biocompatible PD solution. The development of a novel PD solution with a neutral pH, and lower in glucose degradation products (GDPs) compared to its conventional predecessors has been labeled a "biocompatible" solution. While considerable evidence in support of these novel solutions' biocompatibility has emerged from cell culture and animal studies, the clinical benefits as compared to conventional PD solutions are less clear. Neutral pH low GDP (NpHLGDP) PD solutions appear to be effective in reducing infusion pain, but their effects on other clinical endpoints including peritoneal membrane function, preservation of RKF, PD-related infections, and technique and patient survival are less clear. The literature is limited by studies characterized by relatively few patients, short follow-up time, heterogeneity with regards to the novel PD solution type under study, and the different patient populations under study. Nonetheless, the search for a more biocompatible PD solution continues with emerging data on promising non glucose-based solutions.

  3. Overexpression of Rho GDP-dissociation inhibitor alpha predicts poor survival in oral squamous cell carcinoma.

    PubMed

    Chiang, Wei-Fan; Ho, Hsu-Chueh; Chang, Hua-Yuan; Chiu, Chien-Chih; Chen, Yuh-Ling; Hour, Tzyh-Chyuan; Chuang, Shu-Ju; Wu, Yu-Jen; Chen, Hau-Ren; Chen, Jen-Hao; Liu, Shyun-Yeu; Lu, Chin-Li; Chen, Jeff Yi-Fu

    2011-06-01

    Oral cancer has emerged as one of the fastest growing malignancies in Taiwan. However, biomarkers that reliably predict clinical outcomes have yet to be identified. This study was aimed to identify tumor-associated proteins that could be prognostic biomarkers for oral cancer. We compared the protein expression between oral squamous cell carcinoma (OSCC) tissues and adjacent non-cancerous matched tissues (NCMTs) by proteomics. We found that Rho GDP-dissociation inhibitor alpha (RhoGDIα) was differentially expressed in frozen cancerous samples and OSCC cell lines but not in NCMTs. Furthermore, our results indicated that RhoGDIα was selectively upregulated in 78 OSCC tissue sections (p<0.001), and this high expression was significantly correlated with increased tumor size (p<0.05) and poor overall survival (p<0.01). There was a trend that RhoGDIα expression was localized in the cytoplasm of cancer cells but was localized in the plasma membrane of NCMTs. Finally, expression of RhoGDIα was validated to be an independent prognostic indicator for overall survival (p<0.01). These results have identified a novel biomarker that may be useful for prediction of poor prognosis in OSCC patients.

  4. Rice GDP dissociation inhibitor 3 inhibits OsMAPK2 activity through physical interaction.

    PubMed

    Heo, Jae Bok; Yi, Young Byung; Bahk, Jeong Dong

    2011-11-04

    GDP dissociation inhibitor (GDI) plays an essential role in regulating the state of bound nucleotides and subcellular localizations of Rab proteins. In our previous study, we showed that OsGDI3 facilitates the recycling of OsRab11 with a help of OsGAP1. In this study, we show that OsGDI3 complement the yeast sec19-1 mutant, a temperature-sensitive allele of the yeast GDI gene, suggesting that OsGDI3 is a functional ortholog of yeast GDI. To obtain further knowledge on the function of OsGDI3, candidate OsGDI3-interacting proteins were identified by yeast two-hybrid screens. OsMAPK2 is one of OsGDI3 interacting proteins from yeast two-hybrid screens and subject to further analysis. A kinase assay showed that the autophosphorylation activity of OsMAPK2 is inhibited by OsGDI3 in vitro. In addition, ectopic expressions of OsGDI3-in Arabidopsis cause reductions at the level of phosphorylated AtMPK in phosphorylation activity. Taken together, OsGDI3 functions as a negative regulator of OsMAPK2 through modulating its kinase activity.

  5. AtGDI2, a novel Arabidopsis gene encoding a Rab GDP dissociation inhibitor.

    PubMed

    Ueda, T; Yoshizumi, T; Anai, T; Matsui, M; Uchimiya, H; Nakano, A

    1998-01-05

    The GTPase cycle of Rab/Ypt proteins is strictly controlled by several classes of regulators to ensure their proper roles in membrane traffic. GDP dissociation inhibitor (GDI) is known to play essential roles in regulating nucleotide states and subcellular localizations of Rab/Ypt proteins. To obtain further knowledge on this regulator molecule in plants, we isolated and characterized two genes of Arabidopsis thaliana that encode different GDIs. AtGDI1 has been identified by a novel functional cloning in yeast [Ueda et al. (1996) Plant Cell, 8, 2079-2091] and AtGDI2 was isolated by cross-hybridization in this study. AtGDI2, as well as AtGDI1, complements the yeast sec19/gdi1 mutant, indicating that they can replace the function of yeast GDI. Evidence is shown that both AtGDI1 and AtGDI2 can interact with Ara4, an Arabidopsis Rab protein, in the yeast ypt1 mutant cells. AtGDI2 is ubiquitously expressed in Arabidopsis tissues with some difference from AtGDI1 in expression level. Genomic DNA hybridization using specific probes reveals the presence of one more GDI gene in Arabidopsis. This may imply differentiated roles of GDI in higher plants.

  6. Soft computing prediction of economic growth based in science and technology factors

    NASA Astrophysics Data System (ADS)

    Marković, Dušan; Petković, Dalibor; Nikolić, Vlastimir; Milovančević, Miloš; Petković, Biljana

    2017-01-01

    The purpose of this research is to develop and apply the Extreme Learning Machine (ELM) to forecast the gross domestic product (GDP) growth rate. In this study the GDP growth was analyzed based on ten science and technology factors. These factors were: research and development (R&D) expenditure in GDP, scientific and technical journal articles, patent applications for nonresidents, patent applications for residents, trademark applications for nonresidents, trademark applications for residents, total trademark applications, researchers in R&D, technicians in R&D and high-technology exports. The ELM results were compared with genetic programming (GP), artificial neural network (ANN) and fuzzy logic results. Based upon simulation results, it is demonstrated that ELM has better forecasting capability for the GDP growth rate.

  7. Hitting cancers' weak spots: vulnerabilities imposed by p53 mutation.

    PubMed

    Gurpinar, Evrim; Vousden, Karen H

    2015-08-01

    The tumor suppressor protein p53 plays a critical role in limiting malignant development and progression. Almost all cancers show loss of p53 function, through either mutation in the p53 gene itself or defects in the mechanisms that activate p53. While reactivation of p53 can effectively limit tumor growth, this is a difficult therapeutic goal to achieve in the many cancers that do not retain wild type p53. An alternative approach focuses on identifying vulnerabilities imposed on cancers by virtue of the loss of or alterations in p53, to identify additional pathways that can be targeted to specifically kill or inhibit the growth of p53 mutated cells. These indirect ways of exploiting mutations in p53 - which occur in more than half of all human cancers - provide numerous exciting therapeutic possibilities.

  8. NDK Interacts with FtsZ and Converts GDP to GTP to Trigger FtsZ Polymerisation - A Novel Role for NDK

    PubMed Central

    Mishra, Saurabh; Jakkala, Kishor; Srinivasan, Ramanujam; Arumugam, Muthu; Ranjeri, Raghavendra; Gupta, Prabuddha; Rajeswari, Haryadi; Ajitkumar, Parthasarathi

    2015-01-01

    Introduction Nucleoside diphosphate kinase (NDK), conserved across bacteria to humans, synthesises NTP from NDP and ATP. The eukaryotic homologue, the NDPK, uses ATP to phosphorylate the tubulin-bound GDP to GTP for tubulin polymerisation. The bacterial cytokinetic protein FtsZ, which is the tubulin homologue, also uses GTP for polymerisation. Therefore, we examined whether NDK can interact with FtsZ to convert FtsZ-bound GDP and/or free GDP to GTP to trigger FtsZ polymerisation. Methods Recombinant and native NDK and FtsZ proteins of Mycobacterium smegmatis and Mycobacterium tuberculosis were used as the experimental samples. FtsZ polymersation was monitored using 90° light scattering and FtsZ polymer pelleting assays. The γ32P-GTP synthesised by NDK from GDP and γ32P-ATP was detected using thin layer chromatography and quantitated using phosphorimager. The FtsZ bound 32P-GTP was quantitated using phosphorimager, after UV-crosslinking, followed by SDS-PAGE. The NDK-FtsZ interaction was determined using Ni2+-NTA-pulldown assay and co-immunoprecipitation of the recombinant and native proteins in vitro and ex vivo, respectively. Results NDK triggered instantaneous polymerisation of GDP-precharged recombinant FtsZ in the presence of ATP, similar to the polymerisation of recombinant FtsZ (not GDP-precharged) upon the direct addition of GTP. Similarly, NDK triggered polymerisation of recombinant FtsZ (not GDP-precharged) in the presence of free GDP and ATP as well. Mutant NDK, partially deficient in GTP synthesis from ATP and GDP, triggered low level of polymerisation of MsFtsZ, but not of MtFtsZ. As characteristic of NDK’s NTP substrate non-specificity, it used CTP, TTP, and UTP also to convert GDP to GTP, to trigger FtsZ polymerisation. The NDK of one mycobacterial species could trigger the polymerisation of the FtsZ of another mycobacterial species. Both the recombinant and the native NDK and FtsZ showed interaction with each other in vitro and ex vivo, alluding

  9. Causal relationship between CO₂ emissions, real GDP, energy consumption, financial development, trade openness, and urbanization in Tunisia.

    PubMed

    Farhani, Sahbi; Ozturk, Ilhan

    2015-10-01

    The aim of this paper is to examine the causal relationship between CO2 emissions, real GDP, energy consumption, financial development, trade openness, and urbanization in Tunisia over the period of 1971-2012. The long-run relationship is investigated by the auto-regressive distributed lag (ARDL) bounds testing approach to cointegration and error correction method (ECM). The results of the analysis reveal a positive sign for the coefficient of financial development, suggesting that the financial development in Tunisia has taken place at the expense of environmental pollution. The Tunisian case also shows a positive monotonic relationship between real GDP and CO2 emissions. This means that the results do not support the validity of environmental Kuznets curve (EKC) hypothesis. In addition, the paper explores causal relationship between the variables by using Granger causality models and it concludes that financial development plays a vital role in the Tunisian economy.

  10. VvGONST-A and VvGONST-B are Golgi-localised GDP-sugar transporters in grapevine (Vitis vinifera L.).

    PubMed

    Utz, Daniella; Handford, Michael

    2015-02-01

    Plant nucleotide-sugar transporters (NSTs) are responsible for the import of nucleotide-sugar substrates into the Golgi lumen, for subsequent use in glycosylation reactions. NSTs are specific for either GDP- or UDP-sugars, and almost all transporters studied to date have been isolated from Arabidopsis thaliana L. In order to determine the conservation of the import mechanism in other higher plant species, here we report the identification and characterisation of VvGONST-A and VvGONST-B from grapevine (Vitis vinifera L. cv. Thompson Seedless), which are the orthologues of the GDP-sugar transporters GONST3 and GONST4 in Arabidopsis. Both grapevine NSTs possess the molecular features characteristic of GDP-sugar transporters, including a GDP-binding domain (GXL/VNK) towards the C-terminal. VvGONST-A and VvGONST-B expression is highest at berry setting and decreases throughout berry development and ripening. Moreover, we show using green fluorescent protein (GFP) tagged versions and brefeldin A treatments, that both are localised in the Golgi apparatus. Additionally, in vitro transport assays after expression of both NSTs in tobacco leaves indicate that VvGONST-A and VvGONST-B are capable of transporting GDP-mannose and GDP-glucose, respectively, but not a range of other UDP- and GDP-sugars. The possible functions of these NSTs in glucomannan synthesis and/or glycosylation of sphingolipids are discussed.

  11. Shock compression of glow discharge polymer (GDP): density functional theory (DFT) simulations and experiments on Sandia's Z-machine

    NASA Astrophysics Data System (ADS)

    Mattsson, Thomas R.; Cochrane, K. R.; Ao, T.; Lemke, R. W.; Flicker, D. G.; Schoff, M. E.; Blue, B. E.; Hamel, S.; Herrmann, M. C.

    2015-11-01

    Glow discharge polymer (GDP) is used extensively as capsule/ablation material in inertial confinement fusion (ICF) capsules. Accurate knowledge of the equation of state (EOS) under shock and release is particularly important for high-fidelity design, analysis, and optimization of ICF experiments since the capsule material is subject to several converging shocks as well as release towards the cryogenic fuel. We performed Density Functional Theory (DFT) based quantum molecular dynamics (QMD) simulations, to gain knowledge of the behavior of GDP - including the effect of changes in chemical composition. The shock pressures calculated from DFT are compared experimental data taken on magnetically launched flyer plate impact experiments on at Sandia's Z-machine. Large GDP samples were grown in a planar geometry to improve the sample quality and maintained in a nitrogen atmosphere following manufacturing, thus allowing for a direct comparison to the DFT/QMD simulations. Sandia National Laboratories is a multi program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's NNSA under contract DE-AC04-94AL85000.

  12. The biocompatibility of neutral pH, low-GDP peritoneal dialysis solutions: benefit at bench, bedside, or both?

    PubMed

    Perl, Jeffrey; Nessim, Sharon J; Bargman, Joanne M

    2011-04-01

    For patients on peritoneal dialysis (PD), the development of peritonitis, the decline of residual kidney function, and the loss of peritoneal membrane function are central events that affect both patient and technique survival. The use of glucose as the osmotic agent in conventional PD solutions may increase the susceptibility to each of these events. However, its use may also be associated with systemic metabolic perturbations and, in turn, an increase in cardiovascular morbidity. Both in vitro and in vivo evidence suggest that both the local peritoneal and systemic toxicity induced by the use of glucose may be in part mediated by the presence of glucose degradation products (GDPs) coupled with the hyperosmolarity, reduced pH, and use of lactate as the buffer in conventional PD solutions. Therefore, the use of neutral pH, low-GDP (NpHL(GDP)), bicarbonate-buffered PD solutions may represent a promising strategy to attenuate some of these adverse effects. However, the impact of these novel solutions on clinical outcomes remains largely unknown. In this review, we will highlight evidence regarding the biocompatibility of NpHL(GDP) PD solutions, review the utility of current biomarkers in the evaluation of biocompatibility, and discuss the clinical outcome data with these solutions.

  13. Shock compression of glow discharge polymer (GDP): density functional theory (DFT) simulations and experiments on Sandia's Z-machine

    NASA Astrophysics Data System (ADS)

    Cochrane, K. R.; Ao, T.; Hamel, S.; Lemke, R. W.; Schoff, M. E.; Blue, B. E.; Herrmann, M. C.; Mattsson, T. R.

    2015-06-01

    Glow discharge polymer (GDP) is used extensively in inertial confinement fusion (ICF) capsules. Accurate knowledge of the equation of state (EOS) under shock and release is particularly important for high-fidelity design and analysis of ICF experiments since the capsule material is subject to several converging shocks as well as release towards the cryogenic fuel. We performed Density Functional Theory (DFT) based molecular dynamics simulations, to gain knowledge of the behavior of GDP - for example regarding the role of chemical dissociation during shock compression, we find that the dissociation regime along the Hugoniot extends from 50 GPa to 250 GPa. The shock pressures calculated from DFT are compared to experimental data taken on magnetically launched flyer plate impact experiments at Sandia's Z-machine. Large GDP samples were grown in a planar geometry to improve the sample quality and maintained in a nitrogen atmosphere following manufacturing, thus allowing for a direct comparison to the simulations. Sandia National Laboratories is a multi program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's NNSA under Contract DE-AC04-94AL85000

  14. Gorlin syndrome with an ovarian leiomyoma associated with a PTCH1 second hit.

    PubMed

    Akizawa, Yoshika; Miyashita, Toshiyuki; Sasaki, Ryo; Nagata, Reiko; Aoki, Ryoko; Ishitani, Ken; Nagashima, Yoji; Matsui, Hideo; Saito, Kayoko

    2016-04-01

    We describe a Gorlin syndrome (GS) case with two different second hit mutations of PTCH1, one in a keratocystic odontogenic tumor (KCOT) and the other in an ovarian leiomyoma. GS is a rare genetic condition manifesting as multiple basal cell nevi associated with other features such as medulloblastomas, skeletal abnormalities, and ovarian fibromas. A 21-year-old Japanese woman with a history of two KCOTs was diagnosed with GS according to clinical criteria. A PTCH1 mutation, c.1427del T, was detected in peripheral blood. A novel PTCH1 mutation, c.264_265insAATA, had been found in the maxillary KCOT as a second hit mutation. More recently, the ovarian tumor was detected during a gynecological examination. Laparoscopic adnexectomy was performed, and the pathological diagnosis of the ovarian tumor was leiomyoma. Interestingly, another novel mutation, loss of heterozygosity spanning from 9q22.32 to 9q31.2, including PTCH1 and 89 other genes, was detected in this ovarian tumor, providing evidence of a second hit mutation. This is the first report describing a GS-associated ovarian tumor carrying a second hit in the PTCH1 region. We anticipate that accumulation of more cases will clarify the importance of second hit mutations in ovarian tumor formation in GS.

  15. Two Methods for Efficient Solution of the Hitting-Set Problem

    NASA Technical Reports Server (NTRS)

    Vatan, Farrokh; Fijany, Amir

    2005-01-01

    A paper addresses much of the same subject matter as that of Fast Algorithms for Model-Based Diagnosis (NPO-30582), which appears elsewhere in this issue of NASA Tech Briefs. However, in the paper, the emphasis is more on the hitting-set problem (also known as the transversal problem), which is well known among experts in combinatorics. The authors primary interest in the hitting-set problem lies in its connection to the diagnosis problem: it is a theorem of model-based diagnosis that in the set-theory representation of the components of a system, the minimal diagnoses of a system are the minimal hitting sets of the system. In the paper, the hitting-set problem (and, hence, the diagnosis problem) is translated from a combinatorial to a computational problem by mapping it onto the Boolean satisfiability and integer- programming problems. The paper goes on to describe developments nearly identical to those summarized in the cited companion NASA Tech Briefs article, including the utilization of Boolean-satisfiability and integer- programming techniques to reduce the computation time and/or memory needed to solve the hitting-set problem.

  16. Atomic features of an autoantigen in heparin-induced thrombocytopenia (HIT).

    PubMed

    Cai, Zheng; Zhu, Zhiqiang; Greene, Mark I; Cines, Douglas B

    2016-07-01

    Autoantigen development is poorly understood at the atomic level. Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by antibodies to an antigen composed of platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans (GAGs). In solution, PF4 exists as an equilibrium among monomers, dimers and tetramers. Structural studies of these interacting components helped delineate a multi-step process involved in the pathogenesis of HIT. First, heparin binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation; exposing the 'open' end. Second, PF4 arrays along heparin/GAG chains, which approximate tetramers, form large antigenic complexes that enhance antibody avidity. Third, pathogenic HIT antibodies bind to the 'open' end of stabilized PF4 tetramers to form an IgG/PF4/heparin ternary immune complex and also to propagate the formation of 'ultralarge immune complexes' (ULCs) that contain multiple IgG antibodies. Fourth, ULCs signal through FcγRIIA receptors, activating platelets and monocytes directly and generating thrombin, which transactivates hematopoietic and endothelial cells. A non-pathogenic anti-PF4 antibody prevents tetramer formation, binding of pathogenic antibody, platelet activation and thrombosis, providing a new approach to manage HIT. An improved understanding of the pathogenesis of HIT may lead to novel diagnostics and therapeutics for this autoimmune disease.

  17. The Staphylococcus aureus protein-coding gene gdpS modulates sarS expression via mRNA-mRNA interaction.

    PubMed

    Chen, Chuan; Zhang, Xu; Shang, Fei; Sun, Haipeng; Sun, Baolin; Xue, Ting

    2015-08-01

    Staphylococcus aureus is an important Gram-positive pathogen responsible for numerous diseases ranging from localized skin infections to life-threatening systemic infections. The virulence of S. aureus is essentially determined by a wide spectrum of factors, including cell wall-associated proteins and secreted toxins that are precisely controlled in response to environmental changes. GGDEF domain protein from Staphylococcus (GdpS) is the only conserved staphylococcal GGDEF domain protein that is involved not in c-di-GMP synthesis but in the virulence regulation of S. aureus NCTC8325. Our previous study showed that the inactivation of gdpS generates an extensive change of virulence factors together with, in particular, a major Spa (protein A) surface protein. As reported, sarS is a direct positive regulator of spa. The decreased transcript levels of sarS in the gdpS mutant compared with the parental NCTC8325 strain suggest that gdpS affects spa through interaction with sarS. In this study, site mutation and complementary experiments showed that the translation product of gdpS was not involved in the regulation of transcript levels of sarS. We found that gdpS functioned through direct RNA-RNA base pairing with the 5' untranslated region (5'UTR) of sarS mRNA and that a putative 18-nucleotide region played a significant role in the regulatory process. Furthermore, the mRNA half-life analysis of sarS in the gdpS mutant showed that gdpS positively regulates the mRNA levels of sarS by contributing to the stabilization of sarS mRNA, suggesting that gdpS mRNA may regulate spa expression in an RNA-dependent pathway.

  18. Study on effectiveness of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related non-Hodgkin's lymphoma.

    PubMed

    Zhong, Dong Ta; Shi, Chun Mei; Chen, Qiang; Huang, Jing Ze; Liang, Jian Gang

    2012-11-01

    Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. Even though NHL is commonly chemosensitive to primary treatment, failure or relapse still occurs in a large number of patients. We conducted this retrospective study to evaluate the efficacy and safety of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related NHL (AIDS-NHL). Forty-eight patients with relapsed or refractory AIDS-NHL were treated with intravenous combination chemotherapy with GDP. The overall objective response rate was 54.1% (95% confidence interval, CI, 40.1-68.3%), with 10 complete responses and 16 partial responses. The 2-year overall survival rate (OS) was 70.8% (95% CI 58.0-83.7%), and the 5-year OS was 41.7% (95% CI 27.7-55.6%). The 2-year progression-free survival rate (PFS) was 37.5% (95% CI 23.8-51.2%), and the 5-year PFS was 25.0% (95% CI 12.8-37.3%). The median progression-free survival was 8.8 months (95% CI 0-20.3 months), and the median overall survival was 40.6 months (95% CI 22.6-58.6 months). Patients with B cell tumors who relapsed but had no B symptoms were clinical stage I/II, had infiltration fewer than two extranodal sites, had CD4⁺ counts >200 cells/μL, and had lactate dehydrogenase (LDH) less than the upper limit of normal benefited from GDP. The level of LDH had a significant impact on the response rate to chemotherapy with GDP (P = 0.015). Myelosuppression was the main side effect; the incidence of grade 3-4 anemia was 8.3%; leukopenia, 37.5%; and thrombocytopenia, 48.3%. Univariate and multivariate analyses were performed to determine variables for OS and PFS. This study confirms that GDP is an effective and safe salvage regimen in relapsed or refractory AIDS-NHL, was associated with modest declines in CD4⁺ lymphocyte counts, and did not promote HIV-1 viral replication.

  19. 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.

  20. Visual illusions and the control of ball placement in goal-directed hitting.

    PubMed

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

    2010-12-01

    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 Müller-Lyer illusion on ball placement. After extensive practice in hitting balls to different landing locations, participants (N = 9) had to hit a ball to a distant target specified by the vertex of a single-winged Müller-Lyer configuration. Impact velocity was not significantly "tricked" by the pictorial illusion, suggesting that, even when late corrections in the target area are absent, some motor behaviors are not susceptible to the influence of the visual environment surrounding the target.

  1. Hitting the Fast Ball and Shaggin' Flies: a Physicist Considers Batting and Fielding in Baseball

    NASA Astrophysics Data System (ADS)

    Adair, Robert

    2003-03-01

    I describe some of the information processing that batters and fielders use to hit and field in baseball. The decision to hit the fast ball must be made using information from the first 15 feet of the ball's travel and the batter might as well not scan the last half of the flight. The procedures an outfielder uses to field a fly ball, adopted instinctively by 9 year old Little Leaguers, follows from mechanisms designed for the tracking of prey by predator and the avoidance of predators by prey. To this we add the utility of the acoustics of the bat-ball collision for balls hit directly at outfielders, and strategies for the avoidance of errors on ground balls to infielders.

  2. Late-stage planetary accretion including hit-and-run collisions and fragmentation

    NASA Astrophysics Data System (ADS)

    Chambers, J. E.

    2013-05-01

    To date, most simulations of the final accretion of the terrestrial planets have assumed that all collisions lead to mergers. Recent hydrodynamic simulations of impacts between planetary mass bodies (Leinhardt, Z.M., Stewart, S.T. [2012]. Astrophys. J. 745, 79; Genda, H., Kokubo, E., Ida, S. [2012]. Astrophys J. 744, 137) have parameterized the outcome of planetary collisions in terms of the masses and velocities of the colliding bodies. Using these results, it is now possible to simulate late-stage planetary growth using a more realistic model for collisions. Here, we describe results of eight N-body simulations of terrestrial planet formation that incorporate collisional fragmentation and hit-and-run collisions. The results are compared to simulations using identical initial collisions in which all collisions were assumed to result in mergers (Chambers, J.E. [2001]. Icarus 152, 205-224). The new simulations form 3 to 5 terrestrial planets moving on widely spaced orbits with growth complete by 400 My. The mean time for Earth-like planets to reach half their final mass is 17 My, comparable to the time in simulations without fragmentation. However, the prolonged sweep up of collision fragments lengthens the mean time required for Earth analogues to become fully formed to 159 My. The final planets have somewhat smaller masses m and eccentricities e when fragmentation is included. Masses are particularly reduced in the region now occupied by Mars. The final distributions of m, e and semi-major axis are similar to the terrestrial planets of the Solar System, but the strong concentration of mass in the narrow zone occupied by Earth and Venus is not reproduced. Collisional fragmentation is likely to preferentially eject silicate-rich mantle material leaving a target enriched in iron-rich core material. However, large bodies often reaccrete silicate-rich mantle fragments at a later time, leaving their final composition largely unchanged. The final core mass fractions of

  3. Solution structure of the zinc finger HIT domain in protein FON

    PubMed Central

    He, Fahu; Umehara, Takashi; Tsuda, Kengo; Inoue, Makoto; Kigawa, Takanori; Matsuda, Takayoshi; Yabuki, Takashi; Aoki, Masaaki; Seki, Eiko; Terada, Takaho; Shirouzu, Mikako; Tanaka, Akiko; Sugano, Sumio; Muto, Yutaka; Yokoyama, Shigeyuki

    2007-01-01

    The zinc finger HIT domain is a sequence motif found in many proteins, including thyroid hormone receptor interacting protein 3 (TRIP-3), which is possibly involved in maturity-onset diabetes of the young (MODY). Novel zinc finger motifs are suggested to play important roles in gene regulation and chromatin remodeling. Here, we determined the high-resolution solution structure of the zinc finger HIT domain in ZNHIT2 (protein FON) from Homo sapiens, by an NMR method based on 567 upper distance limits derived from NOE intensities measured in three-dimensional NOESY spectra. The structure yielded a backbone RMSD to the mean coordinates of 0.19 Å for the structured residues 12–48. The fold consists of two consecutive antiparallel β-sheets and two short C-terminal helices packed against the second β-sheet, and binds two zinc ions. Both zinc ions are coordinated tetrahedrally via a CCCC-CCHC motif to the ligand residues of the zf-HIT domain in an interleaved manner. The tertiary structure of the zinc finger HIT domain closely resembles the folds of the B-box, RING finger, and PHD domains with a cross-brace zinc coordination mode, but is distinct from them. The unique three-dimensional structure of the zinc finger HIT domain revealed a novel zinc-binding fold, as a new member of the treble clef domain family. On the basis of the structural data, we discuss the possible functional roles of the zinc finger HIT domain. PMID:17656577

  4. Evaluation of a new nanoparticle-based lateral-flow immunoassay for the exclusion of heparin-induced thrombocytopenia (HIT).

    PubMed

    Sachs, Ulrich J; von Hesberg, Jakob; Santoso, Sentot; Bein, Gregor; Bakchoul, Tamam

    2011-12-01

    Heparin-induced thrombocytopenia (HIT) is an adverse complication of heparin caused by HIT antibodies (abs) that recognise platelet factor 4-heparin (PF4/hep) complexes. Several laboratory tests are available for the confirmation and/or refutation of HIT. A reliable and rapid single-sample test is still pending. It was the objective of this study to evaluate a new lateral-flow immunoassay based on nanoparticle technology. A cohort of 452 surgical and medical patients suspected of having HIT was evaluated. All samples were tested in two IgG-specific ELISAs, in a particle gel immunoassay (PaGIA) and in a newly developed lateral-flow immunoassay (LFI-HIT) as well as in a functional test (HIPA). Clinical pre-test probability was determined using 4T's score. Platelet-activating antibodies were present in 34/452 patients, all of whom had intermediate to high clinical probability. PF4/hep abs were detected in 79, 87, 86, and 63 sera using the four different immunoassays. The negative predictive values (NPV) were 100% for both ELISA tests and LFI-HIT but only 99.2% for PaGIA. There were less false positives (n=29) in the LFI-HIT compared to any other test. Additionally, significantly less time was required to perform LFI-HIT than to perform the other immunoassays. In conclusion, a newly developed lateral-flow assay, LFI-HIT, was capable of identifying all HIT patients in a cohort in a short period of time. Beside an NPV of 100%, the rate of false-positive signals is significantly lower with LFI-HIT than with other immunoassay(s). These performance characteristics suggest a high potency in reducing the risk and costs in patients suspected of having HIT.

  5. Inositol phospholipids regulate the guanine-nucleotide-exchange factor Tiam1 by facilitating its binding to the plasma membrane and regulating GDP/GTP exchange on Rac1

    PubMed Central

    2004-01-01

    Binding of the Rac1-specific guanine-nucleotide-exchange factor, Tiam1, to the plasma membrane requires the N-terminal pleckstrin homology domain. In the present study, we show that membrane-association is mediated by binding of PtdIns(4,5)P2 to the pleckstrin homology domain. Moreover, in 1321N1 astrocytoma cells, translocation of Tiam1 to the cytosol, following receptor-mediated stimulation of PtdIns(4,5)P2 breakdown, correlates with decreased Rac1-GTP levels, indicating that membrane-association is required for GDP/GTP exchange on Rac1. In addition, we show that platelet-derived growth factor activates Rac1 in vivo by increasing PtdIns(3,4,5)P3 concentrations, rather than the closely related lipid, PtdIns(3,4)P2. Finally, the data demonstrate that PtdIns(4,5)P2 and PtdIns(3,4,5)P3 bind to the same pleckstrin homology domain in Tiam1 and that soluble inositol phosphates appear to compete with lipids for this binding. Together, these novel observations provide strong evidence that distinct phosphoinositides regulate different functions of this enzyme, indicating that local concentrations of signalling lipids and the levels of cytosolic inositol phosphates will play crucial roles in determining its activity in vivo. PMID:15242348

  6. Inositol phospholipids regulate the guanine-nucleotide-exchange factor Tiam1 by facilitating its binding to the plasma membrane and regulating GDP/GTP exchange on Rac1.

    PubMed

    Fleming, Ian N; Batty, Ian H; Prescott, Alan R; Gray, Alex; Kular, Gursant S; Stewart, Hazel; Downes, C Peter

    2004-09-15

    Binding of the Rac1-specific guanine-nucleotide-exchange factor, Tiam1, to the plasma membrane requires the N-terminal pleckstrin homology domain. In the present study, we show that membrane-association is mediated by binding of PtdIns(4,5)P(2) to the pleckstrin homology domain. Moreover, in 1321N1 astrocytoma cells, translocation of Tiam1 to the cytosol, following receptor-mediated stimulation of PtdIns(4,5)P(2) breakdown, correlates with decreased Rac1-GTP levels, indicating that membrane-association is required for GDP/GTP exchange on Rac1. In addition, we show that platelet-derived growth factor activates Rac1 in vivo by increasing PtdIns(3,4,5)P(3) concentrations, rather than the closely related lipid, PtdIns(3,4)P(2). Finally, the data demonstrate that PtdIns(4,5)P(2) and PtdIns(3,4,5)P(3) bind to the same pleckstrin homology domain in Tiam1 and that soluble inositol phosphates appear to compete with lipids for this binding. Together, these novel observations provide strong evidence that distinct phosphoinositides regulate different functions of this enzyme, indicating that local concentrations of signalling lipids and the levels of cytosolic inositol phosphates will play crucial roles in determining its activity in vivo.

  7. On hitting children: a review of corporal punishment in the United States.

    PubMed

    Knox, Michele

    2010-01-01

    Research has clearly demonstrated associations between corporal punishment of children and maladaptive behavior patterns such as aggression and delinquency. Hitting children is an act of violence and a clear violation of children's human rights. In this article, the position of the United States on corporal punishment of children is discussed. Professional and international progress on ending corporal punishment is explained, and the relationship between corporal punishment and child abuse is discussed. An appeal is made for prevention efforts such as parent education and removal of social sanctions for hitting children that may hold significant promise for preventing child maltreatment.

  8. Cosmic ray hit frequencies in critical sites in the central nervous system

    NASA Astrophysics Data System (ADS)

    Curtis, S. B.; Vazquez, M. E.; Wilson, J. W.; Atwell, W.; Kim, M.; Capala, J.

    One outstanding question to be addressed in assessing the risk of exposure to space travelers from galactic cosmic rays (GCR) outside the geomagnetosphere is to ascertain the effects of single heavy-ion hits on cells in critical regions of the central nervous system (CNS). As a first step toward this end, it is important to determine how many ``hits'' might be received by a neural cell in several critical CNS areas during an extended mission outside the confines of the earth's magnetic field. Critical sites in the CNS: the macula, and an interior brain point (typical of the genu, thalamus, hippocampus and nucleus basalis of Meynert) were chosen for the calculation of hit frequencies from galactic cosmic rays for a mission to Mars during solar minimum (i.e., at maximum cosmic-ray intensity). The shielding at a given position inside the body was obtained using the Computerized Anatomical Man (CAM) model, and a radiation transport code which includes nuclear fragmentation was used to calculate yearly fluences at the point of interest. Since the final Mars spacecraft shielding configuration has not yet been determined, we considered the minimum amount of aluminum required for pressure vessel-wall requirements in the living quarters of a spacecraft, and a typical duty area as a pressure vessel plus necessary equipment. The conclusions are: (1) variation of the position of the ``target site'' within the head plays only a small role in varying hit frequencies; (2) the average number of hits depends linearly on the cross section of the critical portion of the cell assumed in the calculation; (3) for a three-year mission to Mars at solar minimum (i.e., assuming the 1977 spectrum of galactic cosmic rays), 2% or 13% of the ``critical sites'' of cells in the CNS would be directly hit at least once by iron ions, depending on whether 60 mum^2 or 471 mum^2 is assumed as the critical cross sectional area; and (4) roughly 6 million out of some 43 million hippocampal cells and 55

  9. Dissociation of GDP dissociation inhibitor and membrane translocation are required for efficient activation of Rac by the Dbl homology-pleckstrin homology region of Tiam.

    PubMed

    Robbe, Karine; Otto-Bruc, Annie; Chardin, Pierre; Antonny, Bruno

    2003-02-14

    Small G proteins of the Rho/Rac/Cdc42 family are associated with lipid membranes through their prenylated C termini. Alternatively, these proteins form soluble complexes with GDI proteins. To assess how this membrane partitioning influences the activation of Rac by guanine nucleotide exchange factors, GDP-to-GTP exchange reactions were performed in the presence of liposomes using different forms of Rac-GDP. We show that both non-prenylated Rac-GDP and the soluble complex between prenylated Rac-GDP and GDI are poorly activated by the Dbl homology-pleckstrin homology (DH-PH) domain of the exchange factor Tiam1, whereas prenylated Rac-GDP bound to liposomes is activated about 10 times more rapidly. Sedimentation experiments with liposomes reveal that the DH-PH region of Tiam1 forms, with nucleotide-free prenylated Rac, a membrane-bound complex from which GDI is excluded. Taken together, these experiments demonstrate that the dissociation of Rac-GDP from GDI and its translocation to membrane lipids favor DH-PH-catalyzed nucleotide exchange because the steric hindrance caused by GDI is relieved and because the membrane environment favors functional interaction between the DH-PH domain and the small G protein.

  10. LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes

    PubMed Central

    Carlson, Hanqian L.; Quinn, Jeffrey J.; Yang, Yul W.; Thornburg, Chelsea K.; Chang, Howard Y.; Stadler, H. Scott

    2015-01-01

    Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage. PMID:26633036

  11. X-ray, NMR, and Mutational Studies of the Catalytic Cycle of the GDP-Mannose Mannosyl Hydrolase Reaction

    SciTech Connect

    Gabelli,S.; Azurmendi, H.; Bianchet, M.; Amzel, L.; Mildva, A.

    2006-01-01

    GDP-mannose hydrolase catalyzes the hydrolysis with inversion of GDP-{alpha}-D-hexose to GDP and {beta}-D-hexose by nucleophilic substitution by water at C1 of the sugar. Two new crystal structures (free enzyme and enzyme-substrate complex), NMR, and site-directed mutagenesis data, combined with the structure of the enzyme-product complex reported earlier, suggest a four-stage catalytic cycle. An important loop (L6, residues 119-125) contains a ligand to the essential Mg{sup 2+} (Gln-123), the catalytic base (His-124), and three anionic residues. This loop is not ordered in the X-ray structure of the free enzyme due to dynamic disorder, as indicated by the two-dimensional 1H-15N HMQC spectrum, which shows selective exchange broadening of the imidazole nitrogen resonances of His-124 (k{sub ex} = 6.6 x 10{sup 4} s{sup -1}). The structure of the enzyme-Mg{sup 2+}-GDP-mannose substrate complex of the less active Y103F mutant shows loop L6 in an open conformation, while the structure of the enzyme-Mg{sup 2+}-GDP product complex showed loop L6 in a closed, 'active' conformation. 1H-15N HMQC spectra show the imidazole N of His-124 to be unprotonated, appropriate for general base catalysis. Substituting Mg{sup 2+} with the more electrophilic metal ions Mn{sup 2+} or Co{sup 2+} decreases the pK{sub a} in the pH versus k{sub cat} rate profiles, showing that deprotonation of a metal-bound water is partially rate-limiting. The H124Q mutation, which decreases k{sub cat} 103.4-fold and largely abolishes its pH dependence, is rescued by the Y103F mutation, which increases k{sub cat} 23-fold and restores its pH dependence. The structural basis of the rescue is the fact that the Y103F mutation shifts the conformational equilibrium to the open form moving loop L6 out of the active site, thus permitting direct access of the specific base hydroxide from the solvent. In the proposed dissociative transition state, which occurs in the closed, active conformation of the enzyme, the

  12. Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors

    SciTech Connect

    Zhang, Xuqing; Song, Fengbing; Kuo, Gee-Hong; Xiang, Amy; Gibbs, Alan C.; Abad, Marta C.; Sun, Weimei; Kuo, Lawrence C.; Sui, Zhihua

    2013-11-20

    A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties.

  13. Sub-concussive hit characteristics predict deviant brain metabolism in football athletes.

    PubMed

    Poole, Victoria N; Breedlove, Evan L; Shenk, Trey E; Abbas, Kausar; Robinson, Meghan E; Leverenz, Larry J; Nauman, Eric A; Dydak, Ulrike; Talavage, Thomas M

    2015-01-01

    Magnetic resonance spectroscopy and helmet telemetry were used to monitor the neural metabolic response to repetitive head collisions in 25 high school American football athletes. Specific hit characteristics were determined highly predictive of metabolic alterations, suggesting that sub-concussive blows can produce biochemical changes and potentially lead to neurological problems.

  14. 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

    ..., implementation specifications, and/or certification criteria. Once the HIT Standards Committee is informed of... certification criteria are currently available to meet the priority area; (2) an assessment of where gaps exist... timeline, which may also account for NIST testing where appropriate, and include dates when the...

  15. Data-Based Interval Hitting Program for Female College Volleyball Players

    PubMed Central

    Hurd, Wendy; Hunter-Giordano, Airelle; Axe, Michael; Snyder-Mackler, Lynn

    2009-01-01

    Context: Interval sports programs are a critical rehabilitation element when preparing the injured athlete for a return to preinjury activities. There is currently no published interval hitting program to guide a return to unrestricted play for the volleyball athlete. Therefore, data-based, position-specific overhead hitting programs that control for intensity, time, and number of ball strikes were developed for female college volleyball players. Evidence Acquisition: Records from a single Division I varsity women’s volleyball team were examined for all matches during 7 consecutive years of team play. Data were collected for number of hitting and service attempts per game for each position and the number of games per match. Results: Per game, middle hitters averaged 4.51 attacks and 2.77 service attempts; right-side hitters, 3.58 attacks and 1.26 service attempts; outside hitters, 6.37 attacks and 3.44 service attempts; and setters and defensive specialists, 0.17 attacks and 1.78 service attempts. Conclusion: The interval hitting program can provide rehabilitation specialists with a data-based approach that may facilitate a return to play and minimize the risk of reinjury for volleyball athletes. PMID:23015917

  16. Rich-Poor Income Gap Hits 40-Year High As Poverty Rate Stalls.

    ERIC Educational Resources Information Center

    Center on Budget and Policy Priorities, Washington, DC.

    On September 26, 1990, the Census Bureau released its 1989 figures on poverty and income which showed that no significant progress was made in reducing poverty in 1989, and that gaps between rich and poor and between the wealthy and the middle class hit their widest points in more than 40 years. Although 1989 marked the seventh year of economic…

  17. 76 FR 22397 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-21

    ..., from 10 a.m. to 4 p.m./Eastern Time. Location: Renaissance Dupont Circle Hotel, 1143 New Hampshire Ave... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy...

  18. 75 FR 29762 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Information Technology, HHS. ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  19. 75 FR 51819 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-23

    ... Health Information Technology; HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This... Coordinator for Health Information Technology (ONC). The meeting will be open to the public. Name of...

  20. 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

    ... Health Information Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings... of the National Coordinator for Health Information Technology (ONC). The meetings will be open to...

  1. 75 FR 29761 - Office of the National Coordinator for Health Information Technology: HIT Standards Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology: HIT Standards... Information Technology, HHS. ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  2. 75 FR 151 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-04

    ... Information Technology; HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice... Health Information Technology (ONC). The meeting will be open to the public. Name of Committee:...

  3. 75 FR 65486 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-25

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Information Technology, HHS. ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  4. 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

    ... Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice... Coordinator for Health Information Technology (ONC). The meetings will be open to the public via...

  5. 75 FR 57027 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    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 meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  6. 75 FR 5595 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Information Technology, HHS. ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  7. 75 FR 36657 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ... 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... Coordination, Office of the National Coordinator for Health Information Technology. BILLING CODE 4150-45-P...

  8. 75 FR 21629 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology HIT Policy Committee... committee of the Office of the National Coordinator for Health Information Technology (ONC). The meeting... adoption of a nationwide health information technology infrastructure that permits the electronic...

  9. 75 FR 8954 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-26

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Standards... Information Technology, HHS ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information Technology (ONC)....

  10. 75 FR 151 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-04

    ... Information Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice... Health Information Technology (ONC). The meeting will be open to the public. Name of Committee:...

  11. 75 FR 16126 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Information Technology, HHS. ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  12. 75 FR 57026 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-17

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Information Technology, HHS. ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  13. 75 FR 57276 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-20

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

  14. 75 FR 16126 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Standards... Information Technology, HHS. ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  15. 75 FR 21628 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology HIT Standards... Information Technology, HHS ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information Technology (ONC)....

  16. 75 FR 65636 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-26

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Standards... Information Technology, HHS. ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  17. 75 FR 8953 - Office of the National Coordinator for Health Information Technology HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-26

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology HIT Policy Committee... committee of the Office of the National Coordinator for Health Information Technology (ONC). The meeting... and adoption of a nationwide health information technology infrastructure that permits the...

  18. 75 FR 5595 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology HIT Standards... Information Technology, HHS. ] ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  19. 75 FR 17744 - Office of the National Coordinator for Health Information Technology HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-07

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology HIT Policy Committee... technology infrastructure that permits the electronic exchange and use of health information as is consistent..., Office of Programs and Coordination, Office of the National Coordinator for Health Information...

  20. 76 FR 9784 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-22

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Information Technology, HHS. ACTION: Notice of meeting. This notice announces a forthcoming meeting of a public advisory committee of the Office of the National Coordinator for Health Information...

  1. 75 FR 51820 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-23

    ... Health Information Technology; HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This... Coordinator for Health Information Technology (ONC). The meeting will be open to the public. Name of...

  2. 75 FR 29761 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... 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... Coordination, Office of the National Coordinator for Health Information Technology. BILLING CODE 4150-45-P...

  3. Data Independent Acquisition analysis in ProHits 4.0.

    PubMed

    Liu, Guomin; Knight, James D R; Zhang, Jian Ping; Tsou, Chih-Chiang; Wang, Jian; Lambert, Jean-Philippe; Larsen, Brett; Tyers, Mike; Raught, Brian; Bandeira, Nuno; Nesvizhskii, Alexey I; Choi, Hyungwon; Gingras, Anne-Claude

    2016-10-21

    Affinity purification coupled with mass spectrometry (AP-MS) is a powerful technique for the identification and quantification of physical interactions. AP-MS requires careful experimental design, appropriate control selection and quantitative workflows to successfully identify bona fide interactors amongst a large background of contaminants. We previously introduced ProHits, a Laboratory Information Management System for interaction proteomics, which tracks all samples in a mass spectrometry facility, initiates database searches and provides visualization tools for spectral counting-based AP-MS approaches. More recently, we implemented Significance Analysis of INTeractome (SAINT) within ProHits to provide scoring of interactions based on spectral counts. Here, we provide an update to ProHits to support Data Independent Acquisition (DIA) with identification software (DIA-Umpire and MSPLIT-DIA), quantification tools (through DIA-Umpire, or externally via targeted extraction), and assessment of quantitative enrichment (through mapDIA) and scoring of interactions (through SAINT-intensity). With additional improvements, notably support of the iProphet pipeline, facilitated deposition into ProteomeXchange repositories and enhanced export and viewing functions, ProHits 4.0 offers a comprehensive suite of tools to facilitate affinity proteomics studies.

  4. As the Economic Crisis Hits Home, Colleges Seek Help from Congress

    ERIC Educational Resources Information Center

    Field, Kelly

    2008-01-01

    Congress is crafting a second economic-stimulus bill, and the nation's colleges, hit by the deepening fiscal crisis, want a share of the money. Over the last few weeks, colleges and their lobbyists have bombarded members of Congress with letters and phone calls seeking money for research, student aid, and infrastructure. However, Congress is…

  5. 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 Bayfront, Corpus Christi, TX AGENCY: Coast Guard, DHS. ACTION: Temporary Final rule. SUMMARY: The Coast Guard is establishing a temporary Special Local Regulation in the Corpus Christi Bayfront area...

  6. 76 FR 70455 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure...

  7. 76 FR 50734 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-16

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure...

  8. HITS-CLIP yields genome-wide insights into brain alternative RNA processing

    NASA Astrophysics Data System (ADS)

    Licatalosi, Donny D.; Mele, Aldo; Fak, John J.; Ule, Jernej; Kayikci, Melis; Chi, Sung Wook; Clark, Tyson A.; Schweitzer, Anthony C.; Blume, John E.; Wang, Xuning; Darnell, Jennifer C.; Darnell, Robert B.

    2008-11-01

    Protein-RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome-wide means of mapping protein-RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova revealed extremely reproducible RNA-binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova-RNA interactions in 3' untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo.

  9. Visits, Hits, Caching and Counting on the World Wide Web: Old Wine in New Bottles?

    ERIC Educational Resources Information Center

    Berthon, Pierre; Pitt, Leyland; Prendergast, Gerard

    1997-01-01

    Although web browser caching speeds up retrieval, reduces network traffic, and decreases the load on servers and browser's computers, an unintended consequence for marketing research is that Web servers undercount hits. This article explores counting problems, caching, proxy servers, trawler software and presents a series of correction factors…

  10. Optimization of the Magnetic Recovery of Hits from One-Bead-One-Compound Library Screens.

    PubMed

    Mendes, Kimberly; Ndungu, J M; Clark, Lorraine F; Kodadek, Thomas

    2015-09-14

    On-bead screening of one-bead-one-compound (OBOC) libraries is a useful procedure for the identification of protein ligands. An important aspect of this experiment is the method by which beads that bind the target protein are separated from those that do not. Ideally, such a method would be rapid and convenient and result in the isolation of 100% of the "hits" with no false positives (beads that display compounds that are not good ligands for the target). We introduced a technique in which beads that have bound a labeled target protein can be magnetized, thus allowing their convenient isolation ( Astle et al. Chem. Biol. 2010 , 17 , 38 - 45 ). However, recent work in our laboratory and others has shown that magnetic hit recovery can result in the isolation of large numbers of false positives and has also suggested that many true hit beads are missed. In this study, we employ a well-defined model system to examine the efficiency of various magnetic hit isolation protocols. We show that the choice of reagents and the particular operations employed are critical for optimal results.

  11. Pigeons, unlike humans, do not prefer near hits in a slot-machine-like task.

    PubMed

    Fortes, Inês; Case, Jacob P; Zentall, Thomas R

    2017-02-20

    Slot machines are among the most popular forms of commercial gambling, and the high frequency of losses that come close to winning - near hits - in this game appears to contribute to its popularity. In the present experiment we tested if pigeons, similarly to humans, prefer an alternative that provides near-hit outcomes in a slot-machine-like task. The pigeons received series of three stimuli, one every two seconds: if the three stimuli matched, food was delivered (a win); if they did not match, food was not delivered (a loss). We gave pigeons a choice between two options that provided food with the same probability but they differed in the sequence of stimuli on loss trials. For the near-hit alternative the non-matching stimulus was the third one (defined as a near hit). For the clear-loss alternative the non-matching stimulus was the second one. We found that the pigeons preferred the clear-loss alternative, that is, they preferred to be given information about the outcome sooner. This result is consistent with prior research on suboptimal choice with pigeons that emphasizes the role of information in choice but is inconsistent with the results of research with humans.

  12. Exploring Patterns of Soil Organic Matter Decomposition with Students and the Public Through the Global Decomposition Project (GDP)

    NASA Astrophysics Data System (ADS)

    Wood, J. H.; Natali, S.

    2014-12-01

    The Global Decomposition Project (GDP) is a program designed to introduce and educate students and the general public about soil organic matter and decomposition through a standardized protocol for collecting, reporting, and sharing data. This easy-to-use hands-on activity focuses on questions such as "How do environmental conditions control decomposition of organic matter in soil?" and "Why do some areas accumulate organic matter and others do not?" Soil organic matter is important to local ecosystems because it affects soil structure, regulates soil moisture and temperature, and provides energy and nutrients to soil organisms. It is also important globally because it stores a large amount of carbon, and when microbes "eat", or decompose organic matter they release greenhouse gasses such as carbon dioxide and methane into the atmosphere, which affects the earth's climate. The protocol describes a commonly used method to measure decomposition using a paper made of cellulose, a component of plant cell walls. Participants can receive pre-made cellulose decomposition bags, or make decomposition bags using instructions in the protocol and easily obtained materials (e.g., window screen and lignin-free paper). Individual results will be shared with all participants and the broader public through an online database. We will present decomposition bag results from a research site in Alaskan tundra, as well as from a middle-school-student led experiment in California. The GDP demonstrates how scientific methods can be extended to educate broader audiences, while at the same time, data collected by students and the public can provide new insight into global patterns of soil decomposition. The GDP provides a pathway for scientists and educators to interact and reach meaningful education and research goals.

  13. Mutagenesis in the switch IV of the helical domain of the human Gsalpha reduces its GDP/GTP exchange rate.

    PubMed

    Echeverría, V; Hinrichs, M V; Torrejón, M; Ropero, S; Martinez, J; Toro, M J; Olate, J

    2000-01-01

    The Galpha subunits of heterotrimeric G proteins are constituted by a conserved GTPase "Ras-like" domain (RasD) and by a unique alpha-helical domain (HD). Upon GTP binding, four regions, called switch I, II, III, and IV, have been identified as undergoing structural changes. Switch I, II, and III are located in RasD and switch IV in HD. All Galpha known functions, such as GTPase activity and receptor, effector, and Gbetagamma interaction sites have been found to be localized in RasD, but little is known about the role of HD and its switch IV region. Through the construction of chimeras between human and Xenopus Gsalpha we have previously identified a HD region, encompassing helices alphaA, alphaB, and alphaC, that was responsible for the observed functional differences in their capacity to activate adenylyl cyclase (Antonelli et al. [1994]: FEBS Lett 340:249-254). Since switch IV is located within this region and contains most of the nonconservative amino acid differences between both Gsalpha proteins, in the present work we constructed two human Gsalpha mutant proteins in which we have changed four and five switch IV residues for the ones present in the Xenopus protein. Mutants M15 (hGsalphaalphaS133N, M135P, P138K, P143S) and M17 (hGsalphaalphaS133N, M135P, V137Y, P138K, P143S) were expressed in Escherichia coli, purified, and characterized by their ability to bind GTPgammaS, dissociate GDP, hydrolyze GTP, and activate adenylyl cyclase. A decreased rate of GDP release, GTPgammaS binding, and GTP hydrolysis was observed for both mutants, M17 having considerably slower kinetics than M15 for all functions tested. Reconstituted adenylyl cyclase activity with both mutants showed normal activation in the presence of AlF(4)(-), but a decreased activation with GTPgammaS, which is consistent with the lower GDP dissociating rate they displayed. These data provide new evidence on the role that HD is playing in modulating the GDP/GTP exchange of the Gsalpha subunit.

  14. Combining Computational Methods for Hit to Lead Optimization in Mycobacterium tuberculosis Drug Discovery

    PubMed Central

    Ekins, Sean; Freundlich, Joel S.; Hobrath, Judith V.; White, E. Lucile; Reynolds, Robert C

    2013-01-01

    Purpose Tuberculosis treatments need to be shorter and overcome drug resistance. Our previous large scale phenotypic high-throughput screening against Mycobacterium tuberculosis (Mtb) has identified 737 active compounds and thousands that are inactive. We have used this data for building computational models as an approach to minimize the number of compounds tested. Methods A cheminformatics clustering approach followed by Bayesian machine learning models (based on publicly available Mtb screening data) was used to illustrate that application of these models for screening set selections can enrich the hit rate. Results In order to explore chemical diversity around active cluster scaffolds of the dose-response hits obtained from our previous Mtb screens a set of 1924 commercially available molecules have been selected and evaluated for antitubercular activity and cytotoxicity using Vero, THP-1 and HepG2 cell lines with 4.3%, 4.2% and 2.7% hit rates, respectively. We demonstrate that models incorporating antitubercular and cytotoxicity data in Vero cells can significantly enrich the selection of non-toxic actives compared to random selection. Across all cell lines, the Molecular Libraries Small Molecule Repository (MLSMR) and cytotoxicity model identified ~10% of the hits in the top 1% screened (>10 fold enrichment). We also showed that seven out of nine Mtb active compounds from different academic published studies and eight out of eleven Mtb active compounds from a pharmaceutical screen (GSK) would have been identified by these Bayesian models. Conclusion Combining clustering and Bayesian models represents a useful strategy for compound prioritization and hit-to lead optimization of antitubercular agents. PMID:24132686

  15. Disturbance in hitting accuracy by professional and collegiate baseball players due to intentional change of target position.

    PubMed

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

    2013-04-01

    The present study investigated bat control of skilled baseball batters during tee batting, faced with an intentional change in target position. Twelve, skilled, male baseball players (M age = 24 yr., SD = 4) participated in the study. Participants were instructed to hit a baseball off a tee 0.8 m from the ground (Hitting condition), and also to deliberately swing just above the ball (Air Swing condition). The task for the participants was to perform, in alternate order, 15 swings at a real baseball on a stationary tee and 15 swings at an imaginary ball that was said to be on top of the real baseball. The participants were instructed to hit the ball toward center field just as they would hit in a game. While most participants could hit the real ball in the sweet area of the bat, only one participant did so in the Air Swing condition. Average distances from the center of the sweet area to ball center at the moment of ball-bat contact in the Air Swing condition (85 mm) were significantly greater than the distance in the Hitting condition (38 mm). The larger error in hitting an imaginary ball in the sweet area could be due to perceptual changes following the batter's altered focus, expectation of a lack of contact, and/or lack of feedback from the swing. It was suggested that baseball batters should be aware of the possible error in hitting accurately when they intentionally shifted the target.

  16. Temperature impacts on economic growth warrant stringent mitigation policy

    NASA Astrophysics Data System (ADS)

    Moore, Frances C.; Diaz, Delavane B.

    2015-02-01

    Integrated assessment models compare the costs of greenhouse gas mitigation with damages from climate change to evaluate the social welfare implications of climate policy proposals and inform optimal emissions reduction trajectories. However, these models have been criticized for lacking a strong empirical basis for their damage functions, which do little to alter assumptions of sustained gross domestic product (GDP) growth, even under extreme temperature scenarios. We implement empirical estimates of temperature effects on GDP growth rates in the DICE model through two pathways, total factor productivity growth and capital depreciation. This damage specification, even under optimistic adaptation assumptions, substantially slows GDP growth in poor regions but has more modest effects in rich countries. Optimal climate policy in this model stabilizes global temperature change below 2 °C by eliminating emissions in the near future and implies a social cost of carbon several times larger than previous estimates. A sensitivity analysis shows that the magnitude of climate change impacts on economic growth, the rate of adaptation, and the dynamic interaction between damages and GDP are three critical uncertainties requiring further research. In particular, optimal mitigation rates are much lower if countries become less sensitive to climate change impacts as they develop, making this a major source of uncertainty and an important subject for future research.

  17. Hit rates and radiation doses to nuclei of bone lining cells from alpha-particle-emitting radionuclides

    NASA Technical Reports Server (NTRS)

    Polig, E.; Jee, W. S.; Kruglikov, I. L.

    1992-01-01

    Factors relating the local concentration of a bone-seeking alpha-particle emitter to the mean hit rate have been determined for nuclei of bone lining cells using a Monte Carlo procedure. Cell nuclei were approximated by oblate spheroids with dimensions and location taken from a previous histomorphometric study. The Monte Carlo simulation is applicable for planar and diffuse labels at plane or cylindrical bone surfaces. Additionally, the mean nuclear dose per hit, the dose mean per hit, the mean track segment length and its second moment, the percentage of stoppers, and the frequency distribution of the dose have been determined. Some basic features of the hit statistics for bone lining cells have been outlined, and the consequences of existing standards of radiation protection with regard to the hit frequency to cell nuclei are discussed.

  18. Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP.

    PubMed Central

    Feig, L A; Cooper, G M

    1988-01-01

    Substitution of asparagine for serine at position 17 decreased the affinity of rasH p21 for GTP 20- to 40-fold without significantly affecting its affinity for GDP. Transfection of NIH 3T3 cells with a mammalian expression vector containing the Asn-17 rasH gene and a Neor gene under the control of the same promoter yielded only a small fraction of the expected number of G418-resistant colonies, indicating that expression of Asn-17 p21 inhibited cell proliferation. The inhibitory effect of Asn-17 p21 required its localization to the plasma membrane and was reversed by coexpression of an activated ras gene, indicating that the mutant p21 blocked the endogenous ras function required for NIH 3T3 cell proliferation. NIH 3T3 cells transformed by v-mos and v-raf, but not v-src, were resistant to inhibition by Asn-17 p21, indicating that the requirement for normal ras function can be bypassed by these cytoplasmic oncogenes. The Asn-17 mutant represents a novel reagent for the study of ras function by virtue of its ability to inhibit cellular ras activity in vivo. Since this phenotype is likely associated with the preferential affinity of the mutant protein for GDP, analogous mutations might also yield inhibitors of other proteins whose activities are regulated by guanine nucleotide binding. Images PMID:3145408

  19. Looking for non-linear relation evidences between Brazilian gross domestic product (GDP) and fixed capital stock (K)

    NASA Astrophysics Data System (ADS)

    Kamimura, A.; Guerra, S. M. G.; Sauer, I. L.

    2004-02-01

    This paper deals with the epistemologic problem of searching for experimental evidences of a particular economic model theory. The difficulties of such tasks are well-known due to the peculiarities of the economic system, mainly related to the non-repetitiousness of experiments. Thus, indirect evidence and other related parameter correlations must be looked for. In the present case, a Brazilian macroeconomic historical data set is analysed and some particular phenomena relating correlation between gross domestic production (GDP), fixed capital stock and electricity consumption (EC) and their respectives elasticities are presented. Developed countries, in general, present different behaviour of these variables, compared to emerging economies, not only from the point of view of absolute value aspect, but also from the point of view internal dynamic interaction process. The celebrated correlation between EC and GDP, easily verified in the data of developed countries, becomes actually a myth for the emerging countries. However, this “bad” result could be an evidence of a model proposed by the authors.

  20. Metabolic engineering of Escherichia coli to produce 2'-fucosyllactose via salvage pathway of guanosine 5'-diphosphate (GDP)-l-fucose.

    PubMed

    Chin, Young-Wook; Seo, Nari; Kim, Jae-Han; Seo, Jin-Ho

    2016-11-01

    2'-Fucosyllactose (2-FL) is one of the key oligosaccharides in human milk. In the present study, the salvage guanosine 5'-diphosphate (GDP)-l-fucose biosynthetic pathway from fucose was employed in engineered Escherichia coli BL21star(DE3) for efficient production of 2-FL. Introduction of the fkp gene coding for fucokinase/GDP-l-fucose pyrophosphorylase (Fkp) from Bacteroides fragilis and the fucT2 gene encoding α-1,2-fucosyltransferase from Helicobacter pylori allows the engineered E. coli to produce 2-FL from fucose, lactose and glycerol. To enhance the lactose flux to 2-FL production, the attenuated, and deleted mutants of β-galactosidase were employed. Moreover, the 2-FL yield and productivity were further improved by deletion of the fucI-fucK gene cluster coding for fucose isomerase (FucI) and fuculose kinase (FucK). Finally, fed-batch fermentation of engineered E. coli BL21star(DE3) deleting lacZ and fucI-fucK, and expressing fkp and fucT2 resulted in 23.1 g/L of extracellular concentration of 2-FL and 0.39 g/L/h productivity. Biotechnol. Bioeng. 2016;113: 2443-2452. © 2016 Wiley Periodicals, Inc.

  1. Methods to identify, study and understand End-user participation in HIT development

    PubMed Central

    2011-01-01

    Background Experience has shown that for new health-information-technology (HIT) to be suc-cessful clinicians must obtain positive clinical benefits as a result of its implementation and joint-ownership of the decisions made during the development process. A prerequisite for achieving both success criteria is real end-user-participation. Experience has also shown that further research into developing improved methods to collect more detailed information on social groups participating in HIT development is needed in order to support, facilitate and improve real end-user participation. Methods A case study of an EHR planning-process in a Danish county from October 2003 until April 2006 was conducted using process-analysis. Three social groups (physicians, IT-professionals and administrators) were identified and studied in the local, present perspective. In order to understand the interactions between the three groups, the national, historic perspective was included through a literature-study. Data were collected through observations, interviews, insight gathered from documents and relevant literature. Results In the local, present perspective, the administrator's strategy for the EHR planning process meant that there was no clinical workload-reduction. This was seen as one of the main barriers to the physicians to achieving real influence. In the national, historic perspective, physicians and administrators have had/have different perceptions of the purpose of the patient record and they have both struggled to influence this definition. To date, the administrators have won the battle. This explains the conditions made available for the physicians' participation in this case, which led to their role being reduced to that of clinical consultants - rather than real participants. Conclusion In HIT-development the interests of and the balance of power between the different social groups involved are decisive in determining whether or not the end-users become real

  2. B-HIT - A Tool for Harvesting and Indexing Biodiversity Data.

    PubMed

    Kelbert, Patricia; Droege, Gabriele; Barker, Katharine; Braak, Kyle; Cawsey, E Margaret; Coddington, Jonathan; Robertson, Tim; Whitacre, Jamie; Güntsch, Anton

    2015-01-01

    With the rapidly growing number of data publishers, the process of harvesting and indexing information to offer advanced search and discovery becomes a critical bottleneck in globally distributed primary biodiversity data infrastructures. The Global Biodiversity Information Facility (GBIF) implemented a Harvesting and Indexing Toolkit (HIT), which largely automates data harvesting activities for hundreds of collection and observational data providers. The team of the Botanic Garden and Botanical Museum Berlin-Dahlem has extended this well-established system with a range of additional functions, including improved processing of multiple taxon identifications, the ability to represent associations between specimen and observation units, new data quality control and new reporting capabilities. The open source software B-HIT can be freely installed and used for setting up thematic networks serving the demands of particular user groups.

  3. "Hits" emerge through self-organized coordination in collective response of free agents

    NASA Astrophysics Data System (ADS)

    Chakrabarti, Anindya S.; Sinha, Sitabhra

    2016-10-01

    Individuals in free societies frequently exhibit striking coordination when making independent decisions en masse. Examples include the regular appearance of hit products or memes with substantially higher popularity compared to their otherwise equivalent competitors or extreme polarization in public opinion. Such segregation of events manifests as bimodality in the distribution of collective choices. Here we quantify how apparently independent choices made by individuals result in a significantly polarized but stable distribution of success in the context of the box-office performance of movies and show that it is an emergent feature of a system of noninteracting agents who respond to sequentially arriving signals. The aggregate response exhibits extreme variability amplifying much smaller differences in individual cost of adoption. Due to self-organization of the competitive landscape, most events elicit only a muted response but a few stimulate widespread adoption, emerging as "hits".

  4. Linear energy transfer in water phantom within SHIELD-HIT transport code

    NASA Astrophysics Data System (ADS)

    Ergun, A.; Sobolevsky, N.; Botvina, A. S.; Buyukcizmeci, N.; Latysheva, L.; Ogul, R.

    2017-02-01

    The effect of irradiation in tissue is important in hadron therapy for the dose measurement and treatment planning. This biological effect is defined by an equivalent dose H which depends on the Linear Energy Transfer (LET). Usually, H can be expressed in terms of the absorbed dose D and the quality factor K of the radiation under consideration. In literature, various types of transport codes have been used for modeling and simulation of the interaction of the beams of protons and heavier ions with tissue-equivalent materials. In this presentation we used SHIELD-HIT code to simulate decomposition of the absorbed dose by LET in water for 16O beams. A more detailed description of capabilities of the SHIELD-HIT code can be found in the literature.

  5. Identification and structure solution of fragment hits against kinetoplastid N-myristoyltransferase

    PubMed Central

    Robinson, David A.; Wyatt, Paul G.

    2015-01-01

    Trypanosoma brucei N-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis. Pyrazole sulfonamide (DDD85646), a potent inhibitor of TbNMT, has been identified in previous studies; however, poor central nervous system exposure restricts its use to the haemolymphatic form (stage 1) of the disease. In order to identify new chemical matter, a fragment screen was carried out by ligand-observed NMR spectroscopy, identifying hits that occupy the DDD85646 binding site. Crystal structures of hits from this assay have been obtained in complex with the closely related NMT from Leishmania major, providing a structural starting point for the evolution of novel chemical matter. PMID:25945713

  6. Sleeping beauties in psychology: comparisons of "hits" and "missed signals" in psychological journals.

    PubMed

    Lange, Lydia L

    2005-05-01

    Scientific publications tend to be forgotten quickly. A few works, however, are still cited 100 years and more after their publication. The author used bibliometric methods to compare "hits" (works noticed by the scientific community soon after their publication) with "missed signals" (works that went unnoticed until much later) by investigating 2 psychological journals founded in the 1890s: Zeitschrift für Psychologie and Psychological Review. All articles that were published in either of these journals up to 1920 and cited more than 25 times in the Web of Science up to the year 2000 were considered for inclusion in the analysis. It emerged that hits corresponded more closely to the focus of scientific attention at the time of the publications than missed signals.

  7. Hit and lead criteria in drug discovery for infectious diseases of the developing world.

    PubMed

    Katsuno, Kei; Burrows, Jeremy N; Duncan, Ken; Hooft van Huijsduijnen, Rob; Kaneko, Takushi; Kita, Kiyoshi; Mowbray, Charles E; Schmatz, Dennis; Warner, Peter; Slingsby, B T

    2015-11-01

    Reducing the burden of infectious diseases that affect people in the developing world requires sustained collaborative drug discovery efforts. The quality of the chemical starting points for such projects is a key factor in improving the likelihood of clinical success, and so it is important to set clear go/no-go criteria for the progression of hit and lead compounds. With this in mind, the Japanese Global Health Innovative Technology (GHIT) Fund convened with experts from the Medicines for Malaria Venture, the Drugs for Neglected Diseases initiative and the TB Alliance, together with representatives from the Bill &Melinda Gates Foundation, to set disease-specific criteria for hits and leads for malaria, tuberculosis, visceral leishmaniasis and Chagas disease. Here, we present the agreed criteria and discuss the underlying rationale.

  8. Variation in number of hits for complex searches in Google Scholar

    PubMed Central

    Bramer, Wichor Matthijs

    2016-01-01

    Objective Google Scholar is often used to search for medical literature. Numbers of results reported by Google Scholar outperform the numbers reported by traditional databases. How reliable are these numbers? Why are often not all available 1,000 references shown? Methods For several complex search strategies used in systematic review projects, the number of citations and the total number of versions were calculated. Several search strategies were followed over a two-year period, registering fluctuations in reported search results. Results Changes in numbers of reported search results varied enormously between search strategies and dates. Theories for calculations of the reported and shown number of hits were not proved. Conclusions The number of hits reported in Google Scholar is an unreliable measure. Therefore, its repeatability is problematic, at least when equal results are needed. PMID:27076802

  9. B-HIT - A Tool for Harvesting and Indexing Biodiversity Data

    PubMed Central

    Barker, Katharine; Braak, Kyle; Cawsey, E. Margaret; Coddington, Jonathan; Robertson, Tim; Whitacre, Jamie

    2015-01-01

    With the rapidly growing number of data publishers, the process of harvesting and indexing information to offer advanced search and discovery becomes a critical bottleneck in globally distributed primary biodiversity data infrastructures. The Global Biodiversity Information Facility (GBIF) implemented a Harvesting and Indexing Toolkit (HIT), which largely automates data harvesting activities for hundreds of collection and observational data providers. The team of the Botanic Garden and Botanical Museum Berlin-Dahlem has extended this well-established system with a range of additional functions, including improved processing of multiple taxon identifications, the ability to represent associations between specimen and observation units, new data quality control and new reporting capabilities. The open source software B-HIT can be freely installed and used for setting up thematic networks serving the demands of particular user groups. PMID:26544980

  10. Clinical Computer Systems Survey (CLICS): learning about health information technology (HIT) in its context of use.

    PubMed

    Lichtner, Valentina; Cornford, Tony; Klecun, Ela

    2013-01-01

    Successful health information technology (HIT) implementations need to be informed on the context of use and on users' attitudes. To this end, we developed the CLinical Computer Systems Survey (CLICS) instrument. CLICS reflects a socio-technical view of HIT adoption, and is designed to encompass all members of the clinical team. We used the survey in a large English hospital as part of its internal evaluation of the implementation of an electronic patient record system (EPR). The survey revealed extent and type of use of the EPR; how it related to and integrated with other existing systems; and people's views on its use, usability and emergent safety issues. Significantly, participants really appreciated 'being asked'. They also reminded us of the wider range of administrative roles engaged with EPR. This observation reveals pertinent questions as to our understanding of the boundaries between administrative tasks and clinical medicine - what we propose as the field of 'administrative medicine'.

  11. What Is the Best Launch Angle To Hit a Home Run?

    NASA Astrophysics Data System (ADS)

    Kagan, David

    2010-04-01

    Your students will proudly raise their hands and answer, "45 degrees!" They are, however, answering a different question. It is true that in the absence of air resistance, for a given initial speed, the launch angle that maximizes the range is 45°. For a real homer, there are many complicating factors that make the question far more challenging to answer. Here is a partial list: 1. The initial speed off the bat is not fixed. Garvey's law, "The harder you hit it, the further it goes" is definitely at play; 2. Air resistance is a substantial influence on the flight of the ball. ; 3. The backspin on a well-hit ball creates lift due to the Magnus effect.2; 4. Atmospheric conditions such as humidity, temperature, air density, and the wind affect the motion as well.3; 5. Baseball parks are unique in size and shape. So, a home run in one park may not be a home run in another.

  12. Double hit diffuse large B-cell lymphomas: diagnostic and therapeutic challenges.

    PubMed

    Friedberg, Jonathan W

    2015-03-01

    Although diffuse large B-cell lymphoma (DLBCL) is curable with standard chemoimmunotherapy, over 30% of patients with advanced stage disease experience refractory disease or progression. Recent studies suggest that rearrangement of the myc oncogene occurs in approximately 10% of patients with DLBCL, and confers a very poor prognosis, particularly when there is concomitant rearrangement of bcl-2, a condition referred to as "double hit DLBCL". Using immunohistochemistry, up to 30% of patients have evidence of increased expression of myc, which occurs in both activated B-cell and germinal center type DLBCL. When bcl-2 is also positive by immunohistochemistry, prognosis is also poor. There are no randomized studies guiding treatment for patients with double hit DLBCL, but new datasets are emerging suggesting a possible role for dose-adjusted EPOCH infusional chemotherapy with rituximab. This review will conclude with a survey of novel agents which may be rationally incorporated into chemotherapy platforms for this high risk subset of DLBCL.

  13. Organizations disseminating health messages: the roles of organizational identification and HITs.

    PubMed

    Stephens, Keri K; Goins, Elizabeth S; Dailey, Stephanie L

    2014-01-01

    Research into the dissemination of health information now includes more focus on how various organizations (e.g., beauty shops, schools, workplaces, and churches) and health information technologies (HITs) reach and affect audiences. One relational feature of organizations is identification--the feeling of belongingness. Our study explores how it influences audiences, especially in combination with HITs such as e-mail, websites, and social media. We use social identity theory to predict how organizational identification and social media might function in health communication. Using a 3 × 2 experimental design, we find that people's identification with a message source mediates the effect of social media on outcomes. These findings improve our understanding of when organizations might be most helpful for disseminating health information.

  14. "Hits" emerge through self-organized coordination in collective response of free agents.

    PubMed

    Chakrabarti, Anindya S; Sinha, Sitabhra

    2016-10-01

    Individuals in free societies frequently exhibit striking coordination when making independent decisions en masse. Examples include the regular appearance of hit products or memes with substantially higher popularity compared to their otherwise equivalent competitors or extreme polarization in public opinion. Such segregation of events manifests as bimodality in the distribution of collective choices. Here we quantify how apparently independent choices made by individuals result in a significantly polarized but stable distribution of success in the context of the box-office performance of movies and show that it is an emergent feature of a system of noninteracting agents who respond to sequentially arriving signals. The aggregate response exhibits extreme variability amplifying much smaller differences in individual cost of adoption. Due to self-organization of the competitive landscape, most events elicit only a muted response but a few stimulate widespread adoption, emerging as "hits".

  15. How do output growth-rate distributions look like? Some cross-country, time-series evidence

    NASA Astrophysics Data System (ADS)

    Fagiolo, G.; Napoletano, M.; Roventini, A.

    2007-05-01

    This paper investigates the statistical properties of within-country gross domestic product (GDP) and industrial production (IP) growth-rate distributions. Many empirical contributions have recently pointed out that cross-section growth rates of firms, industries and countries all follow Laplace distributions. In this work, we test whether also within-country, time-series GDP and IP growth rates can be approximated by tent-shaped distributions. We fit output growth rates with the exponential-power (Subbotin) family of densities, which includes as particular cases both Gaussian and Laplace distributions. We find that, for a large number of OECD (Organization for Economic Cooperation and Development) countries including the US, both GDP and IP growth rates are Laplace distributed. Moreover, we show that fat-tailed distributions robustly emerge even after controlling for outliers, autocorrelation and heteroscedasticity.

  16. Validation of concussion risk curves for collegiate football players derived from HITS data.

    PubMed

    Funk, James R; Rowson, Steven; Daniel, Ray W; Duma, Stefan M

    2012-01-01

    For several years, Virginia Tech and other schools have measured the frequency and severity of head impacts sustained by collegiate American football players in real time using the Head Impact Telemetry (HIT) System of helmet-mounted accelerometers. In this study, data from 37,128 head impacts collected at Virginia Tech during games from 2006 to 2010 were analyzed. Peak head acceleration exceeded 100 g in 516 impacts, and the Head Injury Criterion (HIC) exceeded 200 in 468 impacts. Four instrumented players in the dataset sustained a concussion. These data were used to develop risk curves for concussion as a function of peak head acceleration and HIC. The validity of this biomechanical approach was assessed using epidemiological data on concussion incidence from other sources. Two specific aspects of concussion incidence were addressed: the variation by player position, and the frequency of repeat concussions. The HIT System data indicated that linemen sustained the highest overall number of head impacts, while skill positions sustained a higher number of more severe head impacts (peak acceleration > 100 g or HIC > 200). When weighted using injury risk curves, the HIT System data predicted a higher incidence of concussion in skill positions compared to linemen at rates that were in strong agreement with the epidemiological literature (Pearson's r = 0.72-0.87). The predicted rates of repeat concussions (21-39% over one season and 33-50% over five seasons) were somewhat higher than the ranges reported in the epidemiological literature. These analyses demonstrate that simple biomechanical parameters that can be measured by the HIT System possess a high level of power for predicting concussion.

  17. Preventive effects of minocycline in a neurodevelopmental two-hit model with relevance to schizophrenia.

    PubMed

    Giovanoli, S; Engler, H; Engler, A; Richetto, J; Feldon, J; Riva, M A; Schedlowski, M; Meyer, U

    2016-04-05

    Maternal immune activation can increase the vulnerability of the offspring to develop neuroimmune and behavioral abnormalities in response to stress in puberty. In offspring of immune-challenged mothers, stress-induced inflammatory processes precede the adult onset of multiple behavioral dysfunctions. Here, we explored whether an early anti-inflammatory intervention during peripubertal stress exposure might prevent the subsequent emergence of adult behavioral pathology. We used an environmental two-hit model in mice, in which prenatal maternal administration of the viral mimetic poly(I:C) served as the first hit, and exposure to sub-chronic unpredictable stress during peripubertal maturation as the second hit. Using this model, we examined the effectiveness of the tetracycline antibiotic minocycline (MINO) given during stress exposure to block stress-induced inflammatory responses and to prevent subsequent behavioral abnormalities. We found that combined exposure to prenatal immune activation and peripubertal stress caused significant deficits in prepulse inhibition and increased sensitivity to the psychotomimetic drugs amphetamine and dizocilpine in adulthood. MINO treatment during stress exposure prevented the emergence of these behavioral dysfunctions. In addition, the pharmacological intervention blocked hippocampal and prefrontal microglia activation and interleukin-1β expression in offspring exposed to prenatal infection and peripubertal stress. Together, these findings demonstrate that presymptomatic MINO treatment can prevent the subsequent emergence of multiple behavioral abnormalities relevant to human neuropsychiatric disorders with onset in early adulthood, including schizophrenia. Our epidemiologically informed two-hit model may thus encourage attempts to explore the use of anti-inflammatory agents in the early course of brain disorders that are characterized by signs of central nervous system inflammation during development.

  18. Multiple NSAID-Induced Hits Injure the Small Intestine: Underlying Mechanisms and Novel Strategies

    PubMed Central

    Boelsterli, Urs A.

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious gastrointestinal (GI) injury including jejunal/ileal mucosal ulceration, bleeding, and even perforation in susceptible patients. The underlying mechanisms are largely unknown, but they are distinct from those related to gastric injury. Based on recent insights from experimental models, including genetics and pharmacology in rodents typically exposed to diclofenac, indomethacin, or naproxen, we propose a multiple-hit pathogenesis of NSAID enteropathy. The multiple hits start with an initial pharmacokinetic determinant caused by vectorial hepatobiliary excretion and delivery of glucuronidated NSAID or oxidative metabolite conjugates to the distal small intestinal lumen, where bacterial β-glucuronidase produces critical aglycones. The released aglycones are then taken up by enterocytes and further metabolized by intestinal cytochrome P450s to potentially reactive intermediates. The “first hit” is caused by the NSAID and/or oxidative metabolites that induce severe endoplasmic reticulum stress or mitochondrial stress and lead to cell death. The “second hit” is created by the significant subsequent inflammatory response that would follow such a first-hit injury. Based on these putative mechanisms, strategies have been developed to protect the enterocytes from being exposed to the parent NSAID and/or oxidative metabolites. Among these, a novel strategy already demonstrated in a murine model is the selective disruption of bacteria-specific β-glucuronidases with a novel small molecule inhibitor that does not harm the bacteria and that alleviates NSAID-induced enteropathy. Such mechanism-based strategies require further investigation but provide potential avenues for the alleviation of the GI toxicity caused by multiple NSAID hits. PMID:23091168

  19. Hitting the nursing faculty shortage head on: strategies to recruit, retain, and develop nursing faculty.

    PubMed

    Feldman, Harriet R; Greenberg, Martha J; Jaffe-Ruiz, Marilyn; Kaufman, Sophie Revillard; Cignarale, Stacie

    2015-01-01

    More than ever before, schools of nursing are challenged with finding qualified faculty to teach growing numbers of undergraduate and graduate students. Qualified applicants by the thousands are being turned away, in large part because of an insufficient pipeline of faculty. This article describes how one school hit the shortage head on by creating alternate models for employing and growing new faculty, and then instituting a variety of strategies to develop and keep them.

  20. Analysis of impact noise induced by hitting of titanium head golf driver.

    PubMed

    Kim, Young Ho; Kim, Young Chul; Lee, Jun Hee; An, Yong-Hwi; Park, Kyung Tae; Kang, Kyung Min; Kang, Yeon June

    2014-11-01

    The hitting of titanium head golf driver against golf ball creates a short duration, high frequency impact noise. We analyzed the spectra of these impact noises and evaluated the auditory hazards from exposure to the noises. Noises made by 10 titanium head golf drivers with five maximum hits were collected, and the spectra of the pure impact sounds were studied using a noise analysis program. The noise was measured at 1.7 m (position A) and 3.4 m (position B) from the hitting point in front of the hitter and at 3.4 m (position C) behind the hitting point. Average time duration was measured and auditory risk units (ARUs) at position A were calculated using the Auditory Hazard Assessment Algorithm for Humans. The average peak levels at position A were 119.9 dBA at the sound pressure level (SPL) peak and 100.0 dBA at the overall octave level. The average peak levels (SPL and overall octave level) at position B were 111.6 and 96.5 dBA, respectively, and at position C were 111.5 and 96.7 dBA, respectively. The average time duration and ARUs measured at position A were 120.6 ms and 194.9 units, respectively. Although impact noises made by titanium head golf drivers showed relatively low ARUs, individuals enjoying golf frequently may be susceptible to hearing loss due to the repeated exposure of this intense impact noise with short duration and high frequency. Unprotected exposure to impact noises should be limited to prevent cochleovestibular disorders.

  1. Preventive effects of minocycline in a neurodevelopmental two-hit model with relevance to schizophrenia

    PubMed Central

    Giovanoli, S; Engler, H; Engler, A; Richetto, J; Feldon, J; Riva, M A; Schedlowski, M; Meyer, U

    2016-01-01

    Maternal immune activation can increase the vulnerability of the offspring to develop neuroimmune and behavioral abnormalities in response to stress in puberty. In offspring of immune-challenged mothers, stress-induced inflammatory processes precede the adult onset of multiple behavioral dysfunctions. Here, we explored whether an early anti-inflammatory intervention during peripubertal stress exposure might prevent the subsequent emergence of adult behavioral pathology. We used an environmental two-hit model in mice, in which prenatal maternal administration of the viral mimetic poly(I:C) served as the first hit, and exposure to sub-chronic unpredictable stress during peripubertal maturation as the second hit. Using this model, we examined the effectiveness of the tetracycline antibiotic minocycline (MINO) given during stress exposure to block stress-induced inflammatory responses and to prevent subsequent behavioral abnormalities. We found that combined exposure to prenatal immune activation and peripubertal stress caused significant deficits in prepulse inhibition and increased sensitivity to the psychotomimetic drugs amphetamine and dizocilpine in adulthood. MINO treatment during stress exposure prevented the emergence of these behavioral dysfunctions. In addition, the pharmacological intervention blocked hippocampal and prefrontal microglia activation and interleukin-1β expression in offspring exposed to prenatal infection and peripubertal stress. Together, these findings demonstrate that presymptomatic MINO treatment can prevent the subsequent emergence of multiple behavioral abnormalities relevant to human neuropsychiatric disorders with onset in early adulthood, including schizophrenia. Our epidemiologically informed two-hit model may thus encourage attempts to explore the use of anti-inflammatory agents in the early course of brain disorders that are characterized by signs of central nervous system inflammation during development. PMID:27045842

  2. High-Growth Firms and the Future of the American Economy. Kauffman Foundation Research Series: Firm Formation and Economic Growth

    ERIC Educational Resources Information Center

    Stangler, Dane

    2010-01-01

    Into early 2010, more than two years after the recession began, the American economy continues to send out mixed signals with respect to economic recovery: GDP (gross domestic product) growth looks set to recover, while unemployment is projected to remain high for many more years. The most important economic matter facing the country is job…

  3. The impact of the heparin-induced thrombocytopenia (HIT) computerized alert on provider behaviors and patient outcomes

    PubMed Central

    Adelman, Jason S; Reissman, Stan H; Cohen, Hillel W; Billett, Henny H

    2011-01-01

    Objective The aim of this study was to measure the effect of an electronic heparin-induced thrombocytopenia (HIT) alert on provider ordering behaviors and on patient outcomes. Materials and Methods A pop-up alert was created for providers when an individual's platelet values had decreased by 50% or to <100 000/mm3 in the setting of recent heparin exposure. The authors retrospectively compared inpatients admitted between January 24, 2008 and August 24, 2008 to a control group admitted 1 year prior to the HIT alert. The primary outcome was a change in HIT antibody testing. Secondary outcomes included an assessment of incidence of HIT antibody positivity, percentage of patients started on a direct thrombin inhibitor (DTI), length of stay and overall mortality. Results There were 1006 and 1081 patients in the control and intervention groups, respectively. There was a 33% relative increase in HIT antibody test orders (p=0.01), and 33% more of these tests were ordered the first day after the criteria were met when a pop-up alert was given (p=0.03). Heparin was discontinued in 25% more patients in the alerted group (p=0.01), and more direct thrombin inhibitors were ordered for them (p=0.03). The number who tested HIT antibody-positive did not differ, however, between the two groups (p=0.99). The length of stay and mortality were similar in both groups. Conclusions The HIT alert significantly impacted provider behaviors. However, the alert did not result in more cases of HIT being detected or an improvement in overall mortality. Our findings do not support implementation of a computerized HIT alert. PMID:21712374

  4. Protein-Protein Interaction Inhibition (2P2I)-Oriented Chemical Library Accelerates Hit Discovery.

    PubMed

    Milhas, Sabine; Raux, Brigitt; Betzi, Stéphane; Derviaux, Carine; Roche, Philippe; Restouin, Audrey; Basse, Marie-Jeanne; Rebuffet, Etienne; Lugari, Adrien; Badol, Marion; Kashyap, Rudra; Lissitzky, Jean-Claude; Eydoux, Cécilia; Hamon, Véronique; Gourdel, Marie-Edith; Combes, Sébastien; Zimmermann, Pascale; Aurrand-Lions, Michel; Roux, Thomas; Rogers, Catherine; Müller, Susanne; Knapp, Stefan; Trinquet, Eric; Collette, Yves; Guillemot, Jean-Claude; Morelli, Xavier

    2016-08-19

    Protein-protein interactions (PPIs) represent an enormous source of opportunity for therapeutic intervention. We and others have recently pinpointed key rules that will help in identifying the next generation of innovative drugs to tackle this challenging class of targets within the next decade. We used these rules to design an oriented chemical library corresponding to a set of diverse "PPI-like" modulators with cores identified as privileged structures in therapeutics. In this work, we purchased the resulting 1664 structurally diverse compounds and evaluated them on a series of representative protein-protein interfaces with distinct "druggability" potential using homogeneous time-resolved fluorescence (HTRF) technology. For certain PPI classes, analysis of the hit rates revealed up to 100 enrichment factors compared with nonoriented chemical libraries. This observation correlates with the predicted "druggability" of the targets. A specific focus on selectivity profiles, the three-dimensional (3D) molecular modes of action resolved by X-ray crystallography, and the biological activities of identified hits targeting the well-defined "druggable" bromodomains of the bromo and extraterminal (BET) family are presented as a proof-of-concept. Overall, our present study illustrates the potency of machine learning-based oriented chemical libraries to accelerate the identification of hits targeting PPIs. A generalization of this method to a larger set of compounds will accelerate the discovery of original and potent probes for this challenging class of targets.

  5. Guidance for horizontal image translation (HIT) of high definition stereoscopic video production

    NASA Astrophysics Data System (ADS)

    Broberg, David K.

    2011-03-01

    Horizontal image translation (HIT) is an electronic process for shifting the left-eye and right-eye images horizontally as a way to alter the stereoscopic characteristics and alignment of 3D content after signals have been captured by stereoscopic cameras. When used cautiously and with full awareness of the impact on other interrelated aspects of the stereography, HIT is a valuable tool in the post production process as a means to modify stereoscopic content for more comfortable viewing. Most commonly it is used to alter the zero parallax setting (ZPS), to compensate for stereo window violations or to compensate for excessive positive or negative parallax in the source material. As more and more cinematic 3D content migrates to television distribution channels the use of this tool will likely expand. Without proper attention to certain guidelines the use of HIT can actually harm the 3D viewing experience. This paper provides guidance on the most effective use and describes some of the interrelationships and trade-offs. The paper recommends the adoption of the cinematic 2K video format as a 3D source master format for high definition television distribution of stereoscopic 3D video programming.

  6. Engineering and Design of the Steady Inductive Helicity Injected Torus (HIT--SI)

    NASA Astrophysics Data System (ADS)

    Sieck, P. E.; Jarboe, T. R.; Nelson, B. A.; Rogers, J. A.; Shumlak, U.

    1999-11-01

    HIT/SIHI/>Steady Inductive Helicity Injection (SIHI) is an inductive helicity injection method that injects helicity at a nearly constant rate, without open field lines, and without removing any helicity or magnetic energy from the plasma.(T.R. Jarboe, Fusion Technology, 36) (1), p. 85, 1999 SIHI directly produces a rotating magnetic field structure, and in the frame of the rotating field the current profile is nearly time independent. The Steady Inductive Helicity Injected Torus (HIT--SI) is a spheromak designed to implement SIHI so that the current profile in the rotating frame is optimized. The geometry of HIT--SI will be presented, including the manufacturing techniques and metallurgical processes planned for construction of the close-fitting flux conserver. The flux conserver is made of aged chromium copper with 80% the conductivity of pure copper. The detailed electrical insulation requirements in the helicity injector design lead to a complex o-ring seal and a plasma-sprayed alumina insulation coating. This has prompted the construction of an o-ring prototype test fixture having the main features of the o-ring design and the alumina coating. The design and evaluation of this fixture will also be presented with vacuum and voltage test results.

  7. Cosmic Ray Hits in the Central Nervous System at Solar Maximum

    NASA Technical Reports Server (NTRS)

    Curtis, S. B.; Vazquez, M. E.; Wilson, J. W.; Atwell, W.; Kin, M.-H. Y.

    2000-01-01

    It has been suggested that a manned mission to Mars be launched at solar maximum rather than at solar minimum to minimize the radiation exposure to galactic cosmic rays. It is true that the number of hits from highly ionizing particles to critical regions in the brain will be less at solar maximum, and it is of interest to estimate how much less. We present here calculations for several sites within the brain from iron ions (z = 26) and from particles with charge, z, greater than or equal to 15. The same shielding configurations and sites in the brain used in an earlier paper for solar minimum are employed so that direct comparison of results between the two solar activity conditions can be made. A simple pressure-vessel wall and an equipment room onboard a spacecraft are chosen as shielding examples. In the equipment room, typical results for the thalamus are that the probability of any particles with z greater than or equal to 15 and from 2.3 percent to 1.3 percent for iron ions. The extra shielding provided in the equipment room makes little difference in these numbers. We conclude that this decrease in hit frequency (less than a factor of two) does not provide a compelling reason to avoid solar minimum for a manned mission to Mars. This conclusion could be revised, however, if a very small number of hits is found to cause critical malfunction within the brain.

  8. Cosmic Ray Hits in the Central Nervous System at Solar Maximum

    NASA Technical Reports Server (NTRS)

    Curtis, S. B.; Vazquez, M. E.; Wilson, J. W.; Kim, M.-H. Y.

    1997-01-01

    It has been suggested that a manned mission to Mars be launched at solar maximum rather than at solar minimum to minimize the radiation exposure to galactic cosmic rays. It is true that the number of hits from highly ionizing particles to critical regions in the brain will be less at solar maximum, and it is of some interest to estimate how much less. We present here calculations for several sites within the brain from iron ions (z = 26) and from particles with charge, z, greater than or equal to 15. The same shielding configurations and sites in the brain used in an earlier paper for solar minimum are employed so that direct comparison of results between the two solar activity conditions can be made. A simple pressure-vessel wall and an equipment room onboard a spacecraft are chosen as shielding examples. In the equipment room, typical results for the thalamus (100 mm2 area) are that the probability of any given cell nucleus being hit decreases from 10 percent at solar minimum to 6 percent at solar maximum for particles with z greater than or equal to 15 and from 2.3 percent to 1.3 percent for iron ions. We conclude that this modest decrease in hit frequency (less than a factor of two) is not a compelling reason to avoid solar minimum for a manned mission to Mars.

  9. One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists.

    PubMed

    Schiebel, Johannes; Radeva, Nedyalka; Köster, Helene; Metz, Alexander; Krotzky, Timo; Kuhnert, Maren; Diederich, Wibke E; Heine, Andreas; Neumann, Lars; Atmanene, Cedric; Roecklin, Dominique; Vivat-Hannah, Valérie; Renaud, Jean-Paul; Meinecke, Robert; Schlinck, Nina; Sitte, Astrid; Popp, Franziska; Zeeb, Markus; Klebe, Gerhard

    2015-09-01

    Fragment-based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit-to-lead-to-drug optimization, the screening process should distinguish reliably between binders and non-binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease-relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361-entry library by using a reporter-displacement assay, saturation-transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions.

  10. Overview of HIT-SI3 experiment: Simulations, Diagnostics, and Summary of Current Results

    NASA Astrophysics Data System (ADS)

    Penna, James; Jarboe, Thomas; Nelson, Brian; Hossack, Aaron; Sutherland, Derek; Morgan, Kyle; Hansen, Chris; Benedett, Thomas; Everson, Chris; Victor, Brian

    2016-10-01

    The Helicity Injected Torus - Steady Inductive 3(HIT-SI3)experiment forms and maintains spheromaks via Steady Inductive Helicity Injection (SIHI). Three injector units allow for continuous injection of helicity into a copper flux conserver in order to sustain a spheromak. Firing of the injectors with a phase difference allows finite rotation of the plasma to provide a stabilizing effect. Simulations in the MHD code NIMROD and the fluid-model code PSI-TET provide validation and a basis for interpretation of the observed experimental data. Thompson Scattering (TS) and Far Infrared (FIR) Interferometer systems allow temperature and line-averaged density measurements to be taken. An Ion Doppler Spectroscopy (IDS) system allows measurement of the plasma rotation and velocity. HIT-SI3 data has been used for validation of IDCD predictions, in particular the projected impedance of helicity injectors according to the theory. The experimental impedances have been calculated here for the first time for different HIT-SI3 regimes. Such experimental evidence will contribute to the design of future experiments employing IDCD as a current-drive mechanism. Work supported by the D.O.E., Office of Science, Office of Fusion Science.

  11. A business case for HIT adoption: effects of "meaningful use" EHR financial incentives on clinic revenue.

    PubMed

    Behkami, Nima A; Dorr, David A; Morrice, Stuart

    2010-01-01

    The goal of this study is to describe a framework that allows decision makers to efficiently evaluate factors that affect Electronic Health Record (EHR) adoption and test suitable interventions; specifically financial incentives. The United States healthcare delivery system is experiencing a transformation to improve population health. There is strong agreement that "meaningful use" of Health Information Technology (HIT) is a major enabler in this effort. However it's also understood that the high cost of implementing an EHR is an obstacle for adoption. To help understand these complexities we developed a simulation model designed to capture the dynamic nature of policy interventions that affect the adoption of EHR. We found that "Effective" use of HIT approaches break-even-point and larger clinic revenue many times faster that "average" or "poor" use of HIT. This study uses a systems perspective to the evaluate EHR adoption process through the "meaningful use" redesign as proposed in the American Reinvestment and Recovery Act 2009 in the United States healthcare industry by utilizing the System Dynamics methodology and Scenario Analysis.

  12. Prediction of Potential Hit Song and Musical Genre Using Artificial Neural Networks

    NASA Astrophysics Data System (ADS)

    Monterola, Christopher; Abundo, Cheryl; Tugaff, Jeric; Venturina, Lorcel Ericka

    Accurately quantifying the goodness of music based on the seemingly subjective taste of the public is a multi-million industry. Recording companies can make sound decisions on which songs or artists to prioritize if accurate forecasting is achieved. We extract 56 single-valued musical features (e.g. pitch and tempo) from 380 Original Pilipino Music (OPM) songs (190 are hit songs) released from 2004 to 2006. Based on an effect size criterion which measures a variable's discriminating power, the 20 highest ranked features are fed to a classifier tasked to predict hit songs. We show that regardless of musical genre, a trained feed-forward neural network (NN) can predict potential hit songs with an average accuracy of ΦNN = 81%. The accuracy is about +20% higher than those of standard classifiers such as linear discriminant analysis (LDA, ΦLDA = 61%) and classification and regression trees (CART, ΦCART = 57%). Both LDA and CART are above the proportional chance criterion (PCC, ΦPCC = 50%) but are slightly below the suggested acceptable classifier requirement of 1.25*ΦPCC = 63%. Utilizing a similar procedure, we demonstrate that different genres (ballad, alternative rock or rock) of OPM songs can be automatically classified with near perfect accuracy using LDA or NN but only around 77% using CART.

  13. The danger signal plus DNA damage two-hit hypothesis for chronic inflammation in COPD.

    PubMed

    Aoshiba, Kazutetsu; Tsuji, Takao; Yamaguchi, Kazuhiro; Itoh, Masayuki; Nakamura, Hiroyuki

    2013-12-01

    Inflammation in chronic obstructive pulmonary disease (COPD) is thought to originate from the activation of innate immunity by a danger signal (first hit), although this mechanism does not readily explain why the inflammation becomes chronic. Here, we propose a two-hit hypothesis explaining why inflammation becomes chronic in patients with COPD. A more severe degree of inflammation exists in the lungs of patients who develop COPD than in the lungs of healthy smokers, and the large amounts of reactive oxygen species and reactive nitrogen species released from inflammatory cells are likely to induce DNA double-strand breaks (second hit) in the airways and pulmonary alveolar cells, causing apoptosis and cell senescence. The DNA damage response and senescence-associated secretory phenotype (SASP) are also likely to be activated, resulting in the production of pro-inflammatory cytokines. These pro-inflammatory cytokines further stimulate inflammatory cell infiltration, intensifying cell senescence and SASP through a positive-feedback mechanism. This vicious cycle, characterised by mutually reinforcing inflammation and DNA damage, may cause the inflammation in COPD patients to become chronic. Our hypothesis helps explain why COPD tends to occur in the elderly, why the inflammation worsens progressively, why inflammation continues even after smoking cessation, and why COPD is associated with lung cancer.

  14. A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis

    PubMed Central

    Davis, Justin; Eyre, Harris; Jacka, Felice N; Dodd, Seetal; Dean, Olivia; McEwen, Sarah; Debnath, Monojit; McGrath, John; Maes, Michael; Amminger, Paul; McGorry, Patrick D; Pantelis, Christos; Berk, Michael

    2016-01-01

    Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype—the first as an early priming in a genetically predisposed individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders. PMID:27073049

  15. Does Development Make You Happy? Subjective Well-Being and Economic Growth in Developing Countries

    ERIC Educational Resources Information Center

    Kenny, Charles

    2005-01-01

    The evidence for any relationship between GDP/capita growth and growth in subjective wellbeing (SWB) in wealthier countries is disputed, at best. However, there are a number of reasons commonly articulated for thinking the relationship should be stronger in less developed countries (LDCs). This paper looks at both reasons for expecting the…

  16. Rethinking of Economic Growth and Life Satisfaction in Post-WWII Japan--A Fresh Approach

    ERIC Educational Resources Information Center

    Kusago, Takayoshi

    2007-01-01

    Gross Domestic Product (GDP) has been utilized by academics and policy makers to indicate the economic well-being of the people. However, economic growth measures cannot capture fully the overall well-being of the people. This paper has tested quality of economic growth in Japan after World War II as to whether it has brought about positive…

  17. Structure of an ADP-ribosylation factor, ARF1, from Entamoeba histolytica bound to Mg(2+)-GDP.

    PubMed

    Serbzhinskiy, Dmitry A; Clifton, Matthew C; Sankaran, Banumathi; Staker, Bart L; Edwards, Thomas E; Myler, Peter J

    2015-05-01

    Entamoeba histolytica is the etiological agent of amebiasis, a diarrheal disease which causes amoebic liver abscesses and amoebic colitis. Approximately 50 million people are infected worldwide with E. histolytica. With only 10% of infected people developing symptomatic amebiasis, there are still an estimated 100,000 deaths each year. Because of the emergence of resistant strains of the parasite, it is necessary to find a treatment which would be a proper response to this challenge. ADP-ribosylation factor (ARF) is a member of the ARF family of GTP-binding proteins. These proteins are ubiquitous in eukaryotic cells; they generally associate with cell membranes and regulate vesicular traffic and intracellular signalling. The crystal structure of ARF1 from E. histolytica has been determined bound to magnesium and GDP at 1.8 Å resolution. Comparison with other structures of eukaryotic ARF proteins shows a highly conserved structure and supports the interswitch toggle mechanism of communicating the conformational state to partner proteins.

  18. Econometric analysis of the impact of the relationship of GDP and the pension capital

    NASA Astrophysics Data System (ADS)

    Nepp, A. N.; Amiryan, A. A.

    2016-12-01

    The article demonstrates the impact of institutional risks on indicators of compulsory pension insurance and describes the results of a comparative analysis of investment risks faced by the pension systems of the Russian Federation and OECD countries. Efficiency of private companies managing pension funds in Russia and OECD countries is compared and analyzed to show the necessity to liberalize requirements placed on investments of pension savings funds. On the basis of the available statistical data, the article puts forward and discusses the hypothesis that increasing of the basic indicators of the pension system is possible by reducing its institutional risks. It is concluded that if the institutional risks are reduced and the level of trust increases, there will be enhance growth in the pension system key indicators, such as pension payments and the replacement rate.

  19. The Structure of the MUR1 GDP-mannose 4,67-deydratase from A. thaliana: Implications for Ligand Binding Specificity

    SciTech Connect

    Mulichak, A.M.; Bonin, C.P.; Reiter, W.-D.; Garavito, R.M.

    2010-03-08

    GDP-D-mannose 4,6-dehydratase catalyzes the first step in the de novo synthesis of GDP-L-fucose, the activated form of L-fucose, which is a component of glycoconjugates in plants known to be important to the development and strength of stem tissues. We have determined the three-dimensional structure of the MUR1 dehydratase isoform from Arabidopsis thaliana complexed with its NADPH cofactor as well as with the ligands GDP and GDP-D-rhamnose. MUR1 is a member of the nucleoside-diphosphosugar modifying subclass of the short-chain dehydrogenase/reductase enzyme family, having homologous structures and a conserved catalytic triad of Lys, Tyr, and Ser/Thr residues. MUR1 is the first member of this subfamily to be observed as a tetramer, the interface of which reveals a close and intimate overlap of neighboring NADP{sup +}-binding sites. The GDP moiety of the substrate also binds in an unusual syn conformation. The protein-ligand interactions around the hexose moiety of the substrate support the importance of the conserved triad residues and an additional Glu side chain serving as a general base for catalysis. Phe and Arg side chains close to the hexose ring may serve to confer substrate specificity at the O2 position. In the MUR1/GDP-D-rhamnose complex, a single unique monomer within the protein tetramer that has an unoccupied substrate site highlights the conformational changes that accompany substrate binding and may suggest the existence of negative cooperativity in MUR1 function.

  20. The International Baccalaureate and "Growth Scepticism": A "Social Limits" Framework

    ERIC Educational Resources Information Center

    Bunnell, Tristan

    2011-01-01

    The number of schools offering the programmes of the International Baccalaureate (IB) hit 3000 in July 2010. Since 2004 the IB has aimed for further growth within a "wider access" and "greater impact" paradigm. A "further" 7000 schools are expected to be involved by 2020. However, there is now considerable concern about growth, especially within…

  1. Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin-induced thrombocytopenia-reactive antibodies or with true HIT (HIT-reactive antibodies plus thrombocytopenia): An 11-year experience.

    PubMed

    Palatianos, George; Michalis, Alkiviadis; Alivizatos, Petros; Lacoumenda, Stavroula; Geroulanos, Stefanos; Karabinis, Andreas; Iliopoulou, Eugenia; Soufla, Giannoula; Kanthou, Chryso; Khoury, Mazen; Sfyrakis, Petros; Stavridis, George; Astras, George; Vassili, Maria; Antzaka, Christina; Marathias, Katerina; Kriaras, Ioannis; Tasouli, Androniki; Papadopoulos, Kyrillos; Katafygioti, Marina; Matoula, Nikoletta; Angelidis, Antonios; Melissari, Euthemia

    2015-07-01

    Thrombocytopenia and thromboembolism(s) may develop in heparin immune-mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11-year period underwent preoperative HIT assessment by ELISA and a three-point heparin-induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT-reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT-positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT-negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients' own plasma and donor platelets. In parallel, the iloprost "target dose" was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the "target dose" identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified "target dose." This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life-threatening iloprost-induced hypotension in patients diagnosed with HIT-reactive antibodies or true HIT.

  2. Estimate of the trigger inefficiency due to extra hits in H1 and H2, using clean Chi(2) events

    SciTech Connect

    Mussa, R.; /INFN, Turin /Turin U.

    1992-07-01

    An accurate study of the inefficiency of the trigger selection criterium based on the multiplicity of hits in the two hodoscopes has been done using {chi}{sub 2} events take during the 1991 run, selected requiring that both electron tracks were associated to a Cherenkov hit (so that no multiplicity requirement at trigger level was asked), and a {chi}{sup 2} probability for the kinematic fit bigger than 0.01. In a table it is shown the number of events found for different multiplicities in the two hodoscopes. They have 554/1819 = 30.5 {+-} 1.3% of the events with extra-hits in the two hodoscopes, and they can think of 3 possible sources for this effect: (1) accidental {delta} rays due to the interactions of the beam halo inside or against the walls of the beam pipe give an extra activity on H1 that should be uncorrelated to the hits due to real tracks; (2) {delta} rays at large angles emitted by the electrons interacting with the inner layers of the detector, so that they expect extra-hits close to the real tracks; and (3) the conversion of the {delta} inside the beam pipe and in the inner detectors can give an extra-hit in H2 or H1 and H2: this also doubles the number of sources of {delta} rays, so that a big number of these events have 4 H2 firing.

  3. Heparin-induced thrombocytopenia (HIT II) in liver transplant recipients: a retrospective multivariate analysis of prognostic factors.

    PubMed

    Hüser, Norbert; Aßfalg, Volker; Reim, Daniel; Novotny, Alexander; Thorban, Stefan; Cheng, Zhangjun; Kornberg, Arno; Friess, Helmut; Büchler, Peter; Matevossian, Edouard

    2012-07-01

    We investigated the prevalence of HIT II in liver transplant recipients and analysed associated factors. In recipients with clinically suspected HIT II in the 4Ts pretest clinical scoring system HIPA-assay was performed. Next, 37 clinical variables were analysed retrospectively for their association with HIT II. Factors significantly correlated to our findings in univariate analysis were included in a multivariate model and binary logistic regression analysis. Among 46 recipients 21 patients were suspicious in the 4Ts pretest and 14 of them (30.4%) were diagnosed HIT-antibody positive. Patient's age (P = 0.001), postoperative dialysis (P = 0.028), and postoperative hospital stay (P = 0.035) were significantly associated with development of HIT-antibodies in univariate analysis. Postoperative dialysis and postoperative hospital stay turned out as epiphenomena of patient's age, the only independent predictor (P = 0.021). Using multiple χ(2) -testing, a cut-off could be calculated, assigning patients younger than 59 years to a low risk group and patients of 59 years and older to a high risk group. High incidence of peri-operative HIT II seroconversion in liver transplant recipients is not associated with factors known to induce thrombocyte activation, like blood products or cell-saver. Only patients' age was identified as independent predictor.

  4. Growth Versus Government Management Improvement During Economic Downturn

    NASA Astrophysics Data System (ADS)

    Podobnik, Boris; Baaquie, Belal E.; Bishop, Steven; Njavro, Djuro; Li, Baowen

    2013-04-01

    In estimating how economic growth depends on various inputs, economists commonly use long periods of data encompassing both main extremes to fluctuations in the economy: recession and expansion. Here we focus on recession years because during expansion even countries with bad economic policies may experience large growth. Specifically, we study how growth depends on the proportion of public-sector workforce, p and competitiveness, quantified by the Global Competitiveness Index, GCI. For the 2008-2011 economic downturn and for 57 countries, we find that the growth rate of GDP per capita, g, decreases with p, and increases with ΔGCI. Further, more competitive countries attract more foreign direct investments per capita, I, than less competitive countries, where I ~ GCIα. We propose a production function, divided into the private and public sectors, where GDP depends on market capitalization, the public (private)-sector workforce, and competitiveness level, used to quantify the public sector efficiency.

  5. Growth versus government management improvement during economic downturn.

    PubMed

    Podobnik, Boris; Baaquie, Belal E; Bishop, Steven; Njavro, Djuro; Li, Baowen

    2013-01-01

    In estimating how economic growth depends on various inputs, economists commonly use long periods of data encompassing both main extremes to fluctuations in the economy: recession and expansion. Here we focus on recession years because during expansion even countries with bad economic policies may experience large growth. Specifically, we study how growth depends on the proportion of public-sector workforce, p and competitiveness, quantified by the Global Competitiveness Index, GCI. For the 2008-2011 economic downturn and for 57 countries, we find that the growth rate of GDP per capita, g, decreases with p, and increases with ΔGCI. Further, more competitive countries attract more foreign direct investments per capita, I, than less competitive countries, where I is proportional to GCI(α). We propose a production function, divided into the private and public sectors, where GDP depends on market capitalization, the public (private)-sector workforce, and competitiveness level, used to quantify the public sector efficiency.

  6. Growth Versus Government Management Improvement During Economic Downturn

    PubMed Central

    Podobnik, Boris; Baaquie, Belal E.; Bishop, Steven; Njavro, Djuro; Li, Baowen

    2013-01-01

    In estimating how economic growth depends on various inputs, economists commonly use long periods of data encompassing both main extremes to fluctuations in the economy: recession and expansion. Here we focus on recession years because during expansion even countries with bad economic policies may experience large growth. Specifically, we study how growth depends on the proportion of public-sector workforce, p and competitiveness, quantified by the Global Competitiveness Index, GCI. For the 2008–2011 economic downturn and for 57 countries, we find that the growth rate of GDP per capita, g, decreases with p, and increases with ΔGCI. Further, more competitive countries attract more foreign direct investments per capita, I, than less competitive countries, where I ∝ GCIα. We propose a production function, divided into the private and public sectors, where GDP depends on market capitalization, the public (private)-sector workforce, and competitiveness level, used to quantify the public sector efficiency. PMID:23563321

  7. Contribution of Visual Information about Ball Trajectory to Baseball Hitting Accuracy

    PubMed Central

    Higuchi, Takatoshi; Nagami, Tomoyuki; Nakata, Hiroki; Watanabe, Masakazu; Isaka, Tadao; Kanosue, Kazuyuki

    2016-01-01

    The contribution of visual information about a pitched ball to the accuracy of baseball-bat contact may vary depending on the part of trajectory seen. The purpose of the present study was to examine the relationship between hitting accuracy and the segment of the trajectory of the flying ball that can be seen by the batter. Ten college baseball field players participated in the study. The systematic error and standardized variability of ball-bat contact on the bat coordinate system and pitcher-to-catcher direction when hitting a ball launched from a pitching machine were measured with or without visual occlusion and analyzed using analysis of variance. The visual occlusion timing included occlusion from 150 milliseconds (ms) after the ball release (R+150), occlusion from 150 ms before the expected arrival of the launched ball at the home plate (A-150), and a condition with no occlusion (NO). Twelve trials in each condition were performed using two ball speeds (31.9 m·s-1 and 40.3 m·s-1). Visual occlusion did not affect the mean location of ball-bat contact in the bat’s long axis, short axis, and pitcher-to-catcher directions. Although the magnitude of standardized variability was significantly smaller in the bat’s short axis direction than in the bat’s long axis and pitcher-to-catcher directions (p < 0.001), additional visible time from the R+150 condition to the A-150 and NO conditions resulted in a further decrease in standardized variability only in the bat’s short axis direction (p < 0.05). The results suggested that there is directional specificity in the magnitude of standardized variability with different visible time. The present study also confirmed the limitation to visual information is the later part of the ball trajectory for improving hitting accuracy, which is likely due to visuo-motor delay. PMID:26848742

  8. Cytolysis of nucleated cells by complement: cell death displays multi-hit characteristics.

    PubMed Central

    Koski, C L; Ramm, L E; Hammer, C H; Mayer, M M; Shin, M L

    1983-01-01

    Lysis of nucleated cells by complement was studied to determine whether the lytic process by C5b-9 conforms to a one-hit mechanism as in the case of erythrocytes. Two nucleated cell lines, Molt 4 and U937, derived from human T lymphocytes and histiocytes, respectively, were employed as targets. The antibody-sensitized cells were used to develop the titration curves, measuring cell death as a function of limiting quantities of human C6 or C5,6 complex in the presence of an excess of other complement components. The cytolysis curves generated in both experiments were sigmoidal, in sharp contrast to the monotonic curves observed in lysis of erythrocytes treated similarly. The sigmoidal curves of cytolysis indicate a cooperative action of several molecules of C6 or acid-activated C5,6 complex, C(56)a. In contrast to the multi-hit characteristics of cytolysis, dose-response measurements of the release of 86Rb indicated that only one effective molecule of C6 per cell is required for assembly of a 86Rb-releasing channel. This divergence indicates that lysis requires formation of several channels or, alternatively, assembly of large channels that are formed by several molecules of C6. Because prior studies with erythrocyte ghosts have shown that only a single effective molecule of C6 is required for assembly of a transmembrane channel, regardless of size, we prefer to interpret the multi-hit characteristics of nucleated cell lysis as an indication of a multi-channel requirement, rather than channel enlargement. PMID:6602341

  9. Making an Iron Planet: The Case for Repeated Hit and Run Collisions

    NASA Astrophysics Data System (ADS)

    Asphaug, E. I.; Reufer, A.

    2014-12-01

    Earth, Venus, Mars and some of the largest asteroids have massive silicate mantles surrounding iron cores, and chondritic compositions. Against this backdrop are anomalies like the iron planet Mercury, and the Moon with almost no core, and metallic asteroids like Psyche. The Moon can be explained by giant impact, but for Mercury a giant impact (Benz et al., Icarus 1988) is problematic. Mercury must retain substantial volatiles after its obliteration (e.g. Peplowski et al., Science 2011), and must somehow avoid accreting its ejected silicates (Gladman and Coffey, MAPS 2009). SPH simulations have shown (Asphaug and Reufer, Nature Geosciences 2014; Sarid et al., LPSC 2014) that a differentiated chondritic proto-Mercury about 3 times its present mass can be stripped of its mantle in one energetic hit and run collision with a larger planet (proto-Venus or proto-Earth). To preserve Mercury's volatiles we also consider the scenario of lower energy hit and runs, in succession. We show that if 20 Mars-like planets accreted stochastically to form Venus and the Earth, then the statistics of attrition is likely to lead to one planet (Mercury) expressing repeated mantle stripping, and another planet (Mars) relatively undisturbed. For iron asteroids the "missing mantle paradox" likewise looms prominent. Where does it go, and how do we strip away so much mantle rock (in some cases down to a bare iron core; Yang et al., Nature 2007, Moskovitz et al., EPSL 2011) while leaving asteroids like Vesta presumably intact? According to the hit and run hypothesis, the sink for all this missing silicate is the larger accreted bodies at the top of the feeding chain, as they win the pairwise dynamical competition for stripped materials. This exotic origin of relics is only relevant to those few pairwise encounters that do not accrete both bodies. So the small survivors are lucky, and how they are lucky -- their attrition bias -- is manifested as compositional diversity and a preponderance of

  10. The distribution of first hitting times of randomwalks on Erdős–Rényi networks

    NASA Astrophysics Data System (ADS)

    Tishby, Ido; Biham, Ofer; Katzav, Eytan

    2017-03-01

    Analytical results for the distribution of first hitting times of random walks on Erdős–Rényi networks are presented. Starting from a random initial node, a random walker hops between adjacent nodes until it hits a node which it has already visited before. At this point, the path terminates. The path length, namely the number of steps, d, pursued by the random walker from the initial node up to its termination is called the first hitting time or the first intersection length. Using recursion equations, we obtain analytical results for the tail distribution of the path lengths, P(d>\\ell ) . The results are found to be in excellent agreement with numerical simulations. It is found that the distribution P(d>\\ell ) follows a product of an exponential distribution and a Rayleigh distribution. The mean, median and standard deviation of this distribution are also calculated, in terms of the network size and its mean degree. The termination of an RW path may take place either by backtracking to the previous node or by retracing of its path, namely stepping into a node which has been visited two or more time steps earlier. We obtain analytical results for the probabilities, p b and p r , that the cause of termination will be backtracking or retracing, respectively. It is shown that in dilute networks the dominant termination scenario is backtracking while in dense networks most paths terminate by retracing. We also obtain expressions for the conditional distributions P(d=\\ell |b) and P(d=\\ell |r) , for those paths which are terminated by backtracking or by retracing, respectively. These results provide useful insight into the general problem of survival analysis and the statistics of mortality rates when two or more termination scenarios coexist.

  11. The REH theory of protein and nucleic acid divergence - A retrospective update. [Random Evolutionary Hits

    NASA Technical Reports Server (NTRS)

    Holmquist, R.

    1978-01-01

    The random evolutionary hits (REH) theory of evolutionary divergence, originally proposed in 1972, is restated with attention to certain aspects of the theory that have caused confusion. The theory assumes that natural selection and stochastic processes interact and that natural selection restricts those codon sites which may fix mutations. The predicted total number of fixed nucleotide replacements agrees with data for cytochrome c, a-hemoglobin, beta-hemoglobin, and myoglobin. The restatement analyzes the magnitude of possible sources of errors and simplifies calculational methodology by supplying polynomial expressions to replace tables and graphs.

  12. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis.

    PubMed

    Tilg, Herbert; Moschen, Alexander R

    2010-11-01

    Whereas in most cases a fatty liver remains free of inflammation, 10%-20% of patients who have fatty liver develop inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Inflammation may precede steatosis in certain instances. Therefore, NASH could reflect a disease where inflammation is followed by steatosis. In contrast, NASH subsequent to simple steatosis may be the consequence of a failure of antilipotoxic protection. In both situations, many parallel hits derived from the gut and/or the adipose tissue may promote liver inflammation. Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH.

  13. Developmental programming of pediatric nonalcoholic fatty liver disease: redefining the"first hit".

    PubMed

    Stewart, Michael S; Heerwagen, Margaret J R; Friedman, Jacob E

    2013-09-01

    The incidence of pediatric nonalcoholic fatty liver disease has increased dramatically, and growing evidence indicates that the pathophysiology may be unique from the adult form, suggesting a role for early-life events. Recent radiologic techniques have now demonstrated that maternal obesity contributes to hepatic fat storage in newborn infants. In this review, we will explore how maternal obesity and a hyperlipidemic environment can initiate liver histopathogenesis in utero, including steatosis, mitochondrial dysfunction, oxidative stress, and inflammatory priming. Thus, early exposure to excess lipids may represent the "first hit" for the fetal liver, placing it on a trajectory toward future metabolic disease.

  14. Ensemble-based docking: From hit discovery to metabolism and toxicity predictions

    SciTech Connect

    Evangelista, Wilfredo; Weir, Rebecca; Ellingson, Sally; Harris, Jason B.; Kapoor, Karan; Smith, Jeremy C.; Baudry, Jerome

    2016-07-29

    The use of ensemble-based docking for the exploration of biochemical pathways and toxicity prediction of drug candidates is described. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials.

  15. Cardiac surgery and heparin induced thrombocytopaenia (HIT): a case report and short review.

    PubMed

    McMeniman, W J; Chard, R B; Norrie, J; Posen, J

    2012-05-01

    This patient presented for emergency cardiac surgery following two episodes of thrombocytopaenia, one before and one associated with exposure to unfractionated heparin in a seven-week period of intensive care management. Although the diagnosis of heparin induced thrombocytopaenia (HIT) was uncertain on clinical grounds when assessed by current criteria, the positive antibody status directed management in accordance with the internationally recognised guidelines published by the American College of Chest Physicians (ACCP) Evidence-based Clinical Practice Guidelines. An alternative anticoagulant to unfractionated heparin was indicated for cardiopulmonary bypass. Bivalirudin was selected because of recent literature supporting its safe use.

  16. Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor

    PubMed Central

    2015-01-01

    The discovery of inhibitors targeting novel allosteric kinase sites is very challenging. Such compounds, however, once identified could offer exquisite levels of selectivity across the kinome. Herein we report our structure-based optimization strategy of a dibenzodiazepine hit 1, discovered in a fragment-based screen, yielding highly potent and selective inhibitors of PAK1 such as 2 and 3. Compound 2 was cocrystallized with PAK1 to confirm binding to an allosteric site and to reveal novel key interactions. Compound 3 modulated PAK1 at the cellular level and due to its selectivity enabled valuable research to interrogate biological functions of the PAK1 kinase. PMID:26191365

  17. Video observation in HIT development: lessons learned on benefits and challenges

    PubMed Central

    2012-01-01

    Background Experience shows that the precondition for the development of successful health information technologies is a thorough insight into clinical work practice. In contemporary clinical work practice, clinical work and health information technology are integrated, and part of the practice is tacit. When work practice becomes routine, it slips to the background of the conscious awareness and becomes difficult to recognize without the context to support recall. This means that it is difficult to capture with traditional ethnographic research methods or in usability laboratories or clinical set ups. Observation by the use of the video technique within healthcare settings has proven to be capable of providing a thorough insight into the complex clinical work practice and its context - including parts of the tacit practice. The objective of this paper is 1) to argue for the video observation technique to inform and improve health-information-technology development and 2) to share insights and lessons learned on benefits and challenges when using the video observation technique within healthcare settings. Methods A multiple case study including nine case studies conducted by DaCHI researchers 2004–2011 using audio-visual, non-participant video observation for data collection within different healthcare settings. Results In HIT development, video observation is beneficial for 1) informing and improving system design 2) studying changes in work practice 3) identifying new potentials and 4) documenting current work practices. Conclusions The video observation technique used within healthcare settings is superior to other ethnographic research methods when it comes to disclosing the complexity in clinical work practice. The insights gained are far more realistic compared to traditional ethnographic studies or usability studies and studies in clinical set ups. Besides, the data generated through video recordings provide a solid basis for dialog between the health care

  18. Hits identified in library screening demonstrate selective CYP17A1 lyase inhibition.

    PubMed

    Krug, Sebastian J; Hu, Qingzhong; Hartmann, Rolf W

    2013-03-01

    A screening of structurally different steroid hormone synthesis inhibitors was performed in order to find a starting point for the development of a new inhibitor of the bifunctional steroidogenic enzyme CYP17A1. Emphasis was placed on determination of selectivity between the two catalytic steps, namely 17α-hydroxylase and C(17,20)-lyase. For that purpose a new inhibition assay has been developed. Hits identified within this novel assay demonstrated selective inhibition of CYP17A1 lyase activity, and thus mark the basis for the development of selective C(17,20)-lyase inhibitors for the treatment of prostate cancer.

  19. Structural Insights into a Unique Legionella pneumophila Effector LidA Recognizing Both GDP and GTP Bound Rab1 in Their Active State

    PubMed Central

    Lu, Defen; Li, Bingqing; Zhu, Deyu; Chen, Yuzhen; Zhang, Hao; Xu, Sujuan; Chai, Jijie; Gu, Lichuan

    2012-01-01

    The intracellular pathogen Legionella pneumophila hijacks the endoplasmic reticulum (ER)-derived vesicles to create an organelle designated Legionella-containing vacuole (LCV) required for bacterial replication. Maturation of the LCV involved acquisition of Rab1, which is mediated by the bacterial effector protein SidM/DrrA. SidM/DrrA is a bifunctional enzyme having the activity of both Rab1-specific GDP dissociation inhibitor (GDI) displacement factor (GDF) and guanine nucleotide exchange factor (GEF). LidA, another Rab1-interacting bacterial effector protein, was reported to promote SidM/DrrA-mediated recruitment of Rab1 to the LCV as well. Here we report the crystal structures of LidA complexes with GDP- and GTP-bound Rab1 respectively. Structural comparison revealed that GDP-Rab1 bound by LidA exhibits an active and nearly identical conformation with that of GTP-Rab1, suggesting that LidA can disrupt the switch function of Rab1 and render it persistently active. As with GTP, LidA maintains GDP-Rab1 in the active conformation through interaction with its two conserved switch regions. Consistent with the structural observations, biochemical assays showed that LidA binds to GDP- and GTP-Rab1 equally well with an affinity approximately 7.5 nM. We propose that the tight interaction with Rab1 allows LidA to facilitate SidM/DrrA-catalyzed release of Rab1 from GDIs. Taken together, our results support a unique mechanism by which a bacterial effector protein regulates Rab1 recycling. PMID:22416225

  20. Pelvic rotation torque during fast-pitch softball hitting under three ball height conditions.

    PubMed

    Iino, Yoichi; Fukushima, Atsushi; Kojima, Takeji

    2014-08-01

    The purpose of this study was to investigate the relevance of hip joint angles to the production of the pelvic rotation torque in fast-pitch softball hitting and to examine the effect of ball height on this production. Thirteen advanced female softball players hit stationary balls at three different heights: high, middle, and low. The pelvic rotation torque, defined as the torque acting on the pelvis through the hip joints about the pelvic superior-inferior axis, was determined from the kinematic and force plate data using inverse dynamics. Irrespective of the ball heights, the rear hip extension, rear hip external rotation, front hip adduction, and front hip flexion torques contributed to the production of pelvic rotation torque. Although the contributions of the adduction and external rotation torques at each hip joint were significantly different among the ball heights, the contributions of the front and rear hip joint torques were similar among the three ball heights owing to cancelation of the two torque components. The timings of the peaks of the hip joint torque components were significantly different, suggesting that softball hitters may need to adjust the timings of the torque exertions fairly precisely to rotate the upper body effectively.

  1. How to hit home runs: Optimum baseball bat swing parameters for maximum range trajectories

    NASA Astrophysics Data System (ADS)

    Sawicki, Gregory S.; Hubbard, Mont; Stronge, William J.

    2003-11-01

    Improved models for the pitch, batting, and post-impact flight phases of a baseball are used in an optimal control context to find bat swing parameters that produce maximum range. The improved batted flight model incorporates experimental lift and drag profiles (including the drag crisis). An improved model for bat-ball impact includes the dependence of the coefficient of restitution on the approach relative velocity and the dependence of the incoming pitched ball angle on speed. The undercut distance and bat swing angle are chosen to maximize the range of the batted ball. The sensitivity of the maximum range is calculated for all model parameters including bat and ball speed, bat and ball spin, and wind speed. Post-impact conditions are found to be independent of the ball-bat coefficient of friction. The lift is enhanced by backspin produced by undercutting the ball during batting. An optimally hit curve ball will travel farther than an optimally hit fastball or knuckleball due to increased lift during flight.

  2. Influence of patterning the TCO layer on the series resistance of thin film HIT solar cells

    NASA Astrophysics Data System (ADS)

    Champory, Romain; Mandorlo, Fabien; Seassal, Christian; Fave, Alain

    2017-01-01

    Thin HIT solar cells combine efficient surface passivation and high open circuit voltage leading to high conversion efficiencies. They require a TCO layer in order to ease carriers transfer to the top surface fingers. This Transparent Conductive Oxide layer induces parasitic absorption in the low wavelength range of the solar spectrum that limits the maximum short circuit current. In case of thin film HIT solar cells, the front surface is patterned in order to increase the effective life time of photons in the active material, and the TCO layer is often deposited with a conformal way leading to additional material on the sidewalls of the patterns. In this article, we propose an alternative scheme with a local etching of both the TCO and the front a-Si:H layers in order to reduce the parasitic absorption. We study how the local resistivity of the TCO evolves as a function of the patterns, and demonstrate how the increase of the series resistance can be compensated in order to increase the conversion efficiency.

  3. Enrichment of virtual hits by progressive shape-matching and docking.

    PubMed

    Choi, Jiwon; He, Ningning; Kim, Nayoung; Yoon, Sukjoon

    2012-02-01

    The main applications of virtual chemical screening include the selection of a minimal receptor-relevant subset of a chemical library with a maximal chemical diversity. We have previously reported that the combination of ligand-centric and receptor-centric virtual screening methods may provide a compromise between computational time and accuracy during the hit enrichment process. In the present work, we propose a "progressive distributed docking" method that improves the virtual screening process using an iterative combination of shape-matching and docking steps. Known ligands with low docking scores were used as initial 3D templates for the shape comparisons with the chemical library. Next, new compounds with good template shape matches and low receptor docking scores were selected for the next round of shape searching and docking. The present iterative virtual screening process was tested for enriching peroxisome proliferator-activated receptor and phosphoinositide 3-kinase relevant compounds from a selected subset of the chemical libraries. It was demonstrated that the iterative combination improved the lead-hopping practice by improving the chemical diversity in the selected list of virtual hits.

  4. The Head Tracks and Gaze Predicts: How the World’s Best Batters Hit a Ball

    PubMed Central

    Mann, David L.; Spratford, Wayne; Abernethy, Bruce

    2013-01-01

    Hitters in fast ball-sports do not align their gaze with the ball throughout ball-flight; rather, they use predictive eye movement strategies that contribute towards their level of interceptive skill. Existing studies claim that (i) baseball and cricket batters cannot track the ball because it moves too quickly to be tracked by the eyes, and that consequently (ii) batters do not – and possibly cannot – watch the ball at the moment they hit it. However, to date no studies have examined the gaze of truly elite batters. We examined the eye and head movements of two of the world’s best cricket batters and found both claims do not apply to these batters. Remarkably, the batters coupled the rotation of their head to the movement of the ball, ensuring the ball remained in a consistent direction relative to their head. To this end, the ball could be followed if the batters simply moved their head and kept their eyes still. Instead of doing so, we show the elite batters used distinctive eye movement strategies, usually relying on two predictive saccades to anticipate (i) the location of ball-bounce, and (ii) the location of bat-ball contact, ensuring they could direct their gaze towards the ball as they hit it. These specific head and eye movement strategies play important functional roles in contributing towards interceptive expertise. PMID:23516460

  5. Bis-Benzimidazole Hits against Naegleria fowleri Discovered with New High-Throughput Screens

    PubMed Central

    Rice, Christopher A.; Colon, Beatrice L.; Alp, Mehmet; Göker, Hakan; Boykin, David W.

    2015-01-01

    Naegleria fowleri is a pathogenic free-living amoeba (FLA) that causes an acute fatal disease known as primary amoebic meningoencephalitis (PAM). The major problem for infections with any pathogenic FLA is a lack of effective therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new drugs that are potent and have rapid onset of action are needed to enhance the treatment regimens for PAM. Diamidines have demonstrated potency against multiple pathogens, including FLA, and are known to cross the blood-brain barrier to cure other protozoan diseases of the central nervous system. Therefore, amidino derivatives serve as an important chemotype for discovery of new drugs. In this study, we validated two new in vitro assays suitable for medium- or high-throughput drug discovery and used these for N. fowleri. We next screened over 150 amidino derivatives of multiple structural classes and identified two hit series with nM potency that are suitable for further lead optimization as new drugs for this neglected disease. These include both mono- and diamidino derivatives, with the most potent compound (DB173) having a 50% inhibitory concentration (IC50) of 177 nM. Similarly, we identified 10 additional analogues with IC50s of <1 μM, with many of these having reasonable selectivity indices. The most potent hits were >500 times more potent than pentamidine. In summary, the mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections with N. fowleri. PMID:25605363

  6. Transient coaxial helicity injection for solenoid-free plasma startup in HIT-II

    SciTech Connect

    Raman, R.; Jarboe, T. R; Hamp, W. T.; Redd, A. J.; Nelson, B. A.; O'Neill, R. G.; Sieck, P. E.; Smith, R. J.

    2007-02-15

    The favorable properties of the spherical torus (ST) arise from its very small aspect ratio. Methods for initiating the plasma current without relying on induction from a central solenoid are essential for the viability of the ST concept. In steady state tokamaks, the central solenoid can be dispensed with if suitable methods for initiating the plasma current are on hand. Coaxial helicity injection (CHI) is a promising candidate for solenoid-free plasma current startup in STs and tokamaks. Experiments on the Helicity Injected Torus (HIT-II) machine at the University of Washington [T. R. Jarboe, Fusion Technol. 15, 7 (1989)] have demonstrated the capability of a new method, referred to as transient CHI, to produce a high quality closed-flux equilibrium that has been successfully coupled to induction demonstrating that this new plasma current startup method is compatible with the conventional inductive method. This paper presents physics requirements for implementing this method in STs and tokamaks and supporting experimental results from the HIT-II device.

  7. Highly textured conductive and transparent ZnO films for HIT solar cell applications

    NASA Astrophysics Data System (ADS)

    Xiao, Shaoqing; Zhou, Jingjing; Huang, Shiyong; Xiao, Peng; Gu, Xiaofeng; Yan, Dawei; Xu, Shuyan

    2015-08-01

    In this paper, aluminium-doped zinc oxide (AZO) thin-films were fabricated on both glass and silicon substrates by radio-frequency magnetron sputtering at various working pressures of 0.15-0.46 Pa. The effect of working pressure on the structural, electrical, and optical properties of the deposited AZO films was carefully studied. The lower working pressure is more favourable to large grain size, smooth surface, low electrical resistivity, and moderate optical transparency. For the AZO films deposited at lower working pressures, the larger grain size can be ascribed to the higher kinetic energy of the sputtered particles while the lower electrical resistivity is strongly related to both the presence of fewer grain boundaries due to the larger grain size and more activated amount of dopants in the films. We then applied AZO films deposited at 0.15 Pa to Al/AZO/n-a-Si : H/i-a-Si : H/p-c-Si/Al heterojunction Si solar cells with intrinsic thin layer (HIT) solar cells and achieved highly textured surfaces via acid etching. The HIT solar cells after acid texturing showed a higher external quantum efficiency (EQE) value than those with smooth AZO films mainly in the wavelength region from 300 to 500 nm, leading to an obvious increase in the conversion efficiency from 14.1% to 14.7%.

  8. An Analytic Model for the Success Rate of a Robotic Actuator System in Hitting Random Targets

    PubMed Central

    Bradley, Stuart

    2015-01-01

    Autonomous robotic systems are increasingly being used in a wide range of applications such as precision agriculture, medicine, and the military. These systems have common features which often includes an action by an “actuator” interacting with a target. While simulations and measurements exist for the success rate of hitting targets by some systems, there is a dearth of analytic models which can give insight into, and guidance on optimization, of new robotic systems. The present paper develops a simple model for estimation of the success rate for hitting random targets from a moving platform. The model has two main dimensionless parameters: the ratio of actuator spacing to target diameter; and the ratio of platform distance moved (between actuator “firings”) to the target diameter. It is found that regions of parameter space having specified high success are described by simple equations, providing guidance on design. The role of a “cost function” is introduced which, when minimized, provides optimization of design, operating, and risk mitigation costs. PMID:26610500

  9. Utility of Redundant Combinatorial Libraries in Distinguishing High and Low Quality Screening Hits

    PubMed Central

    2014-01-01

    Large one-bead one-compound (OBOC) combinatorial libraries can be constructed relatively easily by solid-phase split and pool synthesis. The use of resins with hydrophilic surfaces, such as TentaGel, allows the beads to be used directly in screens for compounds that bind selectively to labeled proteins, nucleic acids, or other biomolecules. However, we have found that this method, while useful, has a high false positive rate. In other words, beads that are scored as hits often display compounds that prove to be poor ligands for the target of interest when they are resynthesized and carried through validation trials. This results in a significant waste of time and resources in cases where putative hits cannot be validated without resynthesis. Here, we report that this problem can be largely eliminated through the use of redundant OBOC libraries, where more than one bead displaying the same compound is present in the screen. We show that compounds isolated more than once are likely to be high quality ligands for the target of interest, whereas compounds isolated only once have a much higher likelihood of being poor ligands. While the use of redundant libraries does limit the number of unique compounds that can be screened at one time in this format, the overall savings in time, effort, and materials makes this a more efficient route to the isolation of useful ligands for biomolecules. PMID:24749624

  10. Internal magnetic field measurements on the Helicity Injected Tokamak (HIT) using the Transient Internal Probe (TIP)

    SciTech Connect

    Galambos, J.P.; Bohnet, M.A.; Jarboe, T.R.; Mattick, A.T.

    1996-12-31

    The Transient Internal Probe (TIP) is a novel diagnostic designed to measure internal magnetic fields in hot plasmas. The diagnostic involves shooting a magneto-optic probe through the plasma at high velocities (greater than 2 km/s) using a two stage light gas gun. Local fields are obtained by illuminating the probe with an argon ion laser and measuring the amount of Faraday rotation in the laser light reflected from the moving probe. Currently, internal magnetic profile measurements are being conducted on the Helicity Injected tokamak (HIT). HIT is a low aspect ratio (A = 1.5) tokamak designed to investigate steady state current drive using coaxial helicity injection. Operating parameters are T{sub e} {approx} 100, n{sub e} {approx} 5 {times} 10{sup 13} cm{sup {minus}3} and I{sub p} = 250 kA. Internal magnetic field profile data will be presented. The TIP diagnostic has a spatial resolution of 1 cm and 20 gauss magnetic field resolution. System frequency response is 10 MHz.

  11. HITS-CLIP: panoramic views of protein-RNA regulation in living cells

    PubMed Central

    Darnell, Robert B.

    2011-01-01

    The study of gene regulation in cells has recently begun to shift from a period dominated by the study of transcription factor-DNA interactions to a new focus on RNA regulation. This was sparked by the still-emerging recognition of the central role for RNA in cellular complexity emanating from the RNA World hypothesis, and has been facilitated by technologic advances, in particular high throughput RNA sequencing and crosslinking methods (RNA-Seq, CLIP, and HITS-CLIP). This article will place these advances in context, and, focusing on CLIP, will explain the method, what it can be used for, and how to approach using it. Examples of the successes, limitations and future of the technique will be discussed. Crosslinking immunoprecipitation (CLIP), coupled with high throughput sequencing (HITS-CLIP), has caught the attention of the RNA community as a means of achieving a new depth of understanding about how protein-RNA complexes interactions regulate gene expression in living cells1–4. This review will describe the context in which CLIP was developed, and provide an up-to-date review of its uses in developing genome-wide maps of RNA-protein interactions and, more recently, microRNA (miRNA) binding sites. The uses, limitations, and future of CLIP will be discussed. PMID:21935890

  12. Achieving Size Independent Hit-Rate in Single Particle Mass Spectrometry

    SciTech Connect

    Zelenyuk, Alla; Yang, Juan; Imre, Dan G.; Choi, Eric Y.

    2009-04-01

    Recent improvements in single particle mass spectrometers make it possible to optically detect, size, and characterize the compositions of individual particles with diameters larger than a micron and smaller than 100 nm. Based on particle detection in two stages of optical detection these instruments generate a precisely timed trigger pulse, which is used to fire the ion generation laser or lasers. Practical experience shows that the wide size range results in small, but significant differences in laser trigger timing between small and large particles. If not treated, the instrument hit-rate becomes size dependent and instrument operator is forced to optimize the instrument for the desired size range, while having to contend with a lower hit-rate for the other. The present paper presents an analysis of the problem, demonstrating that size dependence of laser trigger timing stems from the differences in the particle position within the detection laser beam at the instant of detection. It shows that it is possible to compensate for these differences by generation a laser trigger delay coefficient for individual particles as a function of particle time of flight, i.e. its size. The study also shows that a single function can be used to characterize particles with a wide range of densities.

  13. Bis-benzimidazole hits against Naegleria fowleri discovered with new high-throughput screens.

    PubMed

    Rice, Christopher A; Colon, Beatrice L; Alp, Mehmet; Göker, Hakan; Boykin, David W; Kyle, Dennis E

    2015-04-01

    Naegleria fowleri is a pathogenic free-living amoeba (FLA) that causes an acute fatal disease known as primary amoebic meningoencephalitis (PAM). The major problem for infections with any pathogenic FLA is a lack of effective therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new drugs that are potent and have rapid onset of action are needed to enhance the treatment regimens for PAM. Diamidines have demonstrated potency against multiple pathogens, including FLA, and are known to cross the blood-brain barrier to cure other protozoan diseases of the central nervous system. Therefore, amidino derivatives serve as an important chemotype for discovery of new drugs. In this study, we validated two new in vitro assays suitable for medium- or high-throughput drug discovery and used these for N. fowleri. We next screened over 150 amidino derivatives of multiple structural classes and identified two hit series with nM potency that are suitable for further lead optimization as new drugs for this neglected disease. These include both mono- and diamidino derivatives, with the most potent compound (DB173) having a 50% inhibitory concentration (IC50) of 177 nM. Similarly, we identified 10 additional analogues with IC50s of <1 μM, with many of these having reasonable selectivity indices. The most potent hits were >500 times more potent than pentamidine. In summary, the mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections with N. fowleri.

  14. 3D MHD Simulations of Injector Coupling and Current Drive in HIT-SI

    NASA Astrophysics Data System (ADS)

    Hansen, Chris; Marklin, George; Jarboe, Thomas

    2013-10-01

    A new non-linear reduced MHD code has been developed using the PSI-TET framework, which is capable of modeling the full HIT-SI geometry with consistent boundary conditions for the insulator coated flux conserver. The PSI-TET framework provides general mechanics supporting the development of multi-physics simulation using high order finite methods with a tetrahedral spatial discretization. Using these capabilities an implementation of reduced Hall-MHD was developed where temperature and density are assumed to be uniform and constant, reducing the full MHD equations to the momentum and induction equations. A Nedelec vector basis set is used for the magnetic field, which preserves the divergence free property of the induction equation, and a scalar Lagrange basis is used for each component of the velocity. The equation system is advanced using a time centered implicit scheme, which is solved using a multi-grid preconditioned Newton-Krylov method. Results will be presented focusing on internal injector dynamics and coupling to the Spheromak region. Comparison between this code and experimental data as well as existing NIMROD simulations of HIT-SI, which model the injector operation with boundary conditions on an axisymmetric grid, will also be shown. Work supported by DOE.

  15. Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH)

    PubMed Central

    Takaki, Akinobu; Kawai, Daisuke; Yamamoto, Kazuhide

    2013-01-01

    Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease. PMID:24132155

  16. The hit-and-run in fatal pedestrian accidents: victims, circumstances and drivers.

    PubMed

    Solnick, S J; Hemenway, D

    1995-10-01

    Hit-and-run pedestrian fatalities are classified as to victim characteristics, accident circumstances and driver characteristics. Over 18,000 pedestrian fatalities are reported in the Fatal Accident Recording System for 1989-1991. Twenty percent of the drivers involved left the accident scene. Children and senior citizens are the least likely to be left. Drivers more commonly run in urban areas, outside the South, on weekends and at night. Comparing motorists who left the scene but were later identified with the drivers who remained, drivers aged 66 and older are half as likely as younger drivers to leave the accident scene and male drivers are 60% more likely than female drivers to run. Drivers with previous driving while intoxicated arrests are twice as likely to run as those with no such arrests. Forty-nine percent of hit-and-run motorists involved in pedestrian fatalities are ultimately identified by the police. Other factors constant, drivers are more likely to be identified if the victim was female or a child. Drivers are identified 2.5 times as often when the incident occurred in daylight. Drivers appear to run more often when they are at fault and will be severely punished (e.g. when they are intoxicated) and when it is likely that they can escape detection (e.g. at night).

  17. An Analytic Model for the Success Rate of a Robotic Actuator System in Hitting Random Targets.

    PubMed

    Bradley, Stuart

    2015-11-20

    Autonomous robotic systems are increasingly being used in a wide range of applications such as precision agriculture, medicine, and the military. These systems have common features which often includes an action by an "actuator" interacting with a target. While simulations and measurements exist for the success rate of hitting targets by some systems, there is a dearth of analytic models which can give insight into, and guidance on optimization, of new robotic systems. The present paper develops a simple model for estimation of the success rate for hitting random targets from a moving platform. The model has two main dimensionless parameters: the ratio of actuator spacing to target diameter; and the ratio of platform distance moved (between actuator "firings") to the target diameter. It is found that regions of parameter space having specified high success are described by simple equations, providing guidance on design. The role of a "cost function" is introduced which, when minimized, provides optimization of design, operating, and risk mitigation costs.

  18. Fragment library screening identifies hits that bind to the non-catalytic surface of Pseudomonas aeruginosa DsbA1

    PubMed Central

    Headey, Stephen J.; Vazirani, Mansha; Shouldice, Stephen R.; Coinçon, Mathieu; Tay, Stephanie; Morton, Craig J.; Simpson, Jamie S.; Martin, Jennifer L.

    2017-01-01

    At a time when the antibiotic drug discovery pipeline has stalled, antibiotic resistance is accelerating with catastrophic implications for our ability to treat bacterial infections. Globally we face the prospect of a future when common infections can once again kill. Anti-virulence approaches that target the capacity of the bacterium to cause disease rather than the growth or survival of the bacterium itself offer a tantalizing prospect of novel antimicrobials. They may also reduce the propensity to induce resistance by removing the strong selection pressure imparted by bactericidal or bacteriostatic agents. In the human pathogen Pseudomonas aeruginosa, disulfide bond protein A (PaDsbA1) plays a central role in the oxidative folding of virulence factors and is therefore an attractive target for the development of new anti-virulence antimicrobials. Using a fragment-based approach we have identified small molecules that bind to PaDsbA1. The fragment hits show selective binding to PaDsbA1 over the DsbA protein from Escherichia coli, suggesting that developing species-specific narrow-spectrum inhibitors of DsbA enzymes may be feasible. Structures of a co-complex of PaDsbA1 with the highest affinity fragment identified in the screen reveal that the fragment binds on the non-catalytic surface of the protein at a domain interface. This biophysical and structural data represent a starting point in the development of higher affinity compounds, which will be assessed for their potential as selective PaDsbA1 inhibitors. PMID:28346540

  19. Leishmania donovani lacking the Golgi GDP-Man transporter LPG2 exhibit attenuated virulence in mammalian hosts.

    PubMed

    Gaur, Upasna; Showalter, Melissa; Hickerson, Suzanne; Dalvi, Rahul; Turco, Salvatore J; Wilson, Mary E; Beverley, Stephen M

    2009-07-01

    Surface phosophoglycans such as lipophosphoglycan (LPG) or proteophosphoglycan (PPG) and glycosylinositol phospholipids (GIPLs) modulate essential interactions between Leishmania and mammalian macrophages. Phosphoglycan synthesis depends on the Golgi GDP-mannose transporter encoded by LPG2. LPG2-null (lpg2(-)) Leishmania major cannot establish macrophage infections or induce acute pathology, whereas lpg2(-)Leishmania mexicana retain virulence. lpg2(-)Leishmania donovani has been reported to survive poorly in cultured macrophages but in vivo survival has not been explored. Herein we discovered that, similar to lpg2(-)L. major, lpg2(-)L. donovani promastigotes exhibited diminished virulence in mice, but persisted at consistently low levels. lpg2(-)L. donovani promastigotes could not establish infection in macrophages and could not transiently inhibit phagolysosomal fusion. Furthermore, lpg2(-) promastigotes of L. major, L. donovani and L. mexicana were highly susceptible to complement-mediated lysis. We conclude that phosphoglycan assembly and expression mediated by L. donovani LPG2 are important for promastigote and amastigote virulence, unlike L. mexicana but similar to L. major.

  20. Structural Studies of the Nudix GDP-mannose Hydrolase from E. coli Reveals a New Motif for Mannose Recognition

    SciTech Connect

    A Boto; W Xu; J Jakoncic; A Pannuri; T Romeo; M Bessman; S Gabelli; L Amzel

    2011-12-31

    The Nudix hydrolase superfamily, characterized by the presence of the signature sequence GX5EX7REUXEEXGU (where U is I, L, or V), is a well-studied family in which relations have been established between primary sequence and substrate specificity for many members. For example, enzymes that hydrolyze the diphosphate linkage of ADP-ribose are characterized by having a proline 15 amino acids C-terminal of the Nudix signature sequence. GDPMK is a Nudix enzyme that conserves this characteristic proline but uses GDP-mannose as the preferred substrate. By investigating the structure of the GDPMK alone, bound to magnesium, and bound to substrate, the structural basis for this divergent substrate specificity and a new rule was identified by which ADP-ribose pyrophosphatases can be distinguished from purine-DP-mannose pyrophosphatases from primary sequence alone. Kinetic and mutagenesis studies showed that GDPMK hydrolysis does not rely on a single glutamate as the catalytic base. Instead, catalysis is dependent on residues that coordinate the magnesium ions and residues that position the substrate properly for catalysis. GDPMK was thought to play a role in biofilm formation because of its upregulation in response to RcsC signaling; however, GDPMK knockout strains show no defect in their capacity of forming biofilms.

  1. Trends in mortality decrease and economic growth.

    PubMed

    Niu, Geng; Melenberg, Bertrand

    2014-10-01

    The vast literature on extrapolative stochastic mortality models focuses mainly on the extrapolation of past mortality trends and summarizes the trends by one or more latent factors. However, the interpretation of these trends is typically not very clear. On the other hand, explanation methods are trying to link mortality dynamics with observable factors. This serves as an intermediate step between the two methods. We perform a comprehensive analysis on the relationship between the latent trend in mortality dynamics and the trend in economic growth represented by gross domestic product (GDP). Subsequently, the Lee-Carter framework is extended through the introduction of GDP as an additional factor next to the latent factor, which provides a better fit and better interpretable forecasts.

  2. Comparison of allocation algorithms for unambiguous registration of hits in presence of charge sharing in pixel detectors

    NASA Astrophysics Data System (ADS)

    Otfinowski, P.; Maj, P.; Deptuch, G.; Fahim, F.; Hoff, J.

    2017-01-01

    Charge sharing is the fractional collection of the charge cloud generated in a detector by two or more adjacent pixels. It may lead to excessive or inefficient registration of hits comparing to the number of impinging photons depending on how discrimination thresholds are set in typical photon counting pixel detector. The problems are particularly exposed for fine pixel sizes and/or for thick planar detectors. Presence of charge sharing is one of the limiting factors that discourages decreasing sizes of pixels in photon counting mode X-ray radiation imaging systems. Currently, a few different approaches tackling with the charge sharing problem exist (e.g. Medipix3RX, PIXIE, miniVIPIC or PIX45). The general idea is, first, to reconstruct the entire signal from adjacent pixels and, secondly, to allocate the hit to a single pixel. This paper focuses on the latter part of the process, i.e. on a comparison of how different hit allocation algorithms affect the spatial accuracy and false registration vs. missed hit probability. Different hit allocation algorithms were simulated, including standard photon counting (no full signal reconstruction) and the C8P1 algorithm. Also, a novel approach, based on a detection of patterns, with significantly limited analog signal processing, was proposed and characterized.

  3. Transgenic cotton expressing synthesized scorpion insect toxin AaHIT gene confers enhanced resistance to cotton bollworm (Heliothis armigera) larvae.

    PubMed

    Wu, Jiahe; Luo, Xiaoli; Wang, Zhian; Tian, Yingchuan; Liang, Aihua; Sun, Yi

    2008-03-01

    A synthetic scorpion Hector Insect Toxin (AaHIT) gene, under the control of a CaMV35S promoter, was cloned into cotton via Agrobacterium tumefaciens-mediated transformation. Southern blot analyses indicated that integration of the transgene varied from one to more than three estimated copies per genome; seven homozygous transgenic lines with one copy of the T-DNA insert were then selected by PCR and Southern blot analysis. AaHIT expression was from 0.02 to 0.43% of total soluble protein determined by western blot. These homozygous transgenic lines killed larvae of cotton bollworm (Heliothis armigera) by 44-98%. The AaHIT gene could used therefore an alternative to Bt toxin and proteinase inhibitor genes for producing transgenic cotton crops with effective control of bollworm.

  4. The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome.

    PubMed

    Daskalakis, Nikolaos P; Bagot, Rosemary C; Parker, Karen J; Vinkers, Christiaan H; de Kloet, E R

    2013-09-01

    Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual's predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances.

  5. Role of Rho GDP dissociation inhibitor α in control of epithelial sodium channel (ENaC)-mediated sodium reabsorption.

    PubMed

    Pavlov, Tengis S; Levchenko, Vladislav; Staruschenko, Alexander

    2014-10-10

    The epithelial sodium channel (ENaC) is expressed in the aldosterone-sensitive distal nephron where it performs sodium reabsorption from the lumen. We have recently shown that ENaC activity contributes to the development of salt-induced hypertension as a result of deficiency of EGF level. Previous studies revealed that Rho GDP-dissociation inhibitor α (RhoGDIα) is involved in the control of salt-sensitive hypertension and renal injury via Rac1, which is one of the small GTPases activating ENaC. Here we investigated the intracellular mechanism mediating the involvement of the RhoGDIα/Rac1 axis in the control of ENaC and the effect of EGF on ENaC in this pathway. We demonstrated that RhoGDIα is highly expressed in the cortical collecting ducts of mice and rats, and its expression is down-regulated in Dahl salt-sensitive rats fed a high salt diet. Knockdown of RhoGDIα in cultured cortical collecting duct principal cells increased ENaC subunits expression and ENaC-mediated sodium reabsorption. Furthermore, RhoGDIα deficiency causes enhanced response to EGF treatment. Patch clamp analysis reveals that RhoGDIα significantly decreases ENaC current density and prevents its up-regulation by RhoA and Rac1. Inhibition of Rho kinase with Y27632 had no effects on ENaC response to EGF either in control or RhoGDIα knocked down cells. However, EGF treatment increased levels of active Rac1, which was further enhanced in RhoGDIα-deficient cells. We conclude that changes in the RhoGDIα-dependent pathway have a permissive role in the Rac1-mediated enhancement of ENaC activity observed in salt-induced hypertension.

  6. Hit-Validation Methodologies for Ligands Isolated from DNA-Encoded Chemical Libraries.

    PubMed

    Zimmermann, Gunther; Li, Yizhou; Rieder, Ulrike; Mattarella, Martin; Neri, Dario; Scheuermann, Jörg

    2017-01-09

    DNA-encoded chemical libraries (DECLs) are large collections of compounds linked to DNA fragments, serving as amplifiable barcodes, which can be screened on target proteins of interest. In typical DECL selections, preferential binders are identified by high-throughput DNA sequencing, by comparing their frequency before and after the affinity capture step. Hits identified in this procedure need to be confirmed, by resynthesis and by performing affinity measurements. In this article we present new methods based on hybridization of oligonucleotide conjugates with fluorescently labeled complementary oligonucleotides; these facilitate the determination of affinity constants and kinetic dissociation constants. The experimental procedures were demonstrated with acetazolamide, a binder to carbonic anhydrase IX with a dissociation constant in the nanomolar range. The detection of binding events was compatible not only with fluorescence polarization methodologies, but also with Alphascreen technology and with microscale thermophoresis.

  7. Drift chamber electronics with multi-hit capability for time and current division measurements

    NASA Astrophysics Data System (ADS)

    Manarin, A.; Pregernig, L.; Rabany, M.; Saban, R.; Vismara, G.

    1983-11-01

    Drift chambers have been installed for luminosity measurements in intersection 5 of the SPS accelerator working in p overlinep colliding mode. The required electronics is described. The system is able to process up to 16 hits per wire with a double pulse resolution of 40 ns; drift time and current division, with 1.25 ns and 1.6% resolution respectively, are recorded. Transconductance preamplifiers and discriminators are directly mounted on the chamber; 160 m of twisted-pair cable bring the signals to the digitizer unit. Coarse time is measured using RAM techniques, while fine time is obtained by means of a microstrip delay associated with a 100 K ECL priority encoder. Current division used a single 50 MHz Flash ADC which allows 26 dB dynamic range with 6 bit resolution. First operational results are reported.

  8. Zero-{beta} modeling of coaxial helicity injection in the HIT-II spherical torus

    SciTech Connect

    Bayliss, R. A.; Sovinec, C. R.; Redd, A. J.

    2011-09-15

    Coaxial helicity injection in the HIT-II [A. J. Redd et al., Phys. Plasmas 9, 2006 (2002)] spherical torus is modeled with time-dependent resistive magnetohydrodynamics computations run to steady state for conditions without strong relaxation. Laboratory and computed results on injector current and plasma current agree reasonably well as toroidal magnetic field and injector flux are scaled. The scalings are consistent with a dimensional estimate from the Grad-Shafranov equation that provides a new perspective on a previously published model based on a current-sheet equilibrium and the magnetic pressure required for the ''bubble-burst'' criterion. Numerical solutions of the Grad-Shafranov equation with an assumed current profile also indicate large qualitative changes as the predicted criterion is crossed.

  9. Award-winning mass media campaign hits home with Dominican youth.

    PubMed

    Black, B

    1997-06-01

    Four television advertisements produced for an AIDS prevention campaign by the AIDS Control and Prevention (AIDSCAP) Project in the Dominican Republic depict young, attractive individuals with multiple partners, and one youth with AIDS. The spots target adolescents and their parents with the message to remain monogamous and use condoms. They were made by a leading Dominican advertising agency, using high-quality production techniques and attractive young actors to convey well-researched public health messages. Hard-hitting radio announcements, posters, and roadside billboards were also developed as part of a comprehensive national campaign launched in 1993 against HIV/AIDS. The campaign's interactive advertising, coordinated approach, and parental and media involvement are described.

  10. Hepatitis C and double-hit B cell lymphoma successfully treated by antiviral therapy

    PubMed Central

    Galati, Giovanni; Rampa, Lorenzo; Vespasiani-Gentilucci, Umberto; Marino, Mirella; Pisani, Francesco; Cota, Carlo; Guidi, Alessandro; Picardi, Antonio

    2016-01-01

    B cells lymphoma is one of the most challenging extra-hepatic manifestations of hepatitis C virus (HCV). Recently, a new kind of B-cell lymphoma, named double-hit B (DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents (DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected. A possible effect of DAAs on DHL regression should be investigated, but eradicating HCV would avoid life-threatening reactivation of viral hepatitis during pharmacological immunosuppression in onco-haematological diseases. PMID:27803769

  11. Hepatitis C and double-hit B cell lymphoma successfully treated by antiviral therapy.

    PubMed

    Galati, Giovanni; Rampa, Lorenzo; Vespasiani-Gentilucci, Umberto; Marino, Mirella; Pisani, Francesco; Cota, Carlo; Guidi, Alessandro; Picardi, Antonio

    2016-10-18

    B cells lymphoma is one of the most challenging extra-hepatic manifestations of hepatitis C virus (HCV). Recently, a new kind of B-cell lymphoma, named double-hit B (DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents (DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected. A possible effect of DAAs on DHL regression should be investigated, but eradicating HCV would avoid life-threatening reactivation of viral hepatitis during pharmacological immunosuppression in onco-haematological diseases.

  12. Smart current collector—fibre optic hit detection system for improved security on railway tracks

    NASA Astrophysics Data System (ADS)

    Schröder, Kerstin; Ecke, Wolfgang; Kautz, Michael; Willett, Simon; Unterwaditzer, Hansjörg; Bosselmann, Thomas; Rothhardt, Manfred

    2013-11-01

    In a deregulated EU railway market, monitoring the vehicle and infrastructure interfaces is mandatory for the enhanced availability of operation and for reducing costs. Therefore, infrastructure managers need monitoring tools on overhead contact lines (OCLs). We know from earlier investigations that a measurement of contact forces alone is not sufficient (Schröder et al 2013 Opt. Lasers Eng. 51 172-9). In this study, we introduce a system which is fast enough to detect short disturbances and which can be used with regular trains. It is based on fibre optic sensors integrated with conventional current collectors (CCs). The system is designed to monitor hard and soft hits on the CC in horizontal (driving) and vertical (contact) direction. It was systematically tested in the laboratory as well as in test runs on commercial railways in several countries. With its help, a variety of minor as well as serious defects have been discovered and repaired at the CC-OCL interface.

  13. Theoretical modeling of the MILES hit profiles in military weapon low-data rate simulators

    NASA Astrophysics Data System (ADS)

    Andrews, L. C.; Phillips, R. L.; Smith, C. A.; Belichki, S. B.; Crabbs, R.; Cofarro, J. T.; Fountain, W.; Tucker, F. M.; Parrish, B. J.

    2016-09-01

    Math modeling of a low-data-rate optical communication system is presented and compared with recent testing results over ranges up to 100 m in an indoor tunnel at Kennedy Space Center. Additional modeling of outdoor testing results at longer ranges in the open atmosphere is also presented. The system modeled is the Army's Multiple Integrated Laser Engagement System (MILES) that has been used as a tactical training system since the early 1980s. The objective of the current modeling and testing is to obtain target hit zone profiles for the M16A2/M4 rifles and establish a data baseline for MILES that will aid in its upgrade using more recently developed lasers and detectors.

  14. A double hit model for the distribution of time to AIDS onset

    NASA Astrophysics Data System (ADS)

    Chillale, Nagaraja Rao

    2013-09-01

    Incubation time is a key epidemiologic descriptor of an infectious disease. In the case of HIV infection this is a random variable and is probably the longest one. The probability distribution of incubation time is the major determinant of the relation between the incidences of HIV infection and its manifestation to Aids. This is also one of the key factors used for accurate estimation of AIDS incidence in a region. The present article i) briefly reviews the work done, points out uncertainties in estimation of AIDS onset time and stresses the need for its precise estimation, ii) highlights some of the modelling features of onset distribution including immune failure mechanism, and iii) proposes a 'Double Hit' model for the distribution of time to AIDS onset in the cases of (a) independent and (b) dependent time variables of the two markers and examined the applicability of a few standard probability models.

  15. Effects of elevated CO{sub 2} on plant-grazer interactions: The importance of urine-hits and simulated grazing on the response of a C{sub 3} grass from Yellowstone National Park

    SciTech Connect

    Wilsey, B.J.; Coleman, J.S.; McNaughton, S.J.

    1995-06-01

    Although grazing mammals are an important component of most grassland ecosystems, previous research on plant responses to elevated CO{sub 2} has rarely considered their effects. In a growth chamber experiment, we tested whether regrowth following simulated grazing was affected by elevated CO{sub 2} and urine hits (40 g/m{sup 2} urea N) in the C{sub 3} grass, Stipa occidentalis, which is common in Yellowstone National Park. Plant response (end of experiment biomass and productivity [biomass + clippings]) to elevated CO{sub 2} depended on whether plants received urine-hits and were clipped: plants only had increased growth in response to CO{sub 2} enrichment if they had received urea and were not clipped. Plants that received the entire grazing treatment (urea and clipping) had biomass and productivity values that were similar to controls. Thus, grazing mammals will tend to dampen the predicted CO{sub 2} effect in grasslands by significantly lowering increases in plant growth response to elevated CO{sub 2} levels.

  16. Integrated Computational Approach for Virtual Hit Identification against Ebola Viral Proteins VP35 and VP40

    PubMed Central

    Mirza, Muhammad Usman; Ikram, Nazia

    2016-01-01

    The Ebola virus (EBOV) has been recognised for nearly 40 years, with the most recent EBOV outbreak being in West Africa, where it created a humanitarian crisis. Mortalities reported up to 30 March 2016 totalled 11,307. However, up until now, EBOV drugs have been far from achieving regulatory (FDA) approval. It is therefore essential to identify parent compounds that have the potential to be developed into effective drugs. Studies on Ebola viral proteins have shown that some can elicit an immunological response in mice, and these are now considered essential components of a vaccine designed to protect against Ebola haemorrhagic fever. The current study focuses on chemoinformatic approaches to identify virtual hits against Ebola viral proteins (VP35 and VP40), including protein binding site prediction, drug-likeness, pharmacokinetic and pharmacodynamic properties, metabolic site prediction, and molecular docking. Retrospective validation was performed using a database of non-active compounds, and early enrichment of EBOV actives at different false positive rates was calculated. Homology modelling and subsequent superimposition of binding site residues on other strains of EBOV were carried out to check residual conformations, and hence to confirm the efficacy of potential compounds. As a mechanism for artefactual inhibition of proteins through non-specific compounds, virtual hits were assessed for their aggregator potential compared with previously reported aggregators. These systematic studies have indicated that a few compounds may be effective inhibitors of EBOV replication and therefore might have the potential to be developed as anti-EBOV drugs after subsequent testing and validation in experiments in vivo. PMID:27792169

  17. Novel Cancer Chemotherapy Hits by Molecular Topology: Dual Akt and Beta-Catenin Inhibitors

    PubMed Central

    Morell, Cecilia; Rodríguez-Henche, Nieves; Recio-Iglesias, Maria Carmen; Garcia-Domenech, Ramon

    2015-01-01

    Background and Purpose Colorectal and prostate cancers are two of the most common types and cause of a high rate of deaths worldwide. Therefore, any strategy to stop or at least slacken the development and progression of malignant cells is an important therapeutic choice. The aim of the present work is the identification of novel cancer chemotherapy agents. Nowadays, many different drug discovery approaches are available, but this paper focuses on Molecular Topology, which has already demonstrated its extraordinary efficacy in this field, particularly in the identification of new hit and lead compounds against cancer. This methodology uses the graph theoretical formalism to numerically characterize molecular structures through the so called topological indices. Once obtained a specific framework, it allows the construction of complex mathematical models that can be used to predict physical, chemical or biological properties of compounds. In addition, Molecular Topology is highly efficient in selecting and designing new hit and lead drugs. According to the aforementioned, Molecular Topology has been applied here for the construction of specific Akt/mTOR and β-catenin inhibition mathematical models in order to identify and select novel antitumor agents. Experimental Approach Based on the results obtained by the selected mathematical models, six novel potential inhibitors of the Akt/mTOR and β-catenin pathways were identified. These compounds were then tested in vitro to confirm their biological activity. Conclusion and Implications Five of the selected compounds, CAS n° 256378-54-8 (Inhibitor n°1), 663203-38-1 (Inhibitor n°2), 247079-73-8 (Inhibitor n°3), 689769-86-6 (Inhibitor n°4) and 431925-096 (Inhibitor n°6) gave positive responses and resulted to be active for Akt/mTOR and/or β-catenin inhibition. This study confirms once again the Molecular Topology’s reliability and efficacy to find out novel drugs in the field of cancer. PMID:25910265

  18. The High Cadence Transient Survey (HITS). I. Survey Design and Supernova Shock Breakout Constraints

    NASA Astrophysics Data System (ADS)

    Förster, F.; Maureira, J. C.; San Martín, J.; Hamuy, M.; Martínez, J.; Huijse, P.; Cabrera, G.; Galbany, L.; de Jaeger, Th.; González–Gaitán, S.; Anderson, J. P.; Kunkarayakti, H.; Pignata, G.; Bufano, F.; Littín, J.; Olivares, F.; Medina, G.; Smith, R. C.; Vivas, A. K.; Estévez, P. A.; Muñoz, R.; Vera, E.

    2016-12-01

    We present the first results of the High Cadence Transient Survey (HiTS), a survey for which the objective is to detect and follow-up optical transients with characteristic timescales from hours to days, especially the earliest hours of supernova (SN) explosions. HiTS uses the Dark Energy Camera and a custom pipeline for image subtraction, candidate filtering and candidate visualization, which runs in real-time to be able to react rapidly to the new transients. We discuss the survey design, the technical challenges associated with the real-time analysis of these large volumes of data and our first results. In our 2013, 2014, and 2015 campaigns, we detected more than 120 young SN candidates, but we did not find a clear signature from the short-lived SN shock breakouts (SBOs) originating after the core collapse of red supergiant stars, which was the initial science aim of this survey. Using the empirical distribution of limiting magnitudes from our observational campaigns, we measured the expected recovery fraction of randomly injected SN light curves, which included SBO optical peaks produced with models from Tominaga et al. (2011) and Nakar & Sari (2010). From this analysis, we cannot rule out the models from Tominaga et al. (2011) under any reasonable distributions of progenitor masses, but we can marginally rule out the brighter and longer-lived SBO models from Nakar & Sari (2010) under our best-guess distribution of progenitor masses. Finally, we highlight the implications of this work for future massive data sets produced by astronomical observatories, such as LSST.

  19. Galactic cosmic rays and cell-hit frequencies outside the magnetosphere.

    PubMed

    Curtis, S B; Letaw, J R

    1989-01-01

    An evaluation of the exposure of space travelers to galactic cosmic radiation outside the earth's magnetosphere is made by calculating fluences of high-energy primary and secondary particles with various charges traversing a sphere of area 100 microns2. Calculations relating to two shielding configurations are presented: the center of a spherical aluminum shell of thickness 1 g/cm2, and the center of a 4 g/cm2 thick aluminum spherical shell within which there is a 30 g/cm2 diameter spherical water phantom with the point of interest 5 g/cm2 from the surface. The area of 100 microns2 was chosen to simulate the nucleus of a cell in the body. The frequencies as a function of charge component in both shielding configurations reflects the odd-even disparity of the incident particle abundances. For a three-year mission, 33% of the cells in the more heavily shielded configuration would be hit by at least one particle with Z greater than 10. Six percent would be hit by at least two such particles. This emphasizes the importance of studying single high-Z particle effects both on cells which might be "at risk" for cancer induction and on critical neural cells or networks which might be vulnerable to inactivation by heavy charged particle tracks. Synergistic effects with the more numerous high-energy protons and helium ions cannot be ruled out. In terms of more conventional radiation risk assessment, the dose equivalent decreased by a factor of 2.85 from free space to that in the more heavily shielded configuration. Roughly half of this was due to the decrease in energy deposition (absorbed dose) and half to the decrease in biological effectiveness (quality factor).

  20. Sepsis Patients with First and Second-Hit Infections Show Different Outcomes Depending on the Causative Organism

    PubMed Central

    Morgan, Matt P.; Szakmany, Tamas; Power, Sarah G.; Olaniyi, Patrick; Hall, Judith E.; Rowan, Kathy; Eberl, Matthias

    2016-01-01

    Objective: With improving rates of initial survival in severe sepsis, second-hit infections that occur following resolution of the primary insult carry an increasing burden of morbidity. However, despite the clinical relevance of these infections, no data are available on differential outcomes in patients with first and second-hit infections depending on the nature of the causative organism. This study aims to explore any differences in these subgroups. Design: In a retrospective, observational cohort study, the United Kingdom Intensive Care National Audit & Research Centre (ICNARC) database was used to explore the outcomes of patient with first-hit infections leading to sepsis, and sepsis patients with second-hit infections grouped according to the Gram status of the causative organism. Setting: General critical care units in England, Wales, and Northern Ireland participating in the ICNARC programme between 1 January, 2007 and 30 June, 2012. Patients: Patient groups analyzed included 2119 patients with and 1319 patients without sepsis who developed an intensive care unit acquired infection in blood. Subgroups included patients with trauma, emergency neurosurgery, elective surgery, and cardiogenic shock. Measurements and main results: Gram-negative organisms were associated with poorer outcomes in first-hit infections. The 90-day mortality of patients who developed a Gram-negative infection was 43.6% following elective surgery and 27.9% following trauma. This compared with a mortality of 25.6 and 20.6%, respectively, in Gram-positive infections. Unexpectedly, an inverse relationship between Gram status and mortality was observed in second-hit infections. Patients with an initial diagnosis of sepsis who developed secondary infections caused by Gram-negative organisms had a 90-day mortality of 40.4%, compared with 43.6% in Gram-positive infections. Conclusions: Our study identifies a fundamental difference in patient outcomes between first-hit and second-hit

  1. Synthetic Medicinal Chemistry in Chagas’ Disease: Compounds at The Final Stage of “Hit-To-Lead” Phase

    PubMed Central

    Cerecetto, Hugo; González, Mercedes

    2010-01-01

    Chagas’ disease, or American trypanosomosiasis, has been the most relevant illness produced by protozoa in Latin America. Synthetic medicinal chemistry efforts have provided an extensive number of chemodiverse hits at the “active-to-hit” stage. However, only a more limited number of these have been studied in vivo in models of Chagas’ disease. Herein, we survey some of the cantidates able to surpass the “hit-to-lead” stage discussing their limitations or merit to enter in clinical trials in the short term. PMID:27713281

  2. Biochemical and Functional Studies on the Burkholderia cepacia Complex bceN Gene, Encoding a GDP-D-Mannose 4,6-Dehydratase

    PubMed Central

    Pinheiro, Pedro F.; Leitão, Jorge H.

    2013-01-01

    This work reports the biochemical and functional analysis of the Burkholderia cenocepacia J2315 bceN gene, encoding a protein with GDP-D-mannose 4,6-dehydratase enzyme activity (E.C.4.2.1.47). Data presented indicate that the protein is active when in the tetrameric form, catalyzing the conversion of GDP-D-mannose into GDP-4-keto-6-deoxy-D-mannose. This sugar nucleotide is the intermediary necessary for the biosynthesis of GDP-D-rhamnose, one of the sugar residues of cepacian, the major exopolysaccharide produced by environmental and human, animal and plant pathogenic isolates of the Burkholderia cepacia complex species. Vmax and Km values of 1.5±0.2 µmol.min−1.mg−1 and 1024±123 µM, respectively, were obtained from the kinetic characterization of the B. cenocepacia J2315 BceN protein by NMR spectroscopy, at 25°C and in the presence of 1 mol MgCl2 per mol of protein. The enzyme activity was strongly inhibited by the substrate, with an estimated Ki of 2913±350 µM. The lack of a functional bceN gene in a mutant derived from B. cepacia IST408 slightly reduced cepacian production. However, in the B. multivorans ATCC17616 with bceN as the single gene in its genome with predicted GMD activity, a bceN mutant did not produce cepacian, indicating that this gene product is required for cepacian biosynthesis. PMID:23460819

  3. Impact of Oxidative Stress on Ascorbate Biosynthesis in Chlamydomonas via Regulation of the VTC2 Gene Encoding a GDP-l-galactose Phosphorylase*

    PubMed Central

    Urzica, Eugen I.; Adler, Lital N.; Page, M. Dudley; Linster, Carole L.; Arbing, Mark A.; Casero, David; Pellegrini, Matteo; Merchant, Sabeeha S.; Clarke, Steven G.

    2012-01-01

    The l-galactose (Smirnoff-Wheeler) pathway represents the major route to l-ascorbic acid (vitamin C) biosynthesis in higher plants. Arabidopsis thaliana VTC2 and its paralogue VTC5 function as GDP-l-galactose phosphorylases converting GDP-l-galactose to l-galactose-1-P, thus catalyzing the first committed step in the biosynthesis of l-ascorbate. Here we report that the l-galactose pathway of ascorbate biosynthesis described in higher plants is conserved in green algae. The Chlamydomonas reinhardtii genome encodes all the enzymes required for vitamin C biosynthesis via the l-galactose pathway. We have characterized recombinant C. reinhardtii VTC2 as an active GDP-l-galactose phosphorylase. C. reinhardtii cells exposed to oxidative stress show increased VTC2 mRNA and l-ascorbate levels. Genes encoding enzymatic components of the ascorbate-glutathione system (e.g. ascorbate peroxidase, manganese superoxide dismutase, and dehydroascorbate reductase) are also up-regulated in response to increased oxidative stress. These results indicate that C. reinhardtii VTC2, like its plant homologs, is a highly regulated enzyme in ascorbate biosynthesis in green algae and that, together with the ascorbate recycling system, the l-galactose pathway represents the major route for providing protective levels of ascorbate in oxidatively stressed algal cells. PMID:22393048

  4. Synthesis of GDP-mannose and mannosylglycerate from labeled mannose by genetically engineered Escherichia coli without loss of specific isotopic enrichment.

    PubMed

    Sampaio, Maria-Manuel; Santos, Helena; Boos, Winfried

    2003-01-01

    We report the construction of an Escherichia coli mutant that harbors two compatible plasmids and that is able to synthesize labeled 2-O-alpha-D-mannosyl-D-glycerate from externally added labeled mannose without the loss of specific isotopic enrichment. The strain carries a deletion in the manA gene, encoding phosphomannose isomerase. This deletion prevents the formation of fructose-6-phosphate from mannose-6-phosphate after the uptake of mannose from the medium by mannose-specific enzyme II of the phosphotransferase system (PtsM). The strain also has a deletion of the cps gene cluster that prevents the synthesis of colanic acid, a mannose-containing polymer. Plasmid-encoded phosphomannomutase (cpsG) and mannose-1-phosphate guanylyltransferase (cpsB) ensure the formation of GDP-mannose. A second plasmid harbors msg, a gene from Rhodothermus marinus that encodes mannosylglycerate synthase, which catalyzes the formation of 2-O-alpha-D-mannosyl-D-glycerate from GDP-mannose and endogenous glycerate. The rate-limiting step in 2-O-alpha-D-mannosyl-D-glycerate formation is the transfer of GDP-mannose to glycerate. 2-O-alpha-D-mannosyl-D-glycerate can be released from cells by treatment with cold-water shock. The final product is formed in a yield exceeding 50% the initial quantity of labeled mannose, including loss during preparation and paper chromatography.

  5. A glutamic finger in the guanine nucleotide exchange factor ARNO displaces Mg2+ and the beta-phosphate to destabilize GDP on ARF1.

    PubMed Central

    Béraud-Dufour, S; Robineau, S; Chardin, P; Paris, S; Chabre, M; Cherfils, J; Antonny, B

    1998-01-01

    The Sec7 domain of the guanine nucleotide exchange factor ARNO (ARNO-Sec7) is responsible for the exchange activity on the small GTP-binding protein ARF1. ARNO-Sec7 forms a stable complex with the nucleotide-free form of [Delta17]ARF1, a soluble truncated form of ARF1. The crystal structure of ARNO-Sec7 has been solved recently, and a site-directed mutagenesis approach identified a hydrophobic groove and an adjacent hydrophilic loop as the ARF1-binding site. We show that Glu156 in the hydrophilic loop of ARNO-Sec7 is involved in the destabilization of Mg2+ and GDP from ARF1. The conservative mutation E156D and the charge reversal mutation E156K reduce the exchange activity of ARNO-Sec7 by several orders of magnitude. Moreover, [E156K]ARNO-Sec7 forms a complex with the Mg2+-free form of [Delta17]ARF1-GDP without inducing the release of GDP. Other mutations in ARNO-Sec7 and in [Delta17]ARF1 suggest that prominent hydrophobic residues of the switch I region of ARF1 insert into the groove of the Sec7 domain, and that Lys73 of the switch II region of ARF1 forms an ion pair with Asp183 of ARNO-Sec7. PMID:9649435

  6. EF-Tu dynamics during pre-translocation complex formation: EF-Tu·GDP exits the ribosome via two different pathways.

    PubMed

    Liu, Wei; Chen, Chunlai; Kavaliauskas, Darius; Knudsen, Charlotte R; Goldman, Yale E; Cooperman, Barry S

    2015-10-30

    The G-protein EF-Tu, which undergoes a major conformational change when EF-Tu·GTP is converted to EF-Tu·GDP, forms part of an aminoacyl(aa)-tRNA·EF-Tu·GTP ternary complex (TC) that accelerates the binding of aa-tRNA to the ribosome during peptide elongation. Such binding, placing a portion of EF-Tu in contact with the GTPase Associated Center (GAC), is followed by GTP hydrolysis and Pi release, and results in formation of a pretranslocation (PRE) complex. Although tRNA movement through the ribosome during PRE complex formation has been extensively studied, comparatively little is known about the dynamics of EF-Tu interaction with either the ribosome or aa-tRNA. Here we examine these dynamics, utilizing ensemble and single molecule assays employing fluorescent labeled derivatives of EF-Tu, tRNA, and the ribosome to measure changes in either FRET efficiency or fluorescence intensity during PRE complex formation. Our results indicate that ribosome-bound EF-Tu separates from the GAC prior to its full separation from aa-tRNA, and suggest that EF-Tu·GDP dissociates from the ribosome by two different pathways. These pathways correspond to either reversible EF-Tu·GDP dissociation from the ribosome prior to the major conformational change in EF-Tu that follows GTP hydrolysis, or irreversible dissociation after or concomitant with this conformational change.

  7. The effects of calcium channel blocker benidipine and calmodulin antagonist W7 on GDP-binding capacity of brown adipose tissue in mice.

    PubMed

    Song, Yuh-Min; Lin, Pi-Yao; Chen, Ming-Der

    2009-03-01

    It has been suggested that increased dietary calcium intake can attenuate obesity. Calcium antagonists, such as benidipine, also have been shown to have an anti-obesity effect. However, the mechanism for calcium-related anti-obesity effect has not yet been established. A defective brown adipose tissue thermogenesis has been shown in obese rodents. This study was designed to examine the direct effects of calcium channel blocker benidipine and calmodulin antagonist W7 administration on the adaptive thermogenesis in brown adipose tissue taken from the genetically obese mice and their lean controls. The GDP binding to brown-fat cell mitochondria was used as a brown adipose tissue thermogenic index. The results show that benidipine treatment had no marked effect on brown-fat cell GDP-binding capacities in both obese and lean mice. However, GDP-binding capacities were significantly reduced in both obese and lean mice after the W7 administration. The results of this study support the previous finding that benidipine did not have direct thermogenic effect on brown adipose tissue and suggest that the change in intracellular calmodulin availability might contribute to the adaptive thermogenesis in brown adipose tissue.

  8. Mutations in GDP-Mannose Pyrophosphorylase B Cause Congenital and Limb-Girdle Muscular Dystrophies Associated with Hypoglycosylation of α-Dystroglycan

    PubMed Central

    Carss, Keren J.; Stevens, Elizabeth; Foley, A. Reghan; Cirak, Sebahattin; Riemersma, Moniek; Torelli, Silvia; Hoischen, Alexander; Willer, Tobias; van Scherpenzeel, Monique; Moore, Steven A.; Messina, Sonia; Bertini, Enrico; Bönnemann, Carsten G.; Abdenur, Jose E.; Grosmann, Carla M.; Kesari, Akanchha; Punetha, Jaya; Quinlivan, Ros; Waddell, Leigh B.; Young, Helen K.; Wraige, Elizabeth; Yau, Shu; Brodd, Lina; Feng, Lucy; Sewry, Caroline; MacArthur, Daniel G.; North, Kathryn N.; Hoffman, Eric; Stemple, Derek L.; Hurles, Matthew E.; van Bokhoven, Hans; Campbell, Kevin P.; Lefeber, Dirk J.; Lin, Yung-Yao; Muntoni, Francesco

    2013-01-01

    Congenital muscular dystrophies with hypoglycosylation of α-dystroglycan (α-DG) are a heterogeneous group of disorders often associated with brain and eye defects in addition to muscular dystrophy. Causative variants in 14 genes thought to be involved in the glycosylation of α-DG have been identified thus far. Allelic mutations in these genes might also cause milder limb-girdle muscular dystrophy phenotypes. Using a combination of exome and Sanger sequencing in eight unrelated individuals, we present evidence that mutations in guanosine diphosphate mannose (GDP-mannose) pyrophosphorylase B (GMPPB) can result in muscular dystrophy variants with hypoglycosylated α-DG. GMPPB catalyzes the formation of GDP-mannose from GTP and mannose-1-phosphate. GDP-mannose is required for O-mannosylation of proteins, including α-DG, and it is the substrate of cytosolic mannosyltransferases. We found reduced α-DG glycosylation in the muscle biopsies of affected individuals and in available fibroblasts. Overexpression of wild-type GMPPB in fibroblasts from an affected individual partially restored glycosylation of α-DG. Whereas wild-type GMPPB localized to the cytoplasm, five of the identified missense mutations caused formation of aggregates in the cytoplasm or near membrane protrusions. Additionally, knockdown of the GMPPB ortholog in zebrafish caused structural muscle defects with decreased motility, eye abnormalities, and reduced glycosylation of α-DG. Together, these data indicate that GMPPB mutations are responsible for congenital and limb-girdle muscular dystrophies with hypoglycosylation of α-DG. PMID:23768512

  9. Female Education as a Determinant of Economic Growth: The Case Study of Pakistan

    ERIC Educational Resources Information Center

    Fatima, Goher

    2011-01-01

    The contribution of female education has been very important in the GDP growth of the country, but this very sector has been ignored by the Government. This paper focuses on the importance of female education and highlights its significance for national development. It also brings out some impediments, obstacles and barriers confronting female…

  10. The role of energy in economic growth.

    PubMed

    Stern, David I

    2011-02-01

    This paper reviews the mainstream, resource economics, and ecological economics models of growth. A possible synthesis of energy-based and mainstream models is presented. This shows that when energy is scarce it imposes a strong constraint on the growth of the economy; however, when energy is abundant, its effect on economic growth is much reduced. The industrial revolution released the constraints on economic growth by the development of new methods of using coal and the discovery of new fossil fuel resources. Time-series analysis shows that energy and GDP cointegrate, and energy use Granger causes GDP when capital and other production inputs are included in the vector autoregression model. However, various mechanisms can weaken the links between energy and growth. Energy used per unit of economic output has declined in developed and some developing countries, owing to both technological change and a shift from poorer quality fuels, such as coal, to the use of higher quality fuels, especially electricity. Substitution of other inputs for energy and sectoral shifts in economic activity play smaller roles.

  11. Stringent Mitigation Policy Implied By Temperature Impacts on Economic Growth

    NASA Astrophysics Data System (ADS)

    Moore, F.; Turner, D.

    2014-12-01

    Integrated assessment models (IAMs) compare the costs of greenhouse gas mitigation with damages from climate change in order to evaluate the social welfare implications of climate policy proposals and inform optimal emissions reduction trajectories. However, these models have been criticized for lacking a strong empirical basis for their damage functions, which do little to alter assumptions of sustained GDP growth, even under extreme temperature scenarios. We implement empirical estimates of temperature effects on GDP growth-rates in the Dynamic Integrated Climate and Economy (DICE) model via two pathways, total factor productivity (TFP) growth and capital depreciation. Even under optimistic adaptation assumptions, this damage specification implies that optimal climate policy involves the elimination of emissions in the near future, the stabilization of global temperature change below 2°C, and a social cost of carbon (SCC) an order of magnitude larger than previous estimates. A sensitivity analysis shows that the magnitude of growth effects, the rate of adaptation, and the dynamic interaction between damages from warming and GDP are three critical uncertainties and an important focus for future research.

  12. Evaluation of trade influence on economic growth rate by computational intelligence approach

    NASA Astrophysics Data System (ADS)

    Sokolov-Mladenović, Svetlana; Milovančević, Milos; Mladenović, Igor

    2017-01-01

    In this study was analyzed the influence of trade parameters on the economic growth forecasting accuracy. Computational intelligence method was used for the analyzing since the method can handle highly nonlinear data. It is known that the economic growth could be modeled based on the different trade parameters. In this study five input parameters were considered. These input parameters were: trade in services, exports of goods and services, imports of goods and services, trade and merchandise trade. All these parameters were calculated as added percentages in gross domestic product (GDP). The main goal was to select which parameters are the most impactful on the economic growth percentage. GDP was used as economic growth indicator. Results show that the imports of goods and services has the highest influence on the economic growth forecasting accuracy.

  13. Probability of cell hits in selected organs and tissues by high-LET particles at the ISS orbit

    NASA Technical Reports Server (NTRS)

    Yasuda, H.; Komiyama, T.; Fujitaka, K.; Badhwar, G. D. (Principal Investigator)

    2002-01-01

    The fluence of high-LET particles (HLP) with LET infinity H2O greater than 15 keV micrometers-1 in selected organs and tissues were measured with plastic nuclear track detectors using a life-size human phantom on the 9th Shuttle-Mir Mission (STS-91). The planar-track fluence of HLP during the 9.8-day mission ranged from 1.9 x 10(3) n cm-2 (bladder) to 5.1 x 10(3) n cm-2 (brain) by a factor of 2.7. Based on these data, a probability of HLP hits to a matured cell of each organ or tissue was roughly estimated for a 90-day ISS mission. In the calculation, all cells were assumed to be spheres with a geometric cross-sectional area of 500 micrometers2 and the cell-hit frequency from isotropic space radiation can be described by the Poisson-distribution function. As results, the probability of one or more than 1 hit to a single cell by HLP for 90 days ranged from 17% to 38%; that of two or more than 2 hits was estimated to be 1.3-8.2%. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  14. The Pharmacotherapy of Heparin-Induced Thrombocytopenia (HIT) : A Review of Contemporary Therapeutic Challenges in Clinical Practice.

    PubMed

    Hassan, Yahaya; Awaisu, Ahmed; Al-Meman, Ahmad Abdulrahman; Aziz, Noorizan Abd

    2008-04-01

    Our objectives were to discuss a general overview on the description and recognition of heparin-induced thrombocytopenia (HIT) and present a critical review of the traditional and most recent advances in its pharmacotherapy. Computerized searches were done on MEDLINE and Iowa Drug Information Service (IDIS) databases from June 2001 until June 2007 and from May 2005 until May 2007, respectively. Search terms used included 'heparin-induced thrombocytopenia', 'heparin-associated thrombocytopenia', therapeutics, HIT, HAT. We largely selected publications within the timeframe above, but did not exclude commonly referenced and highly regarded older publications. The commonly referenced published articles were obtained through manual searches derived from bibliographic citations and retrievals from the authors' personal files. Pertinent literatures (89 key articles) that were thought to have substantially contributed new information to the therapeutics of HIT within the last 6 years were identified, reviewed and presented. The following limits were used for the MEDLINE and IDIS searches: 'human', drug therapy', 'review', 'meta-analysis', 'clinical trial', and case reports. The therapeutics of HIT is rapidly evolving and needs to consider an evidence - based approach. It is imperative that practitioners be aware of the associated risk and be up-to-date with the current advances in the management of this fatal clinical condition.

  15. Combined use of pharmacophoric models together with drug metabolism and genotoxicity "in silico" studies in the hit finding process

    NASA Astrophysics Data System (ADS)

    Jerez, Ma José; Jerez, Miguel; González-García, Coral; Ballester, Sara; Castro, Ana

    2013-01-01

    In this study we propose a virtual screening strategy based on the generation of a pharmacophore hypothesis, followed by an in silico evaluation of some ADME-TOX properties with the aim to apply it to the hit finding process and, specifically, to characterize new chemical entities with potential to control inflammatory processes mediated by T lymphocytes such as multiple sclerosis, systemic lupus erithematosus or rheumatoid arthritis. As a result, three compounds with completely novel scaffolds were selected as final hits for future hit-to-lead optimization due to their anti-inflammatory profile. The biological results showed that the selected compounds increased the intracellular cAMP levels and inhibited cell proliferation in T lymphocytes. Moreover, two of these compounds were able to increase the production of IL-4, an immunoregulatory cytokine involved in the selective deviation of T helper (Th) immune response Th type 2 (Th2), which has been proved to have anti-inflammatory properties in several animal models for autoimmune pathologies as multiple sclerosis or rheumatoid arthritis. Thus our pharmacological strategy has shown to be useful to find molecules with biological activity to control immune responses involved in many inflammatory disorders. Such promising data suggested that this in silico strategy might be useful as hit finding process for future drug development.

  16. Engithidong Xugixudhoy: Their Stories of Long Ago. Told in Deg Hit'an Athabaskan by Belle Deacon of Anvik.

    ERIC Educational Resources Information Center

    Deacon, Belle; Kari, James, Ed.

    Nine stories, told by a woman of the Lower Yukon Valley (Alaska), are presented here in Deg Hit'an Athabaskan on the left page and in English translation on the right page. The storyteller's English version of five of the stories is also included. Introductory sections contain a biography of Belle Deacon and notes on the gathering, transcription,…

  17. Comparing among the Experiences of Self-Cutting, Hitting, and Scratching in Chinese Adolescents Attending Secondary Schools: An Interview Study

    ERIC Educational Resources Information Center

    You, Jianing; Ma, Congfen; Lin, Min-Pei; Leung, Freedom

    2015-01-01

    This study examined adolescents' experiences associated with nonsuicidal self-injury (NSSI) and compared among the experiences of self-cutting, hitting, and scratching. Participants included 42 Chinese adolescents attending secondary schools. They had at least three NSSI episodes in the preceding year. Information about their experiences of NSSI…

  18. The Case against Spanking: How to Discipline Your Child without Hitting. The Jossey-Bass Psychology Series.

    ERIC Educational Resources Information Center

    Hyman, Irwin A.

    The research on discipline is synthesized and presented in a highly readable form making the case against corporal punishment of children. The negative results are presented through examples. Although popular opinion on the subject of hitting has shifted so that many parents as well as educators and therapists realize the connection between…

  19. Using ProHits to store, annotate, and analyze affinity purification-mass spectrometry (AP-MS) data.

    PubMed

    Liu, Guomin; Zhang, Jianping; Choi, Hyungwon; Lambert, Jean-Philippe; Srikumar, Tharan; Larsen, Brett; Nesvizhskii, Alexey I; Raught, Brian; Tyers, Mike; Gingras, Anne-Claude

    2012-09-01

    Affinity purification coupled with mass spectrometry (AP-MS) is a robust technique used to identify protein-protein interactions. With recent improvements in sample preparation, and dramatic advances in MS instrumentation speed and sensitivity, this technique is becoming more widely used throughout the scientific community. To meet the needs of research groups both large and small, we have developed software solutions for tracking, scoring and analyzing AP-MS data. Here, we provide details for the installation and utilization of ProHits, a Laboratory Information Management System designed specifically for AP-MS interaction proteomics. This protocol explains: (i) how to install the complete ProHits system, including modules for the management of mass spectrometry files and the analysis of interaction data, and (ii) alternative options for the use of pre-existing search results in simpler versions of ProHits, including a virtual machine implementation of our ProHits Lite software. We also describe how to use the main features of the software to analyze AP-MS data.

  20. Relationships between Parents' Use of Corporal Punishment and Their Children's Endorsement of Spanking and Hitting Other Children

    ERIC Educational Resources Information Center

    Simons, Dominique A.; Wurtele, Sandy K.

    2010-01-01

    Objectives: To explore the intergenerational cycle of violence, the present study examined the relationship between parental approval and children's approval of corporal punishment (CP) and the subsequent relationship between children's CP experience and preference for hitting to resolve interpersonal conflict. Method: Participants consisted of…

  1. The influence of aqueous content in small scale salt screening--improving hit rate for weakly basic, low solubility drugs.

    PubMed

    Tarsa, Peter B; Towler, Christopher S; Woollam, Grahame; Berghausen, Jörg

    2010-09-11

    Salt screening and selection is a well established approach for improving the properties of drug candidates, including dissolution rate and bioavailability. Typically during early development only small amounts of compound are available for solid state profiling, including salt screening. In order to probe large areas of experimental space, high-throughput screening is utilized and is often designed in a way to search for suitable crystallization parameters within hundreds or even thousands of conditions. However, the hit rate in these types of screens can be very low. In order to allow for selection of a salt form early within the drug development process whilst using smaller amounts of compounds, a screening procedure taking into account the compounds properties and the driving forces for salt formation is described. Experiments were carried out on the model compounds clotrimazole, cinnarizine itraconazole and atropine. We found an increase in crystalline hit rate for water-insoluble drugs crystallized from solutions that included at least 10% aqueous content. Conversely it was observed that compounds with greater water solubility did not benefit from aqueous content in salt screening, instead organic solvents lead to more crystalline screening hits. Results from four model compounds show that the inclusion of an aqueous component to the salt reaction can enhance the chance of salt formation and significantly improve the crystalline hit rate for low water soluble drugs.

  2. Formation and sustainment of a very low aspect ratio tokamak using coaxial helicity injection (the Helicity Injected Torus (HIT) experiment)

    SciTech Connect

    Jarboe, T.R.; Nelson, B.A.

    1992-01-01

    In the paper we will detail the progress of the HIT experiment construction, including the following components: preliminary data and interpretation; diagnostic systems; vacuum vessel and pumping system; helicity source and power supplies; toroidal field coil and power supply; data acquisition system; collaboration with general atomics, with a brief summary given on each.

  3. Inactivation of GDP-fucose transporter gene (Slc35c1) in CHO cells by ZFNs, TALENs and CRISPR-Cas9 for production of fucose-free antibodies.

    PubMed

    Chan, Kah Fai; Shahreel, Wahyu; Wan, Corrine; Teo, Gavin; Hayati, Noor; Tay, Shi Jie; Tong, Wen Han; Yang, Yuansheng; Rudd, Pauline M; Zhang, Peiqing; Song, Zhiwei

    2016-03-01

    Removal of core fucose from N-glycans attached to human IgG1 significantly enhances its affinity for the receptor FcγRIII and thereby dramatically improves its antibody-dependent cellular cytotoxicity activity. While previous works have shown that inactivation of fucosyltransferase 8 results in mutants capable of producing fucose-free antibodies, we report here the use of genome editing techniques, namely ZFNs, TALENs and the CRISPR-Cas9, to inactivate the GDP-fucose transporter (SLC35C1) in Chinese hamster ovary (CHO) cells. A FACS approach coupled with a fucose-specific lectin was developed to rapidly isolate SLC35C1-deficient cells. Mass spectrometry analysis showed that both EPO-Fc produced in mutants arising from CHO-K1 and anti-Her2 antibody produced in mutants arising from a pre-existing antibody-producing CHO-HER line lacked core fucose. Lack of functional SLC35C1 in these cells does not affect cell growth or antibody productivity. Our data demonstrate that inactivating Slc35c1 gene represents an alternative approach to generate CHO cells for production of fucose-free antibodies.

  4. Human Umbilical Cord Blood Mononuclear Cells in a Double-Hit Model of Bronchopulmonary Dysplasia in Neonatal Mice

    PubMed Central

    Mildau, Céline; Shen, Jie; Kasoha, Mariz; Laschke, Matthias W.; Roolfs, Torge; Schmiedl, Andreas; Tschernig, Thomas; Bieback, Karen; Gortner, Ludwig

    2013-01-01

    Background Bronchopulmonary dysplasia (BPD) presents a major threat of very preterm birth and treatment options are still limited. Stem cells from different sources have been used successfully in experimental BPD, induced by postnatal hyperoxia. Objectives We investigated the effect of umbilical cord blood mononuclear cells (MNCs) in a new double-hit mouse model of BPD. Methods For the double-hit, date mated mice were subjected to hypoxia and thereafter the offspring was exposed to hyperoxia. Human umbilical cord blood MNCs were given intraperitoneally by day P7. As outcome variables were defined: physical development (auxology), lung structure (histomorphometry), expression of markers for lung maturation and inflammation on mRNA and protein level. Pre- and postnatal normoxic pups and sham treated double-hit pups served as control groups. Results Compared to normoxic controls, sham treated double-hit animals showed impaired physical and lung development with reduced alveolarization and increased thickness of septa. Electron microscopy revealed reduced volume density of lamellar bodies. Pulmonary expression of mRNA for surfactant proteins B and C, Mtor and Crabp1 was reduced. Expression of Igf1 was increased. Treatment with umbilical cord blood MNCs normalized thickness of septa and mRNA expression of Mtor to levels of normoxic controls. Tgfb3 mRNA expression and pro-inflammatory IL-1β protein concentration were decreased. Conclusion The results of our study demonstrate the therapeutic potential of umbilical cord blood MNCs in a new double-hit model of BPD in newborn mice. We found improved lung structure and effects on molecular level. Further studies are needed to address the role of systemic administration of MNCs in experimental BPD. PMID:24069341

  5. Aftermath of early Hit-and-Run collisions in the Inner Solar System

    NASA Astrophysics Data System (ADS)

    Sarid, Gal; Stewart, Sarah T.; Leinhardt, zoe M.

    2015-08-01

    Planet formation epoch, in the terrestrial planet region and the asteroid belt, was characterized by a vigorous dynamical environment that was conducive to giant impacts among planetary embryos and asteroidal parent bodies, leading to diverse outcomes. Among these the greatest potential for producing diverse end-members lies is the erosive Hit-and-Run regime (small mass ratios, off-axis oblique impacts and non-negligible ejected mass), which is also more probable in terms of the early dynamical encounter configuration in the inner solar system. This collision regime has been invoked to explain outstanding issues, such as planetary volatile loss records, origin of the Moon and mantle stripping from Mercury and some of the larger asteroids (Vesta, Psyche).We performed and analyzed a set of simulations of Hit-and-Run events, covering a large range of mass ratios (1-20), impact parameters (0.25-0.96, for near head-on to barely grazing) and impact velocities (~1.5-5 times the mutual escape velocity, as dependent on the mass ratio). We used an SPH code with tabulated EOS and a nominal simlated time >1 day, to track the collisional shock processing and the provenance of material components. of collision debris. Prior to impact runs, all bodies were allowed to initially settle to negligible particle velocities in isolation, within ~20 simulated hrs. The total number of particles involved in each of our collision simulations was between (1-3 x 105). Resulting configurations include stripped mantles, melting/vaporization of rock and/or iron cores and strong variations of asteroid parent bodies fromcanonical chondritic composition.In the context of large planetary formation simulations, velocity and impact angle distributions are necessary to asses impact probabilities. The mass distribution and interaction within planetary embryo and asteroid swarms depends both on gravitational dynamics and the applied fragmentation mechanism. We will present results pertaining to general

  6. "I Feel like I'm Being Hit from All Directions": Enduring the Bombardment as a Mature-Age Learner Returning to Formal Learning

    ERIC Educational Resources Information Center

    Willans, Julie; Seary, Karen

    2011-01-01

    The mature-age learner's re-engagement with a formal learning environment may be somewhat akin to the novice Paintball player who, unless well positioned and attuned to the rules of the combative game, is bombarded and worn down by constant "hits". For the mature-age learner, such "hits" may come in the form of tensions…

  7. GDP-L-fucose: .beta.-D-galactoside 2-.alpha.-L-fucosyltransferases, DNA sequences encoding the same, method for producing the same and a method of genotyping a person

    SciTech Connect

    Lowe, John B.; Lennon, Gregory; Rouquier, Sylvie; Giorgi, Dominique; Kelly, Robert J.

    1998-01-01

    The gene encoding GDP-L-fucose: .beta.-D-Galactoside 2-.alpha.-L-fucosyltransferase has been cloned, and a mutation in this gene has been found to be responsible for an individual being a non-secretor.

  8. GDP-L-fucose: {beta}-D-galactoside 2-{alpha}-Lfucosyltransferases, DNA sequences encoding the same, method for producing the same and a method of genotyping a person

    DOEpatents

    Lowe, J.B.; Lennon, G.; Rouquier, S.; Giorgi, D.; Kelly, R.J.

    1998-09-15

    The gene encoding GDP-L-fucose: {beta}-D-Galactoside 2-{alpha}-Lfucosyltransferase has been cloned, and a mutation in this gene has been found to be responsible for an individual being a non-secretor. 30 figs.

  9. Some recent advances of intelligent health monitoring systems for civil infrastructures in HIT

    NASA Astrophysics Data System (ADS)

    Ou, Jinping

    2005-06-01

    The intelligent health monitoring systems more and more become a technique for ensuring the health and safety of civil infrastructures and also an important approach for research of the damage accumulation or even disaster evolving characteristics of civil infrastructures, and attracts prodigious research interests and active development interests of scientists and engineers since a great number of civil infrastructures are planning and building each year in mainland China. In this paper, some recent advances on research, development nad implementation of intelligent health monitoring systems for civil infrastructuresin mainland China, especially in Harbin Institute of Technology (HIT), P.R.China. The main contents include smart sensors such as optical fiber Bragg grating (OFBG) and polivinyllidene fluoride (PVDF) sensors, fatigue life gauges, self-sensing mortar and carbon fiber reinforced polymer (CFRP), wireless sensor networks and their implementation in practical infrastructures such as offshore platform structures, hydraulic engineering structures, large span bridges and large space structures. Finally, the relative research projects supported by the national foundation agencies of China are briefly introduced.

  10. [HINT1--a novel tumor suppressor protein of the HIT superfamily].

    PubMed

    Ozga, Magdalena

    2010-01-01

    The histidine triad nucleotide binding protein1 (Hint1) belongs to the first branch of the HIT superfamily. Hint1 catalyses the process of hydrolysis of the P-N bond in AMP-lysine, AMP-alanine, AMP-NH2. The physiological role of this enzyme is still unclear. There is accumulating evidence that HINT1 is a novel tumor suppressor protein, albeit the mechanism of action of HINT1 in respect to tumor suppression is not fully understood. Recent findings have shown that Hint1 inhibits the activity of the transcription factors AP1, MITF and USF2, as well as influences the transcription process of some genes of Wnt/beta-catenin pathway. Thereby, it seems that Hint1 exerts its major cellular function as gene transcription regulator, and thus, this function provides its potential role as a tumor suppressor protein. The clinical relevance of impairments in the Hint1 expression with the respect to specific human cancers is still a matter of extensive studies.

  11. Dimensional measurement of micro parts with high aspect ratio in HIT-UOI

    NASA Astrophysics Data System (ADS)

    Dang, Hong; Cui, Jiwen; Feng, Kunpeng; Li, Junying; Zhao, Shiyuan; Zhang, Haoran; Tan, Jiubin

    2016-11-01

    Micro parts with high aspect ratios have been widely used in different fields including aerospace and defense industries, while the dimensional measurement of these micro parts becomes a challenge in the field of precision measurement and instrument. To deal with this contradiction, several probes for the micro parts precision measurement have been proposed by researchers in Center of Ultra-precision Optoelectronic Instrument (UOI), Harbin Institute of Technology (HIT). In this paper, optical fiber probes with structures of spherical coupling(SC) with double optical fibers, micro focal-length collimation (MFL-collimation) and fiber Bragg grating (FBG) are described in detail. After introducing the sensing principles, both advantages and disadvantages of these probes are analyzed respectively. In order to improve the performances of these probes, several approaches are proposed. A two-dimensional orthogonal path arrangement is propounded to enhance the dimensional measurement ability of MFL-collimation probes, while a high resolution and response speed interrogation method based on differential method is used to improve the accuracy and dynamic characteristics of the FBG probes. The experiments for these special structural fiber probes are given with a focus on the characteristics of these probes, and engineering applications will also be presented to prove the availability of them. In order to improve the accuracy and the instantaneity of the engineering applications, several techniques are used in probe integration. The effectiveness of these fiber probes were therefore verified through both the analysis and experiments.

  12. Average probability that a "cold hit" in a DNA database search results in an erroneous attribution.

    PubMed

    Song, Yun S; Patil, Anand; Murphy, Erin E; Slatkin, Montgomery

    2009-01-01

    We consider a hypothetical series of cases in which the DNA profile of a crime-scene sample is found to match a known profile in a DNA database (i.e., a "cold hit"), resulting in the identification of a suspect based only on genetic evidence. We show that the average probability that there is another person in the population whose profile matches the crime-scene sample but who is not in the database is approximately 2(N - d)p(A), where N is the number of individuals in the population, d is the number of profiles in the database, and p(A) is the average match probability (AMP) for the population. The AMP is estimated by computing the average of the probabilities that two individuals in the population have the same profile. We show further that if a priori each individual in the population is equally likely to have left the crime-scene sample, then the average probability that the database search attributes the crime-scene sample to a wrong person is (N - d)p(A).

  13. Insulin therapy induces changes in the inflammatory response in a murine 2-hit model.

    PubMed

    Barkhausen, Tanja; Probst, Christian; Hildebrand, Frank; Pape, Hans-Christoph; Krettek, Christian; van Griensven, Martijn

    2009-08-01

    Post-traumatic complications commonly seen on intensive care units include sepsis and associated disorders, which are accompanied by alterations in inflammatory cytokine expression patterns and in activation of neutrophils. Hyperglycaemia, often occurring after trauma and sepsis, is a further risk factor for morbidity and mortality among critically ill people. Clinical investigations have suggested that strict glycaemic control by insulin titration reduces overall mortality. This study aimed to further elucidate the pathophysiological and immunomodulative actions of insulin. Femoral fracture was induced in a murine model, followed by 1h of haemorrhage. Two days after the first hit, sepsis was induced by caecal ligation and puncture (CLP). In control animals, laparotomy only was performed. Insulin in two different concentrations (10IU or 20IU) or vehicle was administered daily. Insulin therapy was associated with improvement of clinical parameters, slightly improved survival rates and, in lungs and liver, fewer infiltrating neutrophils and reduced IL-6 and IL-10 mRNA expression. These results suggested that, in this animal model, insulin had a direct anti-inflammatory effect that was independent of modulation of blood glucose levels.

  14. Development of ultra-precision micro-cavity measurement technique in HIT-UOI

    NASA Astrophysics Data System (ADS)

    Cui, Jiwen; Li, Lei; Tan, Jiubin

    2010-08-01

    Micro cavities with high aspect ratio are widely used in different fields including aerospace and defense industries with the development of manufacturing technology. So how to measure the dimension of these cavities has become one of the major research subjects in the field of measurement and instrument. This paper describes some activities of the precision micro cavity measurement technique in Center of Ultra-precision Optoelectronic Instrument (UOI), Harbin Institute of Technology (HIT). The key issue of micro cavity measurement in UOI is called touch-trigger measurement method. The first scheme is double optical fiber coupling, in which light coming from the incident optical fiber is transmitted in the reversal direction via the optical fiber coupling into the effluent optical fiber, the lateral displacement of the touch-trigger sensor is transformed into the deflexion of light coming out from the effluent optical fiber, and the deflexion is transformed into an image signal by the object lens and CCD capturing system. And the second scheme is micro focal-length collimation, in which a fiber stem with a ball mounted on its end is used as a probe and a small segment of it is used as a cylindrical lens to collimate a point light source and image it to a camera, the deflection of the fiber stem can be inferred from the change in image acquired by the camera with ultrahigh displacement sensitivity. Experiments for these activities will be given with a focus on the measurement results and repeatability uncertainty.

  15. Double-hit lymphoma at second relapse of Burkitt-like lymphoma: a case report.

    PubMed

    Tanaka, Hiroaki; Hashimoto, Shinichiro; Abe, Daijiro; Sakai, Shio; Takagi, Toshiyuki

    2011-01-01

    Double-hit lymphoma (DHL) is a rare and extremely unfavorable type of lymphoma with concurrent chromosomal translocations of BCL2 and MYC. It is considered that BCL2 translocation precedes MYC events in lymphomagenesis of DHL. In fact, most cases of DHL arise de novo or following FL. We describe a very rare case of DHL arising from Burkitt-like lymphoma according to the revised European-American classification of lymphoid neoplasms. A 67-year-old Japanese male presented with persistent fever. [(18)F]-fluorodeoxyglucose positron emission tomography revealed multiple abnormal accumulations in the bone marrow, pancreas, and periphery of the left kidney. The patient was diagnosed with Burkitt-like lymphoma according to a bone marrow biopsy. At the disease onset and the first relapse, chemotherapy was effective and the patient experienced sustained and complete remission. At the second relapse, however, the clinical presentation and morphology of lymphoma cells were nearly identical, but a high level of chemoresistance was acquired, and the patient succumbed almost 1 month after hospitalization. Chromosomal analyses revealed a complex karyotype with concurrent t(14;18) and t(8;22) translocations, which have not been previously detected. It is therefore important to note that DHL cannot be diagnosed without chromosomal analysis. Cytogenetic analyses should thus be performed for patients with high-grade B-cell lymphoma and who experience a recurrence of this lymphoma.

  16. The effects of characteristics of substituents on toxicity of the nitroaromatics: HiT QSAR study

    NASA Astrophysics Data System (ADS)

    Kuz'min, Victor E.; Muratov, Eugene N.; Artemenko, Anatoly G.; Gorb, Leonid; Qasim, Mohammad; Leszczynski, Jerzy

    2008-10-01

    The present study applies the Hierarchical Technology for Quantitative Structure-Activity Relationships (HiT QSAR) for (i) evaluation of the influence of the characteristics of 28 nitroaromatic compounds (some of which belong to a widely known class of explosives) as to their toxicity; (ii) prediction of toxicity for new nitroaromatic derivatives; (iii) analysis of the effects of substituents in nitroaromatic compounds on their toxicity in vivo. The 50% lethal dose concentration for rats (LD50) was used to develop the QSAR models based on simplex representation of molecular structure. The preliminary 1D QSAR results show that even the information on the composition of molecules reveals the main tendencies of changes in toxicity. The statistic characteristics for partial least squares 2D QSAR models are quite satisfactory ( R 2 = 0.96-0.98; Q 2 = 0.91-0.93; R 2 test = 0.89-0.92), which allows us to carry out the prediction of activity for 41 novel compounds designed by the application of new combinations of substituents represented in the training set. The comprehensive analysis of toxicity changes as a function of substituent position and nature was carried out. Molecular fragments that promote and interfere with toxicity were defined on the basis of the obtained models. It was shown that the mutual influence of substituents in the benzene ring plays a crucial role regarding toxicity. The influence of different substituents on toxicity can be mediated via different C-H fragments of the aromatic ring.

  17. DGCR8 HITS-CLIP reveals novel functions for the Microprocessor.

    PubMed

    Macias, Sara; Plass, Mireya; Stajuda, Agata; Michlewski, Gracjan; Eyras, Eduardo; Cáceres, Javier F

    2012-08-01

    The Drosha-DGCR8 complex (Microprocessor) is required for microRNA (miRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as the endonuclease. Using high-throughput sequencing and cross-linking immunoprecipitation (HITS-CLIP) we identified RNA targets of DGCR8 in human cells. Unexpectedly, miRNAs were not the most abundant targets. DGCR8-bound RNAs also comprised several hundred mRNAs as well as small nucleolar RNAs (snoRNAs) and long noncoding RNAs. We found that the Microprocessor controlled the abundance of several mRNAs as well as of MALAT1. By contrast, DGCR8-mediated cleavage of snoRNAs was independent of Drosha, suggesting the involvement of DGCR8 in cellular complexes with other endonucleases. Binding of DGCR8 to cassette exons is a new mechanism for regulation of the relative abundance of alternatively spliced isoforms. These data provide insights in the complex role of DGCR8 in controlling the fate of several classes of RNAs.

  18. Ship detection in satellite imagery using rank-order greyscale hit-or-miss transforms

    SciTech Connect

    Harvey, Neal R; Porter, Reid B; Theiler, James

    2010-01-01

    Ship detection from satellite imagery is something that has great utility in various communities. Knowing where ships are and their types provides useful intelligence information. However, detecting and recognizing ships is a difficult problem. Existing techniques suffer from too many false-alarms. We describe approaches we have taken in trying to build ship detection algorithms that have reduced false alarms. Our approach uses a version of the grayscale morphological Hit-or-Miss transform. While this is well known and used in its standard form, we use a version in which we use a rank-order selection for the dilation and erosion parts of the transform, instead of the standard maximum and minimum operators. This provides some slack in the fitting that the algorithm employs and provides a method for tuning the algorithm's performance for particular detection problems. We describe our algorithms, show the effect of the rank-order parameter on the algorithm's performance and illustrate the use of this approach for real ship detection problems with panchromatic satellite imagery.

  19. Ice Hockey Summit II: zero tolerance for head hits and fighting.

    PubMed

    Smith, Aynsley M; Stuart, Michael J; Dodick, David W; Roberts, William O; Alford, Patrick W; Ashare, Alan B; Aubrey, Mark; Benson, Brian W; Burke, Chip J; Dick, Randall; Eickhoff, Chad; Emery, Carolyn A; Flashman, Laura A; Gaz, Daniel V; Giza, Chris C; Greenwald, Richard M; Herring, Stanley A; Hoshizaki, T Blaine; Hudziak, James J; Huston, John; Krause, David; LaVoi, Nicole; Leaf, Matt; Leddy, John J; MacPherson, Alison; McKee, Ann C; Mihalik, Jason P; Moessner, Anne M; Montelpare, William J; Putukian, Margot; Schneider, Kathryn J; Szalkowski, Ron; Tabrum, Mark; Whitehead, James R; Wiese-Bjornstal, Diane M

    2015-01-01

    This study aimed to present currently known basic science and on-ice influences of sport-related concussion (SRC) in hockey, building upon the Ice Hockey Summit I action plan (2011) to reduce SRC. The prior summit proceedings included an action plan intended to reduce SRC. As such, the proceedings from Summit I served as a point of departure for the science and discussion held during Summit II (Mayo Clinic, Rochester, MN, October 2013). Summit II focused on (1) Basic Science of Concussions in Ice Hockey: Taking Science Forward, (2) Acute and Chronic Concussion Care: Making a Difference, (3) Preventing Concussions via Behavior, Rules, Education, and Measuring Effectiveness, (4) Updates in Equipment: Their Relationship to Industry Standards, and (5) Policies and Plans at State, National, and Federal Levels To Reduce SRC. Action strategies derived from the presentations and discussion described in these sectors were voted on subsequently for purposes of prioritization. The following proceedings include the knowledge and research shared by invited faculty, many of whom are health care providers and clinical investigators. The Summit II evidence-based action plan emphasizes the rapidly evolving scientific content of hockey SRC. It includes the most highly prioritized strategies voted on for implementation to decrease concussion. The highest-priority action items identified from the Summit include the following: (1) eliminate head hits from all levels of ice hockey, (2) change body checking policies, and (3) eliminate fighting in all amateur and professional hockey.

  20. The current status of REH theory. [Random Evolutionary Hits in biological molecular evolution

    NASA Technical Reports Server (NTRS)

    Holmquist, R.; Jukes, T. H.

    1981-01-01

    A response is made to the evaluation of Fitch (1980) of REH (random evolutionary hits) theory for the evolutionary divergence of proteins and nucleic acids. Correct calculations for the beta hemoglobin mRNAs of the human, mouse and rabbit in the absence and presence of selective constraints are summarized, and it is shown that the alternative evolutionary analysis of Fitch underestimates the total fixed mutations. It is further shown that the model used by Fitch to test for the completeness of the count of total base substitutions is in fact a variant of REH theory. Considerations of the variance inherent in evolutionary estimations are also presented which show the REH model to produce no more variance than other evolutionary models. In the reply, it is argued that, despite the objections raised, REH theory applied to proteins gives inaccurate estimates of total gene substitutions. It is further contended that REH theory developed for nucleic sequences suffers from problems relating to the frequency of nucleotide substitutions, the identity of the codons accepting silent and amino acid-changing substitutions, and estimate uncertainties.

  1. Recurrent EZH1 mutations are a second hit in autonomous thyroid adenomas

    PubMed Central

    Grassi, Elisa S.; Eszlinger, Markus; Ronchi, Cristina L.; Godbole, Amod; Bathon, Kerstin; Guizzardi, Fabiana; de Filippis, Tiziana; Krohn, Knut; Jaeschke, Holger; Schwarzmayr, Thomas; Gozu, Hulya Iliksu; Sancak, Seda; Niedziela, Marek; Strom, Tim M.; Fassnacht, Martin; Paschke, Ralf

    2016-01-01

    Autonomous thyroid adenomas (ATAs) are a frequent cause of hyperthyroidism. Mutations in the genes encoding the TSH receptor (TSHR) or the Gs protein α subunit (GNAS) are found in approximately 70% of ATAs. The involvement of other genes and the pathogenesis of the remaining cases are presently unknown. Here, we performed whole-exome sequencing in 19 ATAs that were paired with normal DNA samples and identified a recurrent hot-spot mutation (c.1712A>G; p.Gln571Arg) in the enhancer of zeste homolog 1 (EZH1) gene, which codes for a catalytic subunit of the polycomb complex. Targeted screening in an independent cohort confirmed that this mutation occurs with high frequency (27%) in ATAs. EZH1 mutations were strongly associated with known (TSHR, GNAS) or presumed (adenylate cyclase 9 [ADCY9]) alterations in cAMP pathway genes. Furthermore, functional studies revealed that the p.Gln571Arg EZH1 mutation caused increased histone H3 trimethylation and increased proliferation of thyroid cells. In summary, this study revealed that a hot-spot mutation in EZH1 is the second most frequent genetic alteration in ATAs. The association between EZH1 and TSHR mutations suggests a 2-hit model for the pathogenesis of these tumors, whereby constitutive activation of the cAMP pathway and EZH1 mutations cooperate to induce the hyperproliferation of thyroid cells. PMID:27500488

  2. Low incidence of MYC/BCL2 double-hit in Burkitt lymphoma.

    PubMed

    Yoshida, Maki; Ichikawa, Ayako; Miyoshi, Hiroaki; Kiyasu, Junichi; Kimura, Yoshizo; Niino, Daisuke; Ohshima, Koichi

    2015-09-01

    Translocations involving MYC are highly characteristic for Burkitt lymphoma (BL). BCL2 expression has also been found previously in about 10 to 20% of BL cases, and BCL2 translocation is a major mechanism for the deregulation of BCL2 expression in non-Hodgkin lymphomas. However, we know little about the incidence of MYC/BCL2 double-hit (DH) in BL. We examined BL cases to determine how frequently they contained BCL2 translocations in combination with MYC translocations using fluorescence in situ hybridization. We also determined the effect of BCL2 expression on clinical outcomes of BL. BCL2 translocations were detected in 3.5% (2/57 cases) of the cases, and BCL2 expression was detected in 33%. Two cases with BCL2 translocation also showed BCL2 expression. The incidence of BCL2 expression was significantly higher in patients 16 years of age and older (46%) than in patients under 16 years of age (6%). Among patients 16 years of age and older, we did not detect significant differences in overall survival with respect to BCL2 expression status. In conclusion, BCL2 translocation is a rare cytogenetic abnormality in BL, and BL probably accounts for only a small fraction of MYC/BCL2 DH lymphomas. BCL2 expression in BL is probably not associated with BCL2 translocations.

  3. Review of capital investment in economic growth cycle

    NASA Astrophysics Data System (ADS)

    Shaffie, Siti Salihah; Jaaman, Saiful Hafizah; Mohamad, Daud

    2016-11-01

    The study of linkages of macroeconomics factors is prominent in order to understand how the economic cycle affects one another. These factors include interest rate, growth rate, saving and capital investment which are mutually correlated to stabilize the GDP. Part of this study, it will look upon the impact of investment which emphasize the efficiency of capital investment to the economic growth. Capital investment is one investment appraisal that gives impact to the economic growth. It is a long term investment and involve with large amount of capital to incorporate the development of private and public capital investment.

  4. Resource demand growth and sustainability due to increased world consumption

    DOE PAGES

    Balatsky, Alexander V.; Balatsky, Galina I.; Borysov, Stanislav S.

    2015-03-20

    The paper aims at continuing the discussion on sustainability and attempts to forecast the impossibility of the expanding consumption worldwide due to the planet’s limited resources. As the population of China, India and other developing countries continue to increase, they would also require more natural and financial resources to sustain their growth. We coarsely estimate the volumes of these resources (energy, food, freshwater) and the gross domestic product (GDP) that would need to be achieved to bring the population of India and China to the current levels of consumption in the United States. We also provide estimations for potentially neededmore » immediate growth of the world resource consumption to meet this equality requirement. Given the tight historical correlation between GDP and energy consumption, the needed increase of GDP per capita in the developing world to the levels of the U.S. would deplete explored fossil fuel reserves in less than two decades. These estimates predict that the world economy would need to find a development model where growth would be achieved without heavy dependence on fossil fuels.« less

  5. Resource demand growth and sustainability due to increased world consumption

    SciTech Connect

    Balatsky, Alexander V.; Balatsky, Galina I.; Borysov, Stanislav S.

    2015-03-20

    The paper aims at continuing the discussion on sustainability and attempts to forecast the impossibility of the expanding consumption worldwide due to the planet’s limited resources. As the population of China, India and other developing countries continue to increase, they would also require more natural and financial resources to sustain their growth. We coarsely estimate the volumes of these resources (energy, food, freshwater) and the gross domestic product (GDP) that would need to be achieved to bring the population of India and China to the current levels of consumption in the United States. We also provide estimations for potentially needed immediate growth of the world resource consumption to meet this equality requirement. Given the tight historical correlation between GDP and energy consumption, the needed increase of GDP per capita in the developing world to the levels of the U.S. would deplete explored fossil fuel reserves in less than two decades. These estimates predict that the world economy would need to find a development model where growth would be achieved without heavy dependence on fossil fuels.

  6. National health spending in 2011: overall growth remains low, but some payers and services show signs of acceleration.

    PubMed

    Hartman, Micah; Martin, Anne B; Benson, Joseph; Catlin, Aaron

    2013-01-01

    In 2011 US health care spending grew 3.9 percent to reach $2.7 trillion, marking the third consecutive year of relatively slow growth. Growth in national health spending closely tracked growth in nominal gross domestic product (GDP) in 2010 and 2011, and health spending as a share of GDP remained stable from 2009 through 2011, at 17.9 percent. Even as growth in spending at the national level has remained stable, personal health care spending growth accelerated in 2011 (from 3.7 percent to 4.1 percent), in part because of faster growth in spending for prescription drugs and physician and clinical services. There were also divergent trends in spending growth in 2011 depending on the payment source: Medicaid spending growth slowed, while growth in Medicare, private health insurance, and out-of-pocket spending accelerated. Overall, there was relatively slow growth in incomes, jobs, and GDP in 2011, which raises questions about whether US health care spending will rebound over the next few years as it typically has after past economic downturns.

  7. Myristoylation-facilitated binding of the G protein ARF1GDP to membrane phospholipids is required for its activation by a soluble nucleotide exchange factor.

    PubMed

    Franco, M; Chardin, P; Chabre, M; Paris, S

    1996-01-19

    We have investigated the role of N-myristoylation in the activation of bovine ADP-ribosylation factor 1 (ARF1). We previously showed that myristoylation allows some spontaneous GDP-to-GTP exchange to occur on ARF1 at physiological Mg2+ levels in the presence of phospholipid vesicles (Franco, M., Chardin, P., Chabre, M., and Paris, S. (1995) J. Biol. Chem. 270, 1337-1341). Here, we report that this basal nucleotide exchange can be accelerated (by up to 5-fold) by addition of a soluble fraction obtained from bovine retinas. This acceleration is totally abolished by brefeldin A (IC50 = 2 microM) and by trypsin treatment of the retinal extract, as expected for an ARF-specific guanine nucleotide exchange factor. To accelerate GDP release from ARF1, this soluble exchange factor absolutely requires myristoylation of ARF1 and the presence of phospholipid vesicles. The retinal extract also stimulates guanosine 5'-3-O-(thio)-triphosphate (GTP gamma S) release from ARF1 in the presence of phospholipids, but in this case myristoylation of ARF is not required. These observations, together with our previous findings that both myristoylated and non-myristoylated forms of ARF GTP-gamma S but only the myristoylated form of ARFGDP bind to membrane phospholipids, suggest that (i) the retinal exchange factor acts only on membrane-bound ARF, (ii) the myristate is not involved in the protein-protein interaction between ARF1 and the exchange factor, and (iii) N-myristoylation facilitates both spontaneous and catalyzed GDP-to-GTP exchange on ARF1 simply by facilitating the binding of ARFGDP to membrane phospholipids.

  8. Arabidopsis HIT4, a regulator involved in heat-triggered reorganization of chromatin and release of transcriptional gene silencing, relocates from chromocenters to the nucleolus in response to heat stress.

    PubMed

    Wang, Lian-Chin; Wu, Jia-Rong; Hsu, Yi-Ju; Wu, Shaw-Jye

    2015-01-01

    Arabidopsis HIT4 is known to mediate heat-induced decondensation of chromocenters and release from transcriptional gene silencing (TGS) with no change in the level of DNA methylation. It is unclear whether HIT4 and MOM1, a well-known DNA methylation-independent transcriptional silencer, have overlapping regulatory functions. A hit4-1/mom1 double mutant strain was generated. Its nuclear morphology and TGS state were compared with those of wild-type, hit4-1, and mom1 plants. Fluorescent protein tagging was employed to track the fates of HIT4, hit4-1 and MOM1 in vivo under heat stress. HIT4- and MOM1-mediated TGS were distinguishable. Both HIT4 and MOM1 were localized normally to chromocenters. Under heat stress, HIT4 relocated to the nucleolus, whereas MOM1 dispersed with the chromocenters. hit4-1 was able to relocate to the nucleolus under heat stress, but its relocation was insufficient to trigger the decompaction of chromocenters. The hypersensitivity to heat associated with the impaired reactivation of TGS in hit4-1 was not alleviated by mom1-induced release from TGS. HIT4 delineates a novel and MOM1-independent TGS regulation pathway. The involvement of a currently unidentified component that links HIT4 relocation and the large-scale reorganization of chromatin, and which is essential for heat tolerance in plants is hypothesized.

  9. Mozambique Hit by a Flood Disaster, Again: What Role for the Scientific Community

    NASA Astrophysics Data System (ADS)

    Matonse, A. H.; Zucula, P.

    2007-05-01

    The Lower Zambezi basin in Mozambique covers an area of approximately 225,000 km2 from the Cahora Bassa Reservoir to the Zambezi Delta, and supports more than 3.8 million people (25% of the total population of Mozambique). The Zambezi Delta is a broad, flat alluvial plain along the coast of central Mozambique. Some 800 Mozambicans died in floods caused by two cyclones in 2000 and 2001 in the Zambezi River Valley in central Mozambique. Recently, seven years later, the same Zambezi River Valley was hit by heavy rain which was followed by Cyclone Favio. This event triggered flash floods along the Zambezi River and its tributaries, washing away homes, bridges, livestock and crops, and killing at least 45 people. The country's national relief agency INGC established an emergency operation centre to coordinate relief operations. By February 25, 2007, 53,000 people have been moved to accommodation centers and an estimated 36,000 people have lost virtually all their possessions. Due to the extent of the flooded area, rescue and supply operations are very difficult, and conditioned upon the availability of helicopters. Temporary accommodation centres have faced problems of food and fuel shortages, and delays in the distribution of food and fresh water are raising concerns with malnutrition and the outbreak of waterborne diseases. One of the major problems in the region is water management and regulation. The main structure to regulate water discharge in the Zambezi River is the Mozambique's largest Hydro-electric dam, Cahora Bassa. Water regulation from this structure during floods is particularly difficult due to transnational inflows passing through the neighbouring countries of Malawi, Zambia and Zimbabwe. Since the flood disaster of 2000/2001 occurred, the need to improve and strengthen disaster prevention has been a high priority of the Mozambique Government and its donors. Mozambique's Action Plan for the reduction of Absolute Poverty identified vulnerability to such

  10. A liquid chromatography/mass spectrometry-based generic detection method for biochemical assay and hit discovery of histone methyltransferases.

    PubMed

    Li, Shu; Gu, X Justin; Hao, Qin; Fan, Hong; Li, Ling; Zhou, Shaolian; Zhao, Kehao; Chan, Ho Man; Wang, Y Karen

    2013-12-15

    Epigenetic modifications of the genome, such as DNA methylation and posttranslational modifications of histone proteins, contribute to gene regulation. Growing evidence suggests that histone methyltransferases are associated with the development of various human diseases, including cancer, and are promising drug targets. High-quality generic assays will facilitate drug discovery efforts in this area. In this article, we present a liquid chromatography/mass spectrometry (LC/MS)-based S-adenosyl homocysteine (SAH) detection assay for histone methyltransferases (HMTs) and its applications in HMT drug discovery, including analyzing the activity of newly produced enzymes, developing and optimizing assays, performing focused compound library screens and orthogonal assays for hit confirmations, selectivity profiling against a panel of HMTs, and studying mode of action of select hits. This LC/MS-based generic assay has become a critical platform for our methyltransferase drug discovery efforts.

  11. Comparison of Document Index Graph Using TextRank and HITS Weighting Method in Automatic Text Summarization

    NASA Astrophysics Data System (ADS)

    Hadyan, Fadhlil; Shaufiah; Arif Bijaksana, Moch.

    2017-01-01

    Automatic summarization is a system that can help someone to take the core information of a long text instantly. The system can help by summarizing text automatically. there’s Already many summarization systems that have been developed at this time but there are still many problems in those system. In this final task proposed summarization method using document index graph. This method utilizes the PageRank and HITS formula used to assess the web page, adapted to make an assessment of words in the sentences in a text document. The expected outcome of this final task is a system that can do summarization of a single document, by utilizing document index graph with TextRank and HITS to improve the quality of the summary results automatically.

  12. Discovery of New Anti-Schistosomal Hits by Integration of QSAR-Based Virtual Screening and High Content Screening.

    PubMed

    Neves, Bruno J; Dantas, Rafael F; Senger, Mario R; Melo-Filho, Cleber C; Valente, Walter C G; de Almeida, Ana C M; Rezende-Neto, João M; Lima, Elid F C; Paveley, Ross; Furnham, Nicholas; Muratov, Eugene; Kamentsky, Lee; Carpenter, Anne E; Braga, Rodolpho C; Silva-Junior, Floriano P; Andrade, Carolina Horta

    2016-08-11

    Schistosomiasis is a debilitating neglected tropical disease, caused by flatworms of Schistosoma genus. The treatment relies on a single drug, praziquantel (PZQ), making the discovery of new compounds extremely urgent. In this work, we integrated QSAR-based virtual screening (VS) of Schistosoma mansoni thioredoxin glutathione reductase (SmTGR) inhibitors and high content screening (HCS) aiming to discover new antischistosomal agents. Initially, binary QSAR models for inhibition of SmTGR were developed and validated using the Organization for Economic Co-operation and Development (OECD) guidance. Using these models, we prioritized 29 compounds for further testing in two HCS platforms based on image analysis of assay plates. Among them, 2-[2-(3-methyl-4-nitro-5-isoxazolyl)vinyl]pyridine and 2-(benzylsulfonyl)-1,3-benzothiazole, two compounds representing new chemical scaffolds have activity against schistosomula and adult worms at low micromolar concentrations and therefore represent promising antischistosomal hits for further hit-to-lead optimization.

  13. Developing an online and in-person HIT workforce training program using a team-based learning approach.

    PubMed

    Morrison, Frances; Zimmerman, John; Hall, Michelle; Chase, Herbert; Kaushal, Rainu; Ancker, Jessica S

    2011-01-01

    Workforce training in health information technology (HIT) is in demand as electronic health record adoption becomes a nationwide priority. Columbia University and Weill Cornell Medical College worked together to develop a 6-month ONC-supported certificate course. To identify relevant skills and knowledge, we conducted a needs assessment that included: interviews and focus groups with potential employers and current HIT employees; an analysis of both published literature on competencies and actual job listings; and the development of a diverse operations-oriented curriculum advisory committee, which help to synthesize the findings into 6 core curriculum modules. We selected a team-based learning approach, allowing us to train a diverse student body and providing opportunities to build collaboration skills. Our novel hybrid adaptation of team-based learning combines online and in-person activities. Lessons learned from the development of this program are likely to have widespread applicability as training programs in the field become more prevalent.

  14. Developing an Online and In-Person HIT Workforce Training Program Using a Team-Based Learning Approach

    PubMed Central

    Morrison, Frances; Zimmerman, John; Hall, Michelle; Chase, Herbert; Kaushal, Rainu; Ancker, Jessica S.

    2011-01-01

    Workforce training in health information technology (HIT) is in demand as electronic health record adoption becomes a nationwide priority. Columbia University and Weill Cornell Medical College worked together to develop a 6-month ONC-supported certificate course. To identify relevant skills and knowledge, we conducted a needs assessment that included: interviews and focus groups with potential employers and current HIT employees; an analysis of both published literature on competencies and actual job listings; and the development of a diverse operations-oriented curriculum advisory committee, which help to synthesize the findings into 6 core curriculum modules. We selected a team-based learning approach, allowing us to train a diverse student body and providing opportunities to build collaboration skills. Our novel hybrid adaptation of team-based learning combines online and in-person activities. Lessons learned from the development of this program are likely to have widespread applicability as training programs in the field become more prevalent. PMID:22195056

  15. One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug

    PubMed Central

    Hughes, Rebecca E.; Nikolic, Katarina; Ramsay, Rona R.

    2016-01-01

    HIGHLIGHTS Many AD target combinations are being explored for multi-target drug design.New databases and models increase the potential of computational drug designLiraglutide and other antidiabetics are strong candidates for repurposing to AD.Donecopride a dual 5-HT/AChE inhibitor shows promise in pre-clinical studies Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs (MTDs). Intended as an introduction for non-experts, this review describes the key MTD design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch, and the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer's Disease are rasagiline, originally developed for the treatment of Parkinson's Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic. PMID:27199640

  16. A double hit implicates DIAPH3 as an autism risk gene.

    PubMed

    Vorstman, J A S; van Daalen, E; Jalali, G R; Schmidt, E R E; Pasterkamp, R J; de Jonge, M; Hennekam, E A M; Janson, E; Staal, W G; van der Zwaag, B; Burbach, J P H; Kahn, R S; Emanuel, B S; van Engeland, H; Ophoff, R A

    2011-04-01

    Recent studies have shown that more than 10% of autism cases are caused by de novo structural genomic rearrangements. Given that some heritable copy number variants (CNVs) have been observed in patients as well as in healthy controls, to date little attention has been paid to the potential function of these non-de novo CNVs in causing autism. A normally intelligent patient with autism, with non-affected parents, was identified with a maternally inherited 10 Mb deletion at 13q21.2. Sequencing of the genes within the deletion identified a paternally inherited nonsynonymous amino-acid substitution at position 614 of diaphanous homolog 3 (DIAPH3) (proline to threonine; Pro614Thr). This variant, present in a highly conserved domain, was not found in 328 healthy subjects. Experiments showed a transient expression of Diaph3 in the developing murine cerebral cortex, indicating it has a function in brain development. Transfection of Pro614Thr in murine fibroblasts showed a significant reduction in the number of induced filopodia in comparison to the wild-type gene. DIAPH3 is involved in cell migration, axon guidance and neuritogenesis, and is suggested to function downstream of SHANK3. Our findings strongly suggest DIAPH3 as a novel autism susceptibility gene. Moreover, this report of a 'double-hit' compound heterozygote for a large, maternally inherited, genomic deletion and a paternally inherited rare missense mutation shows that not only de novo genomic variants in patients should be taken seriously in further study but that inherited CNVs may also provide valuable information.

  17. Development of the PRE-HIT instrument: patient readiness to engage in health information technology

    PubMed Central

    2014-01-01

    Background Technology-based aids for lifestyle change are becoming more prevalent for chronic conditions. Important “digital divides” remain, as well as concerns about privacy, data security, and lack of motivation. Researchers need a way to characterize participants’ readiness to use health technologies. To address this need, we created an instrument to measure patient readiness to engage with health technologies among adult patients with chronic conditions. Methods Initial focus groups to determine domains, followed by item development and refinement, and exploratory factor analysis to determine final items and factor structure. The development sample included 200 patients with chronic conditions from 6 family medicine clinics. From 98 potential items, 53 best candidate items were examined using exploratory factor analysis. Pearson’s Correlation for Test/Retest reliability at 3 months. Results The final instrument had 28 items that sorted into 8 factors with associated Cronbach’s alpha: 1) Health Information Need (0.84), 2) Computer/Internet Experience (0.87), 3) Computer Anxiety (0.82), 4) Preferred Mode of Interaction (0.73), 5) Relationship with Doctor (0.65), 6) Cell Phone Expertise (0.75), 7) Internet Privacy (0.71), and 8) No News is Good News (0.57). Test-retest reliability for the 8 subscales ranged from (0.60 to 0.85). Conclusion The Patient Readiness to Engage in Health Internet Technology (PRE-HIT) instrument has good psychometric properties and will be an aid to researchers investigating technology-based health interventions. Future work will examine predictive validity. PMID:24472182

  18. One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug.

    PubMed

    Hughes, Rebecca E; Nikolic, Katarina; Ramsay, Rona R

    2016-01-01

    HIGHLIGHTS Many AD target combinations are being explored for multi-target drug design.New databases and models increase the potential of computational drug designLiraglutide and other antidiabetics are strong candidates for repurposing to AD.Donecopride a dual 5-HT/AChE inhibitor shows promise in pre-clinical studies Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs (MTDs). Intended as an introduction for non-experts, this review describes the key MTD design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch, and the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer's Disease are rasagiline, originally developed for the treatment of Parkinson's Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.

  19. Prospective evaluation of a rapid nanoparticle-based lateral flow immunoassay (STic Expert(®) HIT) for the diagnosis of heparin-induced thrombocytopenia.

    PubMed

    Leroux, Dorothée; Hezard, Nathalie; Lebreton, Aurélien; Bauters, Anne; Suchon, Pierre; de Maistre, Emmanuel; Biron, Christine; Huisse, Marie-Genevieve; Ternisien, Catherine; Voisin, Sophie; Gruel, Yves; Pouplard, Claire

    2014-09-01

    A rapid lateral flow immunoassay (LFIA) (STic Expert(®) HIT), recently developed for the diagnosis of heparin-induced thrombocytopenia (HIT), was evaluated in a prospective multicentre cohort of 334 consecutive patients. The risk of HIT was estimated by the 4Ts score as low, intermediate and high in 28·7%, 61·7% and 9·6% of patients, respectively. Definite HIT was diagnosed in 40 patients (12·0%) with positive results on both enzyme-linked immunosorbent assay (Asserachrom(®) HPIA IgG) and serotonin release assay. The inter-reader reproducibility of results obtained was excellent (kappa ratio > 0·9). The negative predictive value of LFIA with plasma samples was 99·6% with a negative likelihood ratio (LR) of 0·03, and was comparable to those of the particle gel immunoassay (H/PF4-PaGIA(®) ) performed in 124 cases. Positive predictive value and positive LR were 44·4% and 5·87, respectively, and the results were similar for serum samples. The probability of HIT in intermediate risk patients decreased from 11·2% to 0·4% when the LFIA result was negative and increased to 42·5% when it was positive. In conclusion, the STic Expert(®) HIT combined with the 4Ts score is a reliable tool to rule out the diagnosis of HIT.

  20. EASY-HIT: HIV Full-Replication Technology for Broad Discovery of Multiple Classes of HIV Inhibitors▿ †

    PubMed Central

    Kremb, Stephan; Helfer, Markus; Heller, Werner; Hoffmann, Dieter; Wolff, Horst; Kleinschmidt, Andrea; Cepok, Sabine; Hemmer, Bernhard; Durner, Jörg; Brack-Werner, Ruth

    2010-01-01

    HIV replication assays are important tools for HIV drug discovery efforts. Here, we present a full HIV replication system (EASY-HIT) for the identification and analysis of HIV inhibitors. This technology is based on adherently growing HIV-susceptible cells, with a stable fluorescent reporter gene activated by HIV Tat and Rev. A fluorescence-based assay was designed that measures HIV infection by two parameters relating to the early and the late phases of HIV replication, respectively. Validation of the assay with a panel of nine reference inhibitors yielded effective inhibitory concentrations consistent with published data and allowed discrimination between inhibitors of early and late phases of HIV replication. Finer resolution of the effects of reference drugs on different steps of HIV replication was achieved in secondary time-of-addition assays. The EASY-HIT assay yielded high Z′ scores (>0.9) and signal stabilities, confirming its robustness. Screening of the LOPAC1280 library identified 10 compounds (0.8%), of which eight were known to inhibit HIV, validating the suitability of this assay for screening applications. Studies evaluating anti-HIV activities of natural products with the EASY-HIT technology led to the identification of three novel inhibitory compounds that apparently act at different steps of HIV-1 replication. Furthermore, we demonstrate successful evaluation of plant extracts for HIV-inhibitory activities, suggesting application of this technology for the surveillance of biological extracts with anti-HIV activities. We conclude that the EASY-HIT technology is a versatile tool for the discovery and characterization of HIV inhibitors. PMID:20876377