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

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.

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."

GDP and efficiency of Russian economy

NASA Astrophysics Data System (ADS)

Borodachev, Sergey M.

2018-01-01

The goal is to study GDP (gross domestic product) as an unobservable characteristic of the Russian national economy state on the basis of more reliable observed data on gross output (systems output) and final consumption (systems control). To do this, the dynamic Leontief model is presented in a system-like form and its parameters and GDP dynamics are estimated by the Kalman filter (KF). We consider that all previous year's investments affect the growth of the gross output by the next year. The weights of these investments in the sum are equal to unity and decrease in geometric progression. The estimation of the model parameters was carried out by the maximum likelihood method. The original data on the gross output and final consumption in the period from 1995 to 2015 years where taken from the Rosstat website, where maximally aggregated economy of Russia is reflected in the system of national accounts. The growth of direct costs and capital expenditures at gross output increase has been discovered, which indicates the extensive character of the development of the economy. Investments are being absorbed 2 - 4 years; any change of them causes a surge of commissioned fixed assets fluctuation with a period of 2 years. Then these parameter values were used in the KF to estimate the states of the system. The emerging tendency of the transition of GDP growth to its fall means that the rate of growth of final consumption is higher than the rate of GDP growth. In general, the behavior of the curve of Rosstat GDP obviously follows the declared investments, whereas in the present calculation it is closer to the behavior of final consumption. Estimated GDP and investments that really increased it were significantly less after the crisis of 2008-2009 years than officially published data.

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

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

Zhao Guohui; Liu Jun; Liu Xiang

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{supmore » -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.« less

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

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

Brzezinski, Krzysztof; Dauter, Zbigniew; Jaskolski, Mariusz

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 crystalmore » 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

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

PubMed Central

Brzezinski, Krzysztof; Dauter, Zbigniew; Jaskolski, Mariusz

2012-01-01

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

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

FX enzyme and GDP-L-Fuc transporter expression in colorectal cancer.

PubMed

Villar-Portela, Susana; Muinelo-Romay, Laura; Cuevas, Elisa; Gil-Martín, Emilio; Fernández-Briera, Almudena

2013-08-01

Fucosylation is regulated by fucosyltransferases, the guanosine diphosphate-L-fucose (GDP-L-Fuc) synthetic pathway, and the GDP-L-fucose transporter (GDP-L-Fuc Tr). We have reported previously an increased level of α(1,6)fucosyltransferase activity and expression in colorectal cancer (CRC). The present study aimed to analyse the expression profiles of the FX enzyme and GDP-L-Fuc Tr in a cohort of operated CRC patients to elucidate their role in α(1,6)fucosylation in this neoplasm. We assessed the immunohistochemical expression of FX and GDP-L-Fuc Tr in a series of tumour samples and healthy tissues from CRC specimens. FX expression was observed in 58 of 91 (63.7%) tumours and 23 of 28 (82.1%) corresponding healthy samples. GDP-L-Fuc Tr expression was detected in 86 of 102 (84.3%) colorectal tumours, and 13 of 27 (48.1%) healthy tissue specimens. The expression of GDP-L-Fuc Tr was statistically higher in tumours than in healthy tissues (P < 0.001). A correlation was found between FX and GDP-L-Fuc Tr expression in tumour samples (P = 0.003). GDP-L-Fuc Tr overexpression in the tumour tissue of CRC patients suggests that GDP-L-Fuc transport to the Golgi apparatus may be an important factor associated with increased α(1,6)fucosylation in CRC. © 2013 John Wiley & Sons Ltd.

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.

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.

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.

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

PubMed Central

Webb, Nicole A.; Mulichak, Anne M.; Lam, Joseph S.; Rocchetta, Heather L.; Garavito, R. Michael

2004-01-01

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 Å 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. PMID:14739333

GDP Matters: Cost Effectiveness of Cochlear Implantation and Deaf Education in Sub-Saharan Africa.

PubMed

Emmett, Susan D; Tucci, Debara L; Smith, Magteld; Macharia, Isaac M; Ndegwa, Serah N; Nakku, Doreen; Mukara, Kaitesi B; Kaitesi, Mukara B; Ibekwe, Titus S; Mulwafu, Wakisa; Gong, Wenfeng; Francis, Howard W; Saunders, James E

2015-09-01

Cochlear implantation and deaf education are cost effective in Sub-Saharan Africa. Cost effectiveness of pediatric cochlear implantation has been well established in developed countries but is unknown in low resource settings, where access to the technology has traditionally been limited. With incidence of severe-to-profound congenital sensorineural hearing loss 5 to 6 times higher in low/middle-income countries than the United States and Europe, developing cost-effective management strategies in these settings is critical. Costs were obtained from experts in Nigeria, South Africa, Kenya, Rwanda, Uganda, and Malawi using known costs and published data, with estimation when necessary. A disability adjusted life years (DALY) model was applied using 3% discounting and 10-year length of analysis. Sensitivity analysis was performed to evaluate the effect of device cost, professional salaries, annual number of implants, and probability of device failure. Cost effectiveness was determined using the WHO standard of cost-effectiveness ratio/gross domestic product per capita (CER/GDP) less than 3. Cochlear implantation was cost effective in South Africa and Nigeria, with CER/GDP of 1.03 and 2.05, respectively. Deaf education was cost effective in all countries investigated, with CER/GDP ranging from 0.55 to 1.56. The most influential factor in the sensitivity analysis was device cost, with the cost-effective threshold reached in all countries using discounted device costs that varied directly with GDP. Cochlear implantation and deaf education are equally cost effective in lower-middle and upper-middle income economies of Nigeria and South Africa. Device cost may have greater impact in the emerging economies of Kenya, Uganda, Rwanda, and Malawi.

Factors related to poor asthma control in Latvian asthma patients between 2013 and 2015

PubMed Central

Smits, Dins; Brigis, Girts; Pavare, Jana; Maurina, Baiba; Barengo, Noël Christopher

2017-01-01

Objectives To investigate whether beliefs about asthma medication, cognitive and emotional factors are related to poor asthma control in a sample of Latvian asthma patients in 2015. Design Cross-sectional, self-administered survey. Subjects Three hundred and fifty two asthma patients (mean age 57.5 years) attending outpatient pulmonologist consultations in Riga, Latvia during September 2013 to December 2015. The sample size was calculated to detect a prevalence of poor asthma control of 50% with a margin of error of 5% and a power of 95%. Main outcome measures The validated Beliefs about Medication Questionnaire (BMQ) and the Brief Illness Perception Questionnaire (brief IPQ) were used. Good asthma control was assessed using the asthma control test (ACT), a validated five-item scale that reliably assesses asthma control over a recall period of four weeks. Logistic regression models were used to predict poor asthma control. Results Patients who had a good control of asthma medication (OR 0.70; 95% CI 0.61–0.79) or were confident that their asthma medication improves illness (OR 0.84; 95% CI 0.74–0.95) had a reduced risk of poor asthma control. The more symptoms (OR 1.63; 95% CI 1.44–1.84) the asthma patients perceived or the more their illness affects their life, the higher the probability of poor asthma control (OR 1.47; 95% CI 1.31–1.65). Some beliefs of necessity and concerns of asthma medication were also statistically significantly related to poor asthma control. Conclusions Beliefs of necessity of asthma medication, cognitive and emotional illness perception factors correlate well with poor asthma control in Latvian patients. PMID:28585881

GDP: A new source for shallow high-resolution seismic exploration

NASA Astrophysics Data System (ADS)

Rashed, Mohamed A.

2009-06-01

Gas-Driven Piston (GDP) is a new source for shallow seismic exploration. This source works by igniting a small amount of gas inside a closed chamber connected to a vertical steel cylinder. The gas explosion drives a steel piston, mounted inside the cylinder, downward so that the piston's thick head hits a steel base at the end of the cylinder generating a strong shock wave into the ground. Experimental field tests conducted near Ismailia, Egypt, prove that the portable, inexpensive and environmentally benign GDP generates stronger seismic waves than the sledgehammer that is commonly used in shallow seismic exploration. Tests also show that GDP is a highly repeatable and controllable and that its seismic waves contain a good amount of high frequencies which makes the GDP an excellent source for shallow seismic exploration.

Genetic metabolic complementation establishes a requirement for GDP-fucose in Leishmania

PubMed Central

Novozhilova, Natalia M.; Turco, Salvatore J.

2017-01-01

To survive in its sand fly vector, the trypanosomatid protozoan parasite Leishmania first attaches to the midgut to avoid excretion, but eventually it must detach for transmission by the next bite. In Leishmania major strain Friedlin, this is controlled by modifications of the stage-specific adhesin lipophosphoglycan (LPG). During differentiation to infective metacyclics, d-arabinopyranose (d-Arap) caps the LPG side-chain galactose residues, blocking interaction with the midgut lectin PpGalec, thereby leading to parasite detachment and transmission. Previously, we characterized two closely related L. major genes (FKP40 and AFKP80) encoding bifunctional proteins with kinase/pyrophosphorylase activities required for salvage and conversion of l-fucose and/or d-Arap into the nucleotide-sugar substrates required by glycosyltransferases. Whereas only AFKP80 yielded GDP-d-Arap from exogenous d-Arap, both proteins were able to salvage l-fucose to GDP-fucose. We now show that Δafkp80− null mutants ablated d-Arap modifications of LPG as predicted, whereas Δfkp40− null mutants resembled wild type (WT). Fucoconjugates had not been reported previously in L. major, but unexpectedly, we were unable to generate fkp40−/afkp80− double mutants, unless one of the A/FKPs was expressed ectopically. To test whether GDP-fucose itself was essential for Leishmania viability, we employed “genetic metabolite complementation.” First, the trypanosome de novo pathway enzymes GDP-mannose dehydratase (GMD) and GDP-fucose synthetase (GMER) were expressed ectopically; from these cells, the Δfkp40−/Δafkp80− double mutant was now readily obtained. As expected, the Δfkp40−/Δafkp80−/+TbGMD-GMER line lacked the capacity to generate GDP-Arap, while synthesizing abundant GDP-fucose. These results establish a requirement for GDP-fucose for L. major viability and predict the existence of an essential fucoconjugate(s). PMID:28465349

Labelled drug-related public expenditure in relation to gross domestic product (gdp) in Europe: A luxury good?

PubMed Central

2010-01-01

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

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

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. Copyright © 2014 Elsevier Inc. All rights reserved.

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. Copyright © 2010 John Wiley & Sons, Ltd.

The crystal structure of human GDP-L-fucose synthase.

PubMed

Zhou, Huan; Sun, Lihua; Li, Jian; Xu, Chunyan; Yu, Feng; Liu, Yahui; Ji, Chaoneng; He, Jianhua

2013-09-01

Human GDP-l-fucose synthase, also known as FX protein, synthesizes GDP-l-fucose from its substrate GDP-4-keto-6-deoxy-d-mannose. The reaction involves epimerization at both C-3 and C-5 followed by an NADPH-dependent reduction of the carbonyl at C-4. In this paper, the first crystal structure of human FX protein was determined at 2.37 Å resolution. The asymmetric unit of the crystal structure contains four molecules which form two homodimers. Each molecule consists of two domains, a Rossmann-fold NADPH-binding motif and a carboxyl terminal domain. Compared with the Escherichia coli GDP-l-fucose synthase, the overall structures of these two enzymes have four major differences. There are four loops in the structure of human FX protein corresponding to two α-helices and two β-sheets in that of the E. coli enzyme. Besides, there are seven different amino acid residues binding with NAPDH comparing human FX protein with that from E. coli. The structure of human FX reveals the key catalytic residues and could be useful for the design of drugs for the treatment of inflammation, auto-immune diseases, and possibly certain types of cancer.

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

Genetic metabolic complementation establishes a requirement for GDP-fucose in Leishmania.

PubMed

Guo, Hongjie; Novozhilova, Natalia M; Bandini, Giulia; Turco, Salvatore J; Ferguson, Michael A J; Beverley, Stephen M

2017-06-23

To survive in its sand fly vector, the trypanosomatid protozoan parasite Leishmania first attaches to the midgut to avoid excretion, but eventually it must detach for transmission by the next bite. In Leishmania major strain Friedlin, this is controlled by modifications of the stage-specific adhesin lipophosphoglycan (LPG). During differentiation to infective metacyclics, d-arabinopyranose (d-Ara p ) caps the LPG side-chain galactose residues, blocking interaction with the midgut lectin PpGalec, thereby leading to parasite detachment and transmission. Previously, we characterized two closely related L. major genes ( FKP40 and AFKP80 ) encoding bifunctional proteins with kinase/pyrophosphorylase activities required for salvage and conversion of l-fucose and/or d-Ara p into the nucleotide-sugar substrates required by glycosyltransferases. Whereas only AFKP80 yielded GDP-d-Ara p from exogenous d-Ara p , both proteins were able to salvage l-fucose to GDP-fucose. We now show that Δ afkp80 - null mutants ablated d-Ara p modifications of LPG as predicted, whereas Δ fkp40 - null mutants resembled wild type (WT). Fucoconjugates had not been reported previously in L. major , but unexpectedly, we were unable to generate fkp40 - / afkp80 - double mutants, unless one of the A/FKPs was expressed ectopically. To test whether GDP-fucose itself was essential for Leishmania viability, we employed "genetic metabolite complementation." First, the trypanosome de novo pathway enzymes GDP-mannose dehydratase (GMD) and GDP-fucose synthetase (GMER) were expressed ectopically; from these cells, the Δ fkp40 - /Δ afkp80 - double mutant was now readily obtained. As expected, the Δ fkp40 - /Δ afkp80 - /+ TbGMD-GMER line lacked the capacity to generate GDP-Ara p , while synthesizing abundant GDP-fucose. These results establish a requirement for GDP-fucose for L. major viability and predict the existence of an essential fucoconjugate(s). © 2017 by The American Society for Biochemistry and

Functional expression of a human GDP-L-fucose transporter in Escherichia coli.

PubMed

Förster-Fromme, Karin; Schneider, Sarah; Sprenger, Georg A; Albermann, Christoph

2017-02-01

To investigate the translocation of nucleotide-activated sugars from the cytosol across a membrane into the endoplasmatic reticulum or the Golgi apparatus which is an important step in the synthesis of glycoproteins and glycolipids in eukaryotes. The heterologous expression of the recombinant and codon-adapted human GDP-L-fucose antiporter gene SLC35C1 (encoding an N-terminal OmpA-signal sequence) led to a functional transporter protein located in the cytoplasmic membrane of Escherichia coli. The in vitro transport was investigated using inverted membrane vesicles. SLC35C1 is an antiporter specific for GDP-L-fucose and depending on the concomitant reverse transport of GMP. The recombinant transporter FucT1 exhibited an activity for the transport of 3 H-GDP-L-fucose with a V max of 8 pmol/min mg with a K m of 4 µM. The functional expression of SLC35C1 in GDP-L-fucose overproducing E. coli led to the export of GDP-L-fucose to the culture supernatant. The export of GDP-L-fucose by E. coli provides the opportunity for the engineering of a periplasmatic fucosylation reaction in recombinant bacterial cells.

Modulation of guanosine nucleotides biosynthetic pathways enhanced GDP-L-fucose production in recombinant Escherichia coli.

PubMed

Lee, Won-Heong; Shin, So-Yeon; Kim, Myoung-Dong; Han, Nam Soo; Seo, Jin-Ho

2012-03-01

Guanosine 5'-triphosphate (GTP) is the key substrate for biosynthesis of guanosine 5'-diphosphate (GDP)-L-fucose. In this study, improvement of GDP-L-fucose production was attempted by manipulating the biosynthetic pathway for guanosine nucleotides in recombinant Escherichia coli-producing GDP-L-fucose. The effects of overexpression of inosine 5'-monophosphate (IMP) dehydrogenase, guanosine 5'-monophosphate (GMP) synthetase (GuaB and GuaA), GMP reductase (GuaC) and guanosine-inosine kinase (Gsk) on GDP-L-fucose production were investigated in a series of fed-batch fermentations. Among the enzymes tested, overexpression of Gsk led to a significant improvement of GDP-L-fucose production. Maximum GDP-L-fucose concentration of 305.5 ± 5.3 mg l(-1) was obtained in the pH-stat fed-batch fermentation of recombinant E. coli-overexpressing Gsk, which corresponds to a 58% enhancement in the GDP-L-fucose production compared with the control strain overexpressing GDP-L-fucose biosynthetic enzymes. Such an enhancement of GDP-L-fucose production could be due to the increase in the intracellular level of GMP.

Enhanced production of GDP-L-fucose by overexpression of NADPH regenerator in recombinant Escherichia coli.

PubMed

Lee, Won-Heong; Chin, Young-Wook; Han, Nam Soo; Kim, Myoung-Dong; Seo, Jin-Ho

2011-08-01

Biosynthesis of guanosine 5'-diphosphate-L-fucose (GDP-L-fucose) requires NADPH as a reducing cofactor. In this study, endogenous NADPH regenerating enzymes such as glucose-6-phosphate dehydrogenase (G6PDH), isocitrate dehydrogenase (Icd), and NADP(+)-dependent malate dehydrogenase (MaeB) were overexpressed to increase GDP-L-fucose production in recombinant Escherichia coli. The effects of overexpression of each NADPH regenerating enzyme on GDP-L-fucose production were investigated in a series of batch and fed-batch fermentations. Batch fermentations showed that overexpression of G6PDH was the most effective for GDP-L-fucose production. However, GDP-L-fucose production was not enhanced by overexpression of G6PDH in the glucose-limited fed-batch fermentation. Hence, a glucose feeding strategy was optimized to enhance GDP-L-fucose production. Fed-batch fermentation with a pH-stat feeding mode for sufficient supply of glucose significantly enhanced GDP-L-fucose production compared with glucose-limited fed-batch fermentation. A maximum GDP-L-fucose concentration of 235.2 ± 3.3 mg l(-1), corresponding to a 21% enhancement in the GDP-L-fucose production compared with the control strain overexpressing GDP-L-fucose biosynthetic enzymes only, was achieved in the pH-stat fed-batch fermentation of the recombinant E. coli overexpressing G6PDH. It was concluded that sufficient glucose supply and efficient NADPH regeneration are crucial for NADPH-dependent GDP-L-fucose production in recombinant E. coli.

GDP Release Preferentially Occurs on the Phosphate Side in Heterotrimeric G-proteins

PubMed Central

Louet, Maxime; Martinez, Jean; Floquet, Nicolas

2012-01-01

After extra-cellular stimulation of G-Protein Coupled Receptors (GPCRs), GDP/GTP exchange appears as the key, rate limiting step of the intracellular activation cycle of heterotrimeric G-proteins. Despite the availability of a large number of X-ray structures, the mechanism of GDP release out of heterotrimeric G-proteins still remains unknown at the molecular level. Starting from the available X-ray structure, extensive unconstrained/constrained molecular dynamics simulations were performed on the complete membrane-anchored Gi heterotrimer complexed to GDP, for a total simulation time overcoming 500 ns. By combining Targeted Molecular Dynamics (TMD) and free energy profiles reconstruction by umbrella sampling, our data suggest that the release of GDP was much more favored on its phosphate side. Interestingly, upon the forced extraction of GDP on this side, the whole protein encountered large, collective motions in perfect agreement with those we described previously including a domain to domain motion between the two ras-like and helical sub-domains of Gα. PMID:22829757

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

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.

Low GDP Solution and Glucose-Sparing Strategies for Peritoneal Dialysis.

PubMed

Szeto, Cheuk Chun; Johnson, David W

2017-01-01

Long-term exposure to a high glucose concentration in conventional peritoneal dialysis (PD) solution has a number of direct and indirect (via glucose degradation products [GDP]) detrimental effects on the peritoneal membrane, as well as systemic metabolism. Glucose- or GDP-sparing strategies often are hypothesized to confer clinical benefits to PD patients. Icodextrin (glucose polymer) solution improves peritoneal ultrafiltration and reduces the risk of fluid overload, but these beneficial effects are probably the result of better fluid removal rather than being glucose sparing. Although frequently used for glucose sparing, the role of amino acid-based solution in this regard has not been tested thoroughly. When glucose-free solutions are used in a combination regimen, published studies showed that glycemic control was improved significantly in diabetic PD patients, and there probably are beneficial effects on peritoneal function. However, the long-term effects of glucose-free solutions, used either alone or as a combination regimen, require further studies. On the other hand, neutral pH-low GDP fluids have been shown convincingly to preserve residual renal function and urine volume. The cost effectiveness of these solutions supports the regular use of neutral pH-low GDP solutions. Nevertheless, further studies are required to determine whether neutral pH-low GDP solutions exert beneficial effects on patient-level outcomes, such as peritonitis, technique survival, and patient survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Biochemical analysis of leishmanial and human GDP-Mannose Pyrophosphorylases and selection of inhibitors as new leads.

PubMed

Mao, Wei; Daligaux, Pierre; Lazar, Noureddine; Ha-Duong, Tâp; Cavé, Christian; van Tilbeurgh, Herman; Loiseau, Philippe M; Pomel, Sébastien

2017-04-07

Leishmaniases are an ensemble of diseases caused by the protozoan parasite of the genus Leishmania. Current antileishmanial treatments are limited and present main issues of toxicity and drug resistance emergence. Therefore, the generation of new inhibitors specifically directed against a leishmanial target is an attractive strategy to expand the chemotherapeutic arsenal. GDP-Mannose Pyrophosphorylase (GDP-MP) is a prominent therapeutic target involved in host-parasite recognition which has been described to be essential for parasite survival. In this work, we produced and purified GDP-MPs from L. mexicana (LmGDP-MP), L. donovani (LdGDP-MP), and human (hGDP-MP), and compared their enzymatic properties. From a rationale design of 100 potential inhibitors, four compounds were identified having a promising and specific inhibitory effect on parasite GDP-MP and antileishmanial activities, one of them exhibits a competitive inhibition on LdGDP-MP and belongs to the 2-substituted quinoline series.

Posttranslational modifications of Rab proteins cause effective displacement of GDP dissociation inhibitor.

PubMed

Oesterlin, Lena K; Goody, Roger S; Itzen, Aymelt

2012-04-10

Intracellular vesicular trafficking is regulated by approximately 60 members of the Rab subfamily of small Ras-like GDP/GTP binding proteins. Rab proteins cycle between inactive and active states as well as between cytosolic and membrane bound forms. Membrane extraction/delivery and cytosolic distribution of Rabs is mediated by interaction with the protein GDP dissociation inhibitor (GDI) that binds to prenylated inactive (GDP-bound) Rab proteins. Because the Rab:GDP:GDI complex is of high affinity, the question arises of how GDI can be displaced efficiently from Rab protein in order to allow the necessary recruitment of the Rab to its specific target membrane. While there is strong evidence that DrrA, as a bacterially encoded GDP/GTP exchange factor, contributes to this event, we show here that posttranslational modifications of Rabs can also modulate the affinity for GDI and thus cause effective displacement of GDI from Rab:GDI complexes. These activities have been found associated with the phosphocholination and adenylylation activities of the enzymes AnkX and DrrA/SidM, respectively, from the pathogenic bacterium Legionella pneumophila. Both modifications occur after spontaneous dissociation of Rab:GDI complexes within their natural equilibrium. Therefore, the effective GDI displacement that is observed is caused by inhibition of reformation of Rab:GDI complexes. Interestingly, in contrast to adenylylation by DrrA, AnkX can covalently modify inactive Rabs with high catalytic efficiency even when GDP is bound to the GTPase and hence can inhibit binding of GDI to Rab:GDP complexes. We therefore speculate that human cells could employ similar mechanisms in the absence of infection to effectively displace Rabs from GDI.

Enzymatic Synthesis of GDP-α-l-fucofuranose by MtdL and Hyg20.

PubMed

Qin, Xiangjing; Xie, Yunchang; Huang, Hongbo; Chen, Qi; Ma, Junying; Li, Qinglian; Ju, Jianhua

2018-02-16

Two mutases, MtdL and Hyg20, are reported. Both are able to functionally drive the biosynthesis of GDP-α-l-fucofuranose. Both enzymes catalyze similar functions, catalytically enabling the bidirectional reaction between GDP-β-l-fucopyranose and GDP-α-l-fucofuranose using only divalent cations as cofactors. This realization is but one of a number of important insights into fucofuranose biosynthesis presented herein.

Immunogenetic Markers Definition in Latvian Patients with Lyme Borreliosis and Lyme Neuroborreliosis

PubMed Central

Kovalchuka, Lilija; Cvetkova, Svetlana; Trofimova, Julija; Eglite, Jelena; Gintere, Sandra; Lucenko, Irina; Oczko-Grzesik, Barbara; Viksna, Ludmila; Krumina, Angelika

2016-01-01

The aim of this study was to determine the human leukocyte antigen (HLA)-DRB1 alleles in two groups of patients in Latvia: patients with Lyme borreliosis and patients with Lyme neuroborreliosis. The study included 216 patients with Lyme borreliosis, 29 patients with Lyme neuroborreliosis and 282 control persons. All surveyed persons were residents of Latvia. The HLA-DR genotyping was performed by polymerase chain reaction- sequence specific primer (PCR-SSP). The predisposition to the Lyme borreliosis is associated with the HLA-DRB1*07, -DRB1*17(03), -DRB1*04, -DRB1*15(02) alleles. The allele -DRB1*11(05), -DRB1*14(06) and -DRB1*13(06) were significantly more frequent in controls. In-group with Lyme neuroborreliosis differences were found for the -DRB1*07 and -DRB1*04 alleles, but only HLA-DRB1*07 allele was statistically significant after Bonferroni correction and associated with Lyme neuroborreliosis in Latvian patients. PMID:27916969

Immunogenetic Markers Definition in Latvian Patients with Lyme Borreliosis and Lyme Neuroborreliosis.

PubMed

Kovalchuka, Lilija; Cvetkova, Svetlana; Trofimova, Julija; Eglite, Jelena; Gintere, Sandra; Lucenko, Irina; Oczko-Grzesik, Barbara; Viksna, Ludmila; Krumina, Angelika

2016-12-01

The aim of this study was to determine the human leukocyte antigen (HLA)-DRB1 alleles in two groups of patients in Latvia: patients with Lyme borreliosis and patients with Lyme neuroborreliosis. The study included 216 patients with Lyme borreliosis, 29 patients with Lyme neuroborreliosis and 282 control persons. All surveyed persons were residents of Latvia. The HLA-DR genotyping was performed by polymerase chain reaction- sequence specific primer (PCR-SSP). The predisposition to the Lyme borreliosis is associated with the HLA-DRB1*07, -DRB1*17(03), -DRB1*04, -DRB1*15(02) alleles. The allele -DRB1*11(05), -DRB1*14(06) and -DRB1*13(06) were significantly more frequent in controls. In-group with Lyme neuroborreliosis differences were found for the -DRB1*07 and -DRB1*04 alleles, but only HLA-DRB1*07 allele was statistically significant after Bonferroni correction and associated with Lyme neuroborreliosis in Latvian patients.

GTP- and GDP-Dependent Rab27a Effectors in Pancreatic Beta-Cells.

PubMed

Yamaoka, Mami; Ishizaki, Toshimasa; Kimura, Toshihide

2015-01-01

Small guanosine triphosphatases (GTPases) participate in a wide variety of cellular functions including proliferation, differentiation, adhesion, and intracellular transport. Conventionally, only the guanosine 5'-triphosphate (GTP)-bound small GTPase interacts with effector proteins, and the resulting downstream signals control specific cellular functions. Therefore, the GTP-bound form is regarded as active, and the focus has been on searching for proteins that bind the GTP form to look for their effectors. The Rab family small GTPase Rab27a is highly expressed in some secretory cells and is involved in the control of membrane traffic. The present study reviews recent progress in our understanding of the roles of Rab27a and its effectors in pancreatic beta-cells. In the basal state, GTP-bound Rab27a controls insulin secretion at pre-exocytic stages via its GTP-dependent effectors. We previously identified novel guanosine 5'-diphosphate (GDP)-bound Rab27-interacting proteins. Interestingly, GDP-bound Rab27a controls endocytosis of the secretory membrane via its interaction with these proteins. We also demonstrated that the insulin secretagogue glucose converts Rab27a from its GTP- to GDP-bound forms. Thus, GTP- and GDP-bound Rab27a regulate pre-exocytic and endocytic stages in membrane traffic, respectively. Since the physiological importance of GDP-bound GTPases has been largely overlooked, we consider that the investigation of GDP-dependent effectors for other GTPases is necessary for further understanding of cellular function.

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-06-07

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

Biochemical characterization of an isoform of GDP-D-mannose-4,6-dehydratase from Mortierella alpina.

PubMed

Wang, Hongchao; Zhang, Chen; Chen, Haiqin; Yang, Qin; Zhou, Xin; Gu, Zhennan; Zhang, Hao; Chen, Wei; Chen, Yong Q

2016-10-01

To clarify the molecular mechanism of GDP-L-fucose biosynthesis in Mortierella alpina. Analysis of the M. alpina genome suggests that there were two isofunctional GDP-D-mannose-4,6-dehydratase genes (GMD1 and GMD2) that have never been found in a microorganism before. GMD2 was expressed heterologously in Escherichia coli and purified to homogeneity. The addition of exogenous NAD(+) or NADP(+) was not essential for GMD2 activity. GMD2 may have considerable importance for GDP-L-fucose biosynthesis under nitrogen starvation. The transcriptional regulation of GMD1 may be more susceptible to GDP and GTP than that of GMD2. Significant changes were observed in the concentration of GDP-L-fucose (30 and 36 % inhibition respectively) and total fatty acids (18 and 12 % inhibition respectively) in M. alpina grown on GMD inhibitors medium, which suggests that GDP-L-fucose is functionally significant in lipid metabolism. This is the first time that an isofunctional GDP-D-mannose-4,6-dehydratase has been characterized in a microorganism.

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.

Negative cooperativity in binding of muscarinic receptor agonists and GDP as a measure of agonist efficacy

PubMed Central

Jakubík, J; Janíčková, H; El-Fakahany, EE; Doležal, V

2011-01-01

BACKGROUND AND PURPOSE Conventional determination of agonist efficacy at G-protein coupled receptors is measured by stimulation of guanosine-5′-γ−thiotriphosphate (GTPγS) binding. We analysed the role of guanosine diphosphate (GDP) in the process of activation of the M2 muscarinic acetylcholine receptor and provide evidence that negative cooperativity between agonist and GDP binding is an alternative measure of agonist efficacy. EXPERIMENTAL APPROACH Filtration and scintillation proximity assays measured equilibrium binding as well as binding kinetics of [35S]GTPγS and [3H]GDP to a mixture of G-proteins as well as individual classes of G-proteins upon binding of structurally different agonists to the M2 muscarinic acetylcholine receptor. KEY RESULTS Agonists displayed biphasic competition curves with the antagonist [3H]-N-methylscopolamine. GTPγS (1 µM) changed the competition curves to monophasic with low affinity and 50 µM GDP produced a similar effect. Depletion of membrane-bound GDP increased the proportion of agonist high-affinity sites. Carbachol accelerated the dissociation of [3H]GDP from membranes. The inverse agonist N-methylscopolamine slowed GDP dissociation and GTPγS binding without changing affinity for GDP. Carbachol affected both GDP association with and dissociation from Gi/o G-proteins but only its dissociation from Gs/olf G-proteins. CONCLUSIONS AND IMPLICATIONS These findings suggest the existence of a low-affinity agonist-receptor conformation complexed with GDP-liganded G-protein. Also the negative cooperativity between GDP and agonist binding at the receptor/G-protein complex determines agonist efficacy. GDP binding reveals differences in action of agonists versus inverse agonists as well as differences in activation of Gi/o versus Gs/olf G-proteins that are not identified by conventional GTPγS binding. PMID:20958290

Negative cooperativity in binding of muscarinic receptor agonists and GDP as a measure of agonist efficacy.

PubMed

Jakubík, J; Janíčková, H; El-Fakahany, E E; Doležal, V

2011-03-01

Conventional determination of agonist efficacy at G-protein coupled receptors is measured by stimulation of guanosine-5'-γ-thiotriphosphate (GTPγS) binding. We analysed the role of guanosine diphosphate (GDP) in the process of activation of the M₂ muscarinic acetylcholine receptor and provide evidence that negative cooperativity between agonist and GDP binding is an alternative measure of agonist efficacy. Filtration and scintillation proximity assays measured equilibrium binding as well as binding kinetics of [³⁵S]GTPγS and [³H]GDP to a mixture of G-proteins as well as individual classes of G-proteins upon binding of structurally different agonists to the M₂ muscarinic acetylcholine receptor. Agonists displayed biphasic competition curves with the antagonist [³H]-N-methylscopolamine. GTPγS (1 µM) changed the competition curves to monophasic with low affinity and 50 µM GDP produced a similar effect. Depletion of membrane-bound GDP increased the proportion of agonist high-affinity sites. Carbachol accelerated the dissociation of [³H]GDP from membranes. The inverse agonist N-methylscopolamine slowed GDP dissociation and GTPγS binding without changing affinity for GDP. Carbachol affected both GDP association with and dissociation from G(i/o) G-proteins but only its dissociation from G(s/olf) G-proteins. These findings suggest the existence of a low-affinity agonist-receptor conformation complexed with GDP-liganded G-protein. Also the negative cooperativity between GDP and agonist binding at the receptor/G-protein complex determines agonist efficacy. GDP binding reveals differences in action of agonists versus inverse agonists as well as differences in activation of G(i/o) versus G(s/olf) G-proteins that are not identified by conventional GTPγS binding. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Macroenvironmental factors including GDP per capita and physical activity in Europe.

PubMed

Cameron, Adrian J; Van Stralen, Maartje M; Kunst, Anton E; Te Velde, Saskia J; Van Lenthe, Frank J; Salmon, Jo; Brug, Johannes

2013-02-01

Socioeconomic inequalities in physical activity at the individual level are well reported. Whether inequalities in economic development and other macroenvironmental variables between countries are also related to physical activity at the country level is comparatively unstudied. We examined the relationship between country-level data on macroenvironmental factors (gross domestic product (GDP) per capita, public sector expenditure on health, percentage living in urban areas, and cars per 1000 population) with country-level physical activity prevalence obtained from previous pan-European studies. Studies that assessed leisuretime physical activity (n = 3 studies including 27 countries in adults, n = 2 studies including 28 countries in children) and total physical activity (n = 3 studies in adults including 16 countries) were analyzed separately as were studies among adults and children. Strong and consistent positive correlations were observed between country prevalence of leisure-time physical activity and country GDP per capita in adults (average r = 0.70; all studies, P G 0.05). In multivariate analysis, country prevalence of leisure-time physical activity among adults remained associated with country GDP per capita (two of three studies) but not urbanization or educational attainment. Among school-age populations, no association was found between country GDP per capita and country prevalence of leisure-time physical activity. In those studies that assessed total physical activity (which also includes occupational and transport physical activity), no association with country GDP per capita was observed. Clear differences in national leisure-time physical activity levels throughout Europe may be a consequence of economic development. Lack of economic development of some countries in Europe may make increasing leisure-time physical activity more difficult. Further examination of the link between country GDP per capita and national physical activity levels (across

GDP-L-fucose is required for boundary definition in plants.

PubMed

Gonçalves, Beatriz; Maugarny-Calès, Aude; Adroher, Bernard; Cortizo, Millán; Borrega, Nero; Blein, Thomas; Hasson, Alice; Gineau, Emilie; Mouille, Grégory; Laufs, Patrick; Arnaud, Nicolas

2017-12-16

The CUP-SHAPED COTYLEDON (CUC) transcription factors control plant boundary formation, thus allowing the emergence of novel growth axes. While the developmental roles of the CUC genes in different organs and across species are well characterized, upstream and downstream events that contribute to their function are still poorly understood. To identify new players in this network, we performed a suppressor screen of CUC2g-m4, a line overexpressing CUC2 that has highly serrated leaves. We identified a mutation that simplifies leaf shape and affects MURUS1 (MUR1), which is responsible for GDP-L-fucose production. Using detailed morphometric analysis, we show that GDP-L-fucose has an essential role in leaf shape acquisition by sustaining differential growth at the leaf margins. Accordingly, reduced CUC2 expression levels are observed in mur1 leaves. Furthermore, genetic analyses reveal a conserved role for GDP-L-fucose in different developmental contexts where it contributes to organ separation in the same pathway as CUC2. Taken together, our results reveal that GDP-L-fucose is necessary for proper establishment of boundary domains in various developmental contexts. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

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

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.

Modulation of GDP-fucose level for generating proteins with reduced rate of fucosylation (WO2010141855).

PubMed

Taupin, Philippe

2011-09-01

The application (WO2010141855) is in the field of glycobiology, and involves the control of the rate of fucosylation of proteins by exogenous factors. It aims at controlling the rate of protein fucosylation with inhibitors (drugs or nucleic acid antagonists) of enzymes involved in the synthesis of GDP-fucose. Mammalian cell lines were cultured in the presence of inhibitors, for example, siRNA. The rates of GDP-fucose in cells and during protein fucosylation were characterized. The level of protein fucosylation decreases rapidly in response to a decrease in GDP-fucose level. The relationship between the rate of fucosylation of proteins and the level of GDP-fucose in a cell is non-linear. Reduction in the rate of protein fucosylation can be achieved with a minimal reduction of the level of GDP-fucose in cells. The paradigm may be used to synthesize proteins and antibodies, with a reduced rate of fucosylation. The application claims that the use of drugs or nucleic acid antagonists that inhibit the enzymes involved in GDP-fucose biosynthesis optimizes the level of GDP-fucose present in cells, and reduces the rate of fucosylation of glycoproteins.

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

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

PubMed

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

2017-02-22

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.

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

DOE PAGES

Rautengarten, Carsten; Ebert, Berit; Liu, Lifeng; ...

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 andmore » is required for proper plant growth and development.« less

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

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

Rautengarten, Carsten; Ebert, Berit; Liu, Lifeng

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 andmore » is required for proper plant growth and development.« less

GDP Spatialization and Economic Differences in South China Based on NPP-VIIRS Nighttime Light Imagery

NASA Astrophysics Data System (ADS)

Zhao, M.

2017-12-01

Accurate data on gross domestic product (GDP) at pixel level are needed to understand the dynamics of regional economies. GDP spatialization is the basis of quantitative analysis on economic diversities of different administrative divisions and areas with different natural or humanistic attributes. Data from the Visible Infrared Imaging Radiometer Suite (VIIRS), carried by the Suomi National Polar-orbiting Partnership (NPP) satellite, are capable of estimating GDP, but few studies have been conducted for mapping GDP at pixel level and further pattern analysis of economic differences in different regions using the VIIRS data. This paper produced a pixel-level (500 m × 500 m) GDP map for South China in 2014 and quantitatively analyzed economic differences among diverse geomorphological types. Based on a regression analysis, the total nighttime light (TNL) of corrected VIIRS data were found to exhibit R2 values of 0.8935 and 0.9243 for prefecture GDP and county GDP, respectively. This demonstrated that TNL showed a more significant capability in reflecting economic status (R2 > 0.88) than other nighttime light indices (R2 < 0.52), and showed quadratic polynomial relationships with GDP rather than simple linear correlations at both prefecture and county levels. The corrected NPP-VIIRS data showed a better fit than the original data, and the estimation at the county level was better than at the prefecture level. The pixel-level GDP map indicated that: (a) economic development in coastal areas was higher than that in inland areas; (b) low altitude plains were the most developed areas, followed by low altitude platforms and low altitude hills; and (c) economic development in middle altitude areas, and low altitude hills and mountains remained to be strengthened.

Epidemiology of Voice Disorders in Latvian School Teachers.

PubMed

Trinite, Baiba

2017-07-01

The prevalence of voice disorders in the teacher population in Latvia has not been studied so far and this is the first epidemiological study whose goal is to investigate the prevalence of voice disorders and their risk factors in this professional group. A wide cross-sectional study using stratified sampling methodology was implemented in the general education schools of Latvia. The self-administered voice risk factor questionnaire and the Voice Handicap Index were completed by 522 teachers. Two teachers groups were formed: the voice disorders group which included 235 teachers with actual voice problems or problems during the last 9 months; and the control group which included 174 teachers without voice disorders. Sixty-six percent of teachers gave a positive answer to the following question: Have you ever had problems with your voice? Voice problems are more often found in female than male teachers (68.2% vs 48.8%). Music teachers suffer from voice disorders more often than teachers of other subjects. Eighty-two percent of teachers first faced voice problems in their professional carrier. The odds of voice disorders increase if the following risk factors exist: extra vocal load, shouting, throat clearing, neglecting of personal health, background noise, chronic illnesses of the upper respiratory tract, allergy, job dissatisfaction, and regular stress in the working place. The study findings indicated a high risk of voice disorders among Latvian teachers. The study confirmed data concerning the multifactorial etiology of voice disorders. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Thermodynamics of the GTP-GDP-operated conformational switch of selenocysteine-specific translation factor SelB.

PubMed

Paleskava, Alena; Konevega, Andrey L; Rodnina, Marina V

2012-08-10

SelB is a specialized translation factor that binds GTP and GDP and delivers selenocysteyl-tRNA (Sec-tRNA(Sec)) to the ribosome. By analogy to elongation factor Tu (EF-Tu), SelB is expected to control the delivery and release of Sec-tRNA(Sec) to the ribosome by the structural switch between GTP- and GDP-bound conformations. However, crystal structures of SelB suggested a similar domain arrangement in the apo form and GDP- and GTP-bound forms of the factor, raising the question of how SelB can fulfill its delivery function. Here, we studied the thermodynamics of guanine nucleotide binding to SelB by isothermal titration calorimetry in the temperature range between 10 and 25 °C using GTP, GDP, and two nonhydrolyzable GTP analogs, guanosine 5'-O-(γ-thio)triphosphate (GTPγS) and guanosine 5'-(β,γ-imido)-triphosphate (GDPNP). The binding of SelB to either guanine nucleotide is characterized by a large heat capacity change (-621, -467, -235, and -275 cal × mol(-1) × K(-1), with GTP, GTPγS, GDPNP, and GDP, respectively), associated with compensatory changes in binding entropy and enthalpy. Changes in heat capacity indicate a large decrease of the solvent-accessible surface area in SelB, amounting to 43 or 32 amino acids buried upon binding of GTP or GTPγS, respectively, and 15-19 amino acids upon binding GDP or GDPNP. The similarity of the GTP and GDP forms in the crystal structures can be attributed to the use of GDPNP, which appears to induce a structure of SelB that is more similar to the GDP than to the GTP-bound form.

Different effects of guanine nucleotides (GDP and GTP) on protein-mediated mitochondrial proton leak.

PubMed

Woyda-Ploszczyca, Andrzej M; Jarmuszkiewicz, Wieslawa

2014-01-01

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

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

PubMed Central

Woyda-Ploszczyca, Andrzej M.; Jarmuszkiewicz, Wieslawa

2014-01-01

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

Recognition and stabilization of geranylgeranylated human Rab5 by the GDP Dissociation Inhibitor (GDI).

PubMed

Edler, Eileen; Stein, Matthias

2017-10-25

The small GTPase Rab5 is the key regulator of early endosomal fusion. It is post-translationally modified by covalent attachment of two geranylgeranyl (GG) chains to adjacent cysteine residues of the C-terminal hypervariable region (HVR). The GDP dissociation inhibitor (GDI) recognizes membrane-associated Rab5(GDP) and serves to release it into the cytoplasm where it is kept in a soluble state. A detailed new structural and dynamic model for human Rab5(GDP) recognition and binding with human GDI at the early endosome membrane and in its dissociated state is presented. In the cytoplasm, the GDI protein accommodates the GG chains in a transient hydrophobic binding pocket. In solution, two different binding modes of the isoprenoid chains inserted into the hydrophobic pocket of the Rab5(GDP):GDI complex can be identified. This equilibrium between the two states helps to stabilize the protein-protein complex in solution. Interprotein contacts between the Rab5 switch regions and characteristic patches of GDI residues from the Rab binding platform (RBP) and the C-terminus coordinating region (CCR) reveal insight on the formation of such a stable complex. GDI binding to membrane-anchored Rab5(GDP) is initially mediated by the solvent accessible switch regions of the Rab-specific RBP. Formation of the membrane-associated Rab5(GDP):GDI complex induces a GDI reorientation to establish additional interactions with the Rab5 HVR. These results allow to devise a detailed structural model for the process of extraction of GG-Rab5(GDP) by GDI from the membrane and the dissociation from targeting factors and effector proteins prior to GDI binding.

Impact of GDP Information Technology in Developing of Regional Central Business (Case 50 Airports IT City Development in Indonesia)

NASA Astrophysics Data System (ADS)

Suyono, Joko; Sukoco, Agus; Ikhsan Setiawan, M.; Suhermin; Rahim, Robbi

2017-12-01

Indonesia a great number of populations and demand of air transportation services keep increasing by the year in line with the increasing of population and welfare its people. Need for telematics solutions to support goods transport and distribution in cities is mainly due to the complexity of the processes taking place in urban transport systems and the importance of the optimisation of transport operations via ensuring adequate availability of linear and point infrastructure, while reducing the adverse impacts of the transport system on the environment. Efficient infrastructure supports economic growth, improves quality of life, and it is important for national security. Impact of GDP Information Technology in developing of Regional Central Business especially SME Business, are very large correlations and very significant supported by Passenger Arrival and Departure, Baggage Loaded and Unloaded, Cargo Loaded and Unloaded, Separated regional asset, Grant, Capital Expenditure, Investment of Regional Gov., GDP Agriculture-Forestry-Fishing, GDP Manufacturing, GDP Electricity-Gas, GDP Water supply- Sewerage-Waste Management-Remediation Activities, GDP Financial-Insurance Activities, GDP Business Activities, GDP Public Administration and Defense-Compulsory Social Security, GDP Education and GDP Other Services Activities

GDP-D-mannose epimerase regulates male gametophyte development, plant growth and leaf senescence in Arabidopsis.

PubMed

Qi, Tiancong; Liu, Zhipeng; Fan, Meng; Chen, Yan; Tian, Haixia; Wu, Dewei; Gao, Hua; Ren, Chunmei; Song, Susheng; Xie, Daoxin

2017-09-04

Plant GDP-D-mannose epimerase (GME) converts GDP-D-mannose to GDP-L-galactose, a precursor of both L-ascorbate (vitamin C) and cell wall polysaccharides. However, the genetic functions of GME in Arabidopsis are unclear. In this study, we found that mutations in Arabidopsis GME affect pollen germination, pollen tube elongation, and transmission and development of the male gametophyte through analysis of the heterozygous GME/gme plants and the homozygous gme plants. Arabidopsis gme mutants also exhibit severe growth defects and early leaf senescence. Surprisingly, the defects in male gametophyte in the gme plants are not restored by L-ascorbate, boric acid or GDP-L-galactose, though boric acid rescues the growth defects of the mutants, indicating that GME may regulate male gametophyte development independent of L-ascorbate and GDP-L-galactose. These results reveal key roles for Arabidopsis GME in reproductive development, vegetative growth and leaf senescence, and suggest that GME regulates plant growth and controls male gametophyte development in different manners.

Thermodynamics of the GTP-GDP-operated Conformational Switch of Selenocysteine-specific Translation Factor SelB*

PubMed Central

Paleskava, Alena; Konevega, Andrey L.; Rodnina, Marina V.

2012-01-01

SelB is a specialized translation factor that binds GTP and GDP and delivers selenocysteyl-tRNA (Sec-tRNASec) to the ribosome. By analogy to elongation factor Tu (EF-Tu), SelB is expected to control the delivery and release of Sec-tRNASec to the ribosome by the structural switch between GTP- and GDP-bound conformations. However, crystal structures of SelB suggested a similar domain arrangement in the apo form and GDP- and GTP-bound forms of the factor, raising the question of how SelB can fulfill its delivery function. Here, we studied the thermodynamics of guanine nucleotide binding to SelB by isothermal titration calorimetry in the temperature range between 10 and 25 °C using GTP, GDP, and two nonhydrolyzable GTP analogs, guanosine 5′-O-(γ-thio)triphosphate (GTPγS) and guanosine 5′-(β,γ-imido)-triphosphate (GDPNP). The binding of SelB to either guanine nucleotide is characterized by a large heat capacity change (−621, −467, −235, and −275 cal × mol−1 × K−1, with GTP, GTPγS, GDPNP, and GDP, respectively), associated with compensatory changes in binding entropy and enthalpy. Changes in heat capacity indicate a large decrease of the solvent-accessible surface area in SelB, amounting to 43 or 32 amino acids buried upon binding of GTP or GTPγS, respectively, and 15–19 amino acids upon binding GDP or GDPNP. The similarity of the GTP and GDP forms in the crystal structures can be attributed to the use of GDPNP, which appears to induce a structure of SelB that is more similar to the GDP than to the GTP-bound form. PMID:22740700

Energy Efficiency and Importance of Renewable Energy Sources in Latvia

NASA Astrophysics Data System (ADS)

Skapare, I.; Kreslins, A.

2007-10-01

The main goal of Latvian energy policy is to ensure safe and environmentally friendly long-term energy supply at cost-effective prices, contributing to enhance competitiveness, and to ensure safe energy transit. The Latvian Parliament approved an Energy Efficiency Strategy in 2000. Its objective is to decrease energy consumption per unit of GDP by 25% by 2010. Awareness raising, implementation of standards and economic incentives for self financing are the main instruments to increase energy efficiency, mentioned in the strategy. Latvia, as many other European Union member states, is dependent on the import of primary energy resources. The Latvian Renewable Energy strategy is still under development. The only recent study on RES was developed in the framework of a PHARE program in year 2000: "Renewable energy resource program", where three main objectives for a future RES strategy were proposed: 1. To increase the use of wood waste and low value wood and forest residues. 2. To improve efficiency of combustion technologies and to replace outdated plants. 3. To increase the use of renewables in Combined Heat and Power plants (CHP). Through the Renewable Energy and Energy Efficiency Partnership, partners will develop a set of new shared activities, and coordinate and strengthen existing efforts in this area.

The Effect of Low-GDP Solution on Ultrafiltration and Solute Transport in Continuous Ambulatory Peritoneal Dialysis Patients

PubMed Central

Cho, Kyu-Hyang; Do, Jun-Young; Park, Jong-Won; Yoon, Kyung-Woo; Kim, Yong-Lim

2013-01-01

♦ Background: Several studies have reported benefits for human peritoneal mesothelial cell function of a neutral-pH dialysate low in glucose degradation products (GDPs). However, the effects of low-GDP solution on ultrafiltration (UF), transport of solutes, and control of body water remain elusive. We therefore investigated the effect of low-GDP solution on UF, solute transport, and control of body water. ♦ Methods: Among 79 new continuous ambulatory peritoneal dialysis (CAPD) patients, 60 completed a 12-month protocol (28 in a lactate-based high-GDP solution group, 32 in a lactate-based low-GDP solution group). Clinical indices—including 24-hour UF volume (UFV), 24-hour urine volume (UV), residual renal function, and dialysis adequacy—were measured at months 1, 6, and 12. At months 1, 6, and 12, UFV, glucose absorption, 4-hour dialysate-to-plasma (D/P) creatinine, and 1-hour D/P Na+ were assessed during a modified 4.25% peritoneal equilibration test (PET). Body composition by bioelectric impedance analysis was measured at months 1 and 12 in 26 CAPD patients. ♦ Results: Daily UFV was lower in the low-GDP group. Despite similar solute transport and aquaporin function, the low-GDP group also showed lower UFV and higher glucose absorption during the PET. Factors associated with UFV during the PET were lactate-based high-GDP solution and 1-hour D/P Na+. No differences in volume status and obesity at month 12 were observed, and improvements in hypervolemia were equal in both groups. ♦ Conclusions: Compared with the high-GDP group, the low-GDP group had a lower UFV during a PET and a lower daily UFV during the first year after peritoneal dialysis initiation. Although the low-GDP group had a lower daily UFV, no difficulties in controlling edema were encountered. PMID:23284074

The effect of low-GDP solution on ultrafiltration and solute transport in continuous ambulatory peritoneal dialysis patients.

PubMed

Cho, Kyu-Hyang; Do, Jun-Young; Park, Jong-Won; Yoon, Kyung-Woo; Kim, Yong-Lim

2013-01-01

Several studies have reported benefits for human peritoneal mesothelial cell function of a neutral-pH dialysate low in glucose degradation products (GDPs). However, the effects of low-GDP solution on ultrafiltration (UF), transport of solutes, and control of body water remain elusive. We therefore investigated the effect of low-GDP solution on UF, solute transport, and control of body water. Among 79 new continuous ambulatory peritoneal dialysis (CAPD) patients, 60 completed a 12-month protocol (28 in a lactate-based high-GDP solution group, 32 in a lactate-based low-GDP solution group). Clinical indices--including 24-hour UF volume (UFV), 24-hour urine volume (UV), residual renal function, and dialysis adequacy--were measured at months 1, 6, and 12. At months 1, 6, and 12, UFV, glucose absorption, 4-hour dialysate-to-plasma (D/P) creatinine, and 1-hour D/P Na(+) were assessed during a modified 4.25% peritoneal equilibration test (PET). Body composition by bioelectric impedance analysis was measured at months 1 and 12 in 26 CAPD patients. Daily UFV was lower in the low-GDP group. Despite similar solute transport and aquaporin function, the low-GDP group also showed lower UFV and higher glucose absorption during the PET. Factors associated with UFV during the PET were lactate-based high-GDP solution and 1-hour D/P Na(+). No differences in volume status and obesity at month 12 were observed, and improvements in hypervolemia were equal in both groups. Compared with the high-GDP group, the low-GDP group had a lower UFV during a PET and a lower daily UFV during the first year after peritoneal dialysis initiation. Although the low-GDP group had a lower daily UFV, no difficulties in controlling edema were encountered.

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…

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

Base-modified GDP-mannose derivatives and their substrate activity towards a yeast mannosyltransferase.

PubMed

Collier, Alice; Wagner, Gerd K

2017-11-27

We have previously developed a new class of inhibitors and chemical probes for glycosyltransferases through base-modification of the sugar-nucleotide donor. The key feature of these donor analogues is the presence of an additional substituent at the nucleobase. To date, the application of this general concept has been limited to UDP-sugars and UDP-sugar-dependent glycosyltransferases. Herein, we report for the first time the application of our approach to a GDP-mannose-dependent mannosyltransferase. We have prepared four GDP-mannose derivatives with an additional substituent at either position 6 or 8 of the nucleobase. These donor analogues were recognised as donor substrates by the mannosyltransferase Kre2p from yeast, albeit with significantly lower turnover rates than the natural donor GDP-mannose. The presence of the additional substituent also redirected enzyme activity from glycosyl transfer to donor hydrolysis. Taken together, our results suggest that modification of the donor nucleobase is, in principle, a viable strategy for probe and inhibitor development against GDP-mannose-dependent GTs. Copyright © 2017 Elsevier Ltd. All rights reserved.

GDP-bound and nucleotide-free intermediates of the guanine nucleotide exchange in the Rab5·Vps9 system.

PubMed

Uejima, Tamami; Ihara, Kentaro; Goh, Tatsuaki; Ito, Emi; Sunada, Mariko; Ueda, Takashi; Nakano, Akihiko; Wakatsuki, Soichi

2010-11-19

Many GTPases regulate intracellular transport and signaling in eukaryotes. Guanine nucleotide exchange factors (GEFs) activate GTPases by catalyzing the exchange of their GDP for GTP. Here we present crystallographic and biochemical studies of a GEF reaction with four crystal structures of Arabidopsis thaliana ARA7, a plant homolog of Rab5 GTPase, in complex with its GEF, VPS9a, in the nucleotide-free and GDP-bound forms, as well as a complex with aminophosphonic acid-guanylate ester and ARA7·VPS9a(D185N) with GDP. Upon complex formation with ARA7, VPS9 wedges into the interswitch region of ARA7, inhibiting the coordination of Mg(2+) and decreasing the stability of GDP binding. The aspartate finger of VPS9a recognizes GDP β-phosphate directly and pulls the P-loop lysine of ARA7 away from GDP β-phosphate toward switch II to further destabilize GDP for its release during the transition from the GDP-bound to nucleotide-free intermediates in the nucleotide exchange reaction.

Characterization of an fungal l-fucokinase involved in Mortierella alpina GDP-l-fucose salvage pathway.

PubMed

Wang, Hongchao; Zhang, Chen; Chen, Haiqin; Yang, Qin; Zhou, Xin; Gu, Zhennan; Zhang, Hao; Chen, Wei; Chen, Yong Q

2016-08-01

GDP-l-fucose functions as a biological donor for fucosyltransferases, which are required for the catalysis of l-fucose to various acceptor molecules including oligosaccharides, glycoproteins and glycolipids. Mortierella alpina is one of the highest lipid-producing fungi and can biosynthesis GDP-l-fucose in the de novo pathway. Analysis of the M. alpina genome suggests that there is a gene encoding l-fucokinase (FUK) for the conversion of fucose to l-fucose-1-phosphate in the GDP-l-fucose salvage pathway, which has never been found in fungi before. This gene was characterized to explore its role in GDP-l-fucose synthesis. The yield of GDP-l-fucose is relatively higher in lipid accumulation phase (0.096 mg per g cell) than that in cell multiplication phase (0.074 mg per g cell) of M. alpina Additionally, the transcript level of FUK is up regulated by nitrogen exhaustion when M. alpina starts to accumulate lipid, highlights the functional significance of FUK in the GDP-l-fucose biosynthesis in M. alpina Gene encoding FUK was expressed heterologously in Escherichia coli and the resulting protein was purified to homogeneity. The product of FUK reaction was analyzed by liquid chromatography and mass spectrometry. Kinetic parameters and other properties of FUK were investigated. Comparative analyses between the FUK protein and other homologous proteins were performed. To our knowledge, this study is the first to report a comprehensive characterization of FUK in a fungus. Mortierella alpina could be used as an alternative source for the production of GDP-l-fucose. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Backbone resonance assignments for G protein α(i3) subunit in the GDP-bound state.

PubMed

Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

2014-10-01

Guanine-nucleotide binding proteins (G proteins) serve as molecular switches in signaling pathways, by coupling the activation of G protein-coupled receptors (GPCRs) at the cell surface to intracellular responses. In the resting state, G protein forms a heterotrimer, consisting of the G protein α subunit with GDP (Gα·GDP) and the G protein βγ subunit (Gβγ). Ligand binding to GPCRs promotes the GDP-GTP exchange on Gα, leading to the dissociation of the GTP-bound form of Gα (Gα·GTP) and Gβγ. Then, Gα·GTP and Gβγ bind to their downstream effector enzymes or ion channels and regulate their activities, leading to a variety of cellular responses. Finally, Gα hydrolyzes the bound GTP to GDP and returns to the resting state by re-associating with Gβγ. The G proteins are classified with four major families based on the amino acid sequences of Gα: i/o, s, q/11, and 12/13. Here, we established the backbone resonance assignments of human Gαi3, a member of the i/o family with a molecular weight of 41 K, in complex with GDP. The chemical shifts were compared with those of Gα(i3) in complex with a GTP-analogue, GTPγS, which we recently reported, indicating that the residues with significant chemical shift differences are mostly consistent with the regions with the structural differences between the GDP- and GTPγS-bound states, as indicated in the crystal structures. The assignments of Gα(i3)·GDP would be useful for the analyses of the dynamics of Gα(i3) and its interactions with various target molecules.

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. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

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

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.

One-pot synthesis of GDP-l-fucose by a four-enzyme cascade expressed in Lactococcus lactis.

PubMed

Li, Ling; Kim, Seul-Ah; Heo, Ji Eun; Kim, Tae-Jip; Seo, Jin-Ho; Han, Nam Soo

2017-12-20

GDP-l-fucose is an l-fucose donor to synthesize fucosylated compounds such as human milk oligosaccharides or Lewis antigen. In this study, we used Lactococcus lactis subsp. cremoris NZ9000 to express 4 enzymes, ManB, ManC, Gmd, and WcaG and produced GDP-l-fucose by using one-pot synthesis method with mannose-6-phosphate as substrate and the enzymes as biocatalyst. For preparation of enzyme mixture, 4 genes (manB, manC, gmd, and wcaG) cloned from Escherichia coli were transformed into L. lactis strains using pNZ8008 and the recombinant cell lysates were obtained after cultivation. When mannose-6-phosphate was used as the substrate, the consecutive reactions with ManB, ManC, Gmd, and WcaG resulted in the successful production of GDP-l-fucose (0.13mM). When GDP-d-mannose was used as the substrate, it was entirely converted to GDP-l-fucose (0.2mM; 0.12g/L) via 2 enzymatic reactions mediated by Gmd and WcaG. This is the first report of GDP-l-fucose production by using multiple enzymes expressed in lactic acid bacteria. Copyright © 2017 Elsevier B.V. All rights reserved.

The CHEK2 del5395 is a founder mutation without direct effects for cancer risk in the latvian population.

PubMed

Plonis, J; Kalniete, D; Nakazawa-Miklasevica, M; Irmejs, A; Vjaters, E; Gardovskis, J; Miklasevics, E

2015-12-01

Our objective was to determine: 1) whether the checkpoint kinase 2 ( CHEK2 ) del5395 (g.27417113-27422508 del, NC_000022.11) is a founder mutation in the Latvian population, 2) if there is an association between CHEK2 del5395 mutation and cancer risk, and 3) and whether the CHEK2 del5395 mutation impacts cancer predisposition in Chernobyl disaster liquidators (the civil and military personnel who were called upon to deal with consequences of the 1986 nuclear disaster) as well as geriatric populations. We recruited 438 breast cancer patients, 568 colorectal cancer patients, 399 ovarian cancer patients, 419 prostate cancer patients, 526 healthy blood donors, 480 Chernobyl disaster liquidators and 444 geriatric cancer-free participants. DNA samples were isolated from blood samples and subjected to multiplex polymerase chain reaction (PCR). The truncation of del5395 was estimated by fragment size of the multiplex PCR.All groups were compared to the healthy blood donors using Fisher's exact test. All p values were two-sided and the odds ratios (OR) calculated by two-by-two table. In cancer groups, the del5395 mutation was most frequently observed in the ovarian cancer group (1.00%, OR = 1.32). In control groups, the del5395 mutation was most frequent (0.76%) in the healthy donors, which exceeded its frequency in the Chernobyl liquidators group and the geriatric group by 0.01 and 0.08%, respectively. For all groups, the OR appeared to be >1 only in ovarian cancer patients. However, OR rates showed no statistical significance in either cancer or control groups, with the p value fluctuating within the range of 0.39-1.00. The CHEK2 gene del5395 is a founder mutation in the Latvian population, which, however, does not have a direct impact on genetic predisposition toward colorectal, breast, ovarian and prostate cancer.

5′-Phospho-RNA Acceptor Specificity of GDP Polyribonucleotidyltransferase of Vesicular Stomatitis Virus in mRNA Capping

PubMed Central

Ogino, Minako

2017-01-01

ABSTRACT 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 (m7G) diphosphates efficiently accepted pRNA, resulting in the formation of DAPpppA, 7-deaza-GpppA, and m7GpppA (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

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.

Comparative study of structural models of Leishmania donovani and human GDP-mannose pyrophosphorylases.

PubMed

Daligaux, Pierre; Bernadat, Guillaume; Tran, Linh; Cavé, Christian; Loiseau, Philippe M; Pomel, Sébastien; Ha-Duong, Tâp

2016-01-01

Leishmania is the parasite responsible for the neglected disease leishmaniasis. Its virulence and survival require biosynthesis of glycoconjugates, whose guanosine diphospho-d-mannose pyrophosphorylase (GDP-MP) is a key player. However, experimentally resolved structures of this enzyme are still lacking. We herein propose structural models of the GDP-MP from human and Leishmania donovani. Based on a multiple sequences alignment, the models were built with MODELLER and then carefully refined with all atom molecular dynamics simulations in explicit solvent. Their quality was evaluated against several standard criteria, including their ability to bind GDP-mannose assessed by redocking calculations. Special attention was given in this study to interactions of the catalytic site residues with the enzyme substrate and competitive inhibitors, opening the perspective of medicinal chemistry developments. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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.

Predicting vehicle sales from GDP in 48 countries : 2005-2011.

DOT National Transportation Integrated Search

2013-02-01

This study examined the relationship between GDP and vehicle sales in 48 developed and : developing countries during the years 2005 through 2011. The countries examined were : Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colo...

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

PubMed

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

2015-01-01

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. 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. 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 to the possibility of direct

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

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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2011-01-01

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

A novel GDP-D-glucose phosphorylase involved in quality control of the nucleoside diphosphate sugar pool in Caenorhabditis elegans and mammals.

PubMed

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

2011-06-17

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

Moving Beyond GDP: Cost Effectiveness of Cochlear Implantation and Deaf Education in Latin America.

PubMed

Emmett, Susan D; Tucci, Debara L; Bento, Ricardo F; Garcia, Juan M; Juman, Solaiman; Chiossone-Kerdel, Juan A; Liu, Ta J; de Muñoz, Patricia Castellanos; Ullauri, Alejandra; Letort, Jose J; Mansilla, Teresita; Urquijo, Diana P; Aparicio, Maria L; Gong, Wenfeng; Francis, Howard W; Saunders, James E

2016-09-01

Cochlear implantation (CI) and deaf education are cost effective management strategies of childhood profound sensorineural hearing loss in Latin America. CI has been widely established as cost effective in North America and Europe and is considered standard of care in those regions, yet cost effectiveness in other economic environments has not been explored. With 80% of the global hearing loss burden existing in low- and middle-income countries, developing cost effective management strategies in these settings is essential. This analysis represents the continuation of a global assessment of CI and deaf education cost effectiveness. Brazil, Colombia, Ecuador, Guatemala, Paraguay, Trinidad and Tobago, and Venezuela participated in the study. A Disability Adjusted Life Years model was applied with 3% discounting and 10-year length of analysis. Experts from each country supplied cost estimates from known costs and published data. Sensitivity analysis was performed to evaluate the effect of device cost, professional salaries, annual number of implants, and probability of device failure. Cost effectiveness was determined using the World Health Organization standard of cost effectiveness ratio/gross domestic product per capita (CER/GDP)<3. Deaf education was very cost effective in all countries (CER/GDP 0.07-0.93). CI was cost effective in all countries (CER/GDP 0.69-2.96), with borderline cost effectiveness in the Guatemalan sensitivity analysis (Max CER/GDP 3.21). Both cochlear implantation and deaf education are widely cost effective in Latin America. In the lower-middle income economy of Guatemala, implant cost may have a larger impact. GDP is less influential in the middle- and high-income economies included in this study.

Microflora of root filled teeth with apical periodontitis in Latvian patients.

PubMed

Mindere, Anda; Kundzina, Rita; Nikolajeva, Vizma; Eze, Daina; Petrina, Zaiga

2010-01-01

The aim of the present study was to investigate the microbial flora of root filled teeth with apical periodontitis and to determine the prevalence of β-lactamase producing strains in isolated bacteria in Latvian patients. 33 root filled teeth with asymptomatic persisting periapical lesions were selected for the present study. During nonsurgical endodontic retreatment, the root filling material was removed and canals were sampled. Determination of microbial species was based on series of biochemical tests using identification kits. All strains of bacteria were tested for β-lactamase production by using chromogenic nitrocefin-impregnated slides. Bacteria were found in 32 (97%) of initial specimens from the teeth. The number of isolated microbial strains in the specimens ranged from one to six (mean 2.7). 79% of the isolated microbial species were Gram-positive bacteria. The most common isolates were Streptococcus (27%), Actinomyces (27%), Staphylococcus (18%), Enterococcus (18%) and Lactobacillus (18%) spp. Yeasts were found as four isolates in 3 cases (9%). β-lactamase-producing bacterial strains were detected in 12 specimens, 36% of the patients. The most common enzyme-producing bacteria belonged to Actinomyces and Staphylococcus spp. The microbial flora in previously treated root canals with apical periodontitis is limited to a small number of predominantly Gram-positive microbial species. The most common isolates are Streptococcus, Actinomyces, Staphylococcus, Enterococcus and Lactobacillus spp. A moderately high prevalence of β-lactamase producing bacterial strains was detected in patients with root filled teeth with apical periodontitis.

EAST/SeSAME syndrome - review of the literature and introduction of four new Latvian patients.

PubMed

Marta, C; Ieva, M; Inna, I; Mareta, A; Sandra, K; Pereca, J; Janis, S; Dita, P; Jurgis, S

2018-05-03

EAST (Epilepsy, Ataxia, Sensorineural deafness, Tubulopathy) or SeSAME (Seizures, Sensorineural deafness, Ataxia, Mental retardation, and Electrolyte imbalance) syndrome is a rare autosomal recessive syndrome first described in 2009 independently by Bockenhauer and Scholl. It is caused by mutations in KCNJ10, which encodes Kir4.1, an inwardly rectifying K + channel found in the brain, inner ear, kidney and eye. To date, 16 mutations in at least 28 patients have been reported. In this paper, we review mutations causing EAST/SeSAME syndrome, clinical manifestations in detail, and efficacy of treatment in previously reported patients. We also report a new Latvian kindred with four patients. In contrast to the majority of previous reports, we found a progressive course of the disorder in terms of hearing impairment and neurologic deficit. The treatment is based on antiepileptic drugs, electrolyte replacement, hearing aids and mobility devices. Future research should concentrate on recognizing the lesions in the central nervous system to evaluate new potential diagnostic criteria and on formally evaluating intellectual disability. This article is protected by copyright. All rights reserved.

Web Supplement to "Teaching Chain-Weight Real GDP Measures."

ERIC Educational Resources Information Center

Cahill, Miles B.

2003-01-01

Describes a Web site that is a companion to the Miles Cahill article, "Teaching Chain-Weight Real GDP Measures." States that the exercises are useful because intermediate level textbooks treat this topic casually. Indicates that the Web site contains the comment tool, an overview of the concepts, and links to article references. (JEH)

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. © 2015 Society for Laboratory Automation and Screening.

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.

What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf.

PubMed

Filchtinski, Daniel; Sharabi, Oz; Rüppel, Alma; Vetter, Ingrid R; Herrmann, Christian; Shifman, Julia M

2010-06-11

Ras is a small GTP-binding protein that is an essential molecular switch for a wide variety of signaling pathways including the control of cell proliferation, cell cycle progression and apoptosis. In the GTP-bound state, Ras can interact with its effectors, triggering various signaling cascades in the cell. In the GDP-bound state, Ras looses its ability to bind to known effectors. The interaction of the GTP-bound Ras (Ras(GTP)) with its effectors has been studied intensively. However, very little is known about the much weaker interaction between the GDP-bound Ras (Ras(GDP)) and Ras effectors. We investigated the factors underlying the nucleotide-dependent differences in Ras interactions with one of its effectors, Raf kinase. Using computational protein design, we generated mutants of the Ras-binding domain of Raf kinase (Raf) that stabilize the complex with Ras(GDP). Most of our designed mutations narrow the gap between the affinity of Raf for Ras(GTP) and Ras(GDP), producing the desired shift in binding specificity towards Ras(GDP). A combination of our best designed mutation, N71R, with another mutation, A85K, yielded a Raf mutant with a 100-fold improvement in affinity towards Ras(GDP). The Raf A85K and Raf N71R/A85K mutants were used to obtain the first high-resolution structures of Ras(GDP) bound to its effector. Surprisingly, these structures reveal that the loop on Ras previously termed the switch I region in the Ras(GDP).Raf mutant complex is found in a conformation similar to that of Ras(GTP) and not Ras(GDP). Moreover, the structures indicate an increased mobility of the switch I region. This greater flexibility compared to the same loop in Ras(GTP) is likely to explain the natural low affinity of Raf and other Ras effectors to Ras(GDP). Our findings demonstrate that an accurate balance between a rigid, high-affinity conformation and conformational flexibility is required to create an efficient and stringent molecular switch. Copyright 2010 Elsevier Ltd

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

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.

Characterization of GDP-mannose dehydrogenase from the brown alga Ectocarpus siliculosus providing the precursor for the alginate polymer.

PubMed

Tenhaken, Raimund; Voglas, Elena; Cock, J Mark; Neu, Volker; Huber, Christian G

2011-05-13

Alginate is a major cell wall polymer of brown algae. The precursor for the polymer is GDP-mannuronic acid, which is believed to be derived from a four-electron oxidation of GDP-mannose through the enzyme GDP-mannose dehydrogenase (GMD). So far no eukaryotic GMD has been biochemically characterized. We have identified a candidate gene in the Ectocarpus siliculosus genome and expressed it as a recombinant protein in Escherichia coli. The GMD from Ectocarpus differs strongly from related enzymes in bacteria and is as distant to the bacterial proteins as it is to the group of UDP-glucose dehydrogenases. It lacks the C-terminal ∼120 amino acid domain present in bacterial GMDs, which is believed to be involved in catalysis. The GMD from brown algae is highly active at alkaline pH and contains a catalytic Cys residue, sensitive to heavy metals. The product GDP-mannuronic acid was analyzed by HPLC and mass spectroscopy. The K(m) for GDP-mannose was 95 μM, and 86 μM for NAD(+). No substrate other than GDP-mannose was oxidized by the enzyme. In gel filtration experiments the enzyme behaved as a dimer. The Ectocarpus GMD is stimulated by salts even at low molar concentrations as a possible adaptation to marine life. It is rapidly inactivated at temperatures above 30 °C.

Disease-Causing Mutations in the G Protein Gαs Subvert the Roles of GDP and GTP.

PubMed

Hu, Qi; Shokat, Kevan M

2018-05-17

The single most frequent cancer-causing mutation across all heterotrimeric G proteins is R201C in Gαs. The current model explaining the gain-of-function activity of the R201 mutations is through the loss of GTPase activity and resulting inability to switch off to the GDP state. Here, we find that the R201C mutation can bypass the need for GTP binding by directly activating GDP-bound Gαs through stabilization of an intramolecular hydrogen bond network. Having found that a gain-of-function mutation can convert GDP into an activator, we postulated that a reciprocal mutation might disrupt the normal role of GTP. Indeed, we found R228C, a loss-of-function mutation in Gαs that causes pseudohypoparathyroidism type 1a (PHP-Ia), compromised the adenylyl cyclase-activating activity of Gαs bound to a non-hydrolyzable GTP analog. These findings show that disease-causing mutations in Gαs can subvert the canonical roles of GDP and GTP, providing new insights into the regulation mechanism of G proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

Interconversion of two GDP-bound conformations and their selection in an Arf-family small G protein.

PubMed

Okamura, Hideyasu; Nishikiori, Masaki; Xiang, Hongyu; Ishikawa, Masayuki; Katoh, Etsuko

2011-07-13

ADP-ribosylation factor (Arf) and other Arf-family small G proteins participate in many cellular functions via their characteristic GTP/GDP conformational cycles, during which a nucleotide(∗)Mg(2+)-binding site communicates with a remote N-terminal helix. However, the conformational interplay between the nucleotides, the helix, the protein core, and Mg(2+) has not been fully delineated. Herein, we report a study of the dynamics of an Arf-family protein, Arl8, under various conditions by means of NMR relaxation spectroscopy. The data indicated that, when GDP is bound, the protein core, which does not include the N-terminal helix, reversibly transition between an Arf-family GDP form and another conformation that resembles the Arf-family GTP form. Additionally, we found that the N-terminal helix and Mg(2+), respectively, stabilize the aforementioned former and latter conformations in a population-shift manner. Given the dynamics of the conformational changes, we can describe the Arl8 GTP/GDP cycle in terms of an energy diagram. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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

Transforming Growth Factor β Signaling Upregulates the Expression of Human GDP-Fucose Transporter by Activating Transcription Factor Sp1

PubMed Central

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

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

7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity.

PubMed

Wypijewska, Anna; Bojarska, Elzbieta; Lukaszewicz, Maciej; Stepinski, Janusz; Jemielity, Jacek; Davis, Richard E; Darzynkiewicz, Edward

2012-10-09

Decapping scavenger (DcpS) enzymes catalyze the cleavage of a residual cap structure following 3' → 5' mRNA decay. Some previous studies suggested that both m(7)GpppG and m(7)GDP were substrates for DcpS hydrolysis. Herein, we show that mononucleoside diphosphates, m(7)GDP (7-methylguanosine diphosphate) and m(3)(2,2,7)GDP (2,2,7-trimethylguanosine diphosphate), resulting from mRNA decapping by the Dcp1/2 complex in the 5' → 3' mRNA decay, are not degraded by recombinant DcpS proteins (human, nematode, and yeast). Furthermore, whereas mononucleoside diphosphates (m(7)GDP and m(3)(2,2,7)GDP) are not hydrolyzed by DcpS, mononucleoside triphosphates (m(7)GTP and m(3)(2,2,7)GTP) are, demonstrating the importance of a triphosphate chain for DcpS hydrolytic activity. m(7)GTP and m(3)(2,2,7)GTP are cleaved at a slower rate than their corresponding dinucleotides (m(7)GpppG and m(3)(2,2,7)GpppG, respectively), indicating an involvement of the second nucleoside for efficient DcpS-mediated digestion. Although DcpS enzymes cannot hydrolyze m(7)GDP, they have a high binding affinity for m(7)GDP and m(7)GDP potently inhibits DcpS hydrolysis of m(7)GpppG, suggesting that m(7)GDP may function as an efficient DcpS inhibitor. Our data have important implications for the regulatory role of m(7)GDP in mRNA metabolic pathways due to its possible interactions with different cap-binding proteins, such as DcpS or eIF4E.

Short-term and long-term effects of GDP on traffic deaths in 18 OECD countries, 1960-2011.

PubMed

Dadgar, Iman; Norström, Thor

2017-02-01

Research suggests that increases in gross domestic product (GDP) lead to increases in traffic deaths plausibly due to the increased road traffic induced by an expanding economy. However, there also seems to exist a long-term effect of economic growth that is manifested in improved traffic safety and reduced rates of traffic deaths. Previous studies focus on either the short-term, procyclical effect, or the long-term, protective effect. The aim of the present study is to estimate the short-term and long-term effects jointly in order to assess the net impact of GDP on traffic mortality. We extracted traffic death rates for the period 1960-2011 from the WHO Mortality Database for 18 OECD countries. Data on GDP/capita were obtained from the Maddison Project. We performed error correction modelling to estimate the short-term and long-term effects of GDP on the traffic death rates. The estimates from the error correction modelling for the entire study period suggested that a one-unit increase (US$1000) in GDP/capita yields an instantaneous short-term increase in the traffic death rate by 0.58 (p<0.001), and a long-term decrease equal to -1.59 (p<0.001). However, period-specific analyses revealed a structural break implying that the procyclical effect outweighs the protective effect in the period prior to 1976, whereas the reverse is true for the period 1976-2011. An increase in GDP leads to an immediate increase in traffic deaths. However, after the mid-1970s this short-term effect is more than outweighed by a markedly stronger protective long-term effect, whereas the reverse is true for the period before the mid-1970s. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The relationship between pollutant emissions, renewable energy, nuclear energy and GDP: empirical evidence from 18 developed and developing countries

NASA Astrophysics Data System (ADS)

Ben Mbarek, Mounir; Saidi, Kais; Amamri, Mounira

2018-07-01

This document investigates the causal relationship between nuclear energy (NE), pollutant emissions (CO2 emissions), gross domestic product (GDP) and renewable energy (RE) using dynamic panel data models for a global panel consisting of 18 countries (developed and developing) covering the 1990-2013 period. Our results indicate that there is a co-integration between variables. The unit root test suggests that all the variables are stationary in first differences. The paper further examines the link using the Granger causality analysis of vector error correction model, which indicates a unidirectional relationship running from GDP per capita to pollutant emissions for the developed and developing countries. However, there is a unidirectional causality from GDP per capita to RE in the short and long run. This finding confirms the conservation hypothesis. Similarly, there is no causality between NE and GDP per capita.

Structural insights into GDP-mediated regulation of a bacterial acyl-CoA thioesterase.

PubMed

Khandokar, Yogesh B; Srivastava, Parul; Cowieson, Nathan; Sarker, Subir; Aragao, David; Das, Shubagata; Smith, Kate M; Raidal, Shane R; Forwood, Jade K

2017-12-15

Thioesterases catalyze the cleavage of thioester bonds within many activated fatty acids and acyl-CoA substrates. They are expressed ubiquitously in both prokaryotes and eukaryotes and are subdivided into 25 thioesterase families according to their catalytic active site, protein oligomerization, and substrate specificity. Although many of these enzyme families are well-characterized in terms of function and substrate specificity, regulation across most thioesterase families is poorly understood. Here, we characterized a TE6 thioesterase from the bacterium Neisseria meningitidis Structural analysis with X-ray crystallographic diffraction data to 2.0-Å revealed that each protein subunit harbors a hot dog-fold and that the TE6 enzyme forms a hexamer with D3 symmetry. An assessment of thioesterase activity against a range of acyl-CoA substrates revealed the greatest activity against acetyl-CoA, and structure-guided mutagenesis of putative active site residues identified Asn 24 and Asp 39 as being essential for activity. Our structural analysis revealed that six GDP nucleotides bound the enzyme in close proximity to an intersubunit disulfide bond interactions that covalently link thioesterase domains in a double hot dog dimer. Structure-guided mutagenesis of residues within the GDP-binding pocket identified Arg 93 as playing a key role in the nucleotide interaction and revealed that GDP is required for activity. All mutations were confirmed to be specific and not to have resulted from structural perturbations by X-ray crystallography. This is the first report of a bacterial GDP-regulated thioesterase and of covalent linkage of thioesterase domains through a disulfide bond, revealing structural similarities with ADP regulation in the human ACOT12 thioesterase. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Sustainable Use Of Macro-Algae For Biogas Production In Latvian Conditions: A Preliminary Study Through An Integrated Mca And Lca Approach

NASA Astrophysics Data System (ADS)

Pastare, Laura; Romagnoli, Francesco; Lauka, Dace; Dzene, Ilze; Kuznecova, Tatjana

2014-12-01

The study focuses on sustainability evaluation of an algae-based energy system in Latvia with a holistic and integrated approach of multi-criteria analysis combined with life cycle assessment (including a practical side - biogas yield experiments of locally available algae). The study shows potential for sustainable use of algae in Latvian conditions and thus that algal biomass can be utilized for the production of biogas. The most sustainable and feasible scenario of using algae for biogas energy production foresees the collection of algae biomass from natural water bodies. Important beneficial effects through the use of algae are related to avoiding global warming potential (GWP) and eutrophication impacts. Biogas batch experiments carried out with the local macrophyte C.demersum have shown a methane yield of 554 l CH4/kg VS.

One pot synthesis of GDP-mannose by a multi-enzyme cascade for enzymatic assembly of lipid-linked oligosaccharides.

PubMed

Rexer, Thomas F T; Schildbach, Anna; Klapproth, Jan; Schierhorn, Angelika; Mahour, Reza; Pietzsch, Markus; Rapp, Erdmann; Reichl, Udo

2018-01-01

Glycosylation of proteins is a key function of the biosynthetic-secretory pathway in the endoplasmic reticulum (ER) and Golgi apparatus. Glycosylated proteins play a crucial role in cell trafficking and signaling, cell-cell adhesion, blood-group antigenicity, and immune response. In addition, the glycosylation of proteins is an important parameter in the optimization of many glycoprotein-based drugs such as monoclonal antibodies. In vitro glycoengineering of proteins requires glycosyltransferases as well as expensive nucleotide sugars. Here, we present a designed pathway consisting of five enzymes, glucokinase (Glk), phosphomannomutase (ManB), mannose-1-phosphate-guanyltransferase (ManC), inorganic pyrophosphatase (PmPpA), and 1-domain polyphosphate kinase 2 (1D-Ppk2) expressed in E. coli for the cell-free production and regeneration of GDP-mannose from mannose and polyphosphate with catalytic amounts of GDP and ADP. It was shown that GDP-mannose is produced at various conditions, that is pH 7-8, temperature 25-35°C and co-factor concentrations of 5-20 mM MgCl 2 . The maximum reaction rate of GDP-mannose achieved was 2.7 μM/min at 30°C and 10 mM MgCl 2 producing 566 nmol GDP-mannose after a reaction time of 240 min. With respect to the initial GDP concentration (0.8 mM) this is equivalent to a yield of 71%. Additionally, the cascade was coupled to purified, transmembrane-deleted Alg1 (ALG1ΔTM), the first mannosyltransferase in the ER-associated lipid-linked oligosaccharide (LLO) assembly. Thereby, in a one-pot reaction, phytanyl-PP-(GlcNAc) 2 -Man 1 was produced with efficient nucleotide sugar regeneration for the first time. Phytanyl-PP-(GlcNAc) 2 -Man 1 can serve as a substrate for the synthesis of LLO for the cell-free in vitro glycosylation of proteins. A high-performance anion exchange chromatography method with UV and conductivity detection (HPAEC-UV/CD) assay was optimized and validated to determine the enzyme kinetics. The established

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. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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.

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

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

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

Anand, Roopsee; Eschenburg, Susanne; Reubold, Thomas F., E-mail: Reubold.Thomas@mh-hannover.de

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

Stability of sterigmatocystin during the bread making process and its occurrence in bread from the Latvian market.

PubMed

Veršilovskis, Aleksandrs; Bartkevičs, Vadims

2012-05-01

Sterigmatocystin (STC) is a carcinogenic and mutagenic mycotoxin produced by fungi of many Aspergillus species. The aim of this research was to test the stability of STC during the bread making process and to check bread samples from the Latvian market for STC contamination, using a previously developed electrospray positive ionisation (ESI(+)) liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Wheat grain naturally contaminated with STC was used for bread baking. STC was found to be stable during the bread-making process. In the food survey 17% of the analysed breads were positive for STC, with concentration levels of 2-7 μg kg(-1). One out of six rye bread samples, one out of nine rye-wheat bread samples and three out of 14 wheat bread samples were contaminated with STC. Four out of five contaminated samples contained whole grains as the main ingredient. We conclude that whole grain bread may be a possible source of STC, although even STC-positive bread samples identified in this study contained quite low toxin levels.

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. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Comparison of gemcitabin, cisplatin, and dexamethasone (GDP), CHOP, and CHOPE in the first-line treatment of peripheral T-cell lymphomas.

PubMed

Jia, Bo; Hu, Shaoxuan; Yang, Jianliang; Zhou, Shengyu; Liu, Peng; Qin, Yan; Gui, Lin; Yang, Sheng; Lin, Hua; Zhang, Changgong; Xing, Puyuan; Wang, Lin; Dong, Mei; Zhou, Liqiang; Sun, Yan; He, Xiaohui; Shi, Yuankai

2016-10-01

Optimal chemotherapy regimen for peripheral T-cell lymphomas (PTCL) has not been fully defined. This study aimed to evaluate the optimal chemotherapy regimen in the first-line treatment for PTCL patients. Between 2003 and 2014, 93 consecutive patients with PTCL were enrolled in this study. Of 93 patients, 42 patients received CHOPE, 40 patients with CHOP, and 11 patients with GDP regimen. Response could be evaluated in 88 of 93 patients at the end of primary treatment. The CR rate for patients received CHOP (n = 38), CHOPE (n = 39), and GDP (n = 11) were 28.9, 51.3, and 45.5%, respectively, (P = 0.132) with an ORR of 65.8, 76.9, and 90.9%, respectively, (P = 0.210). The median follow-up time was 17.1 (1.4-108.3) months. Median progression-free survival (PFS) in CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) groups were 6.0, 15.3, and 9.7 months (P = 0.094) with 1-year PFS of 35.0, 54.8, and 45.5%, respectively, (P = 0.078). One-year OS for patients received CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) were 65.0, 83.3, and 100%, respectively, (P = 0.013) (CHOP vs CHOPE, P = 0.030; CHOP vs GDP, P = 0.024; CHOPE vs GDP, P = 0.174). CHOPE has a trend to improve CR rate, 1-year PFS and OS compared with CHOP alone. GDP shows promising efficacy which worth further exploration in large cohort studies. Clinical experience presented in this study may serve as reference for future large cohort studies.

Quantitative analysis of the interactions between prenyl Rab9, GDP dissociation inhibitor-alpha, and guanine nucleotides.

PubMed

Shapiro, A D; Pfeffer, S R

1995-05-12

Rab9 is a Ras-like GTPase required for the transport of mannose 6-phosphate receptors between late endosomes and the trans Golgi network. Rab9 occurs in the cytosol as a complex with GDP dissociation inhibitor (GDI), which we have shown delivers prenyl Rab9 to late endosomes in a functional form. We report here basal rate constants for guanine nucleotide dissociation and GTP hydrolysis for prenyl Rab9. Both rate constants were influenced in part by the hydrophobic environment of the prenyl group. Guanine nucleotide dissociation and GTP hydrolysis rates were lower in the presence of lipid; detergent stimulated intrinsic nucleotide exchange. GDI-alpha inhibited GDP dissociation from prenyl Rab9 by 2.4-fold. GDI-alpha associated with prenyl Rab9 with a KD of 60 nM in 0.1% Lubrol and 23 nM in 0.02% Lubrol. In 0.1% Lubrol, GDI-alpha inhibited GDP dissociation half maximally at 72 +/- 18 nM, consistent with the KD determinations. These data suggest that GDI-alpha associates with prenyl Rab9 with a KD of < or = 23 nM under physiological conditions. Finally, a previously uncharacterized minor form of GDI-alpha inhibited GDP dissociation from prenyl Rab9 by 1.9-fold and bound prenyl Rab9 with a KD of 67 nM in 0.1% Lubrol.

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. © 2016 Piedra et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

A New Neutral-pH Low-GDP Peritoneal Dialysis Fluid

PubMed Central

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

2012-01-01

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

U.S. Department of Energy physical protection upgrades at the Latvian Academy of Sciences Nuclear Research Center, Latvia

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

Haase, M.; Hine, C.; Robertson, C.

1996-12-31

Approximately five years ago, the Safe, Secure Dismantlement program was started between the US and countries of the Former Soviet Union (FSU). The purpose of the program is to accelerate progress toward reducing the risk of nuclear weapons proliferation, including such threats as theft, diversion, and unauthorized possession of nuclear materials. This would be accomplished by strengthening the material protection, control, and accounting systems within the FSU countries. Under the US Department of Energy`s program of providing cooperative assistance to the FSU countries in the areas of Material Protection, Control, and Accounting (MPC and A), the Latvian Academy of Sciencesmore » Nuclear Research Center (LNRC) near Riga, Latvia, was identified as a candidate site for a cooperative MPC and A project. The LNRC is the site of a 5-megawatt IRT-C pool-type research reactor. This paper describes: the process involved, from initial contracting to project completion, for the physical protection upgrades now in place at the LNRC; the intervening activities; and a brief overview of the technical aspects of the upgrades.« less

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

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

PubMed

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

2015-06-11

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. 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. 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. 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. The findings verify that health care is not a luxury good and income has a robust relationship to health expenditures in OPEC countries.

Genetic evidence for the role of GDP-mannose in plant ascorbic acid (vitamin C) biosynthesis

PubMed Central

Conklin, Patricia L.; Norris, Susan R.; Wheeler, Glen L.; Williams, Elizabeth H.; Smirnoff, Nicholas; Last, Robert L.

1999-01-01

Vitamin C (l-ascorbic acid; AsA) acts as a potent antioxidant and cellular reductant in plants and animals. AsA has long been known to have many critical physiological roles in plants, yet its biosynthesis is only currently being defined. A pathway for AsA biosynthesis that features GDP-mannose and l-galactose has recently been proposed for plants. We have isolated a collection of AsA-deficient mutants of Arabidopsis thaliana that are valuable tools for testing of an AsA biosynthetic pathway. The best-characterized of these mutants (vtc1) contains ≈25% of wild-type AsA and is defective in AsA biosynthesis. By using a combination of biochemical, molecular, and genetic techniques, we have demonstrated that the VTC1 locus encodes a GDP-mannose pyrophosphorylase (mannose-1-P guanyltransferase). This enzyme provides GDP-mannose, which is used for cell wall carbohydrate biosynthesis and protein glycosylation as well as for AsA biosynthesis. In addition to genetically defining the first locus involved in AsA biosynthesis, this work highlights the power of using traditional mutagenesis techniques coupled with the Arabidopsis Genome Initiative to rapidly clone physiologically important genes. PMID:10097187

Overexpression of an alfalfa GDP-mannose 3, 5-epimerase gene enhances acid, drought and salt tolerance in transgenic Arabidopsis by increasing ascorbate accumulation.

PubMed

Ma, Lichao; Wang, Yanrong; Liu, Wenxian; Liu, Zhipeng

2014-11-01

GDP-mannose 3', 5'-epimerase (GME) catalyses the conversion of GDP-D-mannose to GDP-L-galactose, an important step in the ascorbic acid (ascorbic acid) biosynthetic pathway in higher plants. In this study, a novel cDNA fragment (MsGME) encoding a GME protein was isolated and characterised from alfalfa (Medicago sativa). An expression analysis confirmed that MsGME expression was induced by salinity, PEG and acidity stresses. MsGME overexpression in Arabidopsis enhanced tolerance of the transgenic plants to salt, drought and acid. Real-time PCR analysis revealed that the transcript levels of GDP-D-mannose pyrophosphorylase (GMP), L-galactose-phosphate 1-P phosphatase (GP) and GDP-L-galactose phosphorylase (GGP) were increased in transgenic Arabidopsis (T3 generation). Moreover, the ascorbate content was increased in transgenic Arabidopsis. Our results suggest that MsGME can effectively enhance tolerance of transgenic Arabidopsis to acid, drought and salt by increasing ascorbate accumulation.

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.

Body fat in children and adolescents participating in organized sports: Descriptive epidemiological study of 6048 Latvian athletes.

PubMed

Kalnina, Liga; Sauka, Melita; Timpka, Toomas; Dahlström, Örjan; Nylander, Eva; Selga, Guntars; Ligere, Renate; Karklina, Helena; Priedite, Ilga S; Larins, Viesturs

2015-08-01

Pressure among young athletes to meet body composition goals may lead to poor nutrition and affect growth. To examine the proportion of body fat (%BF), measured by bioimpedance analysis, among Latvian children and adolescents participating in organized sports. Our study had a nationally representative sample of 6048 young athletes, aged 10-17 years. Their %BF was measured using a multifrequency, 8-pole, bioelectrical impedance leg-to-hand analyzer. About 19.2% (CI 14.4-20.0) of boys and 15.1% (CI 14.0-16.3) of girls had a %BF value below the recommended levels. The %BF in young female athletes participating in aesthetic sports was lower than among their peers participating in other sports. Young male athletes participating in aesthetic sports had lower %BF levels at 10 and 12 years of age, compared with participants in weight-class sports; and lower levels of %BF from age 10-14 years, compared with participants in non-weight-sensitive sports. Almost every fifth child and adolescent participating in organized sports displayed critically low body fat levels. Body fat needs to be assessed regularly in young athletes, to prevent negative consequences on health. © 2015 the Nordic Societies of Public Health.

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

Superoxide activates a GDP-sensitive proton conductance in skeletal muscle mitochondria from king penguin (Aptenodytes patagonicus).

PubMed

Talbot, Darren A; Hanuise, Nicolas; Rey, Benjamin; Rouanet, Jean-Louis; Duchamp, Claude; Brand, Martin D

2003-12-26

We present the partial nucleotide sequence of the avian uncoupling protein (avUCP) gene from king penguin (Aptenodytes patagonicus), showing that the protein is 88-92% identical to chicken (Gallus gallus), turkey (Meleagris gallopavo), and hummingbird (Eupetomena macroura). We show that superoxide activates the proton conductance of mitochondria isolated from king penguin skeletal muscle. GDP abolishes the superoxide-activated proton conductance, indicating that it is mediated via avUCP. In the absence of superoxide there is no GDP-sensitive component of the proton conductance from penguin muscle mitochondria demonstrating that avUCP plays no role in the basal proton leak.

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

Structural and functional analysis of a FeoB A143S G5 loop mutant explains the accelerated GDP release rate.

PubMed

Guilfoyle, Amy P; Deshpande, Chandrika N; Vincent, Kimberley; Pedroso, Marcelo M; Schenk, Gerhard; Maher, Megan J; Jormakka, Mika

2014-05-01

GTPases (G proteins) hydrolyze the conversion of GTP to GDP and free phosphate, comprising an integral part of prokaryotic and eukaryotic signaling, protein biosynthesis and cell division, as well as membrane transport processes. The G protein cycle is brought to a halt after GTP hydrolysis, and requires the release of GDP before a new cycle can be initiated. For eukaryotic heterotrimeric Gαβγ proteins, the interaction with a membrane-bound G protein-coupled receptor catalyzes the release of GDP from the Gα subunit. Structural and functional studies have implicated one of the nucleotide binding sequence motifs, the G5 motif, as playing an integral part in this release mechanism. Indeed, a Gαs G5 mutant (A366S) was shown to have an accelerated GDP release rate, mimicking a G protein-coupled receptor catalyzed release state. In the present study, we investigate the role of the equivalent residue in the G5 motif (residue A143) in the prokaryotic membrane protein FeoB from Streptococcus thermophilus, which includes an N-terminal soluble G protein domain. The structure of this domain has previously been determined in the apo and GDP-bound states and in the presence of a transition state analogue, revealing conformational changes in the G5 motif. The A143 residue was mutated to a serine and analyzed with respect to changes in GTPase activity, nucleotide release rate, GDP affinity and structural alterations. We conclude that the identity of the residue at this position in the G5 loop plays a key role in the nucleotide release rate by allowing the correct positioning and hydrogen bonding of the nucleotide base. © 2014 FEBS.

Per-capita GDP and nonequilibrium wealth-concentration in a model for trade

NASA Astrophysics Data System (ADS)

Moukarzel, Cristian F.

2013-12-01

Data describing the per-capita Gross Domestic Product of around two hundred countries in years 1960 to 2008 are analyzed and found to decay approximately exponentially with rank. We discuss this experimental fact in the context of a wealth exchange model called Yard-Sale exchange, in which pairs of agents (i.e. nations) 'bet' for a fraction f of the wealth of the poorest of them. If the chances for this poorest agent to win the bet are not large enough, this model presents a 'wealth condensation' phase, in which one lucky agent gets to own the whole wealth in the end. In a recent study of this model [1], it was found that, in the condensed phase, the typical wealth of an agent with rank R decays exponentially with R. By establishing a parallel between wealth of a nation and its per-capita GDP, these observations suggest that international trade rules are such that strong wealth concentration is favored. Possible extensions of this work, that also consider endogenous factors affecting the evolution of GDP, are also discussed.

Brominated, chlorinated and mixed brominated/chlorinated persistent organic pollutants in European eels (Anquilla anquilla) from Latvian lakes.

PubMed

Zacs, Dzintars; Rjabova, Jekaterina; Fernandes, Alwyn; Bartkevics, Vadims

2016-01-01

Fifty-eight European eel (Anquilla anquilla) specimens collected from five Latvian lakes were investigated for six groups of persistent organic pollutants (POPs), including polychlorinated, polybrominated and mixed bromo-chloro dibenzo-p-dioxins and dibenzofurans (PCDD/DFs, PBDD/DFs and PXDD/DFs), polychlorinated and mixed bromo-chloro biphenyls (PCBs and PXBs) and polybrominated diphenyl ethers (PBDEs). PCDD/DFs and PCBs were found to occur in the range 0.85-15.8 pg Total-WHO2005-TEQ g(-1) f.w., and concentrations in most of the samples were below the maximum levels specified in European Commission Regulation (EU) No. 1259/2011. The summed concentrations of 27 PBDEs (∑PBDE) and 16 non-dioxin-like PCBs (∑NDL-PCB) were in the ranges of 0.28-26.7 and 6.37-320 ng g(-1) f.w., respectively. PBDD/DFs, PXDD/DFs and PXBs show average upper-bound concentrations of 0.05, 0.06 and 0.01 pg TEQ f.w. and collectively contributed 3.4% to the sum TEQ of dioxin-like compounds. The highest contaminant concentrations were measured in samples from lakes near the Baltic Sea and the industrialised area near Riga (Liepajas and Kisezers lakes). A correlation of POP concentration with the length of collected specimens was observed.

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.

Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes.

PubMed

Crepin, Thibaut; Shalak, Vyacheslav F; Yaremchuk, Anna D; Vlasenko, Dmytro O; McCarthy, Andrew; Negrutskii, Boris S; Tukalo, Michail A; El'skaya, Anna V

2014-11-10

Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon-anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the 'GTP'- and 'GDP'-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Continuous national gross domestic product (GDP) time series for 195 countries: past observations (1850-2005) harmonized with future projections according to the Shared Socio-economic Pathways (2006-2100)

NASA Astrophysics Data System (ADS)

Geiger, Tobias

2018-04-01

Gross domestic product (GDP) represents a widely used metric to compare economic development across time and space. GDP estimates have been routinely assembled only since the beginning of the second half of the 20th century, making comparisons with prior periods cumbersome or even impossible. In recent years various efforts have been put forward to re-estimate national GDP for specific years in the past centuries and even millennia, providing new insights into past economic development on a snapshot basis. In order to make this wealth of data utilizable across research disciplines, we here present a first continuous and consistent data set of GDP time series for 195 countries from 1850 to 2009, based mainly on data from the Maddison Project and other population and GDP sources. The GDP data are consistent with Penn World Tables v8.1 and future GDP projections from the Shared Socio-economic Pathways (SSPs), and are freely available at http://doi.org/10.5880/pik.2018.010 (Geiger and Frieler, 2018). To ease usability, we additionally provide GDP per capita data and further supplementary and data description files in the online archive. We utilize various methods to handle missing data and discuss the advantages and limitations of our methodology. Despite known shortcomings this data set provides valuable input, e.g., for climate impact research, in order to consistently analyze economic impacts from pre-industrial times to the future.

Meta-Analysis of the Oil Price Elasticity of the GDP for Policy Analysis: Documentation

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

Leiby, Paul Newsome; Bowman, David Charles; Oladosu, Gbadebo A.

Given the important role of oil in economic activities, policy makers are interested in estimates of the potential damage to the economy from oil price shocks, particularly during periods of rapid and large increases that accompany severe shocks. Such estimates are needed to quantify the economic costs of oil price shocks, and to evaluate the potential benefits of alternative policy responses. Although research on the economic impacts of oil price shocks is extensive and has generally found that large increases in oil prices exert negative economic impacts, the range of estimates, summarized by the oil price elasticity of the GDPmore » or other aggregate measure of economic activity, is very wide. There are also conditions under which the relationship between the oil price and the economy could be positive. The range of estimates of the oil price elasticity of the GDP for the United States is typified by averages from the studies of Hamilton (2005, 2012) and Kilian and Vigfusson (2014), in which the implied elasticities were -0.014 to - 0.069 and +0.004 to -0.052, respectively. We employ a meta-regression approach to systematically summarize available estimates of the oil price elasticity of the GDP for oil importing economies, and examine the role of key factors. The resulting regression model was used to estimate the oil price elasticity of the GDP for the United States. Based on this we estimate the mean elasticity for the United States at -0.0238, with a 68% confidence interval of -0.0075 to -0.0402, four quarters after a shock.« less

The impact of HIV prevalence, conflict, corruption, and GDP/capita on treatment cascades: data from 137 countries.

PubMed

Levi, Jacob; Pozniak, Anton; Heath, Katherine; Hill, Andrew

2018-04-01

In 2014, UNAIDS and partners set the 90-90-90 targets for the HIV treatment cascade. Multiple social, political and structural factors might influence progress towards these targets. We assessed how close countries and regions are to reaching these targets, and compared cascade outcomes with HIV prevalence, gross domestic product (GDP)/capita, conflict and corruption. Country-level HIV cascade data on diagnosis, ART coverage and viral suppression, from 2010 to 2016 were extracted from national reports, published papers and the www.AIDSinfoOnline database, and analysed. Weighted least-squares regression was used to assess predictors of cascade achievement: region, HIV prevalence, GDP/capita, the 2016 Corruption Perceptions Index (CPI), which is an international ranking system, and the 2016 Global Peace Index (GPI), which ranks all countries based on three main categories: societal safety, militarisation and conflict. Data were available for diagnosis for 84 countries, ART coverage for 137 countries, and viral suppression for 94 countries. Regions with the lowest ART coverage were South-east Asia and Pacific (36%), Eastern Europe and Central Asia (17%), and Middle East and North Africa (13%). Lower HIV prevalence was associated with poorer cascade results. Countries with higher GDP/capita achieved higher ART coverage ( P <0.001). Furthermore, countries with lower levels of peace and higher corruption had lower ART coverage ( P <0.001). Countries with a GPI >2.5 all had ART coverage of <40%. Only one country has reached the UNAIDS 90-90-90 targets. International comparison remains difficult due to heterogeneous data reporting. Difficulty meeting UNAIDS targets is associated with lower GDP/capita, lower HIV prevalence, higher corruption and conflict levels.

Influence of GTP/GDP and magnesium ion on the solvated structure of the protein FtsZ: a molecular dynamics study.

PubMed

Jamous, Carla; Basdevant, Nathalie; Ha-Duong, Tap

2014-01-01

We present here a structural analysis of ten extensive all-atom molecular dynamics simulations of the monomeric protein FtsZ in various binding states. Since the polymerization and GTPase activities of FtsZ depend on the nature of a bound nucleotide as well as on the presence of a magnesium ion, we studied the structural differences between the average conformations of the following five systems: FtsZ-Apo, FtsZ-GTP, FtsZ-GDP, FtsZ-GTP-Mg, and FtsZ-GDP-Mg. The in silico solvated average structure of FtsZ-Apo significantly differs from the crystallographic structure 1W59 of FtsZ which was crystallized in a dimeric form without nucleotide and magnesium. The simulated Apo form of the protein also clearly differs from the FtsZ structures when it is bound to its ligand, the most important discrepancies being located in the loops surrounding the nucleotide binding pocket. The three average structures of FtsZ-GTP, FtsZ-GDP, and FtsZ-GTP-Mg are overall similar, except for the loop T7 located at the opposite side of the binding pocket and whose conformation in FtsZ-GDP notably differs from the one in FtsZ-GTP and FtsZ-GTP-Mg. The presence of a magnesium ion in the binding pocket has no impact on the FtsZ conformation when it is bound to GTP. In contrast, when the protein is bound to GDP, the divalent cation causes a translation of the nucleotide outwards the pocket, inducing a significant conformational change of the loop H6-H7 and the top of helix H7.

Chemical synthesis of guanosine diphosphate mannuronic acid (GDP-ManA) and its C-4-O-methyl and C-4-deoxy congeners.

PubMed

Zhang, Qingju; Howell, P Lynne; Overkleeft, Herman S; Filippov, Dmitri V; van der Marel, Gijsbert A; Codée, Jeroen D C

2017-10-10

Described is the first synthesis of guanosine diphosphate mannuronic acid (GDP-ManA), the sugar donor used by algae and bacteria for the production of alginate, an anionic polysaccharide composed of β-d-mannuronic acid (ManA) and α-l-guluronic acid (GulA). Understanding the biosynthesis of these polyanionic polysaccharides on the molecular level, opens up avenues to use and modulate the biosynthesis machinery for biotechnological and therapeutic applications. The synthesis reported here delivers multi-milligram amounts of the GDP-ManA donor that can be used to study the polymerase (Alg8 in Pseudomonas aeruginosa) that generates the poly-ManA chain. Also reported is the assembly of two close analogues of GDP-ManA: the first bears a C-4-O-methyl group, while the second has been deoxygenated at this position. Both molecules may be used as "chain stoppers" in future enzymatic ManA polymerisation reactions. The crucial pyrophosphate linkage of the GDP-mannuronic acids has been constructed by the phosphorylation of the appropriate ManA-1-phosphates with a guanosine phosphoramidite. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploring the correlation between the sequence composition of the nucleotide binding G5 loop of the FeoB GTPase domain (NFeoB) and intrinsic rate of GDP release.

PubMed

Guilfoyle, Amy P; Deshpande, Chandrika N; Schenk, Gerhard; Maher, Megan J; Jormakka, Mika

2014-12-12

GDP release from GTPases is usually extremely slow and is in general assisted by external factors, such as association with guanine exchange factors or membrane-embedded GPCRs (G protein-coupled receptors), which accelerate the release of GDP by several orders of magnitude. Intrinsic factors can also play a significant role; a single amino acid substitution in one of the guanine nucleotide recognition motifs, G5, results in a drastically altered GDP release rate, indicating that the sequence composition of this motif plays an important role in spontaneous GDP release. In the present study, we used the GTPase domain from EcNFeoB (Escherichia coli FeoB) as a model and applied biochemical and structural approaches to evaluate the role of all the individual residues in the G5 loop. Our study confirms that several of the residues in the G5 motif have an important role in the intrinsic affinity and release of GDP. In particular, a T151A mutant (third residue of the G5 loop) leads to a reduced nucleotide affinity and provokes a drastically accelerated dissociation of GDP.

Health insurance or subsidy has universal advantage for management of hospital malnutrition unrelated to GDP.

PubMed

Klek, Stanislaw; Chourdakis, Michael; Abosaleh, Dima Abdulqudos; Amestoy, Alejandra; Baik, Hyun Wook; Baptista, Gertrudis; Barazzoni, Rocco; Fukushima, Ryoji; Hartono, Josef; Jayawardena, Ranil; Garcia, Rafael Jimenez; Krznaric, Zeljko; Nyulasi, Ibolya; Parallada, Gabriela; Francisco, Eliza Mei Perez; Panisic-Sekeljic, Marina; Perman, Mario; Prins, Arina; Del Rio Requejo, Isabel Martinez; Reddy, Ravinder; Singer, Pierre; Sioson, Marianna; Ukleja, Andrew; Vartanian, Carla; Fuentes, Nicolas Velasco; Waitzberg, Dan Linetzky; Zoungrana, Steve Leonce; Galas, Aleksander

2017-03-01

Protein-energy and micronutrient malnutrition are global public health problems which, when not prevented and severe, require medical management by clinicians with nutrition expertise, preferably as a collectively skilled team, especially when disease-related. This study aimed to investigate barriers and facilitators of clinical nutrition services (CNS), especially the use of oral, enteral (EN) and parenteral (PN) nutrition in institutional and home settings. An international survey was performed between January and December 2014 in twenty-six countries from all continents. Electronic questionnaires were distributed to 28 representatives of clinical nutrition (PEN) societies, 27 of whom responded. The questionnaire comprised questions regarding a country's economy, reimbursement for CNS, education about and the use of EN and PN. The prevalence of malnutrition was not related to gross domestic product (GDP) at purchasing power parity (PPP) per capita (p=0.186). EN and PN were used in all countries surveyed (100%), but to different extents. Reimbursement of neither EN nor PN use depended on GDP, but was associated with increased use of EN and PN in hospitals (p=0.035), although not evident for home or chronic care facilities. The size of GDP did not affect the use of EN (p=0.256), but it mattered for PN (p=0.019). A worldwide survey by nutrition support societies did not find a link between national economic performance and the implementation of medical nutrition services. Reimbursement for CNS, available through health insurance systems, is a factor in effective nutrition management.

Gene expression studies in kiwifruit and gene over-expression in Arabidopsis indicates that GDP-L-galactose guanyltransferase is a major control point of vitamin C biosynthesis

PubMed Central

Bulley, Sean M.; Rassam, Maysoon; Hoser, Dana; Otto, Wolfgang; Schünemann, Nicole; Wright, Michele; MacRae, Elspeth; Gleave, Andrew; Laing, William

2009-01-01

Vitamin C (L-ascorbic acid, AsA) is an essential metabolite for plants and animals. Kiwifruit (Actinidia spp.) are a rich dietary source of AsA for humans. To understand AsA biosynthesis in kiwifruit, AsA levels and the relative expression of genes putatively involved in AsA biosynthesis, regeneration, and transport were correlated by quantitative polymerase chain reaction in leaves and during fruit development in four kiwifruit genotypes (three species; A. eriantha, A. chinensis, and A. deliciosa). During fruit development, fruit AsA concentration peaked between 4 and 6 weeks after anthesis with A. eriantha having 3–16-fold higher AsA than other genotypes. The rise in AsA concentration typically occurred close to the peak in expression of the L-galactose pathway biosynthetic genes, particularly the GDP-L-galactose guanyltransferase gene. The high concentration of AsA found in the fruit of A. eriantha is probably due to higher expression of the GDP-mannose-3′,5′-epimerase and GDP-L-galactose guanyltransferase genes. Over-expression of the kiwifruit GDP-L-galactose guanyltransferase gene in Arabidopsis resulted in up to a 4-fold increase in AsA, while up to a 7-fold increase in AsA was observed in transient expression studies where both GDP-L-galactose guanyltransferase and GDP-mannose-3′,5′-epimerase genes were co-expressed. These studies show the importance of GDP-L-galactose guanyltransferase as a rate-limiting step to AsA, and demonstrate how AsA can be significantly increased in plants. PMID:19129165

Gene expression studies in kiwifruit and gene over-expression in Arabidopsis indicates that GDP-L-galactose guanyltransferase is a major control point of vitamin C biosynthesis.

PubMed

Bulley, Sean M; Rassam, Maysoon; Hoser, Dana; Otto, Wolfgang; Schünemann, Nicole; Wright, Michele; MacRae, Elspeth; Gleave, Andrew; Laing, William

2009-01-01

Vitamin C (L-ascorbic acid, AsA) is an essential metabolite for plants and animals. Kiwifruit (Actinidia spp.) are a rich dietary source of AsA for humans. To understand AsA biosynthesis in kiwifruit, AsA levels and the relative expression of genes putatively involved in AsA biosynthesis, regeneration, and transport were correlated by quantitative polymerase chain reaction in leaves and during fruit development in four kiwifruit genotypes (three species; A. eriantha, A. chinensis, and A. deliciosa). During fruit development, fruit AsA concentration peaked between 4 and 6 weeks after anthesis with A. eriantha having 3-16-fold higher AsA than other genotypes. The rise in AsA concentration typically occurred close to the peak in expression of the L-galactose pathway biosynthetic genes, particularly the GDP-L-galactose guanyltransferase gene. The high concentration of AsA found in the fruit of A. eriantha is probably due to higher expression of the GDP-mannose-3',5'-epimerase and GDP-L-galactose guanyltransferase genes. Over-expression of the kiwifruit GDP-L-galactose guanyltransferase gene in Arabidopsis resulted in up to a 4-fold increase in AsA, while up to a 7-fold increase in AsA was observed in transient expression studies where both GDP-L-galactose guanyltransferase and GDP-mannose-3',5'-epimerase genes were co-expressed. These studies show the importance of GDP-L-galactose guanyltransferase as a rate-limiting step to AsA, and demonstrate how AsA can be significantly increased in plants.

The effect of carbon tax on carbon emission abatement and GDP: a case study

NASA Astrophysics Data System (ADS)

Liu, Xiao; Leung, Yee; Xu, Yuan; Yung, Linda Chor Wing

2017-10-01

Carbon tax has been advocated as an effective economic instrument for the abatement of CO2 emission by various countries, including China, the world's biggest carbon emission country. However, carbon emission abatement cannot be done while ignoring the impact on economic growth. A delicate balance needs to be achieved between the two to find an appropriate pathway for sustainable development. This paper applies a multi-objective optimization approach to analyze the impact of levying carbon tax on the energy-intensive sectors of Guangdong province in China under the constraint of emission reduction target. This approach allows us to evaluate carbon emission minimization while maximizing GDP. For policy analysis, we construct five scenarios for evaluation and optimal choice. The results of the analysis show that a lower initial carbon tax rate is not necessarily better, and that a carbon tax is an effective means to reduce CO2 emissions while maintaining a certain level of GDP growth.

Assessment of the Present and Future Offshore Wind Power Potential: A Case Study in a Target Territory of the Baltic Sea Near the Latvian Coast

PubMed Central

Teilans, Artis

2013-01-01

Offshore wind energy development promises to be a significant domestic renewable energy source in Latvia. The reliable prediction of present and future wind resources at offshore sites is crucial for planning and selecting the location for wind farms. The overall goal of this paper is the assessment of offshore wind power potential in a target territory of the Baltic Sea near the Latvian coast as well as the identification of a trend in the future wind energy potential for the study territory. The regional climate model CLM and High Resolution Limited Area Model (Hirlam) simulations were used to obtain the wind climatology data for the study area. The results indicated that offshore wind energy is promising for expanding the national electricity generation and will continue to be a stable resource for electricity generation in the region over the 21st century. PMID:23983619

Assessment of the present and future offshore wind power potential: a case study in a target territory of the Baltic Sea near the Latvian coast.

PubMed

Lizuma, Lita; Avotniece, Zanita; Rupainis, Sergejs; Teilans, Artis

2013-01-01

Offshore wind energy development promises to be a significant domestic renewable energy source in Latvia. The reliable prediction of present and future wind resources at offshore sites is crucial for planning and selecting the location for wind farms. The overall goal of this paper is the assessment of offshore wind power potential in a target territory of the Baltic Sea near the Latvian coast as well as the identification of a trend in the future wind energy potential for the study territory. The regional climate model CLM and High Resolution Limited Area Model (Hirlam) simulations were used to obtain the wind climatology data for the study area. The results indicated that offshore wind energy is promising for expanding the national electricity generation and will continue to be a stable resource for electricity generation in the region over the 21st century.

Crystal Structures of the Scaffolding Protein LGN Reveal the General Mechanism by Which GoLoco Binding Motifs Inhibit the Release of GDP from Gαi *

PubMed Central

Jia, Min; Li, Jianchao; Zhu, Jinwei; Wen, Wenyu; Zhang, Mingjie; Wang, Wenning

2012-01-01

GoLoco (GL) motif-containing proteins regulate G protein signaling by binding to Gα subunit and acting as guanine nucleotide dissociation inhibitors. GLs of LGN are also known to bind the GDP form of Gαi/o during asymmetric cell division. Here, we show that the C-terminal GL domain of LGN binds four molecules of Gαi·GDP. The crystal structures of Gαi·GDP in complex with LGN GL3 and GL4, respectively, reveal distinct GL/Gαi interaction features when compared with the only high resolution structure known with GL/Gαi interaction between RGS14 and Gαi1. Only a few residues C-terminal to the conserved GL sequence are required for LGN GLs to bind to Gαi·GDP. A highly conserved “double Arg finger” sequence (RΨ(D/E)(D/E)QR) is responsible for LGN GL to bind to GDP bound to Gαi. Together with the sequence alignment, we suggest that the LGN GL/Gαi interaction represents a general binding mode between GL motifs and Gαi. We also show that LGN GLs are potent guanine nucleotide dissociation inhibitors. PMID:22952234

Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified.

PubMed

Qi, Fei; Dong, Mei; He, Xiaohui; Li, Yexiong; Wang, Weihu; Liu, Peng; Yang, Jianliang; Gui, Lin; Zhang, Changgong; Yang, Sheng; Zhou, Shengyu; Shi, Yuankai

2017-02-01

Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2-8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p < .01). In addition, the low International Prognostic Index, low Prognostic Index for T cell lymphoma, or normal level of LDH in serum was associated with favorable prognosis. Grade 3/4 adverse effect was observed in 10 of 25 patients treated with GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL-NOS.

Performance Analysis of Air-to-Water Heat Pump in Latvian Climate Conditions

NASA Astrophysics Data System (ADS)

Kazjonovs, Janis; Sipkevics, Andrejs; Jakovics, Andris; Dancigs, Andris; Bajare, Diana; Dancigs, Leonards

2014-12-01

Strategy of the European Union in efficient energy usage demands to have a higher proportion of renewable energy in the energy market. Since heat pumps are considered to be one of the most efficient heating and cooling systems, they will play an important role in the energy consumption reduction in buildings aimed to meet the target of nearly zero energy buildings set out in the EU Directive 2010/31/EU. Unfortunately, the declared heat pump Coefficient of Performance (COP) corresponds to a certain outdoor temperature (+7 °C), therefore different climate conditions, building characteristics and settings result in different COP values during the year. The aim of this research is to investigate the Seasonal Performance factor (SPF) values of air-to-water heat pump which better characterize the effectiveness of heat pump in a longer selected period of time, especially during the winter season, in different types of residential buildings in Latvian climate conditions. Latvia has four pronounced seasons of near-equal length. Winter starts in mid-December and lasts until mid-March. Latvia is characterized by cold, maritime climate (duration of the average heating period being 203 days, the average outdoor air temperature during the heating period being 0.0 °C, the coldest five-day average temperature being -20.7 °C, the average annual air temperature being +6.2 °C, the daily average relative humidity being 79 %). The first part of this research consists of operational air-towater heat pump energy performance monitoring in different residential buildings during the winter season. The second part of the research takes place under natural conditions in an experimental construction stand which is located in an urban environment in Riga, Latvia. The inner area of this test stand, where air-to-water heat pump performance is analyzed, is 9 m2. The ceiling height is 3 m, all external wall constructions (U = 0.16 W/(m2K)) have ventilated facades. To calculate SPF, the

Concordant gene regulation related to perturbations of three GDP-mannose-related genes.

PubMed

Törmä, Anssi; Pitkänen, Juha-Pekka; Huopaniemi, Laura; Mattila, Pirkko; Renkonen, Risto

2009-02-01

Glycosylation of proteins is one of the most crucial post-translational modifications. In order to access system-level and state-dependent data related to the regulation of glycosylation events, we cultivated yeast cell strains each harboring a selected conditional knockdown construct for a gene (either SEC53, VRG4 or DPM1) related to GDP-mannose synthesis or its utilization in glycan biosynthesis. In order to carry this out efficiently, we developed automated sampling from bioreactor cultivations, a collection of in silico workflows for data analysis as well as their integration into a large data warehouse. Using the above-mentioned approaches, we could show that conditional knocking down of transcripts related to GDP-mannose synthesis or transportation led to altered levels of over 300 transcripts. These transcripts and their corresponding proteins were characterized by their gene ontology (GO) annotations, and their putative transcriptional regulation was analyzed. Furthermore, novel pathways were generated indicating interactions between GO categories with common proteins, putative transcriptional regulators of such induced GO categories, and the large protein-protein interaction network among the proteins whose transcripts indicated altered expression levels. When these results are always added to an ever-expanding data warehouse as annotations, they will incrementally increase the knowledge of biological systems.

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

PubMed Central

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

2016-01-01

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. PMID:27458202

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. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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.

Alcohol-Attributable Fraction in Liver Disease: Does GDP Per Capita Matter?

PubMed

Kröner, Paul T; Mankal, Pavan Kumar; Dalapathi, Vijay; Shroff, Kavin; Abed, Jean; Kotler, Donald P

2015-01-01

The alcohol-attributable fraction (AAF) quantifies alcohol's disease burden. Alcoholic liver disease (ALD) is influenced by alcohol consumption per capita, duration, gender, ethnicity, and other comorbidities. In this study, we investigated the association between AAF/alcohol-related liver mortality and alcohol consumption per capita, while stratifying to per-capita gross domestic product (GDP). Data obtained from the World Health Organization and World Bank for both genders on AAF on liver disease, per-capita alcohol consumption (L/y), and per-capita GDP (USD/y) were used to conduct a cross-sectional study. Countries were classified as "high-income" and "very low income" if their respective per-capita GDP was greater than $30,000 or less than $1,000. Differences in total alcohol consumption per capita and AAF were calculated using a 2-sample t test. Scatterplots were generated to supplement the Pearson correlation coefficients, and F test was conducted to assess for differences in variance of ALD between high-income and very low income countries. Twenty-six and 27 countries met the criteria for high-income and very low income countries, respectively. Alcohol consumption per capita was higher in high-income countries. AAF and alcohol consumption per capita for both genders in high-income and very low income countries had a positive correlation. The F test yielded an F value of 1.44 with P = .357. No statistically significant correlation was found among alcohol types and AAF. Significantly higher mortality from ALD was found in very low income countries relative to high-income countries. Previous studies had noted a decreased AAF in low-income countries as compared to higher-income countries. However, the non-statistically significant difference between AAF variances of low-income and high-income countries was found by this study. A possible explanation is that both high-income and low-income populations will consume sufficient amount of alcohol, irrespective of its

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

Expression and crystallographic studies of the Arabidopsis thaliana GDP-D-mannose pyrophosphorylase VTC1.

PubMed

Zhao, Shun; Liu, Lin

2016-10-01

GDP-D-mannose pyrophosphorylase catalyzes the production of GDP-D-mannose, an intermediate product in the plant ascorbic acid (AsA) biosynthetic pathway. This enzyme is a key regulatory target in AsA biosynthesis and is encoded by VITAMIN C DEFECTIVE 1 (VTC1) in the Arabidopsis thaliana genome. Here, recombinant VTC1 was expressed, purified and crystallized. Diffraction data were obtained from VTC1 crystals grown in the absence and presence of substrate using X-rays. The ligand-free VTC1 crystal diffracted X-rays to 3.3 Å resolution and belonged to space group R32, with unit-cell parameters a = b = 183.6, c = 368.5 Å, α = β = 90, γ = 120°; the crystal of VTC1 in the presence of substrate diffracted X-rays to 1.75 Å resolution and belonged to space group P2 1 , with unit-cell parameters a = 70.8, b = 83.9, c = 74.5 Å, α = γ = 90.0, β = 114.9°.

A step function model to evaluate the real monetary value of man-sievert with real GDP.

PubMed

Na, Seong H; Kim, Sun G

2009-01-01

For use in a cost-benefit analysis to establish optimum levels of radiation protection in Korea under the ALARA principle, we introduce a discrete step function model to evaluate man-sievert monetary value in the real economic value. The model formula, which is unique and country-specific, is composed of real GDP, the nominal risk coefficient for cancer and hereditary effects, the aversion factor against radiation exposure, and average life expectancy. Unlike previous researches on alpha-value assessment, we show different alpha values in the real term, differentiated with respect to the range of individual doses, which would be more realistic and informative for application to the radiation protection practices. GDP deflators of economy can reflect the society's situations. Finally, we suggest that the Korean model can be generalized simply to other countries without normalizing any country-specific factors.

Concurrent IMRT and weekly cisplatin followed by GDP chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell lymphoma.

PubMed

Ke, Q-H; Zhou, S-Q; Du, W; Liang, G; Lei, Y; Luo, F

2014-12-12

On the basis of the benefits of frontline radiation in early-stage, extranodal natural killer (NK)/T-cell lymphoma (ENKTL), we conducted the trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of gemcitabine, dexamethasone and cisplatin (GDP). Thirty-two patients with newly diagnosed, stage IE to IIE, nasal ENKTL received CCRT (that is, all patients received intensity-modulated radiotherapy 56 Gy and cisplatin 30 mg/m(2) weekly, 3-5 weeks). Three cycles of GDP (gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4 and cisplatin 75 mg/m(2) i.v. on day 1 (GDP), every 21 days as an outpatient were scheduled after CCRT. All patients completed CCRT, which resulted in 100% response that included 24 complete responses (CRs) and eight partial responses. The CR rate after CCRT was 75.0% (that is, 24 of 32 responses). Twenty-eight of the 32 patients completed the planned three cycles of GDP, whereas four patients did not because they withdrew (n = 1) or because they had an infection (n = 3). The overall response rate and the CR rate were 90.6% (that is, 29 of 32 responses) and 84.4% (that is, 27 of 32 responses), respectively. Only two patient experienced grade 3 toxicity during CCRT (nausea), whereas 13 of the 30 patients experienced grade 4 neutropenia. The estimated 3-year overall survival and progression-free rates were 87.50% and 84.38%, respectively. In conclusion, CCRT followed by GDP chemotherapy can be a feasible and effective treatment strategy for stage IE to IIE nasal ENKTL.

Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes

PubMed Central

Crepin, Thibaut; Shalak, Vyacheslav F.; Yaremchuk, Anna D.; Vlasenko, Dmytro O.; McCarthy, Andrew; Negrutskii, Boris S.; Tukalo, Michail A.; El'skaya, Anna V.

2014-01-01

Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon–anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the ‘GTP’- and ‘GDP’-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. PMID:25326326

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.

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

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…

In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the enzymes involved in GDP-L-fucose synthesis and Golgi import

PubMed Central

2013-01-01

Background Carbohydrate structures of surface-expressed and secreted/excreted glycoconjugates of the human blood fluke Schistosoma mansoni are key determinants that mediate host-parasite interactions in both snail and mammalian hosts. Fucose is a major constituent of these immunologically important glycans, and recent studies have sought to characterize fucosylation-associated enzymes, including the Golgi-localized fucosyltransferases that catalyze the transfer of L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. Importantly, GDP-L-fucose is the only nucleotide-sugar donor used by fucosyltransferases and its availability represents a bottleneck in fucosyl-glycotope expression. Methods A homology-based genome-wide bioinformatics approach was used to identify and molecularly characterize the enzymes that contribute to GDP-L-fucose synthesis and Golgi import in S. mansoni. Putative functions were further investigated through molecular phylogenetic and immunocytochemical analyses. Results We identified homologs of GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (GMER), which constitute a de novo pathway for GDP-L-fucose synthesis, in addition to a GDP-L-fucose transporter (GFT) that putatively imports cytosolic GDP-L-fucose into the Golgi. In silico primary sequence analyses identified characteristic Rossman loop and short-chain dehydrogenase/reductase motifs in GMD and GMER as well as 10 transmembrane domains in GFT. All genes are alternatively spliced, generating variants of unknown function. Observed quantitative differences in steady-state transcript levels between miracidia and primary sporocysts may contribute to differential glycotope expression in early larval development. Additionally, analyses of protein expression suggest the occurrence of cytosolic GMD and GMER in the ciliated epidermal plates and tegument of miracidia and primary sporocysts, respectively, which is consistent with previous

In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the enzymes involved in GDP-L-fucose synthesis and Golgi import.

PubMed

Peterson, Nathan A; Anderson, Tavis K; Wu, Xiao-Jun; Yoshino, Timothy P

2013-07-09

Carbohydrate structures of surface-expressed and secreted/excreted glycoconjugates of the human blood fluke Schistosoma mansoni are key determinants that mediate host-parasite interactions in both snail and mammalian hosts. Fucose is a major constituent of these immunologically important glycans, and recent studies have sought to characterize fucosylation-associated enzymes, including the Golgi-localized fucosyltransferases that catalyze the transfer of L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. Importantly, GDP-L-fucose is the only nucleotide-sugar donor used by fucosyltransferases and its availability represents a bottleneck in fucosyl-glycotope expression. A homology-based genome-wide bioinformatics approach was used to identify and molecularly characterize the enzymes that contribute to GDP-L-fucose synthesis and Golgi import in S. mansoni. Putative functions were further investigated through molecular phylogenetic and immunocytochemical analyses. We identified homologs of GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (GMER), which constitute a de novo pathway for GDP-L-fucose synthesis, in addition to a GDP-L-fucose transporter (GFT) that putatively imports cytosolic GDP-L-fucose into the Golgi. In silico primary sequence analyses identified characteristic Rossman loop and short-chain dehydrogenase/reductase motifs in GMD and GMER as well as 10 transmembrane domains in GFT. All genes are alternatively spliced, generating variants of unknown function. Observed quantitative differences in steady-state transcript levels between miracidia and primary sporocysts may contribute to differential glycotope expression in early larval development. Additionally, analyses of protein expression suggest the occurrence of cytosolic GMD and GMER in the ciliated epidermal plates and tegument of miracidia and primary sporocysts, respectively, which is consistent with previous localization of highly

The Drosophila Neurally Altered Carbohydrate Mutant Has a Defective Golgi GDP-fucose Transporter*

PubMed Central

Geisler, Christoph; Kotu, Varshika; Sharrow, Mary; Rendić, Dubravko; Pöltl, Gerald; Tiemeyer, Michael; Wilson, Iain B. H.; Jarvis, Donald L.

2012-01-01

Studying genetic disorders in model organisms can provide insights into heritable human diseases. The Drosophila neurally altered carbohydrate (nac) mutant is deficient for neural expression of the HRP epitope, which consists of N-glycans with core α1,3-linked fucose residues. Here, we show that a conserved serine residue in the Golgi GDP-fucose transporter (GFR) is substituted by leucine in nac1 flies, which abolishes GDP-fucose transport in vivo and in vitro. This loss of function is due to a biochemical defect, not to destabilization or mistargeting of the mutant GFR protein. Mass spectrometry and HPLC analysis showed that nac1 mutants lack not only core α1,3-linked, but also core α1,6-linked fucose residues on their N-glycans. Thus, the nac1 Gfr mutation produces a previously unrecognized general defect in N-glycan core fucosylation. Transgenic expression of a wild-type Gfr gene restored the HRP epitope in neural tissues, directly demonstrating that the Gfr mutation is solely responsible for the neural HRP epitope deficiency in the nac1 mutant. These results validate the Drosophila nac1 mutant as a model for the human congenital disorder of glycosylation, CDG-IIc (also known as LAD-II), which is also the result of a GFR deficiency. PMID:22745127

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

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

Sawake, Shota; Tajima, Noriaki; Mortimer, Jenny C.

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,more » 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.« less

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. © 2015 American Society of Plant Biologists. All rights reserved.

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

PubMed Central

Sawake, Shota; Tajima, Noriaki; Lao, Jeemeng; Ishikawa, Toshiki; Yu, Xiaolan; Yamanashi, Yukiko; Yoshimi, Yoshihisa; Kawai-Yamada, Maki

2015-01-01

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. PMID:26672069

The Arf-GDP-regulated recruitment of GBF1 to Golgi membranes requires domains HDS1 and HDS2 and a Golgi-localized protein receptor.

PubMed

Quilty, Douglas; Chan, Calvin J; Yurkiw, Katherine; Bain, Alexandra; Babolmorad, Ghazal; Melançon, Paul

2018-04-19

We previously proposed a novel mechanism by which the enzyme Golgi-specific Brefeldin A resistance factor 1 (GBF1) is recruited to the membranes of the cis -Golgi, based on in vivo experiments. Here, we extended our in vivo analysis on the production of regulatory Arf-GDP and observed that ArfGAP2 and ArfGAP3 do not play a role in GBF1 recruitment. We confirm that Arf-GDP localization is critical, as a TGN-localized Arf-GDP mutant protein fails to promote GBF1 recruitment. We also reported the establishment of an in vitro GBF1 recruitment assay that supports the regulation of GBF1 recruitment by Arf-GDP. This in vitro assay yielded further evidence for the requirement of a Golgi-localized protein because heat denaturation or protease treatment of Golgi membranes abrogated GBF1 recruitment. Finally, combined in vivo and in vitro measurements indicated that the recruitment to Golgi membranes via a putative receptor requires only the HDS1 and HDS2 domains in the C-terminal half of GBF1. © 2018. Published by The Company of Biologists Ltd.

A multifactor approach to forecasting Romanian gross domestic product (GDP) in the short run.

PubMed

Armeanu, Daniel; Andrei, Jean Vasile; Lache, Leonard; Panait, Mirela

2017-01-01

The purpose of this paper is to investigate the application of a generalized dynamic factor model (GDFM) based on dynamic principal components analysis to forecasting short-term economic growth in Romania. We have used a generalized principal components approach to estimate a dynamic model based on a dataset comprising 86 economic and non-economic variables that are linked to economic output. The model exploits the dynamic correlations between these variables and uses three common components that account for roughly 72% of the information contained in the original space. We show that it is possible to generate reliable forecasts of quarterly real gross domestic product (GDP) using just the common components while also assessing the contribution of the individual variables to the dynamics of real GDP. In order to assess the relative performance of the GDFM to standard models based on principal components analysis, we have also estimated two Stock-Watson (SW) models that were used to perform the same out-of-sample forecasts as the GDFM. The results indicate significantly better performance of the GDFM compared with the competing SW models, which empirically confirms our expectations that the GDFM produces more accurate forecasts when dealing with large datasets.

Disruption of the GDP-mannose synthesis pathway in Streptomyces coelicolor results in antibiotic hyper-susceptible phenotypes.

PubMed

Howlett, Robert; Anttonen, Katri; Read, Nicholas; Smith, Margaret C M

2018-04-01

Actinomycete bacteria use polyprenol phosphate mannose as a lipid linked sugar donor for extra-cytoplasmic glycosyl transferases that transfer mannose to cell envelope polymers, including glycoproteins and glycolipids. We showed recently that strains of Streptomyces coelicolor with mutations in the gene ppm1 encoding polyprenol phosphate mannose synthase were both resistant to phage φC31 and have greatly increased susceptibility to antibiotics that mostly act on cell wall biogenesis. Here we show that mutations in the genes encoding enzymes that act upstream of Ppm1 in the polyprenol phosphate mannose synthesis pathway can also confer phage resistance and antibiotic hyper-susceptibility. GDP-mannose is a substrate for Ppm1 and is synthesised by GDP-mannose pyrophosphorylase (GMP; ManC) which uses GTP and mannose-1-phosphate as substrates. Phosphomannomutase (PMM; ManB) converts mannose-6-phosphate to mannose-1-phosphate. S. coelicolor strains with knocked down GMP activity or with a mutation in sco3028 encoding PMM acquire phenotypes that resemble those of the ppm1 - mutants i.e. φC31 resistant and susceptible to antibiotics. Differences in the phenotypes of the strains were observed, however. While the ppm1 - strains have a small colony phenotype, the sco3028 :: Tn5062 mutants had an extremely small colony phenotype indicative of an even greater growth defect. Moreover we were unable to generate a strain in which GMP activity encoded by sco3039 and sco4238 is completely knocked out, indicating that GMP is also an important enzyme for growth. Possibly GDP-mannose is at a metabolic branch point that supplies alternative nucleotide sugar donors.

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.

Low-GDP peritoneal dialysis fluid ('balance') has less impact in vitro and ex vivo on epithelial-to-mesenchymal transition (EMT) of mesothelial cells than a standard fluid.

PubMed

Bajo, María Auxiliadora; Pérez-Lozano, María Luisa; Albar-Vizcaino, Patricia; del Peso, Gloria; Castro, María-José; Gonzalez-Mateo, Guadalupe; Fernández-Perpén, Antonio; Aguilera, Abelardo; Sánchez-Villanueva, Rafael; Sánchez-Tomero, J Antonio; López-Cabrera, Manuel; Peter, Mirjam E; Passlick-Deetjen, Jutta; Selgas, Rafael

2011-01-01

Peritoneal membrane deterioration during peritoneal dialysis (PD) is associated with epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MC), which is believed to be mainly due to glucose degradation products (GDPs) present in PD solutions. Here we investigate the impact of GDPs in PD solutions on the EMT of MC in vitro and ex vivo. For in vitro studies, omentum-derived MC were incubated with standard PD fluid or low-GDP solution diluted 1:1 with culture medium. For ex vivo studies, 33 patients, who were distributed at random to either the 'standard' or the 'low GDP' groups, were followed over 24 months. Effluents were collected every 6 months to determine EMT markers in effluent MC. Exposure of MC to standard fluid in vitro resulted in morphological change into a non-epitheloid shape, down-regulation of E-cadherin, indicative of EMT, and in a strong induction of vascular endothelial growth factor (VEGF) expression. In contrast, in vitro exposure of MC to low-GDP solution did not lead to these phenotype changes. This could be confirmed ex vivo, as the prevalence of non-epitheloid phenotype of MC in the standard group was significantly higher with increasing PD duration and MC isolated from this group showed significantly higher levels of EMT-associated molecules including fibronectin, collagen I, VEGF, IL-8 and TGF-β levels when compared with the low-GDP group. Over time, the expression of E-cadherin also decreased in the standard but increased in the low-GDP group. In addition, the levels of EMT-associated molecules (fibronectin, VEGF and IL-8) increased in the standard but decreased in the low-GDP group. A similar trend was also observed for collagen I and for TGF-β (for the first year), but did not reach global statistical significance. Accordingly, effluent MC with non-epitheloid morphology showed significantly lower levels of E-cadherin and greater levels of fibronectin, collagen I, VEGF and IL 8 when compared with MC with epitheloid phenotype

A multifactor approach to forecasting Romanian gross domestic product (GDP) in the short run

PubMed Central

Armeanu, Daniel; Lache, Leonard; Panait, Mirela

2017-01-01

The purpose of this paper is to investigate the application of a generalized dynamic factor model (GDFM) based on dynamic principal components analysis to forecasting short-term economic growth in Romania. We have used a generalized principal components approach to estimate a dynamic model based on a dataset comprising 86 economic and non-economic variables that are linked to economic output. The model exploits the dynamic correlations between these variables and uses three common components that account for roughly 72% of the information contained in the original space. We show that it is possible to generate reliable forecasts of quarterly real gross domestic product (GDP) using just the common components while also assessing the contribution of the individual variables to the dynamics of real GDP. In order to assess the relative performance of the GDFM to standard models based on principal components analysis, we have also estimated two Stock-Watson (SW) models that were used to perform the same out-of-sample forecasts as the GDFM. The results indicate significantly better performance of the GDFM compared with the competing SW models, which empirically confirms our expectations that the GDFM produces more accurate forecasts when dealing with large datasets. PMID:28742100

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

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

Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio

2013-06-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2more » is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.« less

The Chloroplast Division Protein ARC6 Acts to Inhibit Disassembly of GDP-bound FtsZ2.

PubMed

Sung, Min Woo; Shaik, Rahamthulla; TerBush, Allan D; Osteryoung, Katherine W; Vitha, Stanislav; Holzenburg, Andreas

2018-05-16

Chloroplasts host photosynthesis and fulfill other metabolic functions that are essential to plant life. They have to divide by binary fission to maintain their numbers throughout cycles of cell division. Chloroplast division is achieved by a complex ring-shaped division machinery located on both the inner (stromal) and the outer (cytosolic) side of the chloroplast envelope. The inner division ring (termed the Z ring) is formed by the assembly of tubulin-like FtsZ1 and FtsZ2 proteins. ARC6 is a key chloroplast division protein that interacts with the Z ring. ARC6 spans the inner envelope membrane, is known to stabilize or maintain the Z ring, and anchors the Z ring to the inner membrane through interaction with FtsZ2. The underlying mechanism of Z-ring stabilization is not well understood. Here, biochemical and structural characterization of ARC6 was conducted using light scattering, sedimentation, and light and transmission electron microscopy. The recombinant protein was purified as a dimer. The results indicated that a truncated form of ARC6 (tARC6), representing the stromal portion of ARC6, affects FtsZ2 assembly without forming higher-order structures, and exerts its effect via FtsZ2 dynamics. tARC6 prevented GDP-induced FtsZ2 disassembly and caused a significant net increase in FtsZ2 assembly when GDP was present. Single particle analysis and 3D reconstruction were performed to elucidate the structural basis of ARC6 activity. Together, the data reveal that a dimeric form of tARC6 binds to FtsZ2 filaments and does not increase FtsZ polymerization rates but rather inhibits GDP-associated FtsZ2 disassembly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Kinesin expands and stabilizes the GDP-microtubule lattice

NASA Astrophysics Data System (ADS)

Peet, Daniel R.; Burroughs, Nigel J.; Cross, Robert A.

2018-05-01

Kinesin-1 is a nanoscale molecular motor that walks towards the fast-growing (plus) ends of microtubules, hauling molecular cargo to specific reaction sites in cells. Kinesin-driven transport is central to the self-organization of eukaryotic cells and shows great promise as a tool for nano-engineering1. Recent work hints that kinesin may also play a role in modulating the stability of its microtubule track, both in vitro2,3 and in vivo4, but the results are conflicting5-7 and the mechanisms are unclear. Here, we report a new dimension to the kinesin-microtubule interaction, whereby strong-binding state (adenosine triphosphate (ATP)-bound and apo) kinesin-1 motor domains inhibit the shrinkage of guanosine diphosphate (GDP) microtubules by up to two orders of magnitude and expand their lattice spacing by 1.6%. Our data reveal an unexpected mechanism by which the mechanochemical cycles of kinesin and tubulin interlock, and so allow motile kinesins to influence the structure, stability and mechanics of their microtubule track.

Impact of GDP, spending on R&D, number of universities and scientific journals on research publications among Asian countries.

PubMed

Meo, Sultan Ayoub; Al Masri, Abeer A; Usmani, Adnan Mahmood; Memon, Almas Naeem; Zaidi, Syed Ziauddin

2013-01-01

This study aimed to compare the impact of Gross Domestic Product (GDP) per capita, spending on Research and Development (R&D), number of universities, and Indexed Scientific Journals on total number of research documents (papers), citations per document and Hirsch index (H-index) in various science and social science subjects among Asian countries. In this study, 40 Asian countries were included. The information regarding Asian countries, their GDP per capita, spending on R&D, total number of universities and indexed scientific journals were collected. We recorded the bibliometric indicators, including total number of research documents, citations per document and H-index in various science and social sciences subjects during the period 1996-2011. The main sources for information were World Bank, SCI-mago/Scopus and Web of Science; Thomson Reuters. The mean per capita GDP for all the Asian countries is 14448.31±2854.40 US$, yearly per capita spending on R&D 0.64±0.16 US$, number of universities 72.37±18.32 and mean number of ISI indexed journal per country is 17.97±7.35. The mean of research documents published in various science and social science subjects among all the Asian countries during the period 1996-2011 is 158086.92±69204.09; citations per document 8.67±0.48; and H-index 122.8±19.21. Spending on R&D, number of universities and indexed journals have a positive correlation with number of published documents, citations per document and H-index in various science and social science subjects. However, there was no association between the per capita GDP and research outcomes. The Asian countries who spend more on R&D have a large number of universities and scientific indexed journals produced more in research outcomes including total number of research publication, citations per documents and H-index in various science and social science subjects.

Impact of GDP, Spending on R&D, Number of Universities and Scientific Journals on Research Publications among Asian Countries

PubMed Central

Meo, Sultan Ayoub; Al Masri, Abeer A.; Usmani, Adnan Mahmood; Memon, Almas Naeem; Zaidi, Syed Ziauddin

2013-01-01

Objectives This study aimed to compare the impact of Gross Domestic Product (GDP) per capita, spending on Research and Development (R&D), number of universities, and Indexed Scientific Journals on total number of research documents (papers), citations per document and Hirsch index (H-index) in various science and social science subjects among Asian countries. Materials and Methods In this study, 40 Asian countries were included. The information regarding Asian countries, their GDP per capita, spending on R&D, total number of universities and indexed scientific journals were collected. We recorded the bibliometric indicators, including total number of research documents, citations per document and H-index in various science and social sciences subjects during the period 1996–2011. The main sources for information were World Bank, SCI-mago/Scopus and Web of Science; Thomson Reuters. Results The mean per capita GDP for all the Asian countries is 14448.31±2854.40 US$, yearly per capita spending on R&D 0.64±0.16 US$, number of universities 72.37±18.32 and mean number of ISI indexed journal per country is 17.97±7.35. The mean of research documents published in various science and social science subjects among all the Asian countries during the period 1996–2011 is 158086.92±69204.09; citations per document 8.67±0.48; and H-index 122.8±19.21. Spending on R&D, number of universities and indexed journals have a positive correlation with number of published documents, citations per document and H-index in various science and social science subjects. However, there was no association between the per capita GDP and research outcomes. Conclusion The Asian countries who spend more on R&D have a large number of universities and scientific indexed journals produced more in research outcomes including total number of research publication, citations per documents and H-index in various science and social science subjects. PMID:23840471

Prevalence of type 2 diabetes in the Arab world: impact of GDP and energy consumption.

PubMed

Meo, S A; Usmani, A M; Qalbani, E

2017-03-01

Diabetes Mellitus (DM) is a rapidly growing and most challenging health issue of the 21st century. This study aimed to investigate the prevalence of type-2 DM and its association with Gross Domestic Product (GDP) and energy consumption in the Arab world countries. We identified 88 articles through systematic searches including Institute of Scientific Information (ISI) Web of Science, PubMed and EMBASE databases published between 1980-2015. The related literature was searched by using the keywords including diabetes mellitus, prevalence, incidence, epidemiology of type-2 diabetes mellitus (T2DM), and names of the individual Arab world countries. The articles were selected and investigated for the prevalence of T2DM. No limitations were imposed in the design of the study or publication language. Finally, 50 peer-reviewed publications were included and the rest were excluded. Arab world countries with the highest prevalence of T2DM are: Kingdom of Saudi Arabia 31.6%, Oman 29%, Kuwait 25.4%, Bahrain 25.0% and United Arab Emirates 25.0%. The lowest prevalence was found in Mauritania (4.7%) and Somalia (3.9%). The highest prevalence was observed in Gulf Cooperation Council (GCC) countries (25.45%) whilst non-GCC countries had the lowest prevalence (12.69%). The combined mean prevalence of T2DM in both GCC and Non-GCC Arab countries was 16.17%. The prevalence of T2DM was found to be significantly associated with higher Gross Domestic Product (GDP) (p=0.020) and energy consumption (p=0.017). In the Arab world, the countries with the highest prevalence of type 2 diabetes mellitus are: Saudi Arabia, Oman, Kuwait, Bahrain and UAE, whilst the countries with the lowest prevalence are Mauritania and Somalia. This prevalence was significantly associated with high GDP per capita and energy consumption. Arab states must incorporate diabetes preventive policies on a war-footing basis to minimize the burden of the disease.

Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

PubMed

Moccia, Alden A; Hitz, Felicitas; Hoskins, Paul; Klasa, Richard; Power, Maryse M; Savage, Kerry J; Shenkier, Tamara; Shepherd, John D; Slack, Graham W; Song, Kevin W; Gascoyne, Randy D; Connors, Joseph M; Sehn, Laurie H

2017-02-01

The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

Impact of GDP, spending on R&D, number of universities and scientific journals on research publications in pharmacological sciences in Middle East.

PubMed

Meo, S A; Usmani, A M; Vohra, M S; Bukhari, I A

2013-10-01

Research in pharmacological science is vital to support the health needs of human beings. Measuring the research output provides information that forms the basis of strategic decisions. This study aimed to investigate the impact of Gross Domestic Product (GDP), spending on Research and Development (R&D), number of universities and scientific journals on research documents (papers), citable documents, citations per document and H-index in pharmacological science among Middle East countries. All the 16 Middle East countries were included in the study. The information regarding GDP, spending on R&D, total number of universities and indexed scientific journals were collected. We recorded the total number of research documents, citable documents, citations per document and H-index in pharmacological science during the period 1996-2011. The main sources for information were World Bank, Web of Science, Journal Citation Reports (Thomson Reuters) and SCI-mago/Scopus. The mean per capita GDP of all the Middle East countries is 18125.49±5386.28 US$, spending on R&D 0.63±0.28% of GDP in US$, number of universities 36.56±11.33 and mean ISI indexed journal are 8.25±3.93. The number of research documents published in pharmacological science among the Middle East countries during the period 1996-2011 is 1344.44±499.34; citable documents 1286.37±476.34; citations per document 7.62± 0.84; and H-index is 30.68±6.32. There was a positive correlation between spending on R&D and citations per documents (r = 0.56, p = 0.02), H-Index (r = 0.56, p = 0.02); number of universities and research documents (r = 0.72, p = 0.002), citable documents (r = 0.72, p = 0.001); ISI indexed journals and research documents (r = 0.88, p = 0.0001), citable documents (r = 0.88, p = 0.0001), H-Index (r = 0.67, p = 0.004). However, there was no correlation between the GDP per capita and research outcome in pharmacological science. There is a positive association between spending on R&D, number of

UK and Twenty Comparable Countries GDP-Expenditure-on-Health 1980-2013: The Historic and Continued Low Priority of UK Health-Related Expenditure.

PubMed

Harding, Andrew J E; Pritchard, Colin

2016-07-10

It is well-established that for a considerable period the United Kingdom has spent proportionally less of its gross domestic product (GDP) on health-related services than almost any other comparable country. Average European spending on health (as a % of GDP) in the period 1980 to 2013 has been 19% higher than the United Kingdom, indicating that comparable countries give far greater fiscal priority to its health services, irrespective of its actual fiscal value or configuration. While the UK National Health Service (NHS) is a comparatively lean healthcare system, it is often regarded to be at a 'crisis' point on account of low levels of funding. Indeed, many state that currently the NHS has a sizeable funding gap, in part due to its recently reduced GDP devoted to health but mainly the challenges around increases in longevity, expectation and new medical costs. The right level of health funding is a political value judgement. As the data in this paper outline, if the UK 'afforded' the same proportional level of funding as the mean average European country, total expenditure would currently increase by one-fifth. © 2016 by Kerman University of Medical Sciences.

Salvage chemotherapy of gemcitabine, dexamethasone, and cisplatin (GDP) for patients with relapsed or refractory peripheral T-cell lymphomas: a consortium for improving survival of lymphoma (CISL) trial.

PubMed

Park, Byeong-Bae; Kim, Won Seog; Suh, Cheolwon; Shin, Dong-Yeop; Kim, Jeong-A; Kim, Hoon-Gu; Lee, Won Sik

2015-11-01

There is no standard salvage chemotherapy for relapsed or refractory peripheral T-cell lymphomas (PTCLs). Gemcitabine combined with cisplatin has been known as an effective regimen for lymphoma treatment in the salvage setting. We investigated the efficacy and toxicity of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory PTCLs in search of a more effective and less toxic therapy. Patients with relapsed or refractory PTCLs with more than one previous regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4, and cisplatin 70 mg/m(2) i.v. on day 1, and then every 21 days. Patients could proceed to autologous stem cell transplantation (ASCT) after four cycles of GDP or receive up to six treatment cycles. Twenty-five eligible patients were evaluated for toxicity and response. The diagnoses of participants included 14 cases of PTCL-not otherwise specified (NOS) (56 %) and four cases of angioimmunoblastic T-cell lymphoma (16 %) among others. The median age of the patients was 59 years (range 20-75 years). After treatments with GDP, which delivered a median of four GDP cycles, there were 12 patients with complete responses (CR; 48 %) and six with partial responses (PR; 24 %). The overall response rate (RR) was 72 %. Four patients preceded to ASCT, and three patients finally achieved CR. The median progression free survival was 9.3 months (95 % confidence interval (CI); 4.1-14.6) with a median follow-up duration of 27.1 months. In a total of 86 cycles of GDP, grade 3 or 4 neutropenia and thrombocytopenia occurred in 16.3 and 12.8 % of cycles, respectively. Three patients (3.3 %) experienced febrile neutropenia. GDP is a highly effective and optimal salvage regimen for relapsed or refractory PTCLs and can be administered with acceptable toxicity.

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.

Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of α-dystroglycan.

PubMed

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

2013-07-11

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. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Modulation of IgG1 immunoeffector function by glycoengineering of the GDP-fucose biosynthesis pathway.

PubMed

Kelly, Ronan M; Kowle, Ronald L; Lian, Zhirui; Strifler, Beth A; Witcher, Derrick R; Parekh, Bhavin S; Wang, Tongtong; Frye, Christopher C

2018-03-01

Cross-linking of the Fcγ receptors expressed on the surface of hematopoietic cells by IgG immune complexes triggers the activation of key immune effector mechanisms, including antibody-dependent cell mediated cytotoxicity (ADCC). A conserved N-glycan positioned at the N-terminal region of the IgG C H 2 domain is critical in maintaining the quaternary structure of the molecule for Fcγ receptor engagement. The removal of a single core fucose residue from the N-glycan results in a considerable increase in affinity for FcγRIIIa leading to an enhanced receptor-mediated immunoeffector function. The enhanced potency of the molecule translates into a number of distinct advantages in the development of IgG antibodies for cancer therapy. In an effort to significantly increase the potency of an anti-CD20, IgG1 molecule, we selectively targeted the de novo GDP-fucose biosynthesis pathway of the host CHO cell line to generate >80% afucosylated IgG1 resulting in enhanced FcγRIIIa binding (13-fold) and in vitro ADCC cell-based activity (11-fold). In addition, this effective glycoengineering strategy also allowed for the utilization of the alternate GDP-fucose salvage pathway to provide a fast and efficient mechanism to manipulate the N-glycan fucosylation level to modulate IgG immune effector function. © 2017 Wiley Periodicals, Inc.

Dissociation of Rac1(GDP)·RhoGDI Complexes by the Cooperative Action of Anionic Liposomes Containing Phosphatidylinositol 3,4,5-Trisphosphate, Rac Guanine Nucleotide Exchange Factor, and GTP*

PubMed Central

Ugolev, Yelena; Berdichevsky, Yevgeny; Weinbaum, Carolyn; Pick, Edgar

2008-01-01

Rac plays a pivotal role in the assembly of the superoxide-generating NADPH oxidase of phagocytes. In resting cells, Rac is found in the cytosol in complex with Rho GDP dissociation inhibitor (RhoGDI). NADPH oxidase assembly involves dissociation of the Rac·RhoGDI complex and translocation of Rac to the membrane. We reported that liposomes containing high concentrations of monovalent anionic phospholipids cause Rac·RhoGDI complex dissociation (Ugolev, Y., Molshanski-Mor, S., Weinbaum, C., and Pick, E. (2006) J. Biol. Chem.281 ,19204 -1921916702219). We now designed an in vitro model mimicking membrane phospholipid remodeling during phagocyte stimulation in vivo. We showed that liposomes of “resting cell membrane” composition (less than 20 mol % monovalent anionic phospholipids), supplemented with 1 mol % of polyvalent anionic phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) in conjunction with constitutively active forms of the guanine nucleotide exchange factors (GEFs) for Rac, Trio, or Tiam1 and a non-hydrolyzable GTP analogue, cause dissociation of Rac1(GDP)·RhoGDI complexes, GDP to GTP exchange on Rac1, and binding of Rac1(GTP) to the liposomes. Complexes were not dissociated in the absence of GEF and GTP, and optimal dissociation required the presence of PtdIns(3,4,5)P3 in the liposomes. Dissociation of Rac1(GDP)·RhoGDI complexes was correlated with the affinity of particular GEF constructs, via the N-terminal pleckstrin homology domain, for PtdIns(3,4,5)P3 and involved GEF-mediated GDP to GTP exchange on Rac1. Phagocyte membranes enriched in PtdIns(3,4,5)P3 responded by NADPH oxidase activation upon exposure in vitro to Rac1(GDP)·RhoGDI complexes, p67phox, GTP, and Rac GEF constructs with affinity for PtdIns(3,4,5)P3 at a level superior to that of native membranes. PMID:18505730

The GMD1 and GMD2 genes of Arabidopsis encode isoforms of GDP-D-mannose 4,6-dehydratase with cell type-specific expression patterns.

PubMed

Bonin, Christopher P; Freshour, Glenn; Hahn, Michael G; Vanzin, Gary F; Reiter, Wolf-Dieter

2003-06-01

l-Fucose (l-Fuc) is a monosaccharide constituent of plant cell wall polysaccharides and glycoproteins. The committing step in the de novo synthesis of l-Fuc is catalyzed by GDP-d-mannose 4,6-dehydratase, which, in Arabidopsis, is encoded by the GMD1 and GMD2 (MUR1) genes. To determine the functional significance of this genetic redundancy, the expression patterns of both genes were investigated via promoter-beta-glucuronidase fusions and immunolocalization of a Fuc-containing epitope. GMD2 is expressed in most cell types of the root, with the notable exception of the root tip where strong expression of GMD1 is observed. Within shoot organs, GMD1::GUS expression is confined to stipules and pollen grains leading to fucosylation of the walls of these cell types in the mur1 mutant. These results suggest that GMD2 represents the major housekeeping gene for the de novo synthesis of GDP-l-Fuc, whereas GMD1 expression is limited to a number of specialized cell types. We conclude that the synthesis of GDP-l-Fuc is controlled in a cell-autonomous manner by differential expression of two isoforms of the same enzyme.

China's Pathways to Achieving 40% ~ 45% Reduction in CO{sub 2} Emissions per Unit of GDP in 2020: Sectoral Outlook and Assessment of Savings Potential

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

Zheng, Nina; Fridley, David; Zhou, Nan

2011-09-30

Achieving China’s goal of reducing its carbon intensity (CO{sub 2} per unit of GDP) by 40% to 45% percent below 2005 levels by 2020 will require the strengthening and expansion of energy efficiency policies across the buildings, industries and transport sectors. This study uses a bottom-up, end-use model and two scenarios -- an enhanced energy efficiency (E3) scenario and an alternative maximum technically feasible energy efficiency improvement (Max Tech) scenario – to evaluate what policies and technical improvements are needed to achieve the 2020 carbon intensity reduction target. The findings from this study show that a determined approach by Chinamore » can lead to the achievement of its 2020 goal. In particular, with full success in deepening its energy efficiency policies and programs but following the same general approach used during the 11th Five Year Plan, it is possible to achieve 49% reduction in CO{sub 2} emissions per unit of GDP (CO{sub 2} emissions intensity) in 2020 from 2005 levels (E3 case). Under the more optimistic but feasible assumptions of development and penetration of advanced energy efficiency technology (Max Tech case), China could achieve a 56% reduction in CO{sub 2} emissions intensity in 2020 relative to 2005 with cumulative reduction of energy use by 2700 Mtce and of CO{sub 2} emissions of 8107 Mt CO{sub 2} between 2010 and 2020. Energy savings and CO{sub 2} mitigation potential varies by sector but most of the energy savings potential is found in energy-intensive industry. At the same time, electricity savings and the associated emissions reduction are magnified by increasing renewable generation and improving coal generation efficiency, underscoring the dual importance of end-use efficiency improvements and power sector decarbonization.« less

GDP-GTP exchange processes of G{alpha}i1 protein are accelerated/decelerated depending on the type and the concentration of added detergents.

PubMed

Kubota, Makoto; Tanaka, Takeshi; Kohno, Toshiyuki; Wakamatsu, Kaori

2009-12-01

Although detergents have been widely used in G-protein studies to increase solubility and stability of the protein, we noticed that detergents modulate the nucleotide-binding properties of G-proteins. Hence, we analysed the effects of detergents on guanine nucleotide exchange reactions of Galpha(i1). Lubrol PX, a non-ionic detergent, which has been widely used in nucleotide dissociation/binding assays, was found to accelerate both GDP dissociation and GTPgammaS binding from/to Galpha in parallel at above its critical micelle concentration (cmc). Sodium cholate, an anionic detergent, which have been used to extract G-proteins from animal tissues, decelerated and accelerated GDP dissociation below and above its cmc, respectively. Surprisingly, micellar cholate decelerated GTPgammaS binding, and the binding rate constant was decreased by three orders of magnitude in the presence of 2% cholate. These results demonstrate that the guanine nucleotide exchange reactions of Galpha(i1) are drastically modulated by detergents differently depending on the type and the state (monomeric or micellar) of the detergents and that dissociation of GDP from Galpha(i1) does not necessarily lead to immediate binding of GTP to Galpha(i1) in some cases. These effects of detergents on G-proteins must be taken into account in G-protein experiments.

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...

JPRS Report, Science & Technology, USSR: Science & Technology Policy

DTIC Science & Technology

1988-11-14

the Chemistry Department of Latvian State University. But even prior to graduating from Latvian State University, he joined the Riga Citric Acid ...introduction into production of a technology of micro- biological production of citric acid from molasses. On graduating from Latvian State University...R.Ya. Karklin received a proposal in 1952 to become the chief engineer of the Riga Citric Acid Plant. One of the young chief engineer’s first

Gadolinium heteropoly complex K 17[Gd(P 2W 17O 61) 2] as a potential MRI contrast agent

NASA Astrophysics Data System (ADS)

Sun, Guoying; Feng, Jianghua; Wu, Huifeng; Pei, Fengkui; Fang, Ke; Lei, Hao

2004-10-01

Gadolinium heteropoly complex K17[Gd(P2W17O61)2] has been evaluated by in vitro and in vivo experiments as a potential contrast agent for magnetic resonance imaging (MRI). The thermal analysis and conductivity study indicate that this complex has good thermal stability and wide pH stability range. The T1 relaxivity is 7.59 mM-1 s-1 in aqueous solution and 7.97 mM-1 s-1 in 0.725 mmol l-1 bovine serum albumin (BSA) solution at 25 °C and 9.39 T, respectively. MR imaging of three male Sprague-Dawley rats showed remarkable enhancement in rat liver after intravenous injection, which persisted longer than with Gd-DTPA. The signal intensity increased by 57.1±16.9% during the whole imaging period at 0.082 mmol kg-1dose. Our preliminary in vitro and in vivo studies indicate that K17[Gd(P2W17O61)2] is a potential liver-specific MRI contrast agent.

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. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

The GDP-switched GAF domain of DcpA modulates the concerted synthesis/hydrolysis of c-di-GMP in Mycobacterium smegmatis.

PubMed

Chen, Hui-Jie; Li, Na; Luo, Ye; Jiang, Yong-Liang; Zhou, Cong-Zhao; Chen, Yuxing; Li, Qiong

2018-04-09

The second messenger c-di-GMP [bis-(3'-5')-cyclic dimeric guanosine monophosphate] plays a key role in bacterial growth, survival and pathogenesis, and thus its intracellular homeostasis should be finely maintained. Mycobacterium smegmatis encodes a GAF (mammalian c G MP-regulated phosphodiesterases, Anabaena a denylyl cyclases and Escherichia coli transcription activator F hlA) domain containing bifunctional enzyme DcpA ( d iguanylate c yclase and p hosphodiesterase A ) that catalyzes the synthesis and hydrolysis of c-di-GMP . Here, we found that M. smegmatis DcpA catalyzes the hydrolysis of c-di-GMP at a higher velocity, compared with synthetic activity, resulting in a sum reaction from the ultimate substrate GTP to the final product pGpG [5'-phosphoguanylyl-(3'-5')-guanosine]. Fusion with the N-terminal GAF domain enables the GGDEF (Gly-Gly-Asp-Glu-Phe) domain of DcpA to dimerize and accordingly gain synthetic activity. Screening of putative metabolites revealed that GDP is the ligand of the GAF domain. Binding of GDP to the GAF domain down-regulates synthetic activity, but up-regulates hydrolytic activity, which, in consequence, might enable a timely response to the transient accumulation of c-di-GMP at the stationary phase or under stresses. Combined with the crystal structure of the EAL (Glu-Ala-Leu) domain and the small-angle X-ray scattering data, we propose a putative regulatory model of the GAF domain finely tuned by the intracellular GTP/GDP ratio. These findings help us to better understand the concerted control of the synthesis and hydrolysis of c-di-GMP in M. smegmatis in various microenvironments. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

A conserved phenylalanine as a relay between the α5 helix and the GDP binding region of heterotrimeric Gi protein α subunit.

PubMed

Kaya, Ali I; Lokits, Alyssa D; Gilbert, James A; Iverson, Tina M; Meiler, Jens; Hamm, Heidi E

2014-08-29

G protein activation by G protein-coupled receptors is one of the critical steps for many cellular signal transduction pathways. Previously, we and other groups reported that the α5 helix in the G protein α subunit plays a major role during this activation process. However, the precise signaling pathway between the α5 helix and the guanosine diphosphate (GDP) binding pocket remains elusive. Here, using structural, biochemical, and computational techniques, we probed different residues around the α5 helix for their role in signaling. Our data showed that perturbing the Phe-336 residue disturbs hydrophobic interactions with the β2-β3 strands and α1 helix, leading to high basal nucleotide exchange. However, mutations in β strands β5 and β6 do not perturb G protein activation. We have highlighted critical residues that leverage Phe-336 as a relay. Conformational changes are transmitted starting from Phe-336 via β2-β3/α1 to Switch I and the phosphate binding loop, decreasing the stability of the GDP binding pocket and triggering nucleotide release. When the α1 and α5 helices were cross-linked, inhibiting the receptor-mediated displacement of the C-terminal α5 helix, mutation of Phe-336 still leads to high basal exchange rates. This suggests that unlike receptor-mediated activation, helix 5 rotation and translocation are not necessary for GDP release from the α subunit. Rather, destabilization of the backdoor region of the Gα subunit is sufficient for triggering the activation process. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Lenalidomide combined with R-GDP in a patient with refractory CD5-positive diffuse large B-cell lymphoma: A promising response and review.

PubMed

Zhang, Yaping; Wang, Xinfeng; Liu, Yifei; Sun, Chunfeng; Shi, Wenyu; Huang, Hongming

2018-07-03

CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is associated with poor survival compared with CD5-negative DLBCL. The clinical characteristics of CD5+ DLBCL are different from both CD5-negative DLBCL and other CD5+ B cell lymphomas. There is currently no promising chemotherapy for CD5+ DLBCL. Herein, we report a 49-year-old Asian male with refractory CD5+ DLBCL. He complained of aggravated abdominal pain and weight loss. Computed tomography scan revealed abdominal masses, widespread lymphadenopathy, splenomegaly, and intussusception of the ileocecal junction with bowel wall thickening. Core needle aspiration biopsy of an abdominal mass was performed and immunohistochemistry revealed DLBCL of nongerminal center type. In this report, the dose-intensified R-Hyper CVAD (A) regimen as salvage therapy was introduced but failed to result in substantial improvement over the initially standard R-CHOP regimen. Next, the R-GDP regimen was administered as second-line treatment, but only resulted in a partial response. However, the addition of lenalidomide to R-GDP (R2-GDP) resulted in complete remission. The clinical features, pathogenesis, and possible mechanism of action of lenalidomide in CD5+ DLBCL have been described in the literature. The results of the present case report and literature searches indicate that CD5+ DLBCL may share a common pathway with activated B-cell like (ABC) DLBCL as determined by gene expression profiling. Lenalidomide is expected to induce favorable responses in patients with CD5+ DLBCL.

NMR 1H,13C, 15N backbone and 13C side chain resonance assignment of the G12C mutant of human K-Ras bound to GDP.

PubMed

Sharma, Alok K; Lee, Seung-Joo; Rigby, Alan C; Townson, Sharon A

2018-05-02

K-Ras is a key driver of oncogenesis, accounting for approximately 80% of Ras-driven human cancers. The small GTPase cycles between an inactive, GDP-bound and an active, GTP-bound state, regulated by guanine nucleotide exchange factors and GTPase activating proteins, respectively. Activated K-Ras regulates cell proliferation, differentiation and survival by signaling through several effector pathways, including Raf-MAPK. Oncogenic mutations that impair the GTPase activity of K-Ras result in a hyperactivated state, leading to uncontrolled cellular proliferation and tumorogenesis. A cysteine mutation at glycine 12 is commonly found in K-Ras associated cancers, and has become a recent focus for therapeutic intervention. We report here 1 H N, 15 N, and 13 C resonance assignments for the 19.3 kDa (aa 1-169) human K-Ras protein harboring an oncogenic G12C mutation in the GDP-bound form (K-RAS G12C-GDP ), using heteronuclear, multidimensional NMR spectroscopy. Backbone 1 H- 15 N correlations have been assigned for all non-proline residues, except for the first methionine residue.

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 E; Ferrantelli, E; Ter Wee, Pieter M; Beelen, Robert H J; van Ittersum, Frans J

2017-01-01

♦ BACKGROUND: The use of pH-neutral peritoneal dialysis (PD) fluids low in glucose degradation products (GDP) may better preserve the peritoneal membrane and have fewer systemic effects. The effects of conversion from conventional to neutral-pH, low-GDP PD fluids in prevalent patients are unclear. Few studies on the role of neutral-pH, low-GDP PD have studied residual renal function, ultrafiltration, peritonitis incidence and technique failure, transport characteristics, and local and systemic markers of inflammation in prevalent PD patients. ♦ METHODS: In a multi-center open-label randomized clinical trial (RCT), we randomly assigned 40 of 78 stable continuous ambulatory PD (CAPD) and automated PD (APD) patients to treatment with bicarbonate/lactate, neutral-pH, low-GDP PD fluid (Physioneal; Baxter Healthcare Corporation, Deerfield, IL, USA) and compared them with 38 patients continuing their current standard lactate-buffered PD fluid (PDF) (Dianeal; Baxter Healthcare Corporation, Deerfield, IL, USA) during 2 years. Primary outcome was residual renal function (RRF) and ultrafiltration (UF) during peritoneal equilibration test (PET); peritonitis incidence was a secondary outcome. Furthermore, clinical parameters as well as several biomarkers in effluents and serum were measured. ♦ RESULTS: During follow-up, RRF did not differ between the groups. In the Physioneal group ultrafiltration (UF) during PET remained more or less stable (-20 mL [confidence interval (CI): -163.5 - 123.5 mL]; p = 0.7 over 24 months), whereas it declined in the Dianeal group (-243 mL [CI: -376.6 to -109.4 mL]; p < 0.0001 over 24 months), resulting in a difference of 233.7 mL [95% CI 41.0 - 425.5 mL]; p = 0.017 between the groups at 24 months. The peritonitis rate was lower in the Physioneal group: adjusted odds ratio (OR) 0.38 (0.15 - 0.97) p = 0.043. No differences were observed between the 2 groups in peritoneal adequacy or transport characteristics nor effluent markers of local

GDP beta S enhances the activation of phospholipase C caused by thrombin in human platelets: evidence for involvement of an inhibitory GTP-binding protein

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

Oberdisse, E.; Lapetina, E.G.

1987-05-14

Guanosine 5'-O-thiotriphosphate (GTP gamma S) and thrombin stimulate the activity of phospholipase C in platelets that have been permeabilized with saponin and whose inositol phospholipids have been prelabeled with (/sup 3/H)inositol. Ca/sup 2 +/ has opposite effects on the formation of (/sup 3/H)inositol phosphates induced by thrombin or GTP gamma S. While the action of GTP gamma S on the formation of (/sup 3/H)inositol phosphates is inhibited by Ca/sup 2 +/, action of thrombin is stimulated by Ca/sup 2 +/. Guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), which inhibits the function of GTP-binding proteins, also inhibits the effect of GTP gamma Smore » on phospholipase C stimulation but, surprisingly, increases the effect of thrombin. Ca/sup 2 +/ increases the inhibitory effect of GDP beta S on GTP gamma S activation of phospholipase C, but Ca/sup 2 +/ further enhances the stimulatory effect of GDP beta S on the thrombin activation of phospholipase C. This indicates that two mechanisms are responsible for the activation of phospholipase C in platelets. A GTP-binding protein is responsible for regulation of phospholipase C induced by GTP gamma S, while the effect of thrombin on the stimulation of phospholipase C is independent of GTP-binding proteins. However, the effect of thrombin may be modulated by the action of an inhibitory GTP-binding protein.« less

Phase 1 study of inotuzumab ozogamicin combined with R-GDP for the treatment of patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma.

PubMed

Sangha, Randeep; Davies, Andrew; Dang, Nam H; Ogura, Michinori; MacDonald, David A; Ananthakrishnan, Revathi; Paccagnella, M Luisa; Vandendries, Erik; Boni, Joseph; Goh, Yeow Tee

2017-01-01

Objective : To evaluate safety, tolerability, and preliminary activity of inotuzumab ozogamicin (InO) plus rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) in patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma (NHL). Methods : Patients received InO plus R-GDP (21-day cycle; six-cycle maximum) using up-and-down dose-escalation schema for gemcitabine and cisplatin to define the highest dosage regimen(s) with acceptable toxicity (Part 1; n  = 27). Part 2 ( n  = 10) confirmed safety and tolerability; Part 3 ( n  = 18) evaluated preliminary efficacy. Results: Among 55 patients enrolled, 42% were refractory at baseline (median 2 [range, 1-6] prior therapies); 38% had diffuse large B-cell lymphoma (DLBCL). The highest dosage regimen with acceptable toxicity was InO 0.8 mg/m 2 , rituximab 375 mg/m 2 , cisplatin 50 mg/m 2 , gemcitabine 500 mg/m 2 (day 1 only) and dexamethasone 40 mg (days 1-4); this was confirmed in Part 2, in which three patients had dose-limiting toxicities (grade 4 thrombocytopenia [ n  = 2], febrile neutropenia [ n  = 2]). Most frequent treatment-related adverse events were thrombocytopenia (any grade, 85%; grade ≥3, 75%) and neutropenia (69%; 62%). Overall (objective) response rate (ORR) was 53% (11 complete, 18 partial responses); ORR was 71%, 33%, and 62% in patients with follicular lymphoma ( n  = 14), DLBCL ( n  = 21), and mantle cell lymphoma ( n  = 13), respectively. Conclusions: InO 0.8 mg/m 2 plus R-GDP was associated with manageable toxicity, although gemcitabine and cisplatin doses were lower than in the standard R-GDP regimen due to hematologic toxicity. Evidence of antitumor activity was observed; however, these exploratory data should be interpreted with caution due to the small sample size and short follow-up duration (Clinicaltrials.gov number: NCT01055496).

The Discourse on Dangerous Reading in Nineteenth-Century Latvia.

PubMed

Daija, Pauls; Eglāja-Kristsone, Eva

During the nineteenth century, Latvian society experienced significant social and cultural changes due to a transition from agrarian to modern society and the emergence of a Latvian national culture. Reading, previously a mostly religious and practical activity, took new forms among the Latvian middle class and steadily began to be depicted as a dangerous pastime. In this essay, we have explored the connection between social change and pathological reading by turning attention to the rhetoric of the dangerous reading discourse, representations of effects of reading in the press, and the condemnation of female reading.

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. © 2016 Wiley Periodicals, Inc.

"Mama" and "Papa" in Child Language

ERIC Educational Resources Information Center

Ruke-Dravina, Velta

1976-01-01

This case study of two Latvian children attempts to show how the parental terms for"mummy" and "daddy" in Latvian are acquired, paying particular attention to the changing relationship between the input and output forms during the acquisition process. (Author/RM)

Recurrent De Novo Mutations Disturbing the GTP/GDP Binding Pocket of RAB11B Cause Intellectual Disability and a Distinctive Brain Phenotype.

PubMed

Lamers, Ideke J C; Reijnders, Margot R F; Venselaar, Hanka; Kraus, Alison; Jansen, Sandra; de Vries, Bert B A; Houge, Gunnar; Gradek, Gyri Aasland; Seo, Jieun; Choi, Murim; Chae, Jong-Hee; van der Burgt, Ineke; Pfundt, Rolph; Letteboer, Stef J F; van Beersum, Sylvia E C; Dusseljee, Simone; Brunner, Han G; Doherty, Dan; Kleefstra, Tjitske; Roepman, Ronald

2017-11-02

The Rab GTPase family comprises ∼70 GTP-binding proteins, functioning in vesicle formation, transport and fusion. They are activated by a conformational change induced by GTP-binding, allowing interactions with downstream effectors. Here, we report five individuals with two recurrent de novo missense mutations in RAB11B; c.64G>A; p.Val22Met in three individuals and c.202G>A; p.Ala68Thr in two individuals. An overlapping neurodevelopmental phenotype, including severe intellectual disability with absent speech, epilepsy, and hypotonia was observed in all affected individuals. Additionally, visual problems, musculoskeletal abnormalities, and microcephaly were present in the majority of cases. Re-evaluation of brain MRI images of four individuals showed a shared distinct brain phenotype, consisting of abnormal white matter (severely decreased volume and abnormal signal), thin corpus callosum, cerebellar vermis hypoplasia, optic nerve hypoplasia and mild ventriculomegaly. To compare the effects of both variants with known inactive GDP- and active GTP-bound RAB11B mutants, we modeled the variants on the three-dimensional protein structure and performed subcellular localization studies. We predicted that both variants alter the GTP/GDP binding pocket and show that they both have localization patterns similar to inactive RAB11B. Evaluation of their influence on the affinity of RAB11B to a series of binary interactors, both effectors and guanine nucleotide exchange factors (GEFs), showed induction of RAB11B binding to the GEF SH3BP5, again similar to inactive RAB11B. In conclusion, we report two recurrent dominant mutations in RAB11B leading to a neurodevelopmental syndrome, likely caused by altered GDP/GTP binding that inactivate the protein and induce GEF binding and protein mislocalization. Copyright © 2017 American Society of Human Genetics. All rights reserved.

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.

The role of the legislative and regulatory branches in promoting the use of geothermal energy in Latvia

NASA Astrophysics Data System (ADS)

Skapare, I.; Kreslins, A.; Cers, A.

2016-09-01

Latvia currently is self-sufficient in energy resources up to approximately 35 %. Annual fossil energy prices rise and risks of security of energy supply promote the development legislation in the matter of renewable resources. One of the Latvian Ministry of Economics' recent products is a new draft law called the "Renewable Energy Law", which has been created due to one of the European Union and Latvian national energy policy objectives: to increase the share of renewable energy up to 40 % by 2020 (Moore and Vanags, 2012). Currently, geothermal energy potential is assessed at 1 × 1013 kWh; nevertheless, it is difficult for geothermal energy to compete with other renewable energy resources in the Latvian energy market. A great job has been done in recent years at the legislative branch to choose the right methods for supporting the use of renewable energy resources. This paper aims is analysis of current situation and assessment of Latvian legislation possibilities to promote the use of geothermal energy.

Biosynthesis of the fungal cell wall polysaccharide galactomannan requires intraluminal GDP-mannose.

PubMed

Engel, Jakob; Schmalhorst, Philipp S; Routier, Françoise H

2012-12-28

Fungal cell walls frequently contain a polymer of mannose and galactose called galactomannan. In the pathogenic filamentous fungus Aspergillus fumigatus, this polysaccharide is made of a linear mannan backbone with side chains of galactofuran and is anchored to the plasma membrane via a glycosylphosphatidylinositol or is covalently linked to the cell wall. To date, the biosynthesis and significance of this polysaccharide are unknown. The present data demonstrate that deletion of the Golgi UDP-galactofuranose transporter GlfB or the GDP-mannose transporter GmtA leads to the absence of galactofuran or galactomannan, respectively. This indicates that the biosynthesis of galactomannan probably occurs in the lumen of the Golgi apparatus and thus contrasts with the biosynthesis of other fungal cell wall polysaccharides studied to date that takes place at the plasma membrane. Transglycosylation of galactomannan from the membrane to the cell wall is hypothesized because both the cell wall-bound and membrane-bound polysaccharide forms are affected in the generated mutants. Considering the severe growth defect of the A. fumigatus GmtA-deficient mutant, proving this paradigm might provide new targets for antifungal therapy.

Molecular and Phenotypic Analysis of CaVRG4, Encoding an Essential Golgi Apparatus GDP-Mannose Transporter

PubMed Central

Nishikawa, Akiko; Poster, Jay B.; Jigami, Yoshifumi; Dean, Neta

2002-01-01

Cell surface mannan is implicated in almost every aspect of pathogenicity of Candida albicans. In Saccharomyces cerevisiae, the Vrg4 protein acts as a master regulator of mannan synthesis through its role in substrate provision. The substrate for mannosylation of proteins and lipids in the Golgi apparatus is GDP-mannose, whose lumenal transport is catalyzed by Vrg4p. This nucleotide sugar is synthesized in the cytoplasm by pathways that are highly conserved in all eukaryotes, but its lumenal transport (and hence Golgi apparatus-specific mannosylation) is a fungus-specific process. To begin to study the role of Golgi mannosylation in C. albicans, we isolated the CaVRG4 gene and analyzed the effects of loss of its function. CaVRG4 encodes a functional homologue of the S. cerevisiae GDP-mannose transporter. CaVrg4p localized to punctate spots within the cytoplasm of C. albicans in a pattern reminiscent of localization of Vrg4p in the Golgi apparatus in S. cerevisiae. Like partial loss of ScVRG4 function, partial loss of CaVRG4 function resulted in mannosylation defects, which in turn led to a number of cell wall-associated phenotypes. While heterozygotes displayed no growth phenotypes, a hemizygous strain, containing a single copy of CaVRG4 under control of the methionine-repressible MET3 promoter, did not grow in the presence of methionine and cysteine, demonstrating that CaVRG4 is essential for viability. Mutant Candida vrg4 strains were defective in hyphal formation but exhibited a constitutive polarized mode of pseudohyphal growth. Because the VRG4 gene is essential for yeast viability but does not have a mammalian homologue, it is a particularly attractive target for development of antifungal therapies. PMID:11741841

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

DOEpatents

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.

Biosynthesis of the Common Polysaccharide Antigen of Pseudomonas aeruginosa PAO1: Characterization and Role of GDP-D-Rhamnose:GlcNAc/GalNAc-Diphosphate-Lipid α1,3-D-Rhamnosyltransferase WbpZ.

PubMed

Wang, Shuo; Hao, Youai; Lam, Joseph S; Vlahakis, Jason Z; Szarek, Walter A; Vinnikova, Anna; Veselovsky, Vladimir V; Brockhausen, Inka

2015-06-15

The opportunistic pathogen Pseudomonas aeruginosa produces two major cell surface lipopolysaccharides, characterized by distinct O antigens, called common polysaccharide antigen (CPA) and O-specific antigen (OSA). CPA contains a polymer of D-rhamnose (D-Rha) in α1-2 and α1-3 linkages. Three putative glycosyltransferase genes, wbpX, wbpY, and wbpZ, are part of the CPA biosynthesis cluster. To characterize the enzymatic function of the wbpZ gene product, we chemically synthesized the donor substrate GDP-D-Rha and enzymatically synthesized GDP-D-[(3)H]Rha. Using nuclear magnetic resonance (NMR) spectroscopy, we showed that WbpZ transferred one D-Rha residue from GDP-D-Rha in α1-3 linkage to both GlcNAc- and GalNAc-diphosphate-lipid acceptor substrates. WbpZ is also capable of transferring D-mannose (D-Man) to these acceptors. Therefore, WbpZ has a relaxed specificity with respect to both acceptor and donor substrates. The diphosphate group of the acceptor, however, is required for activity. WbpZ does not require divalent metal ion for activity and exhibits an unusually high pH optimum of 9. WbpZ from PAO1 is therefore a GDP-D-Rha:GlcNAc/GalNAc-diphosphate-lipid α1,3-D-rhamnosyltransferase that has significant activity of GDP-D-Man:GlcNAc/GalNAc-diphosphate-lipid α1,3-D-mannosyltransferase. We used site-directed mutagenesis to replace the Asp residues of the two DXD motifs with Ala. Neither of the mutant constructs of wbpZ (D172A or D254A) could be used to rescue CPA biosynthesis in the ΔwbpZ knockout mutant in a complementation assay. This suggested that D172 and D254 are essential for WbpZ function. This work is the first detailed characterization study of a D-Rha-transferase and a critical step in the development of CPA synthesis inhibitors. This is the first characterization of a D-rhamnosyltransferase and shows that it is essential in Pseudomonas aeruginosa for the synthesis of the common polysaccharide antigen. Copyright © 2015, American Society for

Competitiveness and Quality of Higher Education: Graduates' Evaluation

ERIC Educational Resources Information Center

Bikse, Veronika; Rivza, Baiba; Brence, Ieva

2013-01-01

The aim of the paper is to find the competitiveness of Latvian university graduates in Latvia and the European Union labour market concerning aspects of entrepreneurship education. To achieve the purpose of this study to determine the competitive and qualitative levels of Latvian universities and necessary improvements that need to be made, a…

Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside antibiotic A201A unveils a GDP-l-galactose mutase

PubMed Central

Zhu, Qinghua; Chen, Qi; Song, Yongxiang; Huang, Hongbo; Li, Jun; Ma, Junying; Li, Qinglian; Ju, Jianhua

2017-01-01

Galactose, a monosaccharide capable of assuming two possible configurational isomers (d-/l-), can exist as a six-membered ring, galactopyranose (Galp), or as a five-membered ring, galactofuranose (Galf). UDP-galactopyranose mutase (UGM) mediates the conversion of pyranose to furanose thereby providing a precursor for d-Galf. Moreover, UGM is critical to the virulence of numerous eukaryotic and prokaryotic human pathogens and thus represents an excellent antimicrobial drug target. However, the biosynthetic mechanism and relevant enzymes that drive l-Galf production have not yet been characterized. Herein we report that efforts to decipher the sugar biosynthetic pathway and tailoring steps en route to nucleoside antibiotic A201A led to the discovery of a GDP-l-galactose mutase, MtdL. Systematic inactivation of 18 of the 33 biosynthetic genes in the A201A cluster and elucidation of 10 congeners, coupled with feeding and in vitro biochemical experiments, enabled us to: (i) decipher the unique enzyme, GDP-l-galactose mutase associated with production of two unique d-mannose-derived sugars, and (ii) assign two glycosyltransferases, four methyltransferases, and one desaturase that regiospecifically tailor the A201A scaffold and display relaxed substrate specificities. Taken together, these data provide important insight into the origin of l-Galf-containing natural product biosynthetic pathways with likely ramifications in other organisms and possible antimicrobial drug targeting strategies. PMID:28438999

Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside antibiotic A201A unveils a GDP-l-galactose mutase.

PubMed

Zhu, Qinghua; Chen, Qi; Song, Yongxiang; Huang, Hongbo; Li, Jun; Ma, Junying; Li, Qinglian; Ju, Jianhua

2017-05-09

Galactose, a monosaccharide capable of assuming two possible configurational isomers (d-/l-), can exist as a six-membered ring, galactopyranose (Gal p ), or as a five-membered ring, galactofuranose (Gal f ). UDP-galactopyranose mutase (UGM) mediates the conversion of pyranose to furanose thereby providing a precursor for d-Gal f Moreover, UGM is critical to the virulence of numerous eukaryotic and prokaryotic human pathogens and thus represents an excellent antimicrobial drug target. However, the biosynthetic mechanism and relevant enzymes that drive l-Gal f production have not yet been characterized. Herein we report that efforts to decipher the sugar biosynthetic pathway and tailoring steps en route to nucleoside antibiotic A201A led to the discovery of a GDP-l-galactose mutase, MtdL. Systematic inactivation of 18 of the 33 biosynthetic genes in the A201A cluster and elucidation of 10 congeners, coupled with feeding and in vitro biochemical experiments, enabled us to: ( i ) decipher the unique enzyme, GDP-l-galactose mutase associated with production of two unique d-mannose-derived sugars, and ( ii ) assign two glycosyltransferases, four methyltransferases, and one desaturase that regiospecifically tailor the A201A scaffold and display relaxed substrate specificities. Taken together, these data provide important insight into the origin of l-Gal f -containing natural product biosynthetic pathways with likely ramifications in other organisms and possible antimicrobial drug targeting strategies.

Operation Atlantic Resolve

Science.gov Websites

Ukraine, Defense Secretary Ash Carter told service members aboard the USS San Antonio in Estonia. Story . Story U.S. Soldiers, Airmen Train With Latvian Service Members U.S. and Latvian troops conducted airborne training in Latvia while supporting Operation Atlantic Resolve, which focuses on joint training

Global Sea Level Rise and its Impact Estimation Model by Beach Mechanics, GDP, and Shoreline Length using Big Data Approach.

NASA Astrophysics Data System (ADS)

Xu, A. A.

2016-12-01

Existing research has shown consistent increase in global sea levels due to warming of the climate; since 1870, average global sea level has risen by about 20 cm. There are processes that scientists and coastal engineers can follow to estimate the erosion and flooding risk impacts for specific locations based on historical data. However, there are no methods available to assess the risk impacts for locations where little research has been conducted. In this study, we introduce a prototype to better predict sea level change and land loss using big data technology. Our approach combines cluster analysis and artificial intelligence to classify and calculate impacts for locations worldwide. Data from 235 locations (89 countries) on sea level change was gathered from NOAA data investigations and other research organizations, including beach profile data, shoreline length data, and GDP data. The rate of sea level rise varies from -18 to 21 mm/yr. We divide the data into 4 groups (Group A: +0 to 9mm, Group B: +10 to +20mm, Group C: -0 to -9mm, and Group D:-10 to -20mm). Our research focuses on types A and B only since both reflect increase on sea level rise. We find the correlation between the sea level rise and factors such as the economic parameter (α), sea level rise height (h), beach breaker wave (Hb), gravitational constant (g), period of wave (T), foreshore slope (i), and sand sizes (D). We conclude the sea level rise impact ($ lost) can be more scientifically and precisely predicted using our model.

Surveying Language Attitudes and Practices in Latvia

ERIC Educational Resources Information Center

Priedite, Aija

2005-01-01

As a heritage from the Soviet period (1945-1991) about 500,000-700,000 (mostly Russophone) persons (military persons, workers and others) lived in Latvia with little or no command of Latvian. During the same period, the Russian language had replaced Latvian in the public administration. Following the restitution of independence in 1991, one of the…

Identification of a Novel, Putative Rho-specific GDP/GTP Exchange Factor and a RhoA-binding Protein: Control of Neuronal Morphology

PubMed Central

Gebbink, Martijn F.B.G.; Kranenburg, Onno; Poland, Mieke; van Horck, Francis P.G.; Houssa, Brahim; Moolenaar, Wouter H.

1997-01-01

The small GTP-binding protein Rho has been implicated in the control of neuronal morphology. In N1E-115 neuronal cells, the Rho-inactivating C3 toxin stimulates neurite outgrowth and prevents actomyosin-based neurite retraction and cell rounding induced by lysophosphatidic acid (LPA), sphingosine-1-phosphate, or thrombin acting on their cognate G protein–coupled receptors. We have identified a novel putative GDP/GTP exchange factor, RhoGEF (190 kD), that interacts with both wild-type and activated RhoA, but not with Rac or Cdc42. RhoGEF, like activated RhoA, mimics receptor stimulation in inducing cell rounding and in preventing neurite outgrowth. Furthermore, we have identified a 116-kD protein, p116Rip, that interacts with both the GDP- and GTP-bound forms of RhoA in N1E-115 cells. Overexpression of p116Rip stimulates cell flattening and neurite outgrowth in a similar way to dominant-negative RhoA and C3 toxin. Cells overexpressing p116Rip fail to change their shape in response to LPA, as is observed after Rho inactivation. Our results indicate that (a) RhoGEF may link G protein–coupled receptors to RhoA activation and ensuing neurite retraction and cell rounding; and (b) p116Rip inhibits RhoA-stimulated contractility and promotes neurite outgrowth. PMID:9199174

Comparative study of microbiological, chemical and sensory properties of kefirs produced in Estonia, Latvia and Lithuania.

PubMed

Anton, Dea; Raudsepp, Piret; Roasto, Mati; Meremäe, Kadrin; Kuusik, Sirje; Toomik, Peeter; Elias, Priit; Laikoja, Katrin; Kaart, Tanel; Lepiku, Martin; Püssa, Tõnu

2016-02-01

In the current study the microbiological, sensory and chemical properties of 24 kefirs (12 producers) from Estonian, Latvian and Lithuanian retail market were determined using gas chromatography (GC), high performance liquid chromatography (HPLC-MS/MS-Q-TOF and LC-ion trap MS/MS), spectrophotometry and other methods. Antihypertensive, angiotensin-converting enzyme (ACE) inhibiting, antioxidant and antibacterial peptides were found in the kefir samples. According to the results of principal component analysis of 200 most abundant compounds obtained with HPLC-MS/MS-Q-TOF analysis, Estonian kefirs differed from the rest. Kefirs of Latvian and Lithuanian origin showed similarities in several characteristics, probably related to the starter cultures and technological processes. The fatty acids composition of all Baltic kefirs was uniform. The antioxidant capacity of the kefirs varied slightly, whereas intermediate positive correlation (r = 0.32, P < 0.05) was found between antioxidativity and total bacterial count. The lipid oxidation level, estimated as the content of linoleic and oleic acid primary oxidation products, oxylipins, was very low in all studied kefirs. Only one third of analysed kefirs met the requirements of the minimum sum of viable microorganisms, indicated in the Codex Standard for Fermented Milks.

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

PubMed Central

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

2015-01-01

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

National income inequality and declining GDP growth rates are associated with increases in HIV diagnoses among people who inject drugs in Europe: a panel data analysis.

PubMed

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

2015-01-01

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

Measures of native and non-native rhythm in a quantity language.

PubMed

Stockmal, Verna; Markus, Dace; Bond, Dzintra

2005-01-01

The traditional phonetic classification of language rhythm as stress-timed or syllable-timed is attributed to Pike. Recently, two different proposals have been offered for describing the rhythmic structure of languages from acoustic-phonetic measurements. Ramus has suggested a metric based on the proportion of vocalic intervals and the variability (SD) of consonantal intervals. Grabe has proposed Pairwise Variability Indices (nPVI, rPVI) calculated from the differences in vocalic and consonantal durations between successive syllables. We have calculated both the Ramus and Grabe metrics for Latvian, traditionally considered a syllable rhythm language, and for Latvian as spoken by Russian learners. Native speakers and proficient learners were very similar whereas low-proficiency learners showed high variability on some properties. The metrics did not provide an unambiguous classification of Latvian.

An Unmastered Past: Latvia and Russia After NATO and EU Enlargement: Bilateral Issues of Statecraft 2003-2006

DTIC Science & Technology

2006-06-01

relations, World War II, Waffen SS, NATO, European Union, the Abrene district, occupation, state continuity, international relations, foreign policy. 16...Latvian legion of Waffen SS. The chapter argues that the negative attitude of Russian foreign policy makers derives directly from the perception...the role and importance of two divisions of Waffen SS known as the “Latvian Legion” probably has been the most intense and still is one of the most

The detection of financial crisis using combination of volatility and markov switching models based on real output, domestic credit per GDP, and ICI indicators

NASA Astrophysics Data System (ADS)

Sugiyanto; Zukhronah, Etik; Setianingrum, Meganisa

2018-05-01

Open economic system has not only provided ease for every country to interact with each other, but also make it easier to transmitted the crisis. Financial crisis that hit Indonesia in 1997-1998 and 2008 severely impacted the economy, thus a method to detect crisis is required. According to Kamisky et al. [6], crisis can be detected based on several financial indicators such as real output, domestic credit per Gross Domestic Product (GDP), and Indonesia Composite Index (ICI). This research aims to determine the appropriate combination of volatility and Markov switching model to detect financial crisis in Indonesia based on the indicators. Volatility model used for modeling the unconstant-variance of ARMA. Markov switching is an alternative model of time series data with changed conditions in the data, or called state. In this research, we are using three assumption of states namely low volatility state, medium volatility state and high volatility state. The data of each indicator were taken from 1990 until 2016. The result of the study show that MS-ARCH(3,1) can be used to detect the financial crisis that hit Indonesia in 1997-1998 and 2008 based on real output, domestic credit per GDP, and ICI indicators.

Intensity-modulated radiation therapy followed by GDP chemotherapy for newly diagnosed stage I/II extranodal natural killer/T cell lymphoma, nasal type.

PubMed

Huang, Yu; Yang, Jianliang; Liu, Peng; Zhou, Shengyu; Gui, Lin; He, Xiaohui; Qin, Yan; Zhang, Changgong; Yang, Sheng; Xing, Puyuan; Sun, Yan; Shi, Yuankai

2017-09-01

Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at the localized stage. Radiotherapy in combination with chemotherapy has been used for localized ENKTL, but the optimal combination treatment modality and the best first-line chemotherapy regimen have not been defined. In this retrospective study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and received intensity-modulated radiation therapy (IMRT, 50-56 Gy) followed by GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy. The median number of chemotherapy cycles per patient was 4 (range, 2-6 cycles). At the end of treatment, the overall response rate was 95% (42/44), including 39 patients (89%) who attained complete response. Two patients developed systemic progression after IMRT. With a median follow-up of 37.5 months, the 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 85% (95% CI, 74 to 96%) and 77% (95% CI, 64 to 91%), respectively. Locoregional and systemic failure rates for this treatment were 9% (4/44) and 14% (6/44), respectively. The most common grades 3 to 4 adverse events included leukopenia (37%), neutropenia (34%), and mucositis (25%). No treatment-related deaths were observed. This study suggested high efficacy and low toxicity of IMRT followed by GDP regimen chemotherapy for newly diagnosed stage I/II ENKTL patients. These results require further investigation in prospective trials.

Sentence durations and accentedness judgments

NASA Astrophysics Data System (ADS)

Bond, Z. S.; Stockmal, Verna; Markus, Dace

2003-04-01

Talkers in a second language can frequently be identified as speaking with a foreign accent. It is not clear to what degree a foreign accent represents specific deviations from a target language versus more general characteristics. We examined the identifications of native and non-native talkers by listeners with various amount of knowledge of the target language. Native and non-native speakers of Latvian provided materials. All the non-native talkers spoke Russian as their first language and were long-term residents of Latvia. A listening test, containing sentences excerpted from a short recorded passage, was presented to three groups of listeners: native speakers of Latvian, Russians for whom Latvian was a second language, and Americans with no knowledge of either of the two languages. The listeners were asked to judge whether each utterance was produced by a native or non-native talker. The Latvians identified the non-native talkers very accurately, 88%. The Russians were somewhat less accurate, 83%. The American listeners were least accurate, but still identified the non-native talkers at above chance levels, 62%. Sentence durations correlated with the judgments provided by the American listeners but not with the judgments provided by native or L2 listeners.

Deletion of Aspergillus nidulans GDP-mannose transporters affects hyphal morphometry, cell wall architecture, spore surface character, cell adhesion, and biofilm formation.

PubMed

Kadry, Ashraf A; El-Ganiny, Amira M; Mosbah, Rasha A; Kaminskyj, Susan G W

2018-07-01

Systemic human fungal infections are increasingly common. Aspergillus species cause most of the airborne fungal infections. Life-threatening invasive aspergillosis was formerly found only in immune-suppressed patients, but recently some strains of A. fumigatus have become primary pathogens. Many fungal cell wall components are absent from mammalian systems, so they are potential drug targets. Cell-wall-targeting drugs such as echinocandins are used clinically, although echinocandin-resistant strains were discovered shortly after their introduction. Currently there are no fully effective anti-fungal drugs. Fungal cell wall glycoconjugates modulate human immune responses, as well as fungal cell adhesion, biofilm formation, and drug resistance. Guanosine diphosphate (GDP) mannose transporters (GMTs) transfer GDP-mannose from the cytosol to the Golgi lumen prior to mannosylation. Aspergillus nidulans GMTs are encoded by gmtA and gmtB. Here we elucidate the roles of A. nidulans GMTs. Strains engineered to lack either or both GMTs were assessed for hyphal and colonial morphology, cell wall ultrastructure, antifungal susceptibility, spore hydrophobicity, adherence and biofilm formation. The gmt-deleted strains had smaller colonies with reduced sporulation and with thicker hyphal walls. The gmtA deficient spores had reduced hydrophobicity and were less adherent and less able to form biofilms in vitro. Thus, gmtA not only participates in maintaining the cell wall integrity but also plays an important role in biofilm establishment and adherence of A. nidulans. These findings suggested that GMTs have roles in A. nidulans growth and cell-cell interaction and could be a potential target for new antifungals that target virulence determinants.

Maxillofacial trauma and the GDP--specialty recognition and patterns of referral.

PubMed

Willis, D H R; Tong, D C; Thomson, W M; Love, R M

2010-09-01

To investigate New Zealand GDPs' awareness of maxillofacial trauma and to identify their associated referral patterns. Cross-sectional survey of a random sample of GDPs. A nationwide postal questionnaire survey was sent to GDPs on the New Zealand Dental Register, maintained by the Dental Council of New Zealand. The questionnaire requested socio-demographic details, together with information on the availability of specialist services and their need for continuing professional development in oral and maxillofacial surgery (OMS). The questionnaire also asked the GDPs to indicate which specialty (plastic surgery, ear nose and throat (ENT) surgery, OMS and Other) they expected to manage--and to which specialty they would refer-seven types of maxillofacial injury. Some 377 GDPs responded (76.6%). The majority of GDPs expected OMS to manage maxillofacial trauma, except for facial lacerations and isolated nasal fractures which were expected to be managed by plastic surgery (83.0%) and ENT surgery (79.7%), respectively. Most GDPs (48.0% to 87.9%) referred maxillofacial trauma to OMS, except for isolated nasal fractures, for which there were similar proportions referred to ENT surgery and OMS (45.8% and 41.4%, respectively). Differences in awareness of and referral patterns for maxillofacial trauma were identified by dentist characteristics. Most GDPs (96.0%) felt there was a need for continuing professional development in OMS, and most (84.1%) preferred this to be in the form of lectures and seminars. The first-ever study of GDP referral patterns for maxillofacial trauma in New Zealand has revealed that most GDPs in New Zealand referred maxillofacial trauma appropriately to OMS.

Impact of GDP, spending on R&D, the number of universities and scientific journals on research publications in environmental sciences in the Middle East.

PubMed

Meo, Sultan Ayoub; Al Masri, Abeer A; Usmani, Adnan Mahmood; Halepoto, Dost Muhammad

2013-10-01

This study aimed to assess the impact of the Gross Domestic Product (GDP), spending on Research and Development (R&D), the number of universities and scientific journals on the published research documents, citable documents, citations per document and H-index in environmental sciences in the Middle East countries. All the 16 Middle East countries were included in the study. Information regarding the GDP, spending on R&D, the total number of universities and indexed journals was collected. Total number of research documents (papers), citable documents, citations per document and H-index in environmental sciences during the period 1996-2011 was recorded. The study used the World Bank, SCI-mago/Scopus, Web of Science, Journal Citation Reports (Thomson Reuters) as the main sources of information. The mean GDP per capita of all the Middle East countries amounted to 18 125.49±5386.28 US$, spending on R&D was 0.63±0.28 US$, the number of universities equaled 36.56±11.33 and mean ISI indexed journals amounted to 8.25±3.93. The mean number of research documents published in environmental sciences in the Middle East countries during the period 1996-2011 was 2202.12±883.98; citable documents: 2156.87±865.09; citations per document: 8.74±0.73; and the H-index: 35.37±6.17. There was a positive correlation between the money spent on R&D and citations per documents (r = 0.6, p = 0.01), H-Index (r = 0.6, p = 0.01); the number of universities and a total of research documents (r = 0.65, p = 0.006), citable documents (r = 0.65, p = 0.006), H-Index (r = 0.50, p = 0.04), as well as ISI indexed journals and total research documents (r = 0.94, p = 0.0001), citable documents (r = 0.94, p = 0.0001), H-Index (r = 0.73, p = 0.001). The Middle East countries which spend more on R&D and which have a large number of universities and ISI indexed journals are likely to produce more significant volume of research papers in the field of environmental science.

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.

Visualization of time series statistical data by shape analysis (GDP ratio changes among Asia countries)

NASA Astrophysics Data System (ADS)

Shirota, Yukari; Hashimoto, Takako; Fitri Sari, Riri

2018-03-01

It has been very significant to visualize time series big data. In the paper we shall discuss a new analysis method called “statistical shape analysis” or “geometry driven statistics” on time series statistical data in economics. In the paper, we analyse the agriculture, value added and industry, value added (percentage of GDP) changes from 2000 to 2010 in Asia. We handle the data as a set of landmarks on a two-dimensional image to see the deformation using the principal components. The point of the analysis method is the principal components of the given formation which are eigenvectors of its bending energy matrix. The local deformation can be expressed as the set of non-Affine transformations. The transformations give us information about the local differences between in 2000 and in 2010. Because the non-Affine transformation can be decomposed into a set of partial warps, we present the partial warps visually. The statistical shape analysis is widely used in biology but, in economics, no application can be found. In the paper, we investigate its potential to analyse the economic data.

The perverse impact of external reference pricing (ERP): a comparison of orphan drugs affordability in 12 European countries. A call for policy change

PubMed Central

Young, K. E.; Soussi, I.; Toumi, M.

2017-01-01

ABSTRACT Objective: The study compared the relative cost differences of similar orphan drugs among high and low GDP countries in Europe: Bulgaria, France, Germany, Greece, Hungary, Italy, Norway, Poland, Romania, Spain, Sweden, UK. Methods: Annual treatment costs per patient were calculated. Relative costs were computed by dividing the costs by each economic parameter: nominal GDP per capita, GDP in PPP per capita, % GDP contributed by the government, government budget per inhabitant, % GDP spent on healthcare, % GDP spent on pharmaceuticals, and average annual salary. An international comparison of the relative costs was done using UK as the reference country and results were analysed descriptively. Results: 120 orphan drugs were included. The median annual costs of orphan drugs in all countries varied minimally (cost ratios: 0.87 to 1.08). When the costs were adjusted using GDP per capita, the EU-5 and Nordic countries maintained minimal difference in median cost. However, the lower GDP countries showed three to six times higher relative costs. The same pattern was evident when costs were adjusted using the other economic parameters. Conclusion: When the country’s ability to pay is taken into consideration, lower GDP countries pay relatively higher costs for similarly available orphan drugs in Europe. PMID:29081920

Activation by intracellular GDP, metabolic inhibition and pinacidil of a glibenclamide-sensitive K-channel in smooth muscle cells of rat mesenteric artery.

PubMed Central

Zhang, H; Bolton, T B

1995-01-01

1. Single-channel recordings were made from cell-attached and isolated patches, and whole-cell currents were recorded under voltage clamp from single smooth muscle cells obtained by enzymic digestion of a small branch of the rat mesenteric artery. 2. In single voltage-clamped cells 1 mM uridine diphosphate (UDP) or guanidine diphosphate (GDP) added to the pipette solution, or pinacidil (100 microM) a K-channel opener (KCO) applied in the bathing solution, evoked an outward current of up to 100pA which was blocked by glibenclamide (10 microM). In single cells from which recordings were made by the 'perforated patch' (nystatin pipette) technique, metabolic inhibition by 1 mM NaCN and 10 mM 2-deoxy-glucose also evoked a similar glibenclamide-sensitive current. 3. Single K-channel activity was observed in cell-attached patches only infrequently unless the metabolism of the cell was inhibited, whereupon channel activity blocked by glibenclamide was seen; pinacidil applied to the cell evoked similar glibenclamide-sensitive channel activity. If the patch was pulled off the cell to form an isolated inside-out patch, similar glibenclamide-sensitive single-channel currents were observed in the presence of UDP and/or pinacidil to those seen in cell-attached mode; channel conductance was 20 pS (60:130 K-gradient) and openings showed no voltage-dependence and noisy inward currents, typical of the nucleoside diphosphate (NDP) activated K-channel (KNDP) seen previously in rabbit portal vein. 4. Formation of an isolated inside-out patch into an ATP-free solution did not increase the probability of channel opening which declined with time even when some single-channel activity had occurred in the cell-attached mode before detachment. However, application of 1 mM UDP or GDP, but not ATP, to inside-out patches evoked single-channel activity. Application of ATP-free solution to isolated patches, previously exposed to ATP and in which channel activity had been seen, did not evoke

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

"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. © 2017 Wiley Periodicals, Inc.

Oils and hydrocarbon source rocks of the Baltic syneclise

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

Kanev, S.; Margulis, L.; Bojesen-Koefoed, J.A.

Prolific source rock horizons of varying thickness, having considerable areal extent, occur over the Baltic syneclise. These source sediments are rich and have excellent petroleum generation potential. Their state of thermal maturity varies form immature in the northeastern part of the syneclise to peak generation maturity in the southwestern part of the region-the main kitchen area. These maturity variations are manifest in petroleum composition in the region. Hence, mature oils occur in the Polish and Kaliningrad areas, immature oils in small accumulations in Latvian and central Lithuanian onshore areas, and intermediate oils in areas between these extremes. The oil accumulationsmore » probably result from pooling of petroleum generated from a number of different source rocks at varying levels of thermal maturity. Hence, no single source for petroleum occurrences in the Baltic syneclise may be identified. The paper describes the baltic syneclise, source rocks, thermal maturity and oils and extracts.« less

Reducing AsA leads to leaf lesion and defence response in knock-down of the AsA biosynthetic enzyme GDP-D-mannose pyrophosphorylase gene in tomato plant.

PubMed

Zhang, Chanjuan; Ouyang, Bo; Yang, Changxian; Zhang, Xiaohui; Liu, Hui; Zhang, Yuyang; Zhang, Junhong; Li, Hanxia; Ye, Zhibiao

2013-01-01

As a vital antioxidant, L-ascorbic acid (AsA) affects diverse biological processes in higher plants. Lack of AsA in cell impairs plant development. In the present study, we manipulated a gene of GDP-mannose pyrophosphorylase which catalyzes the conversion of D-mannose-1-P to GDP-D-mannose in AsA biosynthetic pathway and found out the phenotype alteration of tomato. In the tomato genome, there are four members of GMP gene family and they constitutively expressed in various tissues in distinct expression patterns. As expected, over-expression of SlGMP3 increased total AsA contents and enhanced the tolerance to oxidative stress in tomato. On the contrary, knock-down of SlGMP3 significantly decreased AsA contents below the threshold level and altered the phenotype of tomato plants with lesions and further senescence. Further analysis indicated the causes for this symptom could result from failing to instantly deplete the reactive oxygen species (ROS) as decline of free radical scavenging activity. More ROS accumulated in the leaves and then triggered expressions of defence-related genes and mimic symptom occurred on the leaves similar to hypersensitive responses against pathogens. Consequently, the photosynthesis of leaves was dramatically fallen. These results suggested the vital roles of AsA as an antioxidant in leaf function and defence response of tomato.

A sodium gadolinium phosphate with two different types of tunnel structure: Synthesis, crystal structure, and optical properties of Na 3GdP 2O 8

NASA Astrophysics Data System (ADS)

Fang, M.; Cheng, W.-D.; Zhang, H.; Zhao, D.; Zhang, W.-L.; Yang, S.-L.

2008-09-01

A sodium gadolinium phosphate crystal, Na 3GdP 2O 8, has been synthesized by a high-temperature solution reaction, and it exhibits a new structural family of the alkali-metal-rare-earth phosphate system. Although many compounds with formula M 3LnP 2O 8 have been reported, but they were shown to be orthorhombic [R. Salmon, C. Parent, M. Vlasse, G. LeFlem, Mater. Res. Bull. 13 (1978) 439] rather than monoclinic as shown in this paper. Single-crystal X-ray diffraction analysis shows the structure to be monoclinic with space group C2/ c and the cell parameters: a=27.55 (25), b=5.312 (4), c=13.935(11) Å, β=91.30(1)°, and V=2038.80 Å 3, Z=4. Its structure features a three-dimensional GdP 2O 83- anionic framework with two different types of interesting tunnels at where Na atoms are located by different manners. The framework is constructed by Gd polyhedra and isolated PO 4 tetrahedra. It is different from the structure of K 3NdP 2O 8 [R. Salmon, C. Parent, M. Vlasse, G. LeFlem, Mater. Res. Bull. 13 (1978) 439] with space group P2 1/ m that shows only one type of tunnel. The emission spectrum and the absorption spectrum of the compound have been investigated. Additionally, the calculations of band structure, density of states, dielectric constants, and refractive indexes have been also performed with the density functional theory method. The obtained results tend to support the experimental data.

Time-varying phononic crystals

NASA Astrophysics Data System (ADS)

Wright, Derek Warren

The primary objective of this thesis was to gain a deeper understanding of acoustic wave propagation in phononic crystals, particularly those that include materials whose properties can be varied periodically in time. This research was accomplished in three ways. First, a 2D phononic crystal was designed, created, and characterized. Its properties closely matched those determined through simulation. The crystal demonstrated band gaps, dispersion, and negative refraction. It served as a means of elucidating the practicalities of phononic crystal design and construction and as a physical verification of their more interesting properties. Next, the transmission matrix method for analyzing 1D phononic crystals was extended to include the effects of time-varying material parameters. The method was then used to provide a closed-form solution for the case of periodically time-varying material parameters. Some intriguing results from the use of the extended method include dramatically altered transmission properties and parametric amplification. New insights can be gained from the governing equations and have helped to identify the conditions that lead to parametric amplification in these structures. Finally, 2D multiple scattering theory was modified to analyze scatterers with time-varying material parameters. It is shown to be highly compatible with existing multiple scattering theories. It allows the total scattered field from a 2D time-varying phononic crystal to be determined. It was shown that time-varying material parameters significantly affect the phononic crystal transmission spectrum, and this was used to switch an incident monochromatic wave. Parametric amplification can occur under certain circumstances, and this effect was investigated using the closed-form solutions provided by the new 1D method. The complexity of the extended methods grows logarithmically as opposed linearly with existing methods, resulting in superior computational complexity for large

Varying electric charge in multiscale spacetimes

NASA Astrophysics Data System (ADS)

Calcagni, Gianluca; Magueijo, João; Fernández, David Rodríguez

2014-01-01

We derive the covariant equations of motion for Maxwell field theory and electrodynamics in multiscale spacetimes with weighted Laplacian. An effective spacetime-dependent electric charge of geometric origin naturally emerges from the theory, thus giving rise to a varying fine-structure constant. The theory is compared with other varying-coupling models, such as those with a varying electric charge or varying speed of light. The theory is also confronted with cosmological observations, which can place constraints on the characteristic scales in the multifractional measure. We note that the model considered here is fundamentally different from those previously proposed in the literature, either of the varying-e or varying-c persuasion.

Holographic cinematography of time-varying reflecting and time-varying phase objects using a Nd:YAG laser.

PubMed

Decker, A J

1982-03-01

The use of a Nd:YAG laser to record holographic motion pictures of time-varying reflecting objects and time-varying phase objects is discussed. Sample frames from both types of holographic motion pictures are presented. The holographic system discussed is intended for three-dimensional flow visualization of the time-varying flows that occur in jet-engine components.

Holographic cinematography of time-varying reflecting and time-varying phase objects using a Nd:YAG laser

NASA Technical Reports Server (NTRS)

Decker, A. J.

1982-01-01

The use of a Nd:YAG laser to record holographic motion pictures of time-varying reflecting objects and time-varying phase objects is discussed. Sample frames from both types of holographic motion pictures are presented. The holographic system discussed is intended for three-dimensional flow visualization of the time-varying flows that occur in jet-engine components.

Time-varying BRDFs.

PubMed

Sun, Bo; Sunkavalli, Kalyan; Ramamoorthi, Ravi; Belhumeur, Peter N; Nayar, Shree K

2007-01-01

The properties of virtually all real-world materials change with time, causing their bidirectional reflectance distribution functions (BRDFs) to be time varying. However, none of the existing BRDF models and databases take time variation into consideration; they represent the appearance of a material at a single time instance. In this paper, we address the acquisition, analysis, modeling, and rendering of a wide range of time-varying BRDFs (TVBRDFs). We have developed an acquisition system that is capable of sampling a material's BRDF at multiple time instances, with each time sample acquired within 36 sec. We have used this acquisition system to measure the BRDFs of a wide range of time-varying phenomena, which include the drying of various types of paints (watercolor, spray, and oil), the drying of wet rough surfaces (cement, plaster, and fabrics), the accumulation of dusts (household and joint compound) on surfaces, and the melting of materials (chocolate). Analytic BRDF functions are fit to these measurements and the model parameters' variations with time are analyzed. Each category exhibits interesting and sometimes nonintuitive parameter trends. These parameter trends are then used to develop analytic TVBRDF models. The analytic TVBRDF models enable us to apply effects such as paint drying and dust accumulation to arbitrary surfaces and novel materials.

The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B

NASA Astrophysics Data System (ADS)

Lu, Shaoyong; Jang, Hyunbum; Nussinov, Ruth; Zhang, Jian

2016-02-01

Ras mediates cell proliferation, survival and differentiation. Mutations in K-Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP-assisted GTP → GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 μs molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4BWT-GTP/GDP) catalytic domain, the K-Ras4BWT-GTP-GAP complex, and the mutants (K-Ras4BG12C/G12D/G12V-GTP/GDP, K-Ras4BG13D-GTP/GDP, K-Ras4BQ61H-GTP/GDP) and their complexes with GAP. In addition, we simulated ‘exchanged’ nucleotide states. These comprehensive simulations reveal that in solution K-Ras4BWT-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4BG12C/G12D-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4B-driven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer.

Neural coding of time-varying interaural time differences and time-varying amplitude in the inferior colliculus

PubMed Central

2017-01-01

Binaural cues occurring in natural environments are frequently time varying, either from the motion of a sound source or through interactions between the cues produced by multiple sources. Yet, a broad understanding of how the auditory system processes dynamic binaural cues is still lacking. In the current study, we directly compared neural responses in the inferior colliculus (IC) of unanesthetized rabbits to broadband noise with time-varying interaural time differences (ITD) with responses to noise with sinusoidal amplitude modulation (SAM) over a wide range of modulation frequencies. On the basis of prior research, we hypothesized that the IC, one of the first stages to exhibit tuning of firing rate to modulation frequency, might use a common mechanism to encode time-varying information in general. Instead, we found weaker temporal coding for dynamic ITD compared with amplitude modulation and stronger effects of adaptation for amplitude modulation. The differences in temporal coding of dynamic ITD compared with SAM at the single-neuron level could be a neural correlate of “binaural sluggishness,” the inability to perceive fluctuations in time-varying binaural cues at high modulation frequencies, for which a physiological explanation has so far remained elusive. At ITD-variation frequencies of 64 Hz and above, where a temporal code was less effective, noise with a dynamic ITD could still be distinguished from noise with a constant ITD through differences in average firing rate in many neurons, suggesting a frequency-dependent tradeoff between rate and temporal coding of time-varying binaural information. NEW & NOTEWORTHY Humans use time-varying binaural cues to parse auditory scenes comprising multiple sound sources and reverberation. However, the neural mechanisms for doing so are poorly understood. Our results demonstrate a potential neural correlate for the reduced detectability of fluctuations in time-varying binaural information at high speeds, as occurs

Ab initio computational study of reaction mechanism of peptide bond formation on HF/6-31G(d,p) level

NASA Astrophysics Data System (ADS)

Siahaan, P.; Lalita, M. N. T.; Cahyono, B.; Laksitorini, M. D.; Hildayani, S. Z.

2017-02-01

Peptide plays an important role in modulation of various cell functions. Therefore, formation reaction of the peptide is important for chemical reactions. One way to probe the reaction of peptide synthesis is a computational method. The purpose of this research is to determine the reaction mechanism for peptide bond formation on Ac-PV-NH2 and Ac-VP-NH2 synthesis from amino acid proline and valine by ab initio computational approach. The calculations were carried out by theory and basis set HF/6-31G(d,p) for four mechanisms (path 1 to 4) that proposed in this research. The results show that the highest of the rate determining step between reactant and transition state (TS) for path 1, 2, 3, and 4 are 163.06 kJ.mol-1, 1868 kJ.mol-1, 5685 kJ.mol-1, and 1837 kJ.mol-1. The calculation shows that the most preferred reaction of Ac-PV-NH2 and Ac-VP-NH2 synthesis from amino acid proline and valine are on the path 1 (initiated with the termination of H+ in proline amino acid) that produce Ac-PV-NH2.

Analysis of Energy Intensive Enterprises under EU Emission Trading System in Latvia

NASA Astrophysics Data System (ADS)

Zahare, Dace; Rosa, Marika

2011-01-01

Climate change and global warming has become one of the main topics worldwide. The European Union Emission Trading System (EU ETS) was established to limit climate change, providing regulations which encourage companies to invest in cleaner production and more energy efficient production. Latvian energy intensive enterprises are operating under the EU ETS from the year 2005. The main goal of this paper is to provide an analysis of energy intensive installations in terms of their energy efficiency. Additionally, an analysis of EU ETS phase III which will start to operate in 2013 under new, more stringent rules has been conducted by modelling three Latvian energy intensive enterprise operations under this phase and estimating the barriers to meet the goal of the EU ETS phase III.

Estimation of Time-Varying Pilot Model Parameters

NASA Technical Reports Server (NTRS)

Zaal, Peter M. T.; Sweet, Barbara T.

2011-01-01

Human control behavior is rarely completely stationary over time due to fatigue or loss of attention. In addition, there are many control tasks for which human operators need to adapt their control strategy to vehicle dynamics that vary in time. In previous studies on the identification of time-varying pilot control behavior wavelets were used to estimate the time-varying frequency response functions. However, the estimation of time-varying pilot model parameters was not considered. Estimating these parameters can be a valuable tool for the quantification of different aspects of human time-varying manual control. This paper presents two methods for the estimation of time-varying pilot model parameters, a two-step method using wavelets and a windowed maximum likelihood estimation method. The methods are evaluated using simulations of a closed-loop control task with time-varying pilot equalization and vehicle dynamics. Simulations are performed with and without remnant. Both methods give accurate results when no pilot remnant is present. The wavelet transform is very sensitive to measurement noise, resulting in inaccurate parameter estimates when considerable pilot remnant is present. Maximum likelihood estimation is less sensitive to pilot remnant, but cannot detect fast changes in pilot control behavior.

Relationship of drug-addicted patients' personality disorders to social problem-solving changes during the rehabilitation process.

PubMed

Kolesnikova, Jelena; Miezitis, Solveiga; Osis, Guntars

2013-08-01

Drug-addicted patients exhibit various personality disorders that interfere with their adaptation to society, as well as their ability to participate in the rehabilitation process. The Latvian Rehabilitation Programme for drug addicts includes social problem-solving training to help patients reintegrate into society. However, the role of personality disorders has not been investigated in relation to this process. The aim of the study is to assess whether personality disorders predict changes in dimensions of social problem-solving after 6 months of rehabilitation for drug-addicted patients. The sample of this study consists of 31 drug-addicted patients from the Latvian rehabilitation centres aged 21-35 (females 21%, males 79%). Two inventories are used: the Social Problem-Solving Inventory--Revised (SPSI-R) and Millon(TM) Clinical Multiaxial Inventory--III (MCMI-III) adapted into Russian. Results of the study indicated that some MCMI-III personality disorders (Schizoid and Histrionic) negatively predicted SPSI-R Positive problem orientation, and narcissistic disorder positively predicted SPSI-R Avoidance style after 6 months in the Latvian Rehabilitation Programme. The other personality disorders did not predict social problem-solving dimensions. The results of the study suggest that some personality disorders are related to changes in social problem-solving dimensions for drug-addicted patients. Hence, it is important to consider the implications of particular personality disorders to facilitate the implementation of social problem-solving rehabilitation programmes.

Government Expenditures on Education as the Percentage of GDP in the EU

ERIC Educational Resources Information Center

Galetic, Fran

2015-01-01

This paper analyzes the government expenditures as the percentage of gross domestic product across countries of the European Union. There is a statistical model based on Z-score, whose aim is to calculate how much each EU country deviates from the average value. The model shows that government expenditures on education vary significantly between…

Clinical aspects of the health disturbances in Chernobyl Nuclear Power Plant accident clean-up workers (liquidators) from Latvia.

PubMed

Eglite, M E; Zvagule, T J; Rainsford, K D; Reste, J D; Curbakova, E V; Kurjane, N N

2009-06-01

The health status of some 6,000 workers from Latvia who went to clean-up the Chernobyl Nuclear Power Plant (CNPP) site following the explosion on 26 April 1986 has been analyzed. The data on these workers have been recorded in the Latvian State Register of Occupational disease patients and people exposed to ionizing radiation due to Chernobyl NPP accident (Latvian State Register) that was established in 1994. From these data, estimates have been made of external ionizing radiation to which these workers were exposed together with observations on the impact of exposure to heavy metals (especially lead and zinc) and radioactive isotopes released during the reactor 'meltdown'. These factors along with psycho-emotional and social-economic stresses account for a marked excess of mortality and morbidity in the group of CNPP accident clean-up workers compared with that of the non-exposed normal Latvian population adjusted for age and sex. The number of diseases or conditions in the CNPP accident clean-up workers has progressively risen from an average of 1.3 in 1986 to 10.9 in 2007. This exceeds for the Latvian population when adjusted for age and sex. The most serious conditions affect the nervous, digestive, respiratory, cardiovascular, endocrine (especially thyroid) and immunological systems. While the morbidity associated with diseases of the respiratory and digestive systems has decreased in recent years that in the other systems is increasing. In recent years, there has been an increased occurrence of cancers affecting the thyroid, prostate and stomach. Clinical and laboratory investigations suggest that surviving CNPP accident clean-up workers exhibit signs of immuno-inflammatory reactions causing premature aging with evidence of autoimmune diseases and immunological deficiencies or abnormalities. It is suggested that the CNPP accident clean-up workers may have a specific syndrome, the 'Chernobyl post-radiation neurosomatic polypathy', due to sustained oxidant

Einstein Equations from Varying Complexity

NASA Astrophysics Data System (ADS)

Czech, Bartłomiej

2018-01-01

A recent proposal equates the circuit complexity of a quantum gravity state with the gravitational action of a certain patch of spacetime. Since Einstein's equations follow from varying the action, it should be possible to derive them by varying complexity. I present such a derivation for vacuum solutions of pure Einstein gravity in three-dimensional asymptotically anti-de Sitter space. The argument relies on known facts about holography and on properties of tensor network renormalization, an algorithm for coarse-graining (and optimizing) tensor networks.

Culture, attention, and emotion.

PubMed

Grossmann, Igor; Ellsworth, Phoebe C; Hong, Ying-yi

2012-02-01

This research provides experimental evidence for cultural influence on one of the most basic elements of emotional processing: attention to positive versus negative stimuli. To this end, we focused on Russian culture, which is characterized by brooding and melancholy. In Study 1, Russians spent significantly more time looking at negative than positive pictures, whereas Americans did not show this tendency. In Study 2, Russian Latvians were randomly primed with symbols of each culture, after which we measured the speed of recognition for positive versus negative trait words. Biculturals were significantly faster in recognizing negative words (as compared with baseline) when primed with Russian versus Latvian cultural symbols. Greater identification with Russian culture facilitated this effect. We provide a theoretical discussion of mental processes underlying cultural differences in emotion research.

Fractal analysis of time varying data

DOEpatents

Vo-Dinh, Tuan; Sadana, Ajit

2002-01-01

Characteristics of time varying data, such as an electrical signal, are analyzed by converting the data from a temporal domain into a spatial domain pattern. Fractal analysis is performed on the spatial domain pattern, thereby producing a fractal dimension D.sub.F. The fractal dimension indicates the regularity of the time varying data.

Evidenced Formal Coverage Index and universal healthcare enactment: A prospective longitudinal study of economic, social, and political predictors of 194 countries.

PubMed

Feigl, Andrea B; Ding, Eric L

2013-11-01

Determinants of universal healthcare (UHC) are poorly empirically understood. We undertook a comprehensive study of UHC development using a novel Evidenced Formal Coverage (EFC) index that combines three key UHC elements: legal framework, population coverage, and accessibility. Applying the EFC index measures (legislation, ≥90% skilled birth attendance, ≥85% formal coverage) to 194 countries, aggregating time-varying data from 1880-2008, this study investigates which macro-economic, political, and social indicators are major longitudinal predictors of developing EFC globally, and in middle-income countries. Overall, 75 of 194 countries implemented legal-text UHC legislation, of which 51 achieved EFC. In a country-year prospective longitudinal analysis of EFC prediction, higher GDP-per-capita (per GDP-per-capita doubling, relative risk [RR]=1.77, 95% CI: 1.49-2.10), higher primary school completion (per +20% completion, RR=2.30, 1.65-3.21), and higher adult literacy were significantly associated with achieving EFC. Results also identify a GDP-per-capita of I$5000 as a minimum level for development of EFC. GDP-per-capita and education were each robust predictors in middle-income countries, and education remained significant even controlling for time-varying GDP growth. For income-inequality, the GINI coefficient was suggestive in its role in predicting EFC (p=0.024). For social and political indicators, a greater degree of ethnic fractionalization (per +25%, RR=0.51, 0.38-0.70), proportional electoral system (RR=2.80, 1.22-6.40), and dictatorships (RR=0.10, 0.05-0.27) were further associated with EFC. The novel EFC index and this longitudinal prospective study together indicate that investment in both economic growth and education should be seen of equal importance for development of UHC. Our findings help in understanding the social and political drivers of universal healthcare, especially for transitioning countries. Copyright © 2013 Elsevier Ireland Ltd. All

Rationale and design of the balANZ trial: a randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function.

PubMed

Johnson, David W; Clarke, Margaret; Wilson, Vanessa; Woods, Feidhlim; Brown, Fiona G

2010-09-16

The main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate. Inclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance) or conventional dialysis solution (Stay.safe) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial. This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients. Australian New Zealand Clinical Trials Registry Number: ACTRN12606000044527.

Rationale and design of the balANZ trial: A randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function

PubMed Central

2010-01-01

Background The main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate. Methods/Design Inclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance®) or conventional dialysis solution (Stay.safe®) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial. Discussion This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients. Trial Registration Australian New Zealand Clinical Trials Registry Number: ACTRN12606000044527 PMID:20843375

Design of 2D time-varying vector fields.

PubMed

Chen, Guoning; Kwatra, Vivek; Wei, Li-Yi; Hansen, Charles D; Zhang, Eugene

2012-10-01

Design of time-varying vector fields, i.e., vector fields that can change over time, has a wide variety of important applications in computer graphics. Existing vector field design techniques do not address time-varying vector fields. In this paper, we present a framework for the design of time-varying vector fields, both for planar domains as well as manifold surfaces. Our system supports the creation and modification of various time-varying vector fields with desired spatial and temporal characteristics through several design metaphors, including streamlines, pathlines, singularity paths, and bifurcations. These design metaphors are integrated into an element-based design to generate the time-varying vector fields via a sequence of basis field summations or spatial constrained optimizations at the sampled times. The key-frame design and field deformation are also introduced to support other user design scenarios. Accordingly, a spatial-temporal constrained optimization and the time-varying transformation are employed to generate the desired fields for these two design scenarios, respectively. We apply the time-varying vector fields generated using our design system to a number of important computer graphics applications that require controllable dynamic effects, such as evolving surface appearance, dynamic scene design, steerable crowd movement, and painterly animation. Many of these are difficult or impossible to achieve via prior simulation-based methods. In these applications, the time-varying vector fields have been applied as either orientation fields or advection fields to control the instantaneous appearance or evolving trajectories of the dynamic effects.

Comprehending idioms cross-linguistically.

PubMed

Bortfeld, Heather

2003-01-01

Speakers of three different languages (English, Latvian, and Mandarin) rated sets of idioms from their language for the analyzability of the relationship between each phrase's literal and figurative meaning. For each language, subsets of idioms were selected based on these ratings. Latvian and Mandarin idioms were literally translated into English. Across three experiments, people classified idioms from the three languages according to their figurative meanings. Response times and error rates indicate that participants were able to interpret unfamiliar (e.g., other languages') idioms depending largely on the degree to which they were analyzable, and that different forms of processing were used both within and between languages depending on this analyzability. Results support arguments for a continuum of analyzability (Bortfeld & McGlone, 2001), along which figurative speech ranges from reflecting general conceptual structures to specific cultural and historical references.

Psychological variables underlying political orientations in an old and a new democracy: A comparative study between Sweden and Latvia.

PubMed

Dimdins, Girts; Sandgren, Maria; Montgomery, Henry

2016-10-01

This study examines in detail the psychological variables underlying ideological political orientation, and structure and contents of this orientation, in Sweden and Latvia. Individual political orientation is conceptualized on two dimensions: acceptance vs. rejection of social change and acceptance vs. rejection of inequality. Swedish (N = 320) and Latvian (N = 264) participants completed measures of political orientation, Social Dominance Orientation (SDO), Right Wing Authoritarianism (RWA), self vs. other orientation, tolerance for ambiguity, humanism and normativism, core political values, system justification, as well as moral foundations questionnaire and portrait values questionnaire. The results showed that the relation among the measured variables was similar in both samples. Swedish participants showed stronger endorsement of egalitarian attitudes and social values, whereas we found more self-enhancing and socially conservative values and attitudes among the Latvian participants. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Genome mining of the sordarin biosynthetic gene cluster from Sordaria araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and GDP-6-deoxyaltrose transferase.

PubMed

Kudo, Fumitaka; Matsuura, Yasunori; Hayashi, Takaaki; Fukushima, Masayuki; Eguchi, Tadashi

2016-07-01

Sordarin is a glycoside antibiotic with a unique tetracyclic diterpene aglycone structure called sordaricin. To understand its intriguing biosynthetic pathway that may include a Diels-Alder-type [4+2]cycloaddition, genome mining of the gene cluster from the draft genome sequence of the producer strain, Sordaria araneosa Cain ATCC 36386, was carried out. A contiguous 67 kb gene cluster consisting of 20 open reading frames encoding a putative diterpene cyclase, a glycosyltransferase, a type I polyketide synthase, and six cytochrome P450 monooxygenases were identified. In vitro enzymatic analysis of the putative diterpene cyclase SdnA showed that it catalyzes the transformation of geranylgeranyl diphosphate to cycloaraneosene, a known biosynthetic intermediate of sordarin. Furthermore, a putative glycosyltransferase SdnJ was found to catalyze the glycosylation of sordaricin in the presence of GDP-6-deoxy-d-altrose to give 4'-O-demethylsordarin. These results suggest that the identified sdn gene cluster is responsible for the biosynthesis of sordarin. Based on the isolated potential biosynthetic intermediates and bioinformatics analysis, a plausible biosynthetic pathway for sordarin is proposed.

Time varying voltage combustion control and diagnostics sensor

DOEpatents

Chorpening, Benjamin T [Morgantown, WV; Thornton, Jimmy D [Morgantown, WV; Huckaby, E David [Morgantown, WV; Fincham, William [Fairmont, WV

2011-04-19

A time-varying voltage is applied to an electrode, or a pair of electrodes, of a sensor installed in a fuel nozzle disposed adjacent the combustion zone of a continuous combustion system, such as of the gas turbine engine type. The time-varying voltage induces a time-varying current in the flame which is measured and used to determine flame capacitance using AC electrical circuit analysis. Flame capacitance is used to accurately determine the position of the flame from the sensor and the fuel/air ratio. The fuel and/or air flow rate (s) is/are then adjusted to provide reduced flame instability problems such as flashback, combustion dynamics and lean blowout, as well as reduced emissions. The time-varying voltage may be an alternating voltage and the time-varying current may be an alternating current.

Novel shock absorber features varying yield strengths

NASA Technical Reports Server (NTRS)

Geier, D. J.

1964-01-01

A shock absorbent webbing of partially drawn synthetic strands is arranged in sections of varying density related to the varying mass of the human body. This is contoured to protect the body at points of contact, when subjected to large acceleration or deceleration forces.

Transferability of results of cost utility analyses for biologicals in inflammatory conditions for Central and Eastern European countries.

PubMed

Gulácsi, László; Rencz, Fanni; Péntek, Márta; Brodszky, Valentin; Lopert, Ruth; Hevér, Noémi V; Baji, Petra

2014-05-01

Several Central and Eastern European (CEE) countries require cost-utility analyses (CUAs) to support reimbursement formulary listing. However, CUAs informed by local evidence are often unavailable, and the cost-effectiveness of the several currently reimbursed biologicals is unclear. To estimate the cost-effectiveness as multiples of per capita GDP/quality adjusted life years (QALY) of four biologicals (infliximab, etanercept, adalimumab, golimumab) currently reimbursed in six CEE countries in six inflammatory rheumatoid and bowel disease conditions. Systematic literature review of published cost-utility analyses in the selected conditions, using the United Kingdom (UK) as reference country and with study selection criteria set to optimize the transfer of results to the CEEs. Prices in each CEE country were pro-rated against UK prices using purchasing power parity (PPP)-adjusted per capita GDP, and local GDP per capita/QALY ratios estimated. Central and Eastern European countries list prices were 144-333% higher than pro rata prices. Out of 85 CUAs identified by previous systematic literature reviews, 15 were selected as a convenience sample for estimating the cost-effectiveness of biologicals in the CEE countries in terms of per capita GDP/QALY. Per capita GDP/QALY values varied from 0.42 to 6.4 across countries and conditions (Bulgaria: 0.97-6.38; Czech Republic: 0.42-2.76; Hungary: 0.54-3.54; Poland: 0.59-3.90; Romania: 0.77-5.07; Slovakia: 0.55-3.61). While results must be interpreted with caution, calculating pro rata (cost-effective) prices and per capita GDP/QALY ratios based on CUAs can aid reimbursement decision-making in the absence of analyses using local data.

Estimating varying coefficients for partial differential equation models.

PubMed

Zhang, Xinyu; Cao, Jiguo; Carroll, Raymond J

2017-09-01

Partial differential equations (PDEs) are used to model complex dynamical systems in multiple dimensions, and their parameters often have important scientific interpretations. In some applications, PDE parameters are not constant but can change depending on the values of covariates, a feature that we call varying coefficients. We propose a parameter cascading method to estimate varying coefficients in PDE models from noisy data. Our estimates of the varying coefficients are shown to be consistent and asymptotically normally distributed. The performance of our method is evaluated by a simulation study and by an empirical study estimating three varying coefficients in a PDE model arising from LIDAR data. © 2017, The International Biometric Society.

Surrogate markers for time-varying treatments and outcomes

PubMed Central

Hsu, Jesse Y; Kennedy, Edward H; Roy, Jason A; Stephens-Shields, Alisa J; Small, Dylan S; Joffe, Marshall M

2015-01-01

Background A surrogate marker is a variable commonly used in clinical trials to guide treatment decisions when the outcome of ultimate interest is not available. A good surrogate marker is one where the treatment effect on the surrogate is a strong predictor of the effect of treatment on the outcome. We review the situation when there is one treatment delivered at baseline, one surrogate measured at one later time point and one ultimate outcome of interest, and discuss new issues arising when variables are time-varying. Methods Most of the literature on surrogate markers has only considered simple settings with one treatment, one surrogate, and one outcome of interest at a fixed time point. However, more complicated time-varying settings are common in practice. In this paper, we describe the unique challenges in two settings, time-varying treatments and time-varying surrogates, while relating the ideas back to the causal-effects and causal-association paradigms. Conclusions In addition to discussing and extending popular notions of surrogacy to time-varying settings, we give examples illustrating that one can be misled by not taking into account time-varying information about the surrogate or treatment. We hope this paper has provided some motivation for future work on estimation and inference in such settings. PMID:25948621

Living in Latvia after stroke: the association between functional, social and personal factors and the level of self-perceived disability-a cross-sectional study.

PubMed

Bērziņa, Guna; Smilškalne, Baiba; Vētra, Anita; Sunnerhagen, Katharina S

2016-06-24

To investigate how functional, social and personal factors are associated with self-perceived level of disability in the chronic phase of stroke in a Latvian stroke population. The consequences of stroke can vary greatly and often leads to long-term disability that, according to the WHO definitions, depends on the interaction between the person and his/her context. Cross-sectional study with retrospective data gathering. Community-dwelling persons who received specialised in-patient rehabilitation after stroke in Latvia. Of 600 persons after stroke who were identified through hospital register and selected for the study, 255 were included in the analysis. The medical information and discharge data of the Functional Independence Measure (FIM) was extracted from medical records. Participants filled out a questionnaire on sociodemographic information and the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), either in Latvian or Russian, depending on their wish when contacted for their oral agreement to participate. Stepwise multiple regression analysis was conducted to find a model that best explains the variance in WHODAS 2.0 scores. The models explained 23-43.5% of variance in outcomes. The best explained WHODAS 2.0 domains were 'mobility' and 'self-care'. The significant factors were level of independence in 'self-care', 'locomotion' and 'communication' according to FIM, as well as working status, time since rehabilitation, age, gender, living alone or in family and preferred language. Functional, social and personal factors are of similar importance when explaining self-perceived disability in the chronic phase of stroke. Some, but not all, of the factors are modifiable by the healthcare system. Therefore, a complex approach and involvement of medical, social and political systems is needed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Learning Time-Varying Coverage Functions

PubMed Central

Du, Nan; Liang, Yingyu; Balcan, Maria-Florina; Song, Le

2015-01-01

Coverage functions are an important class of discrete functions that capture the law of diminishing returns arising naturally from applications in social network analysis, machine learning, and algorithmic game theory. In this paper, we propose a new problem of learning time-varying coverage functions, and develop a novel parametrization of these functions using random features. Based on the connection between time-varying coverage functions and counting processes, we also propose an efficient parameter learning algorithm based on likelihood maximization, and provide a sample complexity analysis. We applied our algorithm to the influence function estimation problem in information diffusion in social networks, and show that with few assumptions about the diffusion processes, our algorithm is able to estimate influence significantly more accurately than existing approaches on both synthetic and real world data. PMID:25960624

Learning Time-Varying Coverage Functions.

PubMed

Du, Nan; Liang, Yingyu; Balcan, Maria-Florina; Song, Le

2014-12-08

Coverage functions are an important class of discrete functions that capture the law of diminishing returns arising naturally from applications in social network analysis, machine learning, and algorithmic game theory. In this paper, we propose a new problem of learning time-varying coverage functions, and develop a novel parametrization of these functions using random features. Based on the connection between time-varying coverage functions and counting processes, we also propose an efficient parameter learning algorithm based on likelihood maximization, and provide a sample complexity analysis. We applied our algorithm to the influence function estimation problem in information diffusion in social networks, and show that with few assumptions about the diffusion processes, our algorithm is able to estimate influence significantly more accurately than existing approaches on both synthetic and real world data.

Generalized semiparametric varying-coefficient models for longitudinal data

NASA Astrophysics Data System (ADS)

Qi, Li

In this dissertation, we investigate the generalized semiparametric varying-coefficient models for longitudinal data that can flexibly model three types of covariate effects: time-constant effects, time-varying effects, and covariate-varying effects, i.e., the covariate effects that depend on other possibly time-dependent exposure variables. First, we consider the model that assumes the time-varying effects are unspecified functions of time while the covariate-varying effects are parametric functions of an exposure variable specified up to a finite number of unknown parameters. The estimation procedures are developed using multivariate local linear smoothing and generalized weighted least squares estimation techniques. The asymptotic properties of the proposed estimators are established. The simulation studies show that the proposed methods have satisfactory finite sample performance. ACTG 244 clinical trial of HIV infected patients are applied to examine the effects of antiretroviral treatment switching before and after HIV developing the 215-mutation. Our analysis shows benefit of treatment switching before developing the 215-mutation. The proposed methods are also applied to the STEP study with MITT cases showing that they have broad applications in medical research.

Synchronized state of coupled dynamics on time-varying networks.

PubMed

Amritkar, R E; Hu, Chin-Kun

2006-03-01

We consider synchronization properties of coupled dynamics on time-varying networks and the corresponding time-average network. We find that if the different Laplacians corresponding to the time-varying networks commute with each other then the stability of the synchronized state for both the time-varying and the time-average topologies are approximately the same. On the other hand for noncommuting Laplacians the stability of the synchronized state for the time-varying topology is in general better than the time-average topology.

Housing Quality and Access to Material and Learning Resources within the Home Environment in Developing Countries

PubMed Central

Bradley, Robert H.; Putnick, Diane L.

2011-01-01

This study examined home environment conditions (housing quality, material resources, formal and informal learning materials) and their relations with the Human Development Index (HDI) in 28 developing countries. Home environment conditions in these countries varied widely. The quality of housing and availability of material resources at home were consistently tied to HDI; the availability of formal and informal learning materials little less so. Gross domestic product (GDP) tended to show a stronger independent relation with housing quality and material resources than life expectancy and education. Formal learning resources were independently related to the GDP and education indices, and informal learning resources were not independently related to any constituent indices of the overall HDI. PMID:22277008

X-linked Inhibitor of Apoptosis Protein (XIAP) Mediates Cancer Cell Motility via Rho GDP Dissociation Inhibitor (RhoGDI)-dependent Regulation of the Cytoskeleton*

PubMed Central

Liu, Jinyi; Zhang, Dongyun; Luo, Wenjing; Yu, Yonghui; Yu, Jianxiu; Li, Jingxia; Zhang, Xinhai; Zhang, Baolin; Chen, Jingyuan; Wu, Xue-Ru; Rosas-Acosta, Germán; Huang, Chuanshu

2011-01-01

X-linked inhibitor of apoptosis protein (XIAP) overexpression has been found to be associated with malignant cancer progression and aggression in individuals with many types of cancers. However, the molecular basis of XIAP in the regulation of cancer cell biological behavior remains largely unknown. In this study, we found that a deficiency of XIAP expression in human cancer cells by either knock-out or knockdown leads to a marked reduction in β-actin polymerization and cytoskeleton formation. Consistently, cell migration and invasion were also decreased in XIAP-deficient cells compared with parental wild-type cells. Subsequent studies demonstrated that the regulation of cell motility by XIAP depends on its interaction with the Rho GDP dissociation inhibitor (RhoGDI) via the XIAP RING domain. Furthermore, XIAP was found to negatively regulate RhoGDI SUMOylation, which might affect its activity in controlling cell motility. Collectively, our studies provide novel insights into the molecular mechanisms by which XIAP regulates cancer invasion and offer a further theoretical basis for setting XIAP as a potential prognostic marker and specific target for treatment of cancers with metastatic properties. PMID:21402697

Mediation analysis with time varying exposures and mediators.

PubMed

VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

2017-06-01

In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

Mediation analysis with time varying exposures and mediators

PubMed Central

VanderWeele, Tyler J.; Tchetgen Tchetgen, Eric J.

2016-01-01

Summary In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the “mediational g-formula.” When there is no mediation, the mediational g-formula reduces to Robins’ regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl’s mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators. PMID:28824285

Facial attractiveness is related to women's cortisol and body fat, but not with immune responsiveness.

PubMed

Rantala, Markus J; Coetzee, Vinet; Moore, Fhionna R; Skrinda, Ilona; Kecko, Sanita; Krama, Tatjana; Kivleniece, Inese; Krams, Indrikis

2013-08-23

Recent studies suggest that facial attractiveness indicates immune responsiveness in men and that this relationship is moderated by stress hormones which interact with testosterone levels. However, studies testing whether facial attractiveness in women signals their immune responsiveness are lacking. Here, we photographed young Latvian women, vaccinated them against hepatitis B and measured the amount of specific antibodies produced, cortisol levels and percentage body fat. Latvian men rated the attractiveness of the women's faces. Interestingly, in women, immune responsiveness (amount of antibodies produced) did not predict facial attractiveness. Instead, plasma cortisol level was negatively associated with attractiveness, indicating that stressed women look less attractive. Fat percentage was curvilinearly associated with facial attractiveness, indicating that being too thin or too fat reduces attractiveness. Our study suggests that in contrast to men, facial attractiveness in women does not indicate immune responsiveness against hepatitis B, but is associated with two other aspects of long-term health and fertility: circulating levels of the stress hormone cortisol and percentage body fat.

Dynamic Factor Analysis Models with Time-Varying Parameters

ERIC Educational Resources Information Center

Chow, Sy-Miin; Zu, Jiyun; Shifren, Kim; Zhang, Guangjian

2011-01-01

Dynamic factor analysis models with time-varying parameters offer a valuable tool for evaluating multivariate time series data with time-varying dynamics and/or measurement properties. We use the Dynamic Model of Activation proposed by Zautra and colleagues (Zautra, Potter, & Reich, 1997) as a motivating example to construct a dynamic factor…

The Varied Roles of Notch in Cancer

PubMed Central

Aster, Jon C.; Pear, Warren S.; Blacklow, Stephen C.

2018-01-01

Notch receptors influence cellular behavior by participating in a seemingly simple signaling pathway, but outcomes produced by Notch signaling are remarkably varied depending on signal dose and cell context. Here, after briefly reviewing new insights into physiologic mechanisms of Notch signaling in healthy tissues and defects in Notch signaling that contribute to congenital disorders and viral infection, we discuss the varied roles of Notch in cancer, focusing on cell autonomous activities that may be either oncogenic or tumor suppressive. PMID:27959635

Proceedings of the Annual Meeting of the Association for Education in Journalism and Mass Communication (76th, Kansas City, Missouri, August 11-14, l993). Part XII: Foreign and International Media.

ERIC Educational Resources Information Center

Association for Education in Journalism and Mass Communication.

The Foreign and International Media section of this collection of conference presentations contains the following 27 papers: "Cultural Orientation in Turkey: Are The Theorists Right about the Effects of Imported Cultural Products?" (Christine Ogan); "The Role of Mass Media in a Newly Emerging Democracy: The Latvian Case Study"…

Hot and Cold Ethnicities in the Baltic States

ERIC Educational Resources Information Center

Ehala, Martin; Zabrodskaja, Anastassia

2014-01-01

The article discusses the temperatures of the main ethnic groups in the Baltic states: Estonians, Latvians, Lithuanians, and their three Russian-speaking communities, and the Latgalian and Polish minority groups in Latvia and Lithuania, respectively. The study uses a triangulated methodology that includes a survey questionnaire for quantitative…

"Most Learn Almost Nothing": Building Democratic Citizenship by Engaging Controversial History through Inquiry in Post-Communist Europe

ERIC Educational Resources Information Center

Misco, Thomas

2011-01-01

This article addresses the challenges and pathways of Holocaust education in post-communist countries through two case studies. I first examine historiographical, institutional and cultural obstacles to deep and meaningful treatments of the Holocaust within Latvian and Romanian schools. Drawing upon the unique experiences both countries had with…

Enzymatic synthesis and characterizations of cyclic GDP-ribose. A procedure for distinguishing enzymes with ADP-ribosyl cyclase activity.

PubMed

Graeff, R M; Walseth, T F; Fryxell, K; Branton, W D; Lee, H C

1994-12-02

Cyclic nucleotides such as cAMP and cGMP are second messengers subserving various signaling pathways. Cyclic ADP-ribose (cADPR), a recently discovered member of the family, is derived from NAD+ and is a mediator of Ca2+ mobilization in various cellular systems. The synthesis and degradation of cADPR are, respectively, catalyzed by ADP-ribosyl cyclase and cADPR hydrolase. CD38, a differentiation antigen of B lymphocytes, has recently been shown to be a bifunctional enzyme catalyzing both the formation and hydrolysis of cADPR. The overall reaction catalyzed by CD38 is the formation of ADP-ribose and nicotinamide from NAD+, identical to that catalyzed by NADase. The difficulties in detecting the formation of cADPR have led to frequent identification of CD38 as a classical NADase. In this study, we show that both ADP-ribosyl cyclase and CD38, but not NADase, can cyclize nicotinamide guanine dinucleotide (NGD+) producing a new nucleotide. Analyses by high performance liquid chromatography and mass spectroscopy indicate the product is cyclic GDP-ribose (cGDPR) with a structure similar to cADPR except with guanine replacing adenine. Compared to cADPR, cGDPR is a more stable compound showing 2.8 times more resistance to heat-induced hydrolysis. These results are consistent with a catalytic scheme for CD38 where the cyclization of the substrate precedes the hydrolytic reaction. Spectroscopic analyses show that cGDPR is fluorescent and has an absorption spectrum different from both NGD+ and GDPR, providing a very convenient way for monitoring its enzymatic formation. The use of NGD+ as substrate for assaying the cyclization reaction was found to be applicable to pure enzymes as well as crude tissue extracts making it a useful diagnostic tool for distinguishing CD38-like enzymes from degradative NADases.

Time-varying value of electric energy efficiency

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

Mims, Natalie A.; Eckman, Tom; Goldman, Charles

Electric energy efficiency resources save energy and may reduce peak demand. Historically, quantification of energy efficiency benefits has largely focused on the economic value of energy savings during the first year and lifetime of the installed measures. Due in part to the lack of publicly available research on end-use load shapes (i.e., the hourly or seasonal timing of electricity savings) and energy savings shapes, consideration of the impact of energy efficiency on peak demand reduction (i.e., capacity savings) has been more limited. End-use load research and the hourly valuation of efficiency savings are used for a variety of electricity planningmore » functions, including load forecasting, demand-side management and evaluation, capacity and demand response planning, long-term resource planning, renewable energy integration, assessing potential grid modernization investments, establishing rates and pricing, and customer service. This study reviews existing literature on the time-varying value of energy efficiency savings, provides examples in four geographically diverse locations of how consideration of the time-varying value of efficiency savings impacts the calculation of power system benefits, and identifies future research needs to enhance the consideration of the time-varying value of energy efficiency in cost-effectiveness screening analysis. Findings from this study include: -The time-varying value of individual energy efficiency measures varies across the locations studied because of the physical and operational characteristics of the individual utility system (e.g., summer or winter peaking, load factor, reserve margin) as well as the time periods during which savings from measures occur. -Across the four locations studied, some of the largest capacity benefits from energy efficiency are derived from the deferral of transmission and distribution system infrastructure upgrades. However, the deferred cost of such upgrades also exhibited the greatest

Enhancing ascorbate in fruits and tubers through over-expression of the L-galactose pathway gene GDP-L-galactose phosphorylase.

PubMed

Bulley, Sean; Wright, Michele; Rommens, Caius; Yan, Hua; Rassam, Maysoon; Lin-Wang, Kui; Andre, Christelle; Brewster, Di; Karunairetnam, Sakuntala; Allan, Andrew C; Laing, William A

2012-05-01

Ascorbate, or vitamin C, is obtained by humans mostly from plant sources. Various approaches have been made to increase ascorbate in plants by transgenic means. Most of these attempts have involved leaf material from model plants, with little success reported using genes from the generally accepted l-galactose pathway of ascorbate biosynthesis. We focused on increasing ascorbate in commercially significant edible plant organs using a gene, GDP-l-galactose phosphorylase (GGP or VTC2), that we had previously shown to increase ascorbate concentration in tobacco and Arabidopsis thaliana. The coding sequence of Actinidia chinensis GGP, under the control of the 35S promoter, was expressed in tomato and strawberry. Potato was transformed with potato or Arabidopsis GGP genes under the control of the 35S promoter or a polyubiquitin promoter (potato only). Five lines of tomato, up to nine lines of potato, and eight lines of strawberry were regenerated for each construct. Three lines of tomato had a threefold to sixfold increase in fruit ascorbate, and all lines of strawberry showed a twofold increase. All but one line of each potato construct also showed an increase in tuber ascorbate of up to threefold. Interestingly, in tomato fruit, increased ascorbate was associated with loss of seed and the jelly of locular tissue surrounding the seed which was not seen in strawberry. In both strawberry and tomato, an increase in polyphenolic content was associated with increased ascorbate. These results show that GGP can be used to raise significantly ascorbate concentration in commercially significant edible crops. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

Definitions of climate and climate change under varying external conditions

NASA Astrophysics Data System (ADS)

Werndl, C.

2014-06-01

Commonly, definitions of climate are endorsed where the external conditions are held constant. This paper argues that these definitions risk being empirically void because in reality the external conditions vary. As a consequence, analogous definitions for varying external conditions are explored with help of the recently developed theory of non-autonomous dynamical systems, and the similarities and differences between the cases of constant and varying external conditions are discussed. It is argued that there are analogous definitions for varying external conditions which are preferable to the definitions where the external conditions are held constant. In this context, a novel definition is proposed (namely, climate as the distribution over time under a regime of varying external conditions), which is argued to be promising.

The application of headspace gas chromatography coupled to tandem quadrupole mass spectrometry for the analysis of furan in baby food samples.

PubMed

Pugajeva, Iveta; Rozentale, Irina; Viksna, Arturs; Bartkiene, Elena; Bartkevics, Vadims

2016-12-01

Selective methodology employing a tandem quadrupole mass spectrometer coupled to a gas chromatograph with headspace autosampler (HS-GC-MS/MS) was elaborated in this study. Application of the elaborated procedure resulted in a limit of detection of 0.021μgkg(-1) and a limit of quantification of 0.071μgkg(-1). The mean recoveries during in-house validation ranged from 89% to 109%, and coefficients of variation for repeatability ranged from 4% to 11%. The proposed analytical method was applied for monitoring the furan content of 30 commercial baby food samples available on the Latvian retail market. The level of furan found in these samples varied from 0.45 to 81.9μgkg(-1), indicating that infants whose sole diet comprises baby food sold in jars and cans are exposed constantly to furan. Samples containing vegetables and meat had higher levels of furan than those containing only fruits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Specimen loading list for the varying temperature experiment

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

Qualls, A.L.; Sitterson, R.G.

1998-09-01

The varying temperature experiment HFIR-RB-13J has been assembled and inserted in the reactor. Approximately 5300 specimens were cleaned, inspected, matched, and loaded into four specimen holders. A listing of each specimen loaded into the steady temperature holder, its position in the capsule, and the identification of the corresponding specimen loaded into the varying temperature holder is presented in this report.

Economic level and human longevity: Spatial and temporal variations and correlation analysis of per capita GDP and longevity indicators in China.

PubMed

Wang, Shaobin; Luo, Kunli; Liu, Yonglin; Zhang, Shixi; Lin, Xiaoxu; Ni, Runxiang; Tian, Xinglei; Gao, Xing

2015-01-01

We show the variation of longevity indicators in China during the past 60 years and its correlation patterns with per capita GDP (GDPpc) both at provincial and inner-provincial level. Population data from six national population censuses in China (1953-2010) at provincial level and in several typical provinces in 2010 at county-level were selected. Four main longevity indicators were calculated. Pearson's r and distributed lags time series analysis between longevity indicators and GDPpc were conducted. The results show that Guangxi and Hainan Provinces maintain relatively high long-lived population (population over the age of 90) across various population censuses. The distributions of the population over the age of 80 and life expectancy are significantly affected by both contemporaneous and historical GDPpc at provincial level. However, areas of high long-lived population (over the age of 90) exhibit continuously stable features that lack any significant correlation with GDPpc both at provincial and inner-provincial level. Our results indicate a mixed distribution pattern of several longevity indexes and different relation to GDPpc. It shows consistent trend with Preston curve, that is, economic conditions may have limited influence on human longevity, especially for those who live longer than 90 years old. This study suggests that the economic development may favor the local residents to have access to live as old as 80 years old, but it is still difficult for most residents to reach the level of centenarians. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of Authoritarianism on the Teaching of National History: The Case of Latvia

ERIC Educational Resources Information Center

Abens, Aija

2015-01-01

Recent research on history teaching has begun to focus on political motivation. This paper is the result of the author's dissertation, which investigates Latvian history teaching under the authoritarian regimes of Ulmanis and Stalin. It reveals the effects of authoritarianism on goals, curriculum, teaching materials and methods, and the teacher's…

Modernisation of Vocational Education and Training in Latvia. National Observatory Country Report, 1999.

ERIC Educational Resources Information Center

Latvian National Observatory, Riga.

The Latvian economy has undergone major changes during transition to a market economy after regaining independence in 1991. The unfavorable world economic situation has caused its growth to fall below potential. The vocational education and training (VET) system has traditionally been school-based. There are 120 VET institutions with a large…

Civic Education for Democracy in Latvia: The Program of the Democracy Advancement Center. ERIC Digest.

ERIC Educational Resources Information Center

Catlaks, Guntars; Sarma, Valts

In May 1990, the Republic of Latvia declared the restoration of its independence from the Soviet Union. After that declaration, many Latvians began to reform their schools' curricula and teaching methods. They replaced Soviet-era citizenship courses with new teaching materials and methods appropriate for educating the young citizens of a…

Technology and Culture in Modern Russia

DTIC Science & Technology

2007-12-01

the altered spelling of Estonia: “eSStonia” makes a reference to the Nazi Waffen SS units of World War II, effectively accusing Estonia of fascism...Russian-speaking population on their territory. Any discussion of honoring the Latvian Legion, a World War II Nazi Waffen SS unit in which tens of

Family Collectivism and Minority Languages as Core Values of Culture among Ethnic Groups in Australia.

ERIC Educational Resources Information Center

Smolicz, Jerzy J.; Secombe, Margaret J.; Hudson, Dorothy M.

2001-01-01

Investigates the relative significance of family collectivism and minority languages as possible core values among four ethnic groups in the context of Australian society in which the English language and social structures of the majority group are dominant. Respondents were young adults drawn from Greek, Latvian, Italian, and Chinese-Australian…

Microwave fidelity studies by varying antenna coupling

NASA Astrophysics Data System (ADS)

Köber, B.; Kuhl, U.; Stöckmann, H.-J.; Gorin, T.; Savin, D. V.; Seligman, T. H.

2010-09-01

The fidelity decay in a microwave billiard is considered, where the coupling to an attached antenna is varied. The resulting quantity, coupling fidelity, is experimentally studied for three different terminators of the varied antenna: a hard-wall reflection, an open wall reflection, and a 50Ω load, corresponding to a totally open channel. The model description in terms of an effective Hamiltonian with a complex coupling constant is given. Quantitative agreement is found with the theory obtained from a modified VWZ approach [J. J. M. Verbaarschot , Phys. Rep. 129, 367 (1985)10.1016/0370-1573(85)90070-5].

Elliptical varied line-space (EVLS) gratings

NASA Astrophysics Data System (ADS)

Thomas, Roger J.

2004-10-01

Imaging spectroscopy at wavelengths below 2000 Å offers an especially powerful method for studying many extended high-temperature astronomical objects, like the Sun and its outer layers. But the technology to make such measurements is also especially challenging, because of the poor reflectance of all standard materials at these wavelengths, and because the observation must be made from above the absorbing effects of the Earth's atmosphere. To solve these problems, single-reflection stigmatic spectrographs for XUV wavelengths have bee flown on several space missions based on designs with toroidal uniform line-space (TULS) or spherical varied line-space (SVLS) gratings that operate at near normal-incidence. More recently, three solar EUV/UV instruments have been selected that use toroidal varied line-space (TVLS) gratings; these are SUMI and RAISE, both sounding rocket payloads, and NEXUS, a SMEX satellite-mission. The next logical extension to such designs is the use of elliptical surfaces for varied line-space (EVLS) rulings. In fact, EVLS designs are found to provide superior imaging even at very large spectrograph magnifications and beam-speeds, permitting extremely high-quality performance in remarkably compact instrument packages. In some cases, such designs may be optimized even further by using a hyperbolic surface for the feeding telescope. The optical characteristics of two solar EUV spectrometers based on these concepts are described: EUS and EUI, both being developed as possible instruments for ESA's Solar Orbiter mission by consortia led by RAL and by MSSL, respectively.

The Frustrations of Reader Generalizability and Grounded Theory: Alternative Considerations for Transferability

ERIC Educational Resources Information Center

Misco, Thomas

2007-01-01

In this paper I convey a recurring problem and possible solution that arose during my doctoral research on the topic of cross-cultural Holocaust curriculum development for Latvian schools. Specifically, as I devised the methodology for my research, I experienced a number of frustrations concerning the issue of transferability and the limitations…

Primary School Teachers' Views on a Holistic Approach to Facilitating the Acquisition of Musical Cultural Values

ERIC Educational Resources Information Center

Badjanova, Jelena

2013-01-01

Recent tendencies in education highlight the need to align the system of general education in Latvia with the tenets of sustainability. In keeping with this broad target orientation, this paper re-examines international and Latvian experiences and perspectives on the application of a holistic approach to the content of primary education. This…

Agricultural growth, the status of women, and fertility.

PubMed

Whittington, L A; Stapleton, D C

1995-08-01

This study tests the hypothesis that fertility is affected differently by economic growth depending upon the specific sector (agriculture, manufacturing, heavy industry, and services) where growth occurred. The hypothesis is that fertility responses are not identical across sectors. The sample includes 51 World Bank member countries in varying stages of development. The econometric model pertains to 1965-88 and the percentage change in the total fertility rate (TFR). During the study period the average TFR declined by over 22%, but the extent of change varied by country and included, for instance, countries such as Ethiopia that experienced fertility increases from 5.8 to 6.5. Hong Kong's TFR declined by 66% from 4.7 to 1.6. Analysis included measures of changes in gross domestic product (GDP) for each of the four sectors and change in real per capita exports in agricultural commodities, resources, and manufactured products. Changes in educational status and changes in infant mortality were also included in some models. There were mixed results for the impact of total GDP. Sectoral analysis shows a positive, small significant impact on TFR from changes in the GDP per capita in agriculture (domestic and export products), and a negative, small significant impact from manufacturing growth. Heavy industry and services produced insignificant impact. In the model with only domestic consumption, results show a stronger coefficient and continued significance for agricultural productivity, agricultural exports, and manufacturing changes per capita. Manufacturing exports produced a negative, insignificant impact. The null hypothesis is rejected only in models comparing aggregate GDP in agriculture and manufacturing industries plus control variables (excluding heavy industry and services). Only secondary education was a negative, significant determinant of fertility. Infant mortality was insignificant when sectoral growth and education were included in the model. The evidence

Genetic polymorphisms in varied environments.

PubMed

Powell, J R

1971-12-03

Thirteen experimenital populationis of Drosophila willistoni were maintained in cages, in some of which the environments were relatively constant and in others varied. After 45 weeks, the populations were assayed by gel electrophoresis for polymorphisms at 22 protein loci. The average heterozygosity per individual and the average unmber of alleles per locus were higher in populations maintained in heterogeneous environments than in populations in more constant enviroments.

Varying potential silicon carbide gas sensor

NASA Technical Reports Server (NTRS)

Shields, Virgil B. (Inventor); Ryan, Margaret A. (Inventor); Williams, Roger M. (Inventor)

1997-01-01

A hydrocarbon gas detection device operates by dissociating or electro-chemically oxidizing hydrocarbons adsorbed to a silicon carbide detection layer. Dissociation or oxidation are driven by a varying potential applied to the detection layer. Different hydrocarbon species undergo reaction at different applied potentials so that the device is able to discriminate among various hydrocarbon species. The device can operate at temperatures between 100.degree. C. and at least 650.degree. C., allowing hydrocarbon detection in hot exhaust gases. The dissociation reaction is detected either as a change in a capacitor or, preferably, as a change of current flow through an FET which incorporates the silicon carbide detection layers. The silicon carbide detection layer can be augmented with a pad of catalytic material which provides a signal without an applied potential. Comparisons between the catalytically produced signal and the varying potential produced signal may further help identify the hydrocarbon present.

Housing quality and access to material and learning resources within the home environment in developing countries.

PubMed

Bradley, Robert H; Putnick, Diane L

2012-01-01

This study examined home environment conditions (housing quality, material resources, formal and informal learning materials) and their relations with the Human Development Index (HDI) in 28 developing countries. Home environment conditions in these countries varied widely. The quality of housing and availability of material resources at home were consistently tied to HDI; the availability of formal and informal learning materials a little less so. Gross domestic product (GDP) tended to show a stronger independent relation with housing quality and material resources than life expectancy and education. Formal learning resources were independently related to the GDP and education indices, and informal learning resources were not independently related to any constituent indices of the overall HDI. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Market uptake of orphan drugs--a European analysis.

PubMed

Picavet, E; Annemans, L; Cleemput, I; Cassiman, D; Simoens, S

2012-12-01

Variations in market uptake of an orphan drug have important implications with respect to access to care and inequality of treatment. Therefore, the aim of this study was to quantify both the sales and volume uptake of orphan drugs in Europe and to assess whether a country's gross domestic product (GDP) and/or health technology assessment (HTA) influences the orphan drugs' market uptake. We analysed the numbers of orphan drugs launched and the sales and volume uptake for 17 orphan drugs in 23 European countries from 2001 until the beginning of 2010 using the IMS Health database. Countries were clustered based on GDP and the availability of a formal HTA-organization. The uptake of orphan drugs varied across European countries. The highest volumes and contributions of orphan drugs in the first year occurred in countries with a high GDP (and implicitly, a higher budget for healthcare), independently of the existence of an HTA-organization. In contrast, in countries with a low GDP, orphan drugs were less available when there was a formal HTA-organization. There, budgetary restrictions can cause the exclusion of less cost-effective orphan drugs. We observed substantial variation in the market uptake of orphan drugs. Such variation may have important implications with respect to access to care and inequality of treatment. The uptake of orphan drugs could be promoted through the clinical added value of orphan drugs (CAVOD) project and various conditional pricing and reimbursement mechanisms. © 2012 Blackwell Publishing Ltd.

Quantity and quality analysis of dental prosthodontics among retirement age residents from nursing homes in different regions of Latvia and retirement age patients from dental clinic in Riga.

PubMed

Vidzis, Aldis; Cema, Ingrida; Brinkmane, Anda; Krasta, Ingrida; Broka, Kristine

2012-01-01

The quality of life is closely related with condition of oral health, influence of subjective factors on the whole human body and patients perception of their oral health. In spite of the fact that the most part of Latvian retirement age residents use low-quality dentures and assess them satisfactory, these patients often have problems associated with quality of dentures. The aim of the present study was to evaluate oral health status, prosthodontics indicators and patients satisfaction with oral health among Latvian retirement age residents. There were examined 465 retirement age volunteers (170 men and 295 women), 116 of them in dental clinic Sandent (Riga, 24.9% - control group), 137 (29.5%) in nursing homes in Zemgale and 212 (45.6%) in nursing homes in Kurzeme (Zemgale and Kurzeme are districts of Latvia). There were assessed quantity of prosthodontics among patients with partial defects of dental arches, there were estimated quality of dentures and patients satisfaction with existing prosthodontics. Oral health indicators among Latvian retirement age population are better than the same indicators among elderly residents of nursing homes. Among nursing homes residents with partial edentulousness in most of cases in oral cavities remained only few residual teeth which needed treatment. Removable and fixed dental prostheses used by nursing homes residents do not meet denture's quality criteria. Self-evaluation of dentures quality among retirement age residents of nursing homes is better and not correspond with existing dentures quality. In Latvia the quantity of prosthodontics in respect of partial removable dentures among the retired who regularly visit a dentist does not significantly differ from European retirement age population's dental prosthodontics quantity. Dental prosthodontics indicators of residents of nursing homes in Latvia are unsatisfactory (p<0.001). In retirement age population self-evaluation with quality of dentures is higher than actually

Time-Varying Value of Energy Efficiency in Michigan

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

Mims, Natalie; Eckman, Tom; Schwartz, Lisa C.

Quantifying the time-varying value of energy efficiency is necessary to properly account for all of its benefits and costs and to identify and implement efficiency resources that contribute to a low-cost, reliable electric system. Historically, most quantification of the benefits of efficiency has focused largely on the economic value of annual energy reduction. Due to the lack of statistically representative metered end-use load shape data in Michigan (i.e., the hourly or seasonal timing of electricity savings), the ability to confidently characterize the time-varying value of energy efficiency savings in the state, especially for weather-sensitive measures such as central air conditioning,more » is limited. Still, electric utilities in Michigan can take advantage of opportunities to incorporate the time-varying value of efficiency into their planning. For example, end-use load research and hourly valuation of efficiency savings can be used for a variety of electricity planning functions, including load forecasting, demand-side management and evaluation, capacity planning, long-term resource planning, renewable energy integration, assessing potential grid modernization investments, establishing rates and pricing, and customer service (KEMA 2012). In addition, accurately calculating the time-varying value of efficiency may help energy efficiency program administrators prioritize existing offerings, set incentive or rebate levels that reflect the full value of efficiency, and design new programs.« less

Foreign Language Skills for Employability in the EU Labour Market

ERIC Educational Resources Information Center

Grasmane, Daina; Grasmane, Sanita

2011-01-01

To confront rising unemployment, skills of the labour force must be improved. With the aim to find out how foreign language skills impact employability, a study was carried out, in which 61 undergraduates, 33 master's students and 33 doctoral students from the Latvian University of Agriculture participated. The findings testify that 38% of the…

JPRS Report, Soviet Union, Political Affairs

DTIC Science & Technology

1990-09-05

Latvian Balto-Slavic Party Considered 90UN2270B Riga SOVETSKAYA MOLODEZH in Russian 23 May 90 p 1 [Article by Oleg Ilenkov: "More About the BSP...freeing of the leaders of the Karabakh and Krunk committees, as well as the Sverd- lovsk journalist S. Kuznetsov . Nowadays "Memorial" is not merely

United States European Command

Science.gov Websites

put to the ultimate training test April 16-27 as they reacted to a simulated 6.0 magnitude earthquake through technical and tactical skills training during exercise Stoney Run in Germany. Nato Support U.S a multinational joint equipment training brief April 2, 2018. Steady Presence Latvian Joint Terminal

Pauls Stradins | NREL

Science.gov Websites

Materials Photovoltaics group. In addition, it involves theory, analytical microscopy, and atomic layer and Technology, his Ph.D. from the Latvian Institute of Physics, then spent five years in Professor Fritzche's group at the University of Chicago followed by another five years in the Thin-Film Si Solar Cells

Time-varying higher order spectra

NASA Astrophysics Data System (ADS)

Boashash, Boualem; O'Shea, Peter

1991-12-01

A general solution for the problem of time-frequency signal representation of nonlinear FM signals is provided, based on a generalization of the Wigner-Ville distribution. The Wigner- Ville distribution (WVD) is a second order time-frequency representation. That is, it is able to give ideal energy concentration for quadratic phase signals and its ensemble average is a second order time-varying spectrum. The same holds for Cohen's class of time-frequency distributions, which are smoothed versions of the WVD. The WVD may be extended so as to achieve ideal energy concentration for higher order phase laws, and such that the expectation is a time-varying higher order spectrum. The usefulness of these generalized Wigner-Ville distributions (GWVD) is twofold. Firstly, because they achieve ideal energy concentration for polynomial phase signals, they may be used for optimal instantaneous frequency estimation. Second, they are useful for discriminating between nonstationary processes of differing higher order moments. In the same way that the WVD is generalized, we generalize Cohen's class of TFDs by defining a class of generalized time-frequency distributions (GTFDs) obtained by a two dimensional smoothing of the GWVD. Another results derived from this approach is a method based on higher order spectra which allows the separation of cross-terms and auto- terms in the WVD.

Stereoscopic depth perception varies with hues

NASA Astrophysics Data System (ADS)

Chen, Zaiqing; Shi, Junsheng; Tai, Yonghang; Yun, Lijun

2012-09-01

The contribution of color information to stereopsis is controversial, and whether the stereoscopic depth perception varies with chromaticity is ambiguous. This study examined the changes in depth perception caused by hue variations. Based on the fact that a greater disparity range indicates more efficient stereoscopic perception, the effect of hue variations on depth perception was evaluated through the disparity range with random-dot stereogram stimuli. The disparity range was obtained by constant-stimulus method for eight chromaticity points sampled from the CIE 1931 chromaticity diagram. Eight sample points include four main color hues: red, yellow, green, and blue at two levels of chroma. The results show that the disparity range for the yellow hue is greater than the red hue, the latter being greater than the blue hue and the disparity range for green hue is smallest. We conclude that the perceived depth is not the same for different hues for a given size of disparity. We suggest that the stereoscopic depth perception can vary with chromaticity.

Social contagions on time-varying community networks

NASA Astrophysics Data System (ADS)

Liu, Mian-Xin; Wang, Wei; Liu, Ying; Tang, Ming; Cai, Shi-Min; Zhang, Hai-Feng

2017-05-01

Time-varying community structures exist widely in real-world networks. However, previous studies on the dynamics of spreading seldom took this characteristic into account, especially those on social contagions. To study the effects of time-varying community structures on social contagions, we propose a non-Markovian social contagion model on time-varying community networks based on the activity-driven network model. A mean-field theory is developed to analyze the proposed model. Through theoretical analyses and numerical simulations, two hierarchical features of the behavior adoption processes are found. That is, when community strength is relatively large, the behavior can easily spread in one of the communities, while in the other community the spreading only occurs at higher behavioral information transmission rates. Meanwhile, in spatial-temporal evolution processes, hierarchical orders are observed for the behavior adoption. Moreover, under different information transmission rates, three distinctive patterns are demonstrated in the change of the whole network's final adoption proportion along with the growing community strength. Within a suitable range of transmission rate, an optimal community strength can be found that can maximize the final adoption proportion. Finally, compared with the average activity potential, the promoting or inhibiting of social contagions is much more influenced by the number of edges generated by active nodes.

Teaching of laser medical topics: Latvian experience

NASA Astrophysics Data System (ADS)

Spigulis, Janis

2002-10-01

Pilot program for Master's studies on Biomedical Optics has been developed and launched at University of Latvia in 1995. The Curriculum contains several basic subjects like Fundamentals of Biomedical Optics, Medical Lightguides, Anatomy and Physiology, Lasers and Non-coherent Light Sources, Optical Instrumentation for Healthcare, Optical Methods for Patient Treatment, Basic Physics, etc. Special English Terminology and Laboratory-Clinical Praxis are also involved, and the Master Theses is the final step for the degree award. Recently a new extensive short course for medical laser users "Lasers and Bio-optics in Medicine" has been prepared in the PowerPoint format and successfully presented in Latvia, Lithuania and Sweden.

The Varied Uses of Readability Measurement.

ERIC Educational Resources Information Center

Fry, Edward

Readability formulas have varied uses. In education they are used to match children's reading ability to the difficulty level of material, select stories and books for classroom use and for individual students' particular needs, select textbooks and other reading materials, aid educational research, and check reading materials of newly literate…

Linear Parameter Varying Identification of Dynamic Joint Stiffness during Time-Varying Voluntary Contractions

PubMed Central

Golkar, Mahsa A.; Sobhani Tehrani, Ehsan; Kearney, Robert E.

2017-01-01

Dynamic joint stiffness is a dynamic, nonlinear relationship between the position of a joint and the torque acting about it, which can be used to describe the biomechanics of the joint and associated limb(s). This paper models and quantifies changes in ankle dynamic stiffness and its individual elements, intrinsic and reflex stiffness, in healthy human subjects during isometric, time-varying (TV) contractions of the ankle plantarflexor muscles. A subspace, linear parameter varying, parallel-cascade (LPV-PC) algorithm was used to identify the model from measured input position perturbations and output torque data using voluntary torque as the LPV scheduling variable (SV). Monte-Carlo simulations demonstrated that the algorithm is accurate, precise, and robust to colored measurement noise. The algorithm was then used to examine stiffness changes associated with TV isometric contractions. The SV was estimated from the Soleus EMG using a Hammerstein model of EMG-torque dynamics identified from unperturbed trials. The LPV-PC algorithm identified (i) a non-parametric LPV impulse response function (LPV IRF) for intrinsic stiffness and (ii) a LPV-Hammerstein model for reflex stiffness consisting of a LPV static nonlinearity followed by a time-invariant state-space model of reflex dynamics. The results demonstrated that: (a) intrinsic stiffness, in particular ankle elasticity, increased significantly and monotonically with activation level; (b) the gain of the reflex pathway increased from rest to around 10–20% of subject's MVC and then declined; and (c) the reflex dynamics were second order. These findings suggest that in healthy human ankle, reflex stiffness contributes most at low muscle contraction levels, whereas, intrinsic contributions monotonically increase with activation level. PMID:28579954

Is a Picture Worth a Thousand Words? Using Mind Maps to Facilitate Participant Recall in Qualitative Research

ERIC Educational Resources Information Center

Wheeldon, Johannes

2011-01-01

Mind maps may provide a new means to gather unsolicited data through qualitative research designs. In this paper, I explore the utility of mind maps through a project designed to uncover the experiences of Latvians involved in a legal technical assistance project. Based on a sample of 19 respondents, the depth and detail of the responses between…

Context-dependent decisions among options varying in a single dimension.

PubMed

Morgan, Kate V; Hurly, T Andrew; Bateson, Melissa; Asher, Lucy; Healy, Susan D

2012-02-01

Contrary to theories of rational choice, adding alternatives to a choice set can change the choices made by both humans and animals. This is usually done by adding an inferior decoy to a choice set of two favoured options that are characterized on two distinct dimensions. We presented wild, free-living rufous hummingbirds (Selasphorus rufus) with choices between two or three options that varied in a single dimension only. The options varied in concentration, in volume or in corolla length. When the options varied in concentration, the addition of a medium option to a choice set of a low and a high concentration caused birds to increase their preference for the high option. However, they decreased their preference for the high concentration option when a low option was added to a choice set of high and medium concentrations. When the options varied only in volume, the addition of a high volume option to a choice set of low and medium options decreased the birds' preference for the medium option. We saw no effects of adding a third option when the options varied in corolla length alone. Hummingbirds, then, make context-dependent decisions even when the options vary in only a single dimension although which effect occurs seems to depend on the dimension being manipulated. None of the current theories alone adequately explain these results. Copyright © 2011 Elsevier B.V. All rights reserved.

Vesicle biomechanics in a time-varying magnetic field.

PubMed

Ye, Hui; Curcuru, Austen

2015-01-01

Cells exhibit distortion when exposed to a strong electric field, suggesting that the field imposes control over cellular biomechanics. Closed pure lipid bilayer membranes (vesicles) have been widely used for the experimental and theoretical studies of cellular biomechanics under this electrodeformation. An alternative method used to generate an electric field is by electromagnetic induction with a time-varying magnetic field. References reporting the magnetic control of cellular mechanics have recently emerged. However, theoretical analysis of the cellular mechanics under a time-varying magnetic field is inadequate. We developed an analytical theory to investigate the biomechanics of a modeled vesicle under a time-varying magnetic field. Following previous publications and to simplify the calculation, this model treated the inner and suspending media as lossy dielectrics, the membrane thickness set at zero, and the electric resistance of the membrane assumed to be negligible. This work provided the first analytical solutions for the surface charges, electric field, radial pressure, overall translational forces, and rotational torques introduced on a vesicle by the time-varying magnetic field. Frequency responses of these measures were analyzed, particularly the frequency used clinically by transcranial magnetic stimulation (TMS). The induced surface charges interacted with the electric field to produce a biomechanical impact upon the vesicle. The distribution of the induced surface charges depended on the orientation of the coil and field frequency. The densities of these charges were trivial at low frequency ranges, but significant at high frequency ranges. The direction of the radial force on the vesicle was dependent on the conductivity ratio between the vesicle and the medium. At relatively low frequencies (<200 KHz), including the frequency used in TMS, the computed radial pressure and translational forces on the vesicle were both negligible. This work

Exact reconstruction analysis/synthesis filter banks with time-varying filters

NASA Technical Reports Server (NTRS)

Arrowood, J. L., Jr.; Smith, M. J. T.

1993-01-01

This paper examines some of the analysis/synthesis issues associated with FIR time-varying filter banks where the filter bank coefficients are allowed to change in response to the input signal. Several issues are identified as being important in order to realize performance gains from time-varying filter banks in image coding applications. These issues relate to the behavior of the filters as transition from one set of filter banks to another occurs. Lattice structure formulations for the time varying filter bank problem are introduced and discussed in terms of their properties and transition characteristics.

Identification of Time-Varying Pilot Control Behavior in Multi-Axis Control Tasks

NASA Technical Reports Server (NTRS)

Zaal, Peter M. T.; Sweet, Barbara T.

2012-01-01

Recent developments in fly-by-wire control architectures for rotorcraft have introduced new interest in the identification of time-varying pilot control behavior in multi-axis control tasks. In this paper a maximum likelihood estimation method is used to estimate the parameters of a pilot model with time-dependent sigmoid functions to characterize time-varying human control behavior. An experiment was performed by 9 general aviation pilots who had to perform a simultaneous roll and pitch control task with time-varying aircraft dynamics. In 8 different conditions, the axis containing the time-varying dynamics and the growth factor of the dynamics were varied, allowing for an analysis of the performance of the estimation method when estimating time-dependent parameter functions. In addition, a detailed analysis of pilots adaptation to the time-varying aircraft dynamics in both the roll and pitch axes could be performed. Pilot control behavior in both axes was significantly affected by the time-varying aircraft dynamics in roll and pitch, and by the growth factor. The main effect was found in the axis that contained the time-varying dynamics. However, pilot control behavior also changed over time in the axis not containing the time-varying aircraft dynamics. This indicates that some cross coupling exists in the perception and control processes between the roll and pitch axes.

Spatially varying dispersion to model breakthrough curves.

PubMed

Li, Guangquan

2011-01-01

Often the water flowing in a karst conduit is a combination of contaminated water entering at a sinkhole and cleaner water released from the limestone matrix. Transport processes in the conduit are controlled by advection, mixing (dilution and dispersion), and retention-release. In this article, a karst transport model considering advection, spatially varying dispersion, and dilution (from matrix seepage) is developed. Two approximate Green's functions are obtained using transformation of variables, respectively, for the initial-value problem and for the boundary-value problem. A numerical example illustrates that mixing associated with strong spatially varying conduit dispersion can cause strong skewness and long tailing in spring breakthrough curves. Comparison of the predicted breakthrough curve against that measured from a dye-tracing experiment between Ames Sink and Indian Spring, Northwest Florida, shows that the conduit dispersivity can be as large as 400 m. Such a large number is believed to imply strong solute interaction between the conduit and the matrix and/or multiple flow paths in a conduit network. It is concluded that Taylor dispersion is not dominant in transport in a karst conduit, and the complicated retention-release process between mobile- and immobile waters may be described by strong spatially varying conduit dispersion. Copyright © 2010 The Author(s). Journal compilation © 2010 National Ground Water Association.

Non-minimally coupled varying constants quantum cosmologies

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

Balcerzak, Adam, E-mail: abalcerz@wmf.univ.szczecin.pl

We consider gravity theory with varying speed of light and varying gravitational constant. Both constants are represented by non-minimally coupled scalar fields. We examine the cosmological evolution in the near curvature singularity regime. We find that at the curvature singularity the speed of light goes to infinity while the gravitational constant vanishes. This corresponds to the Newton's Mechanics limit represented by one of the vertex of the Bronshtein-Zelmanov-Okun cube [1,2]. The cosmological evolution includes both the pre-big-bang and post-big-bang phases separated by the curvature singularity. We also investigate the quantum counterpart of the considered theory and find the probability ofmore » transition of the universe from the collapsing pre-big-bang phase to the expanding post-big-bang phase.« less

Innovative Varied-Fidelity Simulation Mobile Teaching Cart and Education Project.

PubMed

Harding, Andrew D; Cullinane Whalen, Kathryn; Silverman, Bradley S

2015-09-01

The use of a varied-fidelity simulation mobile teaching cart is a teaching tool that offers unique advantages in the acute care setting. The cart is used to demonstrate the use of patient monitoring devices, and there are a variety of software tools available with the monitoring technology to ensure that the outputs, including electrocardiographic waves, are analyzed appropriately by nursing staff using this varied-fidelity simulation mobile teaching cart. Bringing varied-fidelity simulation to the nurses' work area is a unique application setting. Copyright © 2015 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

Varying ultrasound power level to distinguish surgical instruments and tissue.

PubMed

Ren, Hongliang; Anuraj, Banani; Dupont, Pierre E

2018-03-01

We investigate a new framework of surgical instrument detection based on power-varying ultrasound images with simple and efficient pixel-wise intensity processing. Without using complicated feature extraction methods, we identified the instrument with an estimated optimal power level and by comparing pixel values of varying transducer power level images. The proposed framework exploits the physics of ultrasound imaging system by varying the transducer power level to effectively distinguish metallic surgical instruments from tissue. This power-varying image-guidance is motivated from our observations that ultrasound imaging at different power levels exhibit different contrast enhancement capabilities between tissue and instruments in ultrasound-guided robotic beating-heart surgery. Using lower transducer power levels (ranging from 40 to 75% of the rated lowest ultrasound power levels of the two tested ultrasound scanners) can effectively suppress the strong imaging artifacts from metallic instruments and thus, can be utilized together with the images from normal transducer power levels to enhance the separability between instrument and tissue, improving intraoperative instrument tracking accuracy from the acquired noisy ultrasound volumetric images. We performed experiments in phantoms and ex vivo hearts in water tank environments. The proposed multi-level power-varying ultrasound imaging approach can identify robotic instruments of high acoustic impedance from low-signal-to-noise-ratio ultrasound images by power adjustments.

Studies and projections of hydraulic conductivity of Devonian Plavinu and Daugava carbonate aquifers in Latvia

NASA Astrophysics Data System (ADS)

Perkone, E.; Delina, A.; Saks, T.; Raga, B.; Jātnieks, J.; Klints, I.; Popovs, K.; Babre, A.; Bikše, J.; Kalvāns, A.; Retike, I.; Ukass, J.

2012-04-01

Carbonate aquifers show a very wide range of hydrogeological characteristics. Carbonate rock hydrogeology display two extremes: on one hand hydrogeological properties of the carbonates are governed by the pathways of the preferential groundwater flow typical in karstic regions, on the other - some carbonate aquifers behave almost like a homogeneous, isotropic, porous medium. Most lie between these extremes, but these case variations complicates the study of carbonate aquifer properties. In this study the results of the hydraulic conductivity in carbonate aquifers measurements, hydraulic conductivity correlation between sediments lithology and the aquifer surface depth and fractures research is presented. Upper Devonian Frasnian stage Pļaviņu and Daugava carbonate aquifers in the Latvian part of the Baltic basin is considered. The aim of this research is to elaborate characteristic hydraulic conductivity values for each aquifer based on existing data of the pumping test results and other aquifer properties. Pļaviņu and Daugava carbonate aquifers mainly consist of jointed dolomite with intermediate layers of dolomitic marlstone, limestone, clays and gypsum. These aquifers are prevalent in most of the study area, except Northern and South - Eastern parts of the territory. In geological structure Daugava aquifer lies above Pļaviņu aquifer. Daugava aquifer depth changes from 10 - 20 and even less meters in Eastern part to 250 - 300 m in South - West part of study area, but thickness varies from few meters to 30 m. Pļaviņu aquifer surface depth varies from 20 - 30 m, but in uplands surface depth reaches more than 120 m, in Eastern part to more than 300 m in South - West part of study area. Aquifer average thickness varies from 20 - 40 m, but in areas with buried valleys thickness can be less than 10 meters. Outcrops of these sediments are occurring in banks of largest rivers and in some areas aquifers are karstified. In studies of the carbonate aquifers it is

Mixed-effects varying-coefficient model with skewed distribution coupled with cause-specific varying-coefficient hazard model with random-effects for longitudinal-competing risks data analysis.

PubMed

Lu, Tao; Wang, Min; Liu, Guangying; Dong, Guang-Hui; Qian, Feng

2016-01-01

It is well known that there is strong relationship between HIV viral load and CD4 cell counts in AIDS studies. However, the relationship between them changes during the course of treatment and may vary among individuals. During treatments, some individuals may experience terminal events such as death. Because the terminal event may be related to the individual's viral load measurements, the terminal mechanism is non-ignorable. Furthermore, there exists competing risks from multiple types of events, such as AIDS-related death and other death. Most joint models for the analysis of longitudinal-survival data developed in literatures have focused on constant coefficients and assume symmetric distribution for the endpoints, which does not meet the needs for investigating the nature of varying relationship between HIV viral load and CD4 cell counts in practice. We develop a mixed-effects varying-coefficient model with skewed distribution coupled with cause-specific varying-coefficient hazard model with random-effects to deal with varying relationship between the two endpoints for longitudinal-competing risks survival data. A fully Bayesian inference procedure is established to estimate parameters in the joint model. The proposed method is applied to a multicenter AIDS cohort study. Various scenarios-based potential models that account for partial data features are compared. Some interesting findings are presented.

The Thermal Collector With Varied Glass Covers

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

Luminosu, I.; Pop, N.

2010-08-04

The thermal collector with varied glass covers represents an innovation realized in order to build a collector able to reach the desired temperature by collecting the solar radiation from the smallest surface, with the highest efficiency. In the case of the thermal collector with variable cover glasses, the number of the glass plates covering the absorber increases together with the length of the circulation pipe for the working fluid. The thermal collector with varied glass covers compared to the conventional collector better meet user requirements because: for the same temperature increase, has the collecting area smaller; for the same collectionmore » area, realizes the highest temperature increase and has the highest efficiency. This works is addressed to researchers in the solar energy and to engineers responsible with air-conditioning systems design or industrial and agricultural products drying.« less

The Thermal Collector With Varied Glass Covers

NASA Astrophysics Data System (ADS)

Luminosu, I.; Pop, N.

2010-08-01

The thermal collector with varied glass covers represents an innovation realized in order to build a collector able to reach the desired temperature by collecting the solar radiation from the smallest surface, with the highest efficiency. In the case of the thermal collector with variable cover glasses, the number of the glass plates covering the absorber increases together with the length of the circulation pipe for the working fluid. The thermal collector with varied glass covers compared to the conventional collector better meet user requirements because: for the same temperature increase, has the collecting area smaller; for the same collection area, realizes the highest temperature increase and has the highest efficiency. This works is addressed to researchers in the solar energy and to engineers responsible with air-conditioning systems design or industrial and agricultural products drying.

Status of the Topside Vary-Chap Ionospheric Model

NASA Astrophysics Data System (ADS)

Reinisch, Bodo; Nsumei, Patrick; Huang, Xueqin; Bilitza, Dieter

Status of the Topside Vary-Chap Ionospheric Model The general alpha-Chapman function for a multi-constituent gas which includes a continuously varying scale height and was therefore dubbed the Vary-Chap function, can present the topside electron density profiles in analytical form. The Vary-Chap profile is defined by the scale height function H(h) and the height and density of the F2 layer peak. By expressing 80,000 ISIS-2 measured topside density profiles as Vary-Chap functions we derived 80,000 scale height functions, which form the basis for the topside density profile modeling. The normalized scale height profiles Hn = H(h)/Hm were grouped according to season, MLAT, and MLT for each 50 km height bin from 200 km to 1400 km, and the median, lower, and upper quartiles for each bin were calculated. Hm is the scale height at the F2 layer peak. The resulting Hn functions are modeled in terms of hyperbolic tangent functions using 5 parameters that are determined by multivariate least squares, including the transition height hT where the scale height gradient has a maximum. These normalized scale height functions, representing the model of the topside electron density profiles from hmF2 to 1,400 km altitude, are independent of hmF2 and NmF2 and can therefore be directly used for the topside Ne profile in IRI. Similarly, this model can extend measured bottomside profiles to the topside, replacing the simple alpha-Chapman function with constant scale height that is currently used for construction of the topside profile in the Digisondes / ARTIST of the Global Ionospheric Radio Observatory (GIRO). It turns out that Hm(top) calculated from the topside profiles is generally several times larger than Hm(bot) derived from the bottomside profiles. This follows necessarily from the difference in the definition of the scale height functions for the topside and bottomside profiles. The diurnal variations of the ratio Hm(top) / Hm(bot) has been determined for different latitudes

Sensor trustworthiness in uncertain time varying stochastic environments

NASA Astrophysics Data System (ADS)

Verma, Ajay; Fernandes, Ronald; Vadakkeveedu, Kalyan

2011-06-01

Persistent surveillance applications require unattended sensors deployed in remote regions to track and monitor some physical stimulant of interest that can be modeled as output of time varying stochastic process. However, the accuracy or the trustworthiness of the information received through a remote and unattended sensor and sensor network cannot be readily assumed, since sensors may get disabled, corrupted, or even compromised, resulting in unreliable information. The aim of this paper is to develop information theory based metric to determine sensor trustworthiness from the sensor data in an uncertain and time varying stochastic environment. In this paper we show an information theory based determination of sensor data trustworthiness using an adaptive stochastic reference sensor model that tracks the sensor performance for the time varying physical feature, and provides a baseline model that is used to compare and analyze the observed sensor output. We present an approach in which relative entropy is used for reference model adaptation and determination of divergence of the sensor signal from the estimated reference baseline. We show that that KL-divergence is a useful metric that can be successfully used in determination of sensor failures or sensor malice of various types.

Network Inference via the Time-Varying Graphical Lasso

PubMed Central

Hallac, David; Park, Youngsuk; Boyd, Stephen; Leskovec, Jure

2018-01-01

Many important problems can be modeled as a system of interconnected entities, where each entity is recording time-dependent observations or measurements. In order to spot trends, detect anomalies, and interpret the temporal dynamics of such data, it is essential to understand the relationships between the different entities and how these relationships evolve over time. In this paper, we introduce the time-varying graphical lasso (TVGL), a method of inferring time-varying networks from raw time series data. We cast the problem in terms of estimating a sparse time-varying inverse covariance matrix, which reveals a dynamic network of interdependencies between the entities. Since dynamic network inference is a computationally expensive task, we derive a scalable message-passing algorithm based on the Alternating Direction Method of Multipliers (ADMM) to solve this problem in an efficient way. We also discuss several extensions, including a streaming algorithm to update the model and incorporate new observations in real time. Finally, we evaluate our TVGL algorithm on both real and synthetic datasets, obtaining interpretable results and outperforming state-of-the-art baselines in terms of both accuracy and scalability. PMID:29770256

How Do Parenting Concepts Vary within and between the Families?

ERIC Educational Resources Information Center

Roskam, Isabelle; Meunier, Jean Christophe

2009-01-01

How do parenting concepts vary within and between the families? The present study regards parenting as a complex family process by considering three concepts of parenting: styles, differential treatment and coparenting consistency. A main question was addressed: whether and how these parenting concepts vary within the families towards siblings or…

Toroidal varied-line space (TVLS) gratings

NASA Astrophysics Data System (ADS)

Thomas, Roger J.

2003-02-01

It is a particular challenge to develop a stigmatic spectrograph for EUV wavelengths since the very low normal-incidence reflectance of standard materials most often requires that the design be restricted to a single optical element which must simultaneously provide both re-imaging and spectral dispersion. This problem has been solved in the past by the use of toroidal gratings with uniform line-space rulings (TULS). A number of solar EUV spectrographs have been based on such designs, including SOHO/CDS, Solar-B/EIS, and the sounding rockets SERTS and EUNIS. More recently, Kita, Harada, and collaborators have developed the theory of spherical gratings with varied line-space rulings (SVLS) operated at unity magnification, which have been flown on several astronomical satellite missions. These ideas are now combined into a spectrograph concept that considers varied-line space grooves ruled onto toroidal gratings. Such TVLS designs are found to provide excellent imaging even at very large spectrograph magnifications and beam-speeds, permitting extremely high-quality performance in remarkably compact instrument packages. Optical characteristics of two solar spectrographs based on this concept are described: SUMI, proposed as a sounding rocket experiment, and NEXUS, proposed for the Solar Dynamics Observatory mission.

Toroidal Varied-Line Space (TVLS) Gratings

NASA Technical Reports Server (NTRS)

Thomas, Roger J.; Oegerle, William (Technical Monitor)

2002-01-01

It is a particular challenge to develop a stigmatic spectrograph for XUV wavelengths since the very low normal-incidence reflectance of standard materials most often requires that the design be restricted to a single optical element which must simultaneously provide both re-imaging and spectral dispersion. This problem has been solved in the past by the use of toroidal gratings with uniform line-spaced rulings (TULS). A number of solar EUV (Extreme Ultraviolet) spectrometers have been based on such designs, including SOHO/CDS, Solar-B/EIS, and the sounding rockets SERTS and EUNIS. More recently, Kita, Harada, and collaborators have developed the theory of spherical gratings with varied line-space rulings (SVLS) operated at unity magnification, which have been flown on several astronomical satellite missions. We now combine these ideas into a spectrometer concept that puts varied-line space rulings onto toroidal gratings. Such TVLS designs are found to provide excellent imaging even at very large spectrograph magnifications and beam-speeds, permitting extremely high-quality performance in remarkably compact instrument packages. Optical characteristics of two solar spectrometers based on this concept are described: SUMI, proposed as a sounding rocket experiment, and NEXUS, proposed for the Solar Dynamics Observatory mission.

Identifying Life from Varying Atmospheres

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2018-06-01

Theres no hiding changes in Earths atmosphere over the seasons are a dead giveaway to the fact that Earth hosts life. Now a new study explores whether we might use atmospheric seasonality like Earths to detect life on other planets.Looking for ChangeMost of the searches for life beyond our planet focus on identifying static biosignatures, like the presence of methane or large amounts of oxygen in an exoplanetary atmosphere. This approach suffers from many ambiguities, however including a high likelihood of false positives (processes that chemically mimic life signatures but arent life) and false negatives (non-detections despite the presence of life).Earths atmospheric carbon dioxide (top) and methane (bottom) levels vary seasonally, as seen in these data from NOAAs Earth System Research Laboratory. [Olson et al. 2018]In a new study led by Stephanie Olson (UC Riverside and NASA Astrobiology Institute Alternative Earths and Virtual Planetary Laboratory Teams), a team of scientists has proposed an alternative approach: to search for distinctive variability of exoplanet atmospheres that indicates the presence of life.Seasons and Lifeif youre like me, you probably havent spent a lot of time thinking about interactions between the Earths biosphere and its axial tilt. Nonetheless, this interplay is responsible for detectable and distinctive seasonal changes in our planets atmosphere!This schematic shows how oxygen and carbon dioxide levels in the atmosphere vary in opposing phase seasonally, with the increased sunlight in summer driving greater conversion of carbon dioxide into oxygen. [Olson et al. 2018]Since so much of our globe is covered by photosynthesizing life, the seasonal availability of sunlight regulates the conversion of carbon dioxide to oxygen, providing a signature in our atmosphere that varies over the course of the year. And photosynthesis isnt the only culprit! Other biological products evolve seasonally as well as the surface temperature on our globe

Relaxation Assessment with Varied Structured Milieu (RELAX).

ERIC Educational Resources Information Center

Cassel, Russell N.; Cassel, Susie L.

1983-01-01

Describes Relaxation Assessment with Varied Structured Milieu (RELAX), a clinical program designed to assess the degree to which an individual is able to demonstrate self-control for overall general relaxation. The program is designed for use with the Cassel Biosensors biofeedback equipment. (JAC)

Costs of providing tuberculosis diagnosis and treatment services in Viet Nam.

PubMed

Minh, H V; Mai, V Q; Nhung, N V; Hoi, L V; Giang, K B; Chung, L H; Kien, V D; Duyen, N T; Ngoc, N B; Anh, T T; Phuong, T B; Ngan, T T; Khanh, P H

2017-09-01

To estimate the cost of providing tuberculosis (TB) diagnosis and treatment packages at different levels of health facilities in Viet Nam. This was a retrospective costing study from the providers' perspective using a standard costing approach. We included typical services for TB diagnosis and treatment based on standard protocols. The least expensive TB service was the 6-month isoniazid preventive therapy regimen for latent tuberculous infection provided by district health centres (US$7.20-14.30, accounting for 0.3-0.7% of Viet Nam's per capita gross domestic product [GDP] of US$2052.30 in 2014). The cost of diagnosing and treating a patient with drug-susceptible TB (the most common type of TB) ranged between US$51.20 and US$180.70, and represented 2.5-8.8% of Viet Nam's per capita GDP in 2014. The most expensive TB service was the diagnosis and treatment of a multidrug-resistant TB case (US$1568.20-2391.20), accounting for 76.4-116.5% of Viet Nam's per capita GDP in 2014). The cost of TB diagnosis and treatment services in Viet Nam varied according to level of health facility, type of TB, different costing options, and different staff cost scenarios.

Global emission of black carbon from motor vehicles from 1960 to 2006.

PubMed

Wang, Rong; Tao, Shu; Shen, Huizhong; Wang, Xilong; Li, Bengang; Shen, Guofeng; Wang, Bin; Li, Wei; Liu, Xiaopeng; Huang, Ye; Zhang, Yanyan; Lu, Yan; Ouyang, Huiling

2012-01-17

Black carbon (BC) is a key short-lived climate change forcer. Motor vehicles are important sources of BC in the environment. BC emission factors (EF(BC)), defined as BC emitted per mass of fuel consumed, are critical in the development of BC emission inventories for motor vehicles. However, measured EF(BC) for motor vehicles vary in orders of magnitude, which is one of the major sources of uncertainty in the estimation of emissions. In this study, the main factors affecting EF(BC) for motor vehicles were investigated based on 385 measured EF(BC) collected from the literature. It was found that EF(BC) for motor vehicles of a given year in a particular country can be predicted using gross domestic product per capita (GDP(c)), temperature, and the year a country's GDP(c) reached 3000 USD (Y(3000)). GDP(c) represents technical progress in terms of emission control, while Y(3000) suggest the technical transfer from developed to developing countries. For global BC emission calculations, 87 and 64% of the variation can be eliminated for diesel and gasoline vehicles by using this model. In addition to a reduction in uncertainty, the model can be used to develop a global on-road vehicle BC emission inventory with spatial and temporal resolution.

Parasitic modulation of electromagnetic signals caused by time-varying plasma

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

Yang, Min, E-mail: merovingia1911@126.com; Li, Xiaoping; Xie, Kai

2015-02-15

An experiment on the propagation of electromagnetic (EM) signals in continuous time-varying plasma is described. The time-varying characteristics of plasma are considered to cause a parasitic modulation in both amplitude and phase, and the strength of this modulation, which carries the information of the electron density profile, is closely related to the plasma frequency and the incident wave frequency. Through theoretical analysis, we give an explanation and mechanism of the interaction between the continuous time-varying plasma and EM waves, which is verified by a comparative analysis with experiments performed under the same conditions. The effects of this modulation on themore » EM signals in the plasma sheath cannot be ignored.« less

Quantifying the effect of varying GHG's concentration in Regional Climate Models

NASA Astrophysics Data System (ADS)

López-Romero, Jose Maria; Jerez, Sonia; Palacios-Peña, Laura; José Gómez-Navarro, Juan; Jiménez-Guerrero, Pedro; Montavez, Juan Pedro

2017-04-01

Regional Climate Models (RCMs) are driven at the boundaries by Global Circulation Models (GCM), and in the particular case of Climate Change projections, such simulations are forced by varying greenhouse gases (GHGs) concentrations. In hindcast simulations driven by reanalysis products, the climate change signal is usually introduced in the assimilation process as well. An interesting question arising in this context is whether GHGs concentrations have to be varied within the RCMs model itself, or rather they should be kept constant. Some groups keep the GHGs concentrations constant under the assumption that information about climate change signal is given throughout the boundaries; sometimes certain radiation parameterization schemes do not permit such changes. Other approaches vary these concentrations arguing that this preserves the physical coherence respect to the driving conditions for the RCM. This work aims to shed light on this topic. For this task, various regional climate simulations with the WRF model for the 1954-2004 period have been carried out for using a Euro-CORDEX compliant domain. A series of simulations with constant and variable GHGs have been performed using both, a GCM (ECHAM6-OM) and a reanalysis product (ERA-20C) data. Results indicate that there exist noticeable differences when introducing varying GHGs concentrations within the RCM domain. The differences in 2-m temperature series between the experiments with varying or constant GHGs concentration strongly depend on the atmospheric conditions, appearing a strong interannual variability. This suggests that short-term experiments are not recommended if the aim is to assess the role of varying GHGs. In addition, and consistently in both GCM and reanalysis-driven experiments, the magnitude of temperature trends, as well as the spatial pattern represented by varying GHGs experiment, are closer to the driving dataset than in experiments keeping constant the GHGs concentration. These results

MERTK signaling in the retinal pigment epithelium regulates the tyrosine phosphorylation of GDP dissociation inhibitor alpha from the GDI/CHM family of RAB GTPase effectors.

PubMed

Shelby, Shameka J; Feathers, Kecia L; Ganios, Anna M; Jia, Lin; Miller, Jason M; Thompson, Debra A

2015-11-01

Photoreceptor outer segments (OS) in the vertebrate retina undergo a process of continual renewal involving shedding of disc membranes that are cleared by phagocytic uptake into the retinal pigment epithelium (RPE). In dystrophic Royal College of Surgeons (RCS) rats, OS phagocytosis is blocked by a mutation in the gene encoding the receptor tyrosine kinase MERTK. To identify proteins tyrosine-phosphorylated downstream of MERTK in the RPE, MALDI-mass spectrometry with peptide-mass fingerprinting was used in comparative studies of RCS congenic and dystrophic rats. At times corresponding to peak phagocytic activity, the RAB GTPase effector GDP dissociation inhibitor alpha (GDI1) was found to undergo tyrosine phosphorylation only in congenic rats. In cryosections of native RPE/choroid, GDI1 colocalized with MERTK and the intracellular tyrosine-kinase SRC. In cultured RPE-J cells, and in transfected heterologous cells, MERTK stimulated SRC-mediated tyrosine phosphorylation of GDI1. In OS-fed RPE-J cells, GDI1 colocalized with MERTK and SRC on apparent phagosomes located near the apical membrane. In addition, both GDI1 and RAB5, a regulator of vesicular transport, colocalized with ingested OS. Taken together, these findings identify a novel role of MERTK signaling in membrane trafficking in the RPE that is likely to subserve mechanisms of phagosome formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

ICASE/LaRC Symposium on Visualizing Time-Varying Data

NASA Technical Reports Server (NTRS)

Banks, D. C. (Editor); Crockett, T. W. (Editor); Stacy, K. (Editor)

1996-01-01

Time-varying datasets present difficult problems for both analysis and visualization. For example, the data may be terabytes in size, distributed across mass storage systems at several sites, with time scales ranging from femtoseconds to eons. In response to these challenges, ICASE and NASA Langley Research Center, in cooperation with ACM SIGGRAPH, organized the first symposium on visualizing time-varying data. The purpose was to bring the producers of time-varying data together with visualization specialists to assess open issues in the field, present new solutions, and encourage collaborative problem-solving. These proceedings contain the peer-reviewed papers which were presented at the symposium. They cover a broad range of topics, from methods for modeling and compressing data to systems for visualizing CFD simulations and World Wide Web traffic. Because the subject matter is inherently dynamic, a paper proceedings cannot adequately convey all aspects of the work. The accompanying video proceedings provide additional context for several of the papers.

Theory of Turing Patterns on Time Varying Networks.

PubMed

Petit, Julien; Lauwens, Ben; Fanelli, Duccio; Carletti, Timoteo

2017-10-06

The process of pattern formation for a multispecies model anchored on a time varying network is studied. A nonhomogeneous perturbation superposed to an homogeneous stable fixed point can be amplified following the Turing mechanism of instability, solely instigated by the network dynamics. By properly tuning the frequency of the imposed network evolution, one can make the examined system behave as its averaged counterpart, over a finite time window. This is the key observation to derive a closed analytical prediction for the onset of the instability in the time dependent framework. Continuously and piecewise constant periodic time varying networks are analyzed, setting the framework for the proposed approach. The extension to nonperiodic settings is also discussed.

Study on photoemission surface of varied doping GaN photocathode

NASA Astrophysics Data System (ADS)

Qiao, Jianliang; Du, Ruijuan; Ding, Huan; Gao, Youtang; Chang, Benkang

2014-09-01

For varied doping GaN photocathode, from bulk to surface the doping concentrations are distributed from high to low. The varied doping GaN photocathode may produce directional inside electric field within the material, so the higher quantum efficiency can be obtained. The photoemission surface of varied doping GaN photocathode is very important to the high quantum efficiency, but the forming process of the surface state after Cs activation or Cs/O activation has been not known completely. Encircling the photoemission mechanism of varied GaN photocathode, considering the experiment phenomena during the activation and the successful activation results, the varied GaN photocathode surface model [GaN(Mg):Cs]:O-Cs after activation with cesium and oxygen was given. According to GaN photocathode activation process and the change of electronic affinity, the comparatively ideal NEA property can be achieved by Cs or Cs/O activation, and higher quantum efficiency can be obtained. The results show: The effective NEA characteristic of GaN can be gotten only by Cs. [GaN(Mg):Cs] dipoles form the first dipole layer, the positive end is toward the vacuum side. In the activation processing with Cs/O, the second dipole layer is formed by O-Cs dipoles, A O-Cs dipole includes one oxygen atom and two Cs atoms, and the positive end is also toward the vacuum side thus the escape of electrons can be promoted.

Modeling information diffusion in time-varying community networks

NASA Astrophysics Data System (ADS)

Cui, Xuelian; Zhao, Narisa

2017-12-01

Social networks are rarely static, and they typically have time-varying network topologies. A great number of studies have modeled temporal networks and explored social contagion processes within these models; however, few of these studies have considered community structure variations. In this paper, we present a study of how the time-varying property of a modular structure influences the information dissemination. First, we propose a continuous-time Markov model of information diffusion where two parameters, mobility rate and community attractiveness, are introduced to address the time-varying nature of the community structure. The basic reproduction number is derived, and the accuracy of this model is evaluated by comparing the simulation and theoretical results. Furthermore, numerical results illustrate that generally both the mobility rate and community attractiveness significantly promote the information diffusion process, especially in the initial outbreak stage. Moreover, the strength of this promotion effect is much stronger when the modularity is higher. Counterintuitively, it is found that when all communities have the same attractiveness, social mobility no longer accelerates the diffusion process. In addition, we show that the local spreading in the advantage group has been greatly enhanced due to the agglomeration effect caused by the social mobility and community attractiveness difference, which thus increases the global spreading.

A systematic review of studies eliciting willingness-to-pay per quality-adjusted life year: does it justify CE threshold?

PubMed

Nimdet, Khachapon; Chaiyakunapruk, Nathorn; Vichansavakul, Kittaya; Ngorsuraches, Surachat

2015-01-01

A number of studies have been conducted to estimate willingness to pay (WTP) per quality-adjusted life years (QALY) in patients or general population for various diseases. However, there has not been any systematic review summarizing the relationship between WTP per QALY and cost-effectiveness (CE) threshold based on World Health Organization (WHO) recommendation. To systematically review willingness-to-pay per quality-adjusted-life-year (WTP per QALY) literature, to compare WTP per QALY with Cost-effectiveness (CE) threshold recommended by WHO, and to determine potential influencing factors. We searched MEDLINE, EMBASE, Psyinfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Center of Research Dissemination (CRD), and EconLit from inception through 15 July 2014. To be included, studies have to estimate WTP per QALY in health-related issues using stated preference method. Two investigators independently reviewed each abstract, completed full-text reviews, and extracted information for included studies. We compared WTP per QALY to GDP per capita, analyzed, and summarized potential influencing factors. Out of 3,914 articles founded, 14 studies were included. Most studies (92.85%) used contingent valuation method, while only one study used discrete choice experiments. Sample size varied from 104 to 21,896 persons. The ratio between WTP per QALY and GDP per capita varied widely from 0.05 to 5.40, depending on scenario outcomes (e.g., whether it extended/saved life or improved quality of life), severity of hypothetical scenarios, duration of scenario, and source of funding. The average ratio of WTP per QALY and GDP per capita for extending life or saving life (2.03) was significantly higher than the average for improving quality of life (0.59) with the mean difference of 1.43 (95% CI, 1.81 to 1.06). This systematic review provides an overview summary of all studies estimating WTP per QALY studies. The variation of ratio of WTP per QALY and GDP per

A Systematic Review of Studies Eliciting Willingness-to-Pay per Quality-Adjusted Life Year: Does It Justify CE Threshold?

PubMed Central

Nimdet, Khachapon; Chaiyakunapruk, Nathorn; Vichansavakul, Kittaya; Ngorsuraches, Surachat

2015-01-01

Background A number of studies have been conducted to estimate willingness to pay (WTP) per quality-adjusted life years (QALY) in patients or general population for various diseases. However, there has not been any systematic review summarizing the relationship between WTP per QALY and cost-effectiveness (CE) threshold based on World Health Organization (WHO) recommendation. Objective To systematically review willingness-to-pay per quality-adjusted-life-year (WTP per QALY) literature, to compare WTP per QALY with Cost-effectiveness (CE) threshold recommended by WHO, and to determine potential influencing factors. Methods We searched MEDLINE, EMBASE, Psyinfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Center of Research Dissemination (CRD), and EconLit from inception through 15 July 2014. To be included, studies have to estimate WTP per QALY in health-related issues using stated preference method. Two investigators independently reviewed each abstract, completed full-text reviews, and extracted information for included studies. We compared WTP per QALY to GDP per capita, analyzed, and summarized potential influencing factors. Results Out of 3,914 articles founded, 14 studies were included. Most studies (92.85%) used contingent valuation method, while only one study used discrete choice experiments. Sample size varied from 104 to 21,896 persons. The ratio between WTP per QALY and GDP per capita varied widely from 0.05 to 5.40, depending on scenario outcomes (e.g., whether it extended/saved life or improved quality of life), severity of hypothetical scenarios, duration of scenario, and source of funding. The average ratio of WTP per QALY and GDP per capita for extending life or saving life (2.03) was significantly higher than the average for improving quality of life (0.59) with the mean difference of 1.43 (95% CI, 1.81 to 1.06). Conclusion This systematic review provides an overview summary of all studies estimating WTP per QALY studies. The

Fractional domain varying-order differential denoising method

NASA Astrophysics Data System (ADS)

Zhang, Yan-Shan; Zhang, Feng; Li, Bing-Zhao; Tao, Ran

2014-10-01

Removal of noise is an important step in the image restoration process, and it remains a challenging problem in image processing. Denoising is a process used to remove the noise from the corrupted image, while retaining the edges and other detailed features as much as possible. Recently, denoising in the fractional domain is a hot research topic. The fractional-order anisotropic diffusion method can bring a less blocky effect and preserve edges in image denoising, a method that has received much interest in the literature. Based on this method, we propose a new method for image denoising, in which fractional-varying-order differential, rather than constant-order differential, is used. The theoretical analysis and experimental results show that compared with the state-of-the-art fractional-order anisotropic diffusion method, the proposed fractional-varying-order differential denoising model can preserve structure and texture well, while quickly removing noise, and yields good visual effects and better peak signal-to-noise ratio.

An activating mutant of Rac1 that fails to interact with Rho GDP-dissociation inhibitor stimulates membrane ruffling in mammalian cells.

PubMed Central

Gandhi, Payal N; Gibson, Richard M; Tong, Xiaofeng; Miyoshi, Jun; Takai, Yoshimi; Konieczkowski, Martha; Sedor, John R; Wilson-Delfosse, Amy L

2004-01-01

Rac1, a member of the Rho family of small GTP-binding proteins, is involved in the regulation of the actin cytoskeleton via activation of lamellipodia and membrane ruffle formation. RhoGDI (Rho-family-specific GDP-dissociation inhibitor) forms a complex with Rho proteins in the cytosol of mammalian cells. It not only regulates guanine nucleotide binding to Rho proteins, but may also function as a molecular shuttle to carry Rho proteins from an inactive cytosolic pool to the membrane for activation. These studies tested if RhoGDI is necessary for the translocation of Rac1 from the cytosol to the plasma membrane for the formation of membrane ruffles. We describe a novel mutant of Rac1, R66E (Arg66-->Glu), that fails to bind RhoGDI. This RhoGDI-binding-defective mutation is combined with a Rac1-activating mutation G12V, resulting in a double-mutant [Rac1(G12V/R66E)] that fails to interact with RhoGDI in COS-7 cells, but remains constitutively activated. This double mutant stimulates membrane ruffling to a similar extent as that observed after epidermal growth factor treatment of non-transfected cells. To confirm that Rac1 can signal ruffle formation in the absence of interaction with RhoGDI, Rac1(G12V) was overexpressed in cultured mesangial cells derived from a RhoGDI knockout mouse. Rac1-mediated membrane ruffling was indistinguishable between the RhoGDI(-/-) and RhoGDI(+/+) cell lines. In both the COS-7 and cultured mesangial cells, Rac1(G12V) and Rac1(G12V/R66E) co-localize with membrane ruffles. These findings suggest that interaction with RhoGDI is not essential in the mechanism by which Rac1 translocates to the plasma membrane to stimulate ruffle formation. PMID:14629200

Performance Optimizing Adaptive Control with Time-Varying Reference Model Modification

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.; Hashemi, Kelley E.

2017-01-01

This paper presents a new adaptive control approach that involves a performance optimization objective. The control synthesis involves the design of a performance optimizing adaptive controller from a subset of control inputs. The resulting effect of the performance optimizing adaptive controller is to modify the initial reference model into a time-varying reference model which satisfies the performance optimization requirement obtained from an optimal control problem. The time-varying reference model modification is accomplished by the real-time solutions of the time-varying Riccati and Sylvester equations coupled with the least-squares parameter estimation of the sensitivities of the performance metric. The effectiveness of the proposed method is demonstrated by an application of maneuver load alleviation control for a flexible aircraft.

In Vitro Analysis of Fibronectin-Modified Titanium Surfaces

PubMed Central

Chang, Yu-Chi; Lee, Wei-Fang; Feng, Sheng-Wei; Huang, Haw-Ming; Lin, Che-Tong; Teng, Nai-Chia; Chang, Wei Jen

2016-01-01

Background Glow discharge plasma (GDP) procedure is an effective method for grafting various proteins, including albumin, type I collagen, and fibronectin, onto a titanium surface. However, the behavior and impact of titanium (Ti) surface modification is yet to be unraveled. Purpose The purpose of this study is to evaluate and analyze the biological properties of fibronectin-grafted Ti surfaces treated by GDP. Materials and Methods Grade II Ti discs were initially cleaned and autoclaved to obtain original specimens. Subsequently, the specimens were GDP treated and grafted with fibronectin to form Ar-GDP (Argon GDP treatment only) and GDP-fib (fibronectin coating following GDP treatment) groups. Blood coagulation test and MG-63 cell culture were performed to evaluate the biological effects on the specimen. Results There was no significant difference between Ar-GDP and GDP-fib groups in blood compatibility analysis. While in the MTT test, cellular proliferation was benefited from the presence of fibronectin coating. The numbers of cells on Ar-GDP and GDP-fib specimens were greater than those in the original specimens after 24 h of culturing. Conclusions GDP treatment combined with fibronectin grafting favored MG-63 cell adhesion, migration, and proliferation on titanium surfaces, which could be attributed to the improved surface properties. PMID:26731536

USSR Report, Construction and Equipment, No. 78.

DTIC Science & Technology

1982-11-26

synthetic binder, fabricated by the Rostov Rigid Mineral - Wool Panels Plant of the USSR Mintyazhstroy, did not meet the requirements for...Minstroymaterialov, the Riga Cement-Slate Plant of the Latvian SSR Minstroymaterialov, and the Rostov Rigid Mineral - Wool Panels Plant of the USSR Mintyazhstroy. At...many plants, mineral - wool products are stored improperly, violating the standards— about 70 percent of the products is stored outdoors. Laboratory

Morphable Word Clouds for Time-Varying Text Data Visualization.

PubMed

Chi, Ming-Te; Lin, Shih-Syun; Chen, Shiang-Yi; Lin, Chao-Hung; Lee, Tong-Yee

2015-12-01

A word cloud is a visual representation of a collection of text documents that uses various font sizes, colors, and spaces to arrange and depict significant words. The majority of previous studies on time-varying word clouds focuses on layout optimization and temporal trend visualization. However, they do not fully consider the spatial shapes and temporal motions of word clouds, which are important factors for attracting people's attention and are also important cues for human visual systems in capturing information from time-varying text data. This paper presents a novel method that uses rigid body dynamics to arrange multi-temporal word-tags in a specific shape sequence under various constraints. Each word-tag is regarded as a rigid body in dynamics. With the aid of geometric, aesthetic, and temporal coherence constraints, the proposed method can generate a temporally morphable word cloud that not only arranges word-tags in their corresponding shapes but also smoothly transforms the shapes of word clouds over time, thus yielding a pleasing time-varying visualization. Using the proposed frame-by-frame and morphable word clouds, people can observe the overall story of a time-varying text data from the shape transition, and people can also observe the details from the word clouds in frames. Experimental results on various data demonstrate the feasibility and flexibility of the proposed method in morphable word cloud generation. In addition, an application that uses the proposed word clouds in a simulated exhibition demonstrates the usefulness of the proposed method.

Incipient Fault Detection for Rolling Element Bearings under Varying Speed Conditions.

PubMed

Xue, Lang; Li, Naipeng; Lei, Yaguo; Li, Ningbo

2017-06-20

Varying speed conditions bring a huge challenge to incipient fault detection of rolling element bearings because both the change of speed and faults could lead to the amplitude fluctuation of vibration signals. Effective detection methods need to be developed to eliminate the influence of speed variation. This paper proposes an incipient fault detection method for bearings under varying speed conditions. Firstly, relative residual (RR) features are extracted, which are insensitive to the varying speed conditions and are able to reflect the degradation trend of bearings. Then, a health indicator named selected negative log-likelihood probability (SNLLP) is constructed to fuse a feature set including RR features and non-dimensional features. Finally, based on the constructed SNLLP health indicator, a novel alarm trigger mechanism is designed to detect the incipient fault. The proposed method is demonstrated using vibration signals from bearing tests and industrial wind turbines. The results verify the effectiveness of the proposed method for incipient fault detection of rolling element bearings under varying speed conditions.

A Functional Varying-Coefficient Single-Index Model for Functional Response Data

PubMed Central

Li, Jialiang; Huang, Chao; Zhu, Hongtu

2016-01-01

Motivated by the analysis of imaging data, we propose a novel functional varying-coefficient single index model (FVCSIM) to carry out the regression analysis of functional response data on a set of covariates of interest. FVCSIM represents a new extension of varying-coefficient single index models for scalar responses collected from cross-sectional and longitudinal studies. An efficient estimation procedure is developed to iteratively estimate varying coefficient functions, link functions, index parameter vectors, and the covariance function of individual functions. We systematically examine the asymptotic properties of all estimators including the weak convergence of the estimated varying coefficient functions, the asymptotic distribution of the estimated index parameter vectors, and the uniform convergence rate of the estimated covariance function and their spectrum. Simulation studies are carried out to assess the finite-sample performance of the proposed procedure. We apply FVCSIM to investigating the development of white matter diffusivities along the corpus callosum skeleton obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. PMID:29200540

A Functional Varying-Coefficient Single-Index Model for Functional Response Data.

PubMed

Li, Jialiang; Huang, Chao; Zhu, Hongtu

2017-01-01

Motivated by the analysis of imaging data, we propose a novel functional varying-coefficient single index model (FVCSIM) to carry out the regression analysis of functional response data on a set of covariates of interest. FVCSIM represents a new extension of varying-coefficient single index models for scalar responses collected from cross-sectional and longitudinal studies. An efficient estimation procedure is developed to iteratively estimate varying coefficient functions, link functions, index parameter vectors, and the covariance function of individual functions. We systematically examine the asymptotic properties of all estimators including the weak convergence of the estimated varying coefficient functions, the asymptotic distribution of the estimated index parameter vectors, and the uniform convergence rate of the estimated covariance function and their spectrum. Simulation studies are carried out to assess the finite-sample performance of the proposed procedure. We apply FVCSIM to investigating the development of white matter diffusivities along the corpus callosum skeleton obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI) study.

Lower education and living in countries with lower wealth are associated with higher disease activity in rheumatoid arthritis: results from the multinational COMORA study.

PubMed

Putrik, Polina; Ramiro, Sofia; Keszei, Andras P; Hmamouchi, Ihsane; Dougados, Maxime; Uhlig, Till; Kvien, Tore K; Boonen, Annelies

2016-03-01

To investigate the relationship of socioeconomic status (SES) on an individual and country level with disease activity in rheumatoid arthritis (RA) and explore the mediating role of uptake of costly biological disease-modifying antirheumatic drugs (bDMARDs) in this relationship. Data from a cross-sectional multinational study (COMOrbidities in RA) were used. Contribution of individual socioeconomic factors and country of residence to disease activity score with 28-joint assessment (DAS28) was explored in regression models, adjusting for relevant clinical confounders. Next, country of residence was replaced by gross domestic product (GDP) (low vs high) to investigate the contribution of SES by comparing R(2) (model fit). The mediating role of uptake of bDMARDs in the relationship between education or GDP and DAS28 was explored by testing indirect effects. In total, 3920 patients with RA were included (mean age 56 (SD 13) years, 82% women, mean DAS28 3.7 (1.6)). After adjustment, women (vs men) and low-educated (vs university) patients had 0.35 higher DAS28. Adjusted country differences in DAS28, compared with the Netherlands (lowest DAS28), varied from +0.2 (France) to +2.4 (Egypt). Patients from low GDP countries had 0.98 higher DAS28. No interactions between individual-level and country-level variables were observed. A small mediation effect of uptake of bDMARDs in the relationship between education and DAS28 (7.7%) and between GDP and DAS28 (6.7%) was observed. Female gender and lower individual or country SES were independently associated with DAS28, but did not reinforce each other. The association between lower individual SES (education) or lower country welfare (GDP) with higher DAS28 was partially mediated by uptake of bDMARDs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Scaling properties in time-varying networks with memory

NASA Astrophysics Data System (ADS)

Kim, Hyewon; Ha, Meesoon; Jeong, Hawoong

2015-12-01

The formation of network structure is mainly influenced by an individual node's activity and its memory, where activity can usually be interpreted as the individual inherent property and memory can be represented by the interaction strength between nodes. In our study, we define the activity through the appearance pattern in the time-aggregated network representation, and quantify the memory through the contact pattern of empirical temporal networks. To address the role of activity and memory in epidemics on time-varying networks, we propose temporal-pattern coarsening of activity-driven growing networks with memory. In particular, we focus on the relation between time-scale coarsening and spreading dynamics in the context of dynamic scaling and finite-size scaling. Finally, we discuss the universality issue of spreading dynamics on time-varying networks for various memory-causality tests.

On radiating baroclinic instability of zonally varying flow

NASA Technical Reports Server (NTRS)

Finley, Catherine A.; Nathan, Terrence R.

1993-01-01

A quasi-geostrophic, two-layer, beta-plane model is used to study the baroclinic instability characteristics of a zonally inhomogeneous flow. It is assumed that the disturbance varied slowly in the cross-stream direction, and the stability problem was formulated as a 1D initial value problem. Emphasis is placed on determining how the vertically averaged wind, local maximum in vertical wind shear, and length of the locally supercritical region combine to yield local instabilities. Analysis of the local disturbance energetics reveals that, for slowly varying basic states, the baroclinic energy conversion predominates within the locally unstable region. Using calculations of the basic state tendencies, it is shown that the net effect of the local instabilities is to redistribute energy from the baroclinic to the barotropic component of the basic state flow.

Time-Varying Networks of Inter-Ictal Discharging Reveal Epileptogenic Zone.

PubMed

Zhang, Luyan; Liang, Yi; Li, Fali; Sun, Hongbin; Peng, Wenjing; Du, Peishan; Si, Yajing; Song, Limeng; Yu, Liang; Xu, Peng

2017-01-01

The neuronal synchronous discharging may cause an epileptic seizure. Currently, most of the studies conducted to investigate the mechanism of epilepsy are based on EEGs or functional magnetic resonance imaging (fMRI) recorded during the ictal discharging or the resting-state, and few studies have probed into the dynamic patterns during the inter-ictal discharging that are much easier to record in clinical applications. Here, we propose a time-varying network analysis based on adaptive directed transfer function to uncover the dynamic brain network patterns during the inter-ictal discharging. In addition, an algorithm based on the time-varying outflow of information derived from the network analysis is developed to detect the epileptogenic zone. The analysis performed revealed the time-varying network patterns during different stages of inter-ictal discharging; the epileptogenic zone was activated prior to the discharge onset then worked as the source to propagate the activity to other brain regions. Consistence between the epileptogenic zones detected by our proposed approach and the actual epileptogenic zones proved that time-varying network analysis could not only reveal the underlying neural mechanism of epilepsy, but also function as a useful tool in detecting the epileptogenic zone based on the EEGs in the inter-ictal discharging.

Progress on MEVVA source VARIS at GSI

NASA Astrophysics Data System (ADS)

Adonin, A.; Hollinger, R.

2018-05-01

For the last few years, the development of the VARIS (vacuum arc ion source) was concentrated on several aspects. One of them was the production of high current ion beams of heavy metals such as Au, Pb, and Bi. The requested ion charge state for these ion species is 4+. This is quite challenging to produce in vacuum arc driven sources for reasonable beam pulse length (>120 µs) due to the physical properties of these elements. However, the situation can be dramatically improved by using the composite materials or alloys with enhanced physical properties of the cathodes. Another aspect is an increase of the beam brilliance for intense U4+ beams by the optimization of the geometry of the extraction system. A new 7-hole triode extraction system allows an increase of the extraction voltage from 30 kV to 40 kV and also reduces the outer aperture of the extracted ion beam. Thus, a record beam brilliance for the U4+ beam in front of the RFQ (Radio-Frequency Quadrupole) has been achieved, exceeding the RFQ space charge limit for an ion current of 15 mA. Several new projectiles in the middle-heavy region have been successfully developed from VARIS to fulfill the requirements of the future FAIR (Facility for Antiproton and Ion Research) programs. An influence of an auxiliary gas on the production performance of certain ion charge states as well as on operation stability has been investigated. The optimization of the ion source parameters for a maximum production efficiency and highest particle current in front of the RFQ has been performed. The next important aspect of the development will be the increase of the operation repetition rate of VARIS for all elements especially for uranium to 2.7 Hz in order to provide the maximum availability of high current ion beams for future FAIR experiments.

Welfare state regimes and population health: integrating the East Asian welfare states.

PubMed

Abdul Karim, Syahirah; Eikemo, Terje A; Bambra, Clare

2010-01-01

Epidemiological studies have consistently shown that population health varies significantly by welfare state regime. However, these studies have focused exclusively on the welfare states of Europe, North America and Australasia. This focus ignores the existence of welfare states in other parts of the world, specifically in East Asia. This study therefore investigates whether the association between population health (Infant Mortality Rates and Life Expectancy at birth) and welfare state regimes is still valid when the welfare states of East Asia are added into the analysis. It also examines whether population health is worse in the East Asian welfare states. Infant Mortality Rates and Life Expectancy at birth as well as GDP per capita and social and health expenditures as a percentage of GDP were examined in 30 welfare states, categorised into six different regimes (Scandinavian, Anglo-Saxon, Bismarckian, Southern, Eastern European and East Asian). ANOVA analysis showed significant differences by welfare state regime in the magnitude of IMR, LE, SE, HE and GDP per capita. However, when controlling for GDP per capita in the ANCOVA analyses, only Life Expectancy (R(2)=0.58, adjusted R(2)=0.47, p<0.05) and Social Expenditure (R(2)=0.70, adjusted R(2)=0.61, p<0.05) differed significantly by welfare state regime. 47% of the variation in Life Expectancy was explained by welfare state regime type. Further, the East Asian welfare states did not have the worst health outcomes. The study concludes by highlighting the need to expand comparative health analysis both in terms of the range of countries examined and also in terms of incorporating other societal and public health factors-towards a 'public health regime' analysis.

Decoupling in linear time-varying multivariable systems

NASA Technical Reports Server (NTRS)

Sankaran, V.

1973-01-01

The necessary and sufficient conditions for the decoupling of an m-input, m-output, linear time varying dynamical system by state variable feedback is described. The class of feedback matrices which decouple the system are illustrated. Systems which do not satisfy these results are described and systems with disturbances are considered. Some examples are illustrated to clarify the results.

Re-evaluation of constant versus varied punishers using empirically derived consequences.

PubMed

Toole, Lisa M; DeLeon, Iser G; Kahng, SungWoo; Ruffin, Geri E; Pletcher, Carrie A; Bowman, Lynn G

2004-01-01

Charlop, Burgio, Iwata, and Ivancic [J. Appl. Behav. Anal. 21 (1988) 89] demonstrated that varied punishment procedures produced greater or more consistent reductions of problem behavior than a constant punishment procedure. More recently, Fisher and colleagues [Res. Dev. Disabil. 15 (1994) 133; J. Appl. Behav. Anal. 27 (1994) 447] developed a systematic methodology for predicting the efficacy of various punishment procedures. Their procedure identified reinforcers and punishers (termed "empirically derived consequences" or EDC) that, when used in combination, reduced the destructive behavior of individuals with developmental disabilities who displayed automatically maintained destructive behavior. The current investigation combines these two lines of research by comparing the effects of constant versus varied punishers on the self-injury of two individuals with developmental disabilities. The punishing stimuli were selected via the procedures described by Fisher et al. and were predicted to be at varying levels of effectiveness. The varied presentation of punishers resulted in enhanced suppressive effects over the constant presentation of a punisher for one of two individuals, but only in comparison to a single stimulus predicted to be minimally effective. Even then, the differences were small. These results suggest that the additive effects of varied punishment are negligible if clinicians use stimuli predicted to be effective and are discussed in terms of the conditions under which stimulus variation could potentially enhance the effects of punishers.

Low-cost space-varying FIR filter architecture for computational imaging systems

NASA Astrophysics Data System (ADS)

Feng, Guotong; Shoaib, Mohammed; Schwartz, Edward L.; Dirk Robinson, M.

2010-01-01

Recent research demonstrates the advantage of designing electro-optical imaging systems by jointly optimizing the optical and digital subsystems. The optical systems designed using this joint approach intentionally introduce large and often space-varying optical aberrations that produce blurry optical images. Digital sharpening restores reduced contrast due to these intentional optical aberrations. Computational imaging systems designed in this fashion have several advantages including extended depth-of-field, lower system costs, and improved low-light performance. Currently, most consumer imaging systems lack the necessary computational resources to compensate for these optical systems with large aberrations in the digital processor. Hence, the exploitation of the advantages of the jointly designed computational imaging system requires low-complexity algorithms enabling space-varying sharpening. In this paper, we describe a low-cost algorithmic framework and associated hardware enabling the space-varying finite impulse response (FIR) sharpening required to restore largely aberrated optical images. Our framework leverages the space-varying properties of optical images formed using rotationally-symmetric optical lens elements. First, we describe an approach to leverage the rotational symmetry of the point spread function (PSF) about the optical axis allowing computational savings. Second, we employ a specially designed bank of sharpening filters tuned to the specific radial variation common to optical aberrations. We evaluate the computational efficiency and image quality achieved by using this low-cost space-varying FIR filter architecture.

Water-salt exchange during bedrest of varying duration

NASA Technical Reports Server (NTRS)

Natochin, Y. V.

1978-01-01

Problems associated with the status of water-sodium metabolism under bedrest programs of varying lengths were studied. The dynamics of electrolyte concentration in blood serum, functional status of kidney osmosis regulating function, and other problems are discussed.

Spatial variation of fuel loading within varying aged stands of chaparral

Treesearch

Kellie A. Uyeda; Douglas A. Stow; John F. O' Leary; Ian T. Schmidt; Philip J. Riggan

2016-01-01

Questions: How do stand-level biomass and percentage of deadmaterial in chaparral vary as a function of stand age? How do the landscape properties of aggregation index and patch size vary in each of the dominant species groups as a function of stand age? Location: Stands of 7-, 28-and 68-yr-old...

Analysis of Yearly Traffic Fluctuation on Latvian Highways

NASA Astrophysics Data System (ADS)

Freimanis, A.; Paeglı¯tis, A.

2015-11-01

Average annual daily traffic and average annual truck traffic are two most used metrics for road management decisions. They are calculated from data gathered by continuous counting stations embedded in road pavement, manual counting sessions or mobile counting devices. Last two usually do not last longer than a couple of weeks so the information gathered is influenced by yearly traffic fluctuations. Data containing a total of 8,186,871 vehicles or 1989 days from 4 WIM stations installed on highways in Latvia were used in this study. Each of the files was supposed to contain data from only 1 day and additional data were deleted. No other data cleaning steps were performed, which increased the number of vehicles as counting systems sometimes split vehicles into two. Weekly traffic and weekly truck traffic was normalized against respective average values. Each weekly value was then plotted against its number in a year for better visual perception. Weekly traffic amplitudes were used to assess differences between different locations and standard deviations for fluctuation comparison of truck and regular traffic at the same location. Results show that truck traffic fluctuates more than regular traffic during a year, especially around holidays. Differences between counting locations were larger for regular traffic than truck traffic. These results show that average annual daily traffic could be influenced more if short term counting results are adjusted by factors derived from unsuitable continuous counting stations, but truck traffic is more influenced by the time of year in which counting is done.

Users manual for linear Time-Varying Helicopter Simulation (Program TVHIS)

NASA Technical Reports Server (NTRS)

Burns, M. R.

1979-01-01

A linear time-varying helicopter simulation program (TVHIS) is described. The program is designed as a realistic yet efficient helicopter simulation. It is based on a linear time-varying helicopter model which includes rotor, actuator, and sensor models, as well as a simulation of flight computer logic. The TVHIS can generate a mean trajectory simulation along a nominal trajectory, or propagate covariance of helicopter states, including rigid-body, turbulence, control command, controller states, and rigid-body state estimates.

Robustness analysis of multirate and periodically time varying systems

NASA Technical Reports Server (NTRS)

Berg, Martin C.; Mason, Gregory S.

1991-01-01

A new method for analyzing the stability and robustness of multirate and periodically time varying systems is presented. It is shown that a multirate or periodically time varying system can be transformed into an equivalent time invariant system. For a SISO system, traditional gain and phase margins can be found by direct application of the Nyquist criterion to this equivalent time invariant system. For a MIMO system, structured and unstructured singular values can be used to determine the system's robustness. The limitations and implications of utilizing this equivalent time invariant system for calculating gain and phase margins, and for estimating robustness via singular value analysis are discussed.

Yellow-poplar seed quality varies by seed trees, stands, and years

Treesearch

G.A. Limstrom

1959-01-01

The number of year-old yellow-poplar (Liriodendron tulipifera L.) seedlings grown from equal quantities of seed varies as much among individual seed trees within a stand as among stands of different geographic location. Moreover, production will vary from one year to another. This information was obtained from an experiment begun in the Central...

A New Time-varying Concept of Risk in a Changing Climate.

PubMed

Sarhadi, Ali; Ausín, María Concepción; Wiper, Michael P

2016-10-20

In a changing climate arising from anthropogenic global warming, the nature of extreme climatic events is changing over time. Existing analytical stationary-based risk methods, however, assume multi-dimensional extreme climate phenomena will not significantly vary over time. To strengthen the reliability of infrastructure designs and the management of water systems in the changing environment, multidimensional stationary risk studies should be replaced with a new adaptive perspective. The results of a comparison indicate that current multi-dimensional stationary risk frameworks are no longer applicable to projecting the changing behaviour of multi-dimensional extreme climate processes. Using static stationary-based multivariate risk methods may lead to undesirable consequences in designing water system infrastructures. The static stationary concept should be replaced with a flexible multi-dimensional time-varying risk framework. The present study introduces a new multi-dimensional time-varying risk concept to be incorporated in updating infrastructure design strategies under changing environments arising from human-induced climate change. The proposed generalized time-varying risk concept can be applied for all stochastic multi-dimensional systems that are under the influence of changing environments.

Incipient Fault Detection for Rolling Element Bearings under Varying Speed Conditions

PubMed Central

Xue, Lang; Li, Naipeng; Lei, Yaguo; Li, Ningbo

2017-01-01

Varying speed conditions bring a huge challenge to incipient fault detection of rolling element bearings because both the change of speed and faults could lead to the amplitude fluctuation of vibration signals. Effective detection methods need to be developed to eliminate the influence of speed variation. This paper proposes an incipient fault detection method for bearings under varying speed conditions. Firstly, relative residual (RR) features are extracted, which are insensitive to the varying speed conditions and are able to reflect the degradation trend of bearings. Then, a health indicator named selected negative log-likelihood probability (SNLLP) is constructed to fuse a feature set including RR features and non-dimensional features. Finally, based on the constructed SNLLP health indicator, a novel alarm trigger mechanism is designed to detect the incipient fault. The proposed method is demonstrated using vibration signals from bearing tests and industrial wind turbines. The results verify the effectiveness of the proposed method for incipient fault detection of rolling element bearings under varying speed conditions. PMID:28773035

Synthesis procedure for linear time-varying feedback systems with large parameter ignorance

NASA Technical Reports Server (NTRS)

Mcdonald, T. E., Jr.

1972-01-01

The development of synthesis procedures for linear time-varying feedback systems is considered. It is assumed that the plant can be described by linear differential equations with time-varying coefficients; however, ignorance is associated with the plant in that only the range of the time-variations are known instead of exact functional relationships. As a result of this plant ignorance the use of time-varying compensation is ineffective so that only time-invariant compensation is employed. In addition, there is a noise source at the plant output which feeds noise through the feedback elements to the plant input. Because of this noise source the gain of the feedback elements must be as small as possible. No attempt is made to develop a stability criterion for time-varying systems in this work.

Display of high dynamic range images under varying viewing conditions

NASA Astrophysics Data System (ADS)

Borer, Tim

2017-09-01

Recent demonstrations of high dynamic range (HDR) television have shown that superb images are possible. With the emergence of an HDR television production standard (ITU-R Recommendation BT.2100) last year, HDR television production is poised to take off. However research to date has focused principally on HDR image display only under "dark" viewing conditions. HDR television will need to be displayed at varying brightness and under varying illumination (for example to view sport in daytime or on mobile devices). We know, from common practice with conventional TV, that the rendering intent (gamma) should change under brighter conditions, although this is poorly quantified. For HDR the need to render images under varying conditions is all the more acute. This paper seeks to explore the issues surrounding image display under varying conditions. It also describes how visual adaptation is affected by display brightness, surround illumination, screen size and viewing distance. Existing experimental results are presented and extended to try to quantify these effects. Using the experimental results it is described how HDR images may be displayed so that they are perceptually equivalent under different viewing conditions. A new interpretation of the experimental results is reported, yielding a new, luminance invariant model for the appropriate display "gamma". In this way the consistency of HDR image reproduction should be improved, thereby better maintaining "creative intent" in television.

Flexible Demand Management under Time-Varying Prices

NASA Astrophysics Data System (ADS)

Liang, Yong

In this dissertation, the problem of flexible demand management under time-varying prices is studied. This generic problem has many applications, which usually have multiple periods in which decisions on satisfying demand need to be made, and prices in these periods are time-varying. Examples of such applications include multi-period procurement problem, operating room scheduling, and user-end demand scheduling in the Smart Grid, where the last application is used as the main motivating story throughout the dissertation. The current grid is experiencing an upgrade with lots of new designs. What is of particular interest is the idea of passing time-varying prices that reflect electricity market conditions to end users as incentives for load shifting. One key component, consequently, is the demand management system at the user-end. The objective of the system is to find the optimal trade-off between cost saving and discomfort increment resulted from load shifting. In this dissertation, we approach this problem from the following aspects: (1) construct a generic model, solve for Pareto optimal solutions, and analyze the robust solution that optimizes the worst-case payoffs, (2) extend to a distribution-free model for multiple types of demand (appliances), for which an approximate dynamic programming (ADP) approach is developed, and (3) design other efficient algorithms for practical purposes of the flexible demand management system. We first construct a novel multi-objective flexible demand management model, in which there are a finite number of periods with time-varying prices, and demand arrives in each period. In each period, the decision maker chooses to either satisfy or defer outstanding demand to minimize costs and discomfort over a certain number of periods. We consider both the deterministic model, models with stochastic demand or prices, and when only partial information about the stochastic demand or prices is known. We first analyze the stochastic

Regularizing cosmological singularities by varying physical constants

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

Dąbrowski, Mariusz P.; Marosek, Konrad, E-mail: mpdabfz@wmf.univ.szczecin.pl, E-mail: k.marosek@wmf.univ.szczecin.pl

2013-02-01

Varying physical constant cosmologies were claimed to solve standard cosmological problems such as the horizon, the flatness and the Λ-problem. In this paper, we suggest yet another possible application of these theories: solving the singularity problem. By specifying some examples we show that various cosmological singularities may be regularized provided the physical constants evolve in time in an appropriate way.

Varying execution discipline to increase performance

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

Campbell, P.L.; Maccabe, A.B.

1993-12-22

This research investigates the relationship between execution discipline and performance. The hypothesis has two parts: 1. Different execution disciplines exhibit different performance for different computations, and 2. These differences can be effectively predicted by heuristics. A machine model is developed that can vary its execution discipline. That is, the model can execute a given program using either the control-driven, data-driven or demand-driven execution discipline. This model is referred to as a ``variable-execution-discipline`` machine. The instruction set for the model is the Program Dependence Web (PDW). The first part of the hypothesis will be tested by simulating the execution of themore » machine model on a suite of computations, based on the Livermore Fortran Kernel (LFK) Test (a.k.a. the Livermore Loops), using all three execution disciplines. Heuristics are developed to predict relative performance. These heuristics predict (a) the execution time under each discipline for one iteration of each loop and (b) the number of iterations taken by that loop; then the heuristics use those predictions to develop a prediction for the execution of the entire loop. Similar calculations are performed for branch statements. The second part of the hypothesis will be tested by comparing the results of the simulated execution with the predictions produced by the heuristics. If the hypothesis is supported, then the door is open for the development of machines that can vary execution discipline to increase performance.« less

Arbitrarily small amounts of correlation for arbitrarily varying quantum channels

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

Boche, H., E-mail: boche@tum.de, E-mail: janis.noetzel@tum.de; Nötzel, J., E-mail: boche@tum.de, E-mail: janis.noetzel@tum.de

2013-11-15

As our main result show that in order to achieve the randomness assisted message and entanglement transmission capacities of a finite arbitrarily varying quantum channel it is not necessary that sender and receiver share (asymptotically perfect) common randomness. Rather, it is sufficient that they each have access to an unlimited amount of uses of one part of a correlated bipartite source. This access might be restricted to an arbitrary small (nonzero) fraction per channel use, without changing the main result. We investigate the notion of common randomness. It turns out that this is a very costly resource – generically, itmore » cannot be obtained just by local processing of a bipartite source. This result underlines the importance of our main result. Also, the asymptotic equivalence of the maximal- and average error criterion for classical message transmission over finite arbitrarily varying quantum channels is proven. At last, we prove a simplified symmetrizability condition for finite arbitrarily varying quantum channels.« less

Isosurface Extraction in Time-Varying Fields Using a Temporal Hierarchical Index Tree

NASA Technical Reports Server (NTRS)

Shen, Han-Wei; Gerald-Yamasaki, Michael (Technical Monitor)

1998-01-01

Many high-performance isosurface extraction algorithms have been proposed in the past several years as a result of intensive research efforts. When applying these algorithms to large-scale time-varying fields, the storage overhead incurred from storing the search index often becomes overwhelming. this paper proposes an algorithm for locating isosurface cells in time-varying fields. We devise a new data structure, called Temporal Hierarchical Index Tree, which utilizes the temporal coherence that exists in a time-varying field and adoptively coalesces the cells' extreme values over time; the resulting extreme values are then used to create the isosurface cell search index. For a typical time-varying scalar data set, not only does this temporal hierarchical index tree require much less storage space, but also the amount of I/O required to access the indices from the disk at different time steps is substantially reduced. We illustrate the utility and speed of our algorithm with data from several large-scale time-varying CID simulations. Our algorithm can achieve more than 80% of disk-space savings when compared with the existing techniques, while the isosurface extraction time is nearly optimal.

Monoterpene biosynthesis potential of plant subcellular compartments.

PubMed

Dong, Lemeng; Jongedijk, Esmer; Bouwmeester, Harro; Van Der Krol, Alexander

2016-01-01

Subcellular monoterpene biosynthesis capacity based on local geranyl diphosphate (GDP) availability or locally boosted GDP production was determined for plastids, cytosol and mitochondria. A geraniol synthase (GES) was targeted to plastids, cytosol, or mitochondria. Transient expression in Nicotiana benthamiana indicated local GDP availability for each compartment but resulted in different product levels. A GDP synthase from Picea abies (PaGDPS1) was shown to boost GDP production. PaGDPS1 was also targeted to plastids, cytosol or mitochondria and PaGDPS1 and GES were coexpressed in all possible combinations. Geraniol and geraniol-derived products were analyzed by GC-MS and LC-MS, respectively. GES product levels were highest for plastid-targeted GES, followed by mitochondrial- and then cytosolic-targeted GES. For each compartment local boosting of GDP biosynthesis increased GES product levels. GDP exchange between compartments is not equal: while no GDP is exchanged from the cytosol to the plastids, 100% of GDP in mitochondria can be exchanged to plastids, while only 7% of GDP from plastids is available for mitochondria. This suggests a direct exchange mechanism for GDP between plastids and mitochondria. Cytosolic PaGDPS1 competes with plastidial GES activity, suggesting an effective drain of isopentenyl diphosphate from the plastids to the cytosol. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Dawn LAMO Image 175

NASA Image and Video Library

2016-09-20

NASA's Dawn spacecraft obtained this view of Laukumate Crater (19 miles, 30 kilometers wide) on Ceres on June 2, 2016. Laukumate is named for a Latvian goddess of agriculture. Dawn took this image from its low-altitude mapping orbit, at a distance of about 240 miles (385 kilometers) above the surface. The image resolution is 120 feet (35 meters) per pixel. http://photojournal.jpl.nasa.gov/catalog/PIA20937

JPRS Report, Soviet Union, Political Affairs.

DTIC Science & Technology

1989-09-07

Rehabilitates Cardinal Vaivods [SOVETSKAYA LATVIYA, 15 Jun 89] 35 Church Built By Boris Godunov Conducts Religious Services [I. Serebryakov...from 1920 through 1940; —the history of the LSDRP [Latvian Social-Democratic Workers Party] from 1918 ; —the evaluation of the 23 August 1939...parallels with the 1918 situation in Lithuania in our arguments are incorrect. Let us recall the fact alone that Lithuania at that time used 400 tons of

Russian Strategic Communications and Implications for NATO

DTIC Science & Technology

2017-04-06

officially opened its doors on 20 August 2015 in the Latvian capital of Riga. Today, the center conducts analysis and study of Russian information and...Walden: Military Studies Press. 2011. 23 Dr. Steve Tatham and LTC Rita Le Page. NATO Strategic Communication: More to be Done? Case Study . Riga...Fokin, Alexander. Internet Trolling as a Tool of Hybrid Warfare: The Case of Latvia. Case Study , Riga: NATO Strategic Communication Center of

Investigating Time-Varying Drivers of Grid Project Emissions Impacts

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

Barrett, Emily L.; Thayer, Brandon L.; Pal, Seemita

The emissions consequences of smart grid technologies depend heavily on their context and vary not only by geographical location, but by time of year. The same technology operated to meet the same objective may increase the emissions associated with energy generation for part of the year and decrease emissions during other times. The Grid Project Impact Quantification (GridPIQ) tool provides the ability to estimate these seasonal variations and garner insight into the time-varying drivers of grid project emissions impacts. This work leverages GridPIQ to examine the emissions implications across years and seasons of adding energy storage technology to reduce dailymore » peak demand in California and New York.« less

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.

Efficient Encoding and Rendering of Time-Varying Volume Data

NASA Technical Reports Server (NTRS)

Ma, Kwan-Liu; Smith, Diann; Shih, Ming-Yun; Shen, Han-Wei

1998-01-01

Visualization of time-varying volumetric data sets, which may be obtained from numerical simulations or sensing instruments, provides scientists insights into the detailed dynamics of the phenomenon under study. This paper describes a coherent solution based on quantization, coupled with octree and difference encoding for visualizing time-varying volumetric data. Quantization is used to attain voxel-level compression and may have a significant influence on the performance of the subsequent encoding and visualization steps. Octree encoding is used for spatial domain compression, and difference encoding for temporal domain compression. In essence, neighboring voxels may be fused into macro voxels if they have similar values, and subtrees at consecutive time steps may be merged if they are identical. The software rendering process is tailored according to the tree structures and the volume visualization process. With the tree representation, selective rendering may be performed very efficiently. Additionally, the I/O costs are reduced. With these combined savings, a higher level of user interactivity is achieved. We have studied a variety of time-varying volume datasets, performed encoding based on data statistics, and optimized the rendering calculations wherever possible. Preliminary tests on workstations have shown in many cases tremendous reduction by as high as 90% in both storage space and inter-frame delay.

Simulations of Dynamical Friction Including Spatially-Varying Magnetic Fields

NASA Astrophysics Data System (ADS)

Bell, G. I.; Bruhwiler, D. L.; Litvinenko, V. N.; Busby, R.; Abell, D. T.; Messmer, P.; Veitzer, S.; Cary, J. R.

2006-03-01

A proposed luminosity upgrade to the Relativistic Heavy Ion Collider (RHIC) includes a novel electron cooling section, which would use ˜55 MeV electrons to cool fully-ionized 100 GeV/nucleon gold ions. We consider the dynamical friction force exerted on individual ions due to a relevant electron distribution. The electrons may be focussed by a strong solenoid field, with sensitive dependence on errors, or by a wiggler field. In the rest frame of the relativistic co-propagating electron and ion beams, where the friction force can be simulated for nonrelativistic motion and electrostatic fields, the Lorentz transform of these spatially-varying magnetic fields includes strong, rapidly-varying electric fields. Previous friction force simulations for unmagnetized electrons or error-free solenoids used a 4th-order Hermite algorithm, which is not well-suited for the inclusion of strong, rapidly-varying external fields. We present here a new algorithm for friction force simulations, using an exact two-body collision model to accurately resolve close interactions between electron/ion pairs. This field-free binary-collision model is combined with a modified Boris push, using an operator-splitting approach, to include the effects of external fields. The algorithm has been implemented in the VORPAL code and successfully benchmarked.

Edge Modeling by Two Blur Parameters in Varying Contrasts.

PubMed

Seo, Suyoung

2018-06-01

This paper presents a method of modeling edge profiles with two blur parameters, and estimating and predicting those edge parameters with varying brightness combinations and camera-to-object distances (COD). First, the validity of the edge model is proven mathematically. Then, it is proven experimentally with edges from a set of images captured for specifically designed target sheets and with edges from natural images. Estimation of the two blur parameters for each observed edge profile is performed with a brute-force method to find parameters that produce global minimum errors. Then, using the estimated blur parameters, actual blur parameters of edges with arbitrary brightness combinations are predicted using a surface interpolation method (i.e., kriging). The predicted surfaces show that the two blur parameters of the proposed edge model depend on both dark-side edge brightness and light-side edge brightness following a certain global trend. This is similar across varying CODs. The proposed edge model is compared with a one-blur parameter edge model using experiments of the root mean squared error for fitting the edge models to each observed edge profile. The comparison results suggest that the proposed edge model has superiority over the one-blur parameter edge model in most cases where edges have varying brightness combinations.

Simple reaction time to the onset of time-varying sounds.

PubMed

Schlittenlacher, Josef; Ellermeier, Wolfgang

2015-10-01

Although auditory simple reaction time (RT) is usually defined as the time elapsing between the onset of a stimulus and a recorded reaction, a sound cannot be specified by a single point in time. Therefore, the present work investigates how the period of time immediately after onset affects RT. By varying the stimulus duration between 10 and 500 msec, this critical duration was determined to fall between 32 and 40 milliseconds for a 1-kHz pure tone at 70 dB SPL. In a second experiment, the role of the buildup was further investigated by varying the rise time and its shape. The increment in RT for extending the rise time by a factor of ten was about 7 to 8 msec. There was no statistically significant difference in RT between a Gaussian and linear rise shape. A third experiment varied the modulation frequency and point of onset of amplitude-modulated tones, producing onsets at different initial levels with differently rapid increase or decrease immediately afterwards. The results of all three experiments results were explained very well by a straightforward extension of the parallel grains model (Miller and Ulrich Cogn. Psychol. 46, 101-151, 2003), a probabilistic race model employing many parallel channels. The extension of the model to time-varying sounds made the activation of such a grain depend on intensity as a function of time rather than a constant level. A second approach by mechanisms known from loudness produced less accurate predictions.

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database.

PubMed

Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

2009-11-01

To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

Time-varying Concurrent Risk of Extreme Droughts and Heatwaves in California

NASA Astrophysics Data System (ADS)

Sarhadi, A.; Diffenbaugh, N. S.; Ausin, M. C.

2016-12-01

Anthropogenic global warming has changed the nature and the risk of extreme climate phenomena such as droughts and heatwaves. The concurrent of these nature-changing climatic extremes may result in intensifying undesirable consequences in terms of human health and destructive effects in water resources. The present study assesses the risk of concurrent extreme droughts and heatwaves under dynamic nonstationary conditions arising from climate change in California. For doing so, a generalized fully Bayesian time-varying multivariate risk framework is proposed evolving through time under dynamic human-induced environment. In this methodology, an extreme, Bayesian, dynamic copula (Gumbel) is developed to model the time-varying dependence structure between the two different climate extremes. The time-varying extreme marginals are previously modeled using a Generalized Extreme Value (GEV) distribution. Bayesian Markov Chain Monte Carlo (MCMC) inference is integrated to estimate parameters of the nonstationary marginals and copula using a Gibbs sampling method. Modelled marginals and copula are then used to develop a fully Bayesian, time-varying joint return period concept for the estimation of concurrent risk. Here we argue that climate change has increased the chance of concurrent droughts and heatwaves over decades in California. It is also demonstrated that a time-varying multivariate perspective should be incorporated to assess realistic concurrent risk of the extremes for water resources planning and management in a changing climate in this area. The proposed generalized methodology can be applied for other stochastic nature-changing compound climate extremes that are under the influence of climate change.

Additional Surgery after Breast-Conserving Surgery Varies Widely

Cancer.gov

A study published in the Feb. 1, 2012, issue of JAMA found that the number of women who have one or more additional surgeries to remove suspected residual tumor tissue (re-excisions) following breast-conserving surgery (BCS) for breast cancer varies widely across surgeons and hospitals.

A Tentative Application Of Morphological Filters To Time-Varying Images

NASA Astrophysics Data System (ADS)

Billard, D.; Poquillon, B.

1989-03-01

In this paper, morphological filters, which are commonly used to process either 2D or multidimensional static images, are generalized to the analysis of time-varying image sequence. The introduction of the time dimension induces then interesting prop-erties when designing such spatio-temporal morphological filters. In particular, the specification of spatio-temporal structuring ele-ments (equivalent to time-varying spatial structuring elements) can be adjusted according to the temporal variations of the image sequences to be processed : this allows to derive specific morphological transforms to perform noise filtering or moving objects discrimination on dynamic images viewed by a non-stationary sensor. First, a brief introduction to the basic principles underlying morphological filters will be given. Then, a straightforward gener-alization of these principles to time-varying images will be pro-posed. This will lead us to define spatio-temporal opening and closing and to introduce some of their possible applications to process dynamic images. At last, preliminary results obtained us-ing a natural forward looking infrared (FUR) image sequence are presented.

[Design of a miniaturized blood temperature-varying system based on computer distributed control].

PubMed

Xu, Qiang; Zhou, Zhaoying; Peng, Jiegang; Zhu, Junhua

2007-10-01

Blood temperature-varying has been widely applied in clinical practice such as extracorporeal circulation for whole-body perfusion hyperthermia (WBPH), body rewarming and blood temperature-varying in organ transplantation. This paper reports a novel DCS (Computer distributed control)-based blood temperature-varying system which includes therapy management function and whose hardware and software can be extended easily. Simulation results illustrate that this system provides precise temperature control with good performance in various operation conditions.

Networking among women snowboarders: a study of participants at an International Woman Snowboard Camp.

PubMed

Sisjord, M K

2012-02-01

The article focuses on women snowboarders' networking and relationships with national snowboard associations and commercial organizers. The study was conducted at an International Women Snowboard Camp, which attracted women snowboarders from five different countries. A qualitative interview was undertaken with participants from each country, eight in total, plus an interview with one of the organizers (a woman). The results indicate that participants from the Nordic countries adopt a more proactive stand to promote snowboarding by organizing specific groups in relation to national associations, particularly the Norwegians and the Finnish. Furthermore, some collaboration across national boarders appeared. The only Swedish participant was associated with several snowboarding communities; whereas the Italian (only one) and the Latvian snowboarders had links with commercial organizers, apparently male dominated in structure. The findings are discussed in the light of Castells' network theory and identity construction in social movements, and gender perspectives. The participants' doing/undoing gender reveals different strategies in negotiating hegemonic masculinity and the power structure in the organizations. Narratives from the Nordic participants reflect undoing gender that impacts on identity constructions in terms of project and/or resistance identity. The Italians and Latvians seemingly do gender while undertaking a subordinate position in the male-dominated structure. © 2010 John Wiley & Sons A/S.

The Effects of Varying Pictorial Detail and Presentation Strategy on Concept Formation.

ERIC Educational Resources Information Center

Gorman, Don A.

The purpose of this study is to determine the effects of varying pictorial detail and presentation strategy on learners of varying grade levels in a visually transmitted concept formation task. Specifically, line drawings containing only relevant details and halftones containing relevant and irrelevant detail were presented successively and…

Shape and Spatially-Varying Reflectance Estimation from Virtual Exemplars.

PubMed

Hui, Zhuo; Sankaranarayanan, Aswin C

2017-10-01

This paper addresses the problem of estimating the shape of objects that exhibit spatially-varying reflectance. We assume that multiple images of the object are obtained under a fixed view-point and varying illumination, i.e., the setting of photometric stereo. At the core of our techniques is the assumption that the BRDF at each pixel lies in the non-negative span of a known BRDF dictionary. This assumption enables a per-pixel surface normal and BRDF estimation framework that is computationally tractable and requires no initialization in spite of the underlying problem being non-convex. Our estimation framework first solves for the surface normal at each pixel using a variant of example-based photometric stereo. We design an efficient multi-scale search strategy for estimating the surface normal and subsequently, refine this estimate using a gradient descent procedure. Given the surface normal estimate, we solve for the spatially-varying BRDF by constraining the BRDF at each pixel to be in the span of the BRDF dictionary; here, we use additional priors to further regularize the solution. A hallmark of our approach is that it does not require iterative optimization techniques nor the need for careful initialization, both of which are endemic to most state-of-the-art techniques. We showcase the performance of our technique on a wide range of simulated and real scenes where we outperform competing methods.

Locating multiple diffusion sources in time varying networks from sparse observations.

PubMed

Hu, Zhao-Long; Shen, Zhesi; Cao, Shinan; Podobnik, Boris; Yang, Huijie; Wang, Wen-Xu; Lai, Ying-Cheng

2018-02-08

Data based source localization in complex networks has a broad range of applications. Despite recent progress, locating multiple diffusion sources in time varying networks remains to be an outstanding problem. Bridging structural observability and sparse signal reconstruction theories, we develop a general framework to locate diffusion sources in time varying networks based solely on sparse data from a small set of messenger nodes. A general finding is that large degree nodes produce more valuable information than small degree nodes, a result that contrasts that for static networks. Choosing large degree nodes as the messengers, we find that sparse observations from a few such nodes are often sufficient for any number of diffusion sources to be located for a variety of model and empirical networks. Counterintuitively, sources in more rapidly varying networks can be identified more readily with fewer required messenger nodes.

Optimal critic learning for robot control in time-varying environments.

PubMed

Wang, Chen; Li, Yanan; Ge, Shuzhi Sam; Lee, Tong Heng

2015-10-01

In this paper, optimal critic learning is developed for robot control in a time-varying environment. The unknown environment is described as a linear system with time-varying parameters, and impedance control is employed for the interaction control. Desired impedance parameters are obtained in the sense of an optimal realization of the composite of trajectory tracking and force regulation. Q -function-based critic learning is developed to determine the optimal impedance parameters without the knowledge of the system dynamics. The simulation results are presented and compared with existing methods, and the efficacy of the proposed method is verified.

An integrative time-varying frequency detection and channel sounding method for dynamic plasma sheath

NASA Astrophysics Data System (ADS)

Shi, Lei; Yao, Bo; Zhao, Lei; Liu, Xiaotong; Yang, Min; Liu, Yanming

2018-01-01

The plasma sheath-surrounded hypersonic vehicle is a dynamic and time-varying medium and it is almost impossible to calculate time-varying physical parameters directly. The in-fight detection of the time-varying degree is important to understand the dynamic nature of the physical parameters and their effect on re-entry communication. In this paper, a constant envelope zero autocorrelation (CAZAC) sequence based on time-varying frequency detection and channel sounding method is proposed to detect the plasma sheath electronic density time-varying property and wireless channel characteristic. The proposed method utilizes the CAZAC sequence, which has excellent autocorrelation and spread gain characteristics, to realize dynamic time-varying detection/channel sounding under low signal-to-noise ratio in the plasma sheath environment. Theoretical simulation under a typical time-varying radio channel shows that the proposed method is capable of detecting time-variation frequency up to 200 kHz and can trace the channel amplitude and phase in the time domain well under -10 dB. Experimental results conducted in the RF modulation discharge plasma device verified the time variation detection ability in practical dynamic plasma sheath. Meanwhile, nonlinear phenomenon of dynamic plasma sheath on communication signal is observed thorough channel sounding result.

Human Newborn Color Vision: Measurement with Chromatic Stimuli Varying in Excitation Purity.

ERIC Educational Resources Information Center

Adams, Russell J.; Courage, Mary L.

1998-01-01

Habituated 180 neonates to white lights of varying luminance and tested for recovery of habituation to green, yellow, or red lights varying in excitation purity. Found that newborns discriminated chromatic stimuli from white only when excitation purity exceeded levels much higher than those for adults. Results reinforce view that neonates' vision…

Using Activity Schedules to Promote Varied Application Use in Children with Autism

ERIC Educational Resources Information Center

Brodhead, Matthew T.; Courtney, William Timothy; Thaxton, Jackie R.

2018-01-01

We evaluated the effects of an activity schedule embedded within an iPad on varied play across applications. After establishing a pattern of repetitive gameplay, we taught three children with autism to follow the activity schedule using physical guidance. All participants increased their varied play to four applications per session and…

Supported employment for people with severe mental illness: systematic review and meta-analysis of the international evidence.

PubMed

Modini, Matthew; Tan, Leona; Brinchmann, Beate; Wang, Min-Jung; Killackey, Eoin; Glozier, Nicholas; Mykletun, Arnstein; Harvey, Samuel B

2016-07-01

Individual placement and support (IPS) is a vocational rehabilitation programme that was developed in the USA to improve employment outcomes for people with severe mental illness. Its ability to be generalised to other countries and its effectiveness in varying economic conditions remains to be ascertained. To investigate whether IPS is effective across international settings and in different economic conditions. A systematic review and meta-analysis of randomised controlled trials comparing IPS with traditional vocational services was undertaken; 17 studies, as well as 2 follow-up studies, were included. Meta-regressions were carried out to examine whether IPS effectiveness varied according to geographic location, unemployment rates or gross domestic product (GDP) growth. The overall pooled risk ratio for competitive employment using IPS compared with traditional vocational rehabilitation was 2.40 (95% CI 1.99-2.90). Meta-regressions indicated that neither geographic area nor unemployment rates affected the overall effectiveness of IPS. Even when a country's GDP growth was less than 2% IPS was significantly more effective than traditional vocational training, and its benefits remained evident over 2 years. Individual placement and support is an effective intervention across a variety of settings and economic conditions and is more than twice as likely to lead to competitive employment when compared with traditional vocational rehabilitation. © The Royal College of Psychiatrists 2016.

Time-varying output performances of piezoelectric vibration energy harvesting under nonstationary random vibrations

NASA Astrophysics Data System (ADS)

Yoon, Heonjun; Kim, Miso; Park, Choon-Su; Youn, Byeng D.

2018-01-01

Piezoelectric vibration energy harvesting (PVEH) has received much attention as a potential solution that could ultimately realize self-powered wireless sensor networks. Since most ambient vibrations in nature are inherently random and nonstationary, the output performances of PVEH devices also randomly change with time. However, little attention has been paid to investigating the randomly time-varying electroelastic behaviors of PVEH systems both analytically and experimentally. The objective of this study is thus to make a step forward towards a deep understanding of the time-varying performances of PVEH devices under nonstationary random vibrations. Two typical cases of nonstationary random vibration signals are considered: (1) randomly-varying amplitude (amplitude modulation; AM) and (2) randomly-varying amplitude with randomly-varying instantaneous frequency (amplitude and frequency modulation; AM-FM). In both cases, this study pursues well-balanced correlations of analytical predictions and experimental observations to deduce the relationships between the time-varying output performances of the PVEH device and two primary input parameters, such as a central frequency and an external electrical resistance. We introduce three correlation metrics to quantitatively compare analytical prediction and experimental observation, including the normalized root mean square error, the correlation coefficient, and the weighted integrated factor. Analytical predictions are in an excellent agreement with experimental observations both mechanically and electrically. This study provides insightful guidelines for designing PVEH devices to reliably generate electric power under nonstationary random vibrations.

Electro-optic device having a laterally varying region

NASA Technical Reports Server (NTRS)

Andrews, James T. (Inventor); Ladany, Ivan (Inventor)

1989-01-01

A distributed feedback laser comprising a semiconductor body having a channel which varies in width in the laterial direction and is periodic in the longitudinal direction. When the laser is electrically excited constructive interference of reflected light gives rise to a stable single wavelength output due to the periodic variations in the channel.

A Symmetric Time-Varying Cluster Rate of Descent Model

NASA Technical Reports Server (NTRS)

Ray, Eric S.

2015-01-01

A model of the time-varying rate of descent of the Orion vehicle was developed based on the observed correlation between canopy projected area and drag coefficient. This initial version of the model assumes cluster symmetry and only varies the vertical component of velocity. The cluster fly-out angle is modeled as a series of sine waves based on flight test data. The projected area of each canopy is synchronized with the primary fly-out angle mode. The sudden loss of projected area during canopy collisions is modeled at minimum fly-out angles, leading to brief increases in rate of descent. The cluster geometry is converted to drag coefficient using empirically derived constants. A more complete model is under development, which computes the aerodynamic response of each canopy to its local incidence angle.

Generating survival times to simulate Cox proportional hazards models with time-varying covariates.

PubMed

Austin, Peter C

2012-12-20

Simulations and Monte Carlo methods serve an important role in modern statistical research. They allow for an examination of the performance of statistical procedures in settings in which analytic and mathematical derivations may not be feasible. A key element in any statistical simulation is the existence of an appropriate data-generating process: one must be able to simulate data from a specified statistical model. We describe data-generating processes for the Cox proportional hazards model with time-varying covariates when event times follow an exponential, Weibull, or Gompertz distribution. We consider three types of time-varying covariates: first, a dichotomous time-varying covariate that can change at most once from untreated to treated (e.g., organ transplant); second, a continuous time-varying covariate such as cumulative exposure at a constant dose to radiation or to a pharmaceutical agent used for a chronic condition; third, a dichotomous time-varying covariate with a subject being able to move repeatedly between treatment states (e.g., current compliance or use of a medication). In each setting, we derive closed-form expressions that allow one to simulate survival times so that survival times are related to a vector of fixed or time-invariant covariates and to a single time-varying covariate. We illustrate the utility of our closed-form expressions for simulating event times by using Monte Carlo simulations to estimate the statistical power to detect as statistically significant the effect of different types of binary time-varying covariates. This is compared with the statistical power to detect as statistically significant a binary time-invariant covariate. Copyright © 2012 John Wiley & Sons, Ltd.

Fast space-varying convolution using matrix source coding with applications to camera stray light reduction.

PubMed

Wei, Jianing; Bouman, Charles A; Allebach, Jan P

2014-05-01

Many imaging applications require the implementation of space-varying convolution for accurate restoration and reconstruction of images. Here, we use the term space-varying convolution to refer to linear operators whose impulse response has slow spatial variation. In addition, these space-varying convolution operators are often dense, so direct implementation of the convolution operator is typically computationally impractical. One such example is the problem of stray light reduction in digital cameras, which requires the implementation of a dense space-varying deconvolution operator. However, other inverse problems, such as iterative tomographic reconstruction, can also depend on the implementation of dense space-varying convolution. While space-invariant convolution can be efficiently implemented with the fast Fourier transform, this approach does not work for space-varying operators. So direct convolution is often the only option for implementing space-varying convolution. In this paper, we develop a general approach to the efficient implementation of space-varying convolution, and demonstrate its use in the application of stray light reduction. Our approach, which we call matrix source coding, is based on lossy source coding of the dense space-varying convolution matrix. Importantly, by coding the transformation matrix, we not only reduce the memory required to store it; we also dramatically reduce the computation required to implement matrix-vector products. Our algorithm is able to reduce computation by approximately factoring the dense space-varying convolution operator into a product of sparse transforms. Experimental results show that our method can dramatically reduce the computation required for stray light reduction while maintaining high accuracy.

JPRS Report, Soviet Union, Political Affairs.

DTIC Science & Technology

1990-06-08

love, labor... 4 May Latvian Supreme Soviet Acitivities 90UN1929A Riga SOVETSKAYA LATVIYA in Russian 5 May 90 p 1 [LETA "Information Report...each oblast of modern diagnostic centers, an improvement in the protection of mother and child, the development of mass physical culture and sport...groups of people do not want to recognize the realities; their actions are beginning to take on a patently aggressive nature. In a recent interview

JPRS Report, Soviet Union, Political Affairs.

DTIC Science & Technology

1989-07-10

MAKSALA, 11 Mar 89] oy ’Creeping Immigration ’ In Latvian Atomic Energy Enterprise [V. Brinkmanis; LITERATURA UN MAKSLA No 11, 18 Mar 89] /u... therapists ). During the tragic events of 9 April and in subsequent days, 3,515 victims asked for and received out-patient care (students at the First...great deal, and not just belles lettres. After secondary school I graduated from the Faculty of Mathematical Physics at the univer- sity, and I

USSR Report, Political and Sociological Affairs, Number 1309.

DTIC Science & Technology

1982-09-23

the society’s work. There has occurred with this thematic material a turn away from the giving of review lectures to lectures on the concrete and...SOVETSKAYA LATVIYA, 7 Aug 82) 82 Book on Latvian Labor Resource Problems Reviewed ( A . Tsitse; KOMMUNIST SOVETSKOY LATVII, Jul 82) 85...ideological work, which has always been and remains one of CPSU’s primary tasks. This work is variegated and it requires a scientific analysis of the

Insulin, not glutamine dipeptide, reduces lipases expression and prevents fat wasting and weight loss in Walker 256 tumor-bearing rats.

PubMed

de Morais, Hely; de Fatima Silva, Flaviane; da Silva, Francemilson Goulart; Silva, Milene Ortiz; Graciano, Maria Fernanda Rodrigues; Martins, Maria Isabel Lovo; Carpinelli, Ângelo Rafael; Mazucco, Tânia Longo; Bazotte, Roberto Barbosa; de Souza, Helenir Medri

2017-07-05

Cachexia is the main cause of mortality in advanced cancer patients. We investigated the effects of insulin (INS) and glutamine dipeptide (GDP), isolated or associated, on cachexia and metabolic changes induced by Walker 256 tumor in rats. INS (NPH, 40 UI/kg, sc) or GDP (1.5g/kg, oral gavage) was once-daily administered during 11 days after tumor cell inoculation. GDP, INS or INS+GDP treatments did not influence the tumor growth. However, INS and INS+GDP prevented retroperitoneal fat wasting and body weight loss of tumor-bearing rats. In consistency, INS and INS+GDP prevented the increased expression of triacylglycerol lipase (ATGL) and hormone sensitive lipase (HSL), without changing the expression of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the retroperitoneal adipose tissue of tumor-bearing rats. INS and INS+GDP also prevented anorexia and hyperlactatemia of tumor-bearing rats. However, INS and INS+GDP accentuated the loss of muscle mass (gastrocnemius, soleus and long digital extensor) without affecting the myostatin expression in the gastrocnemius muscle and blood corticosterone. GDP treatment did not promote beneficial effects. It can be concluded that treatment with INS (INS or INS+GDP), not with GDP, prevented fat wasting and weight loss in tumor-bearing rats without reducing tumor growth. These effects might be attributed to the reduction of lipases expression (ATGL and LHS) and increased food intake. The results show the physiological function of INS in the suppression of lipolysis induced by cachexia mediators in tumor-bearing rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Dealing with the time-varying parameter problem of robot manipulators performing path tracking tasks

NASA Technical Reports Server (NTRS)

Song, Y. D.; Middleton, R. H.

1992-01-01

Many robotic applications involve time-varying payloads during the operation of the robot. It is therefore of interest to consider control schemes that deal with time-varying parameters. Using the properties of the element by element (or Hadarmad) product of matrices, we obtain the robot dynamics in parameter-isolated form, from which a new control scheme is developed. The controller proposed yields zero asymptotic tracking errors when applied to robotic systems with time-varying parameters by using a switching type control law. The results obtained are global in the initial state of the robot, and can be applied to rapidly varying systems.

Prediction-Correction Algorithms for Time-Varying Constrained Optimization

DOE PAGES

Simonetto, Andrea; Dall'Anese, Emiliano

2017-07-26

This article develops online algorithms to track solutions of time-varying constrained optimization problems. Particularly, resembling workhorse Kalman filtering-based approaches for dynamical systems, the proposed methods involve prediction-correction steps to provably track the trajectory of the optimal solutions of time-varying convex problems. The merits of existing prediction-correction methods have been shown for unconstrained problems and for setups where computing the inverse of the Hessian of the cost function is computationally affordable. This paper addresses the limitations of existing methods by tackling constrained problems and by designing first-order prediction steps that rely on the Hessian of the cost function (and do notmore » require the computation of its inverse). In addition, the proposed methods are shown to improve the convergence speed of existing prediction-correction methods when applied to unconstrained problems. Numerical simulations corroborate the analytical results and showcase performance and benefits of the proposed algorithms. A realistic application of the proposed method to real-time control of energy resources is presented.« less

Parallel Rendering of Large Time-Varying Volume Data

NASA Technical Reports Server (NTRS)

Garbutt, Alexander E.

2005-01-01

Interactive visualization of large time-varying 3D volume datasets has been and still is a great challenge to the modem computational world. It stretches the limits of the memory capacity, the disk space, the network bandwidth and the CPU speed of a conventional computer. In this SURF project, we propose to develop a parallel volume rendering program on SGI's Prism, a cluster computer equipped with state-of-the-art graphic hardware. The proposed program combines both parallel computing and hardware rendering in order to achieve an interactive rendering rate. We use 3D texture mapping and a hardware shader to implement 3D volume rendering on each workstation. We use SGI's VisServer to enable remote rendering using Prism's graphic hardware. And last, we will integrate this new program with ParVox, a parallel distributed visualization system developed at JPL. At the end of the project, we Will demonstrate remote interactive visualization using this new hardware volume renderer on JPL's Prism System using a time-varying dataset from selected JPL applications.

Time-varying wall stress: an index of ventricular vascular coupling.

PubMed

Dell'Italia, L J; Blackwell, G G; Thorn, B T; Pearce, D J; Bishop, S P; Pohost, G M

1992-08-01

Previous work in the isolated heart and intact circulation has suggested that the relationship between wall stress and time during left ventricular (LV) ejection is linear and that the slope, which will be referred to as time-varying wall stress, increases in response to augmentation in afterload. However, the etiology of the increase in slope has not been determined in an intact animal. Magnetic resonance imaging coupled with high-fidelity LV pressure measurement using a nonferrous catheter-tip manometer generates a detailed assessment of wall stress in an animal model where the thorax and pericardium have never been disturbed. Accordingly, six anesthetized dogs were studied during autonomic blockade with atropine and propranolol during angiotensin infusion, producing three widely disparate left ventricular systolic pressures (87 +/- 7 vs. 124 +/- 13 vs. 152 +/- 10 mmHg, P less than 0.001). Time-varying wall stress did not change from low to medium load (-42.4 +/- 9.5 to -27.3 +/- 22.3 g.cm-2.ms-1) but increased significantly at high load (-21.7 +/- 14.9 g.cm-2.ms-1, P less than 0.05). Analysis of the relative contribution of pressure, chamber radius, wall thickness, and long-axis dimension to the changes in time-varying wall stress demonstrated only the pressure component to change its relative contribution at medium (P less than 0.001) and high load (P less than 0.001). Therefore, we conclude that the increase in time-varying wall stress results from augmentation of pressure in the latter one-half of systole that is incompletely offset by shortening and wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program.

PubMed

Grøn, Kathrine Lederballe; Ornbjerg, Lykke Midtbøll; Hetland, Merete Lund; Aslam, Fawad; Khan, Nasim A; Jacobs, Johannes W G; Henrohn, Dan; Rasker, J J; Kauppi, Markku J; Lang, Hui-Chu; Mota, Licia M H; Aggarwal, Amita; Yamanaka, Hisahi; Badsha, Humeira; Gossec, Laure; Cutolo, Maurizio; Ferraccioli, Gianfranco; Gremese, Elisa; Bong Lee, Eun; Inanc, Nevsun; Direskeneli, Haner; Taylor, Peter; Huisman, Margriet; Alten, Rieke; Pohl, Christoph; Oyoo, Omondi; Stropuviene, Sigita; Drosos, Alexandrosos A; Kerzberg, Eduardo; Ancuta, Codorina; Mofti, Ayman; Bergman, Martin; Detert, Jaqueline; Selim, Zaraa I; Abda, Essam A; Rexhepi, Blerta; Sokka, Tuulikki

2014-01-01

The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.

Insight into Temperature Dependence of GTPase Activity in Human Guanylate Binding Protein-1

PubMed Central

Rahman, Safikur; Deep, Shashank; Sau, Apurba Kumar

2012-01-01

Interferon-γ induced human guanylate binding protein-1(hGBP1) belongs to a family of dynamin related large GTPases. Unlike all other GTPases, hGBP1 hydrolyzes GTP to a mixture of GDP and GMP with GMP being the major product at 37°C but GDP became significant when the hydrolysis reaction was carried out at 15°C. The hydrolysis reaction in hGBP1 is believed to involve with a number of catalytic steps. To investigate the effect of temperature in the product formation and on the different catalytic complexes of hGBP1, we carried out temperature dependent GTPase assays, mutational analysis, chemical and thermal denaturation studies. The Arrhenius plot for both GDP and GMP interestingly showed nonlinear behaviour, suggesting that the product formation from the GTP-bound enzyme complex is associated with at least more than one step. The negative activation energy for GDP formation and GTPase assay with external GDP together indicate that GDP formation occurs through the reversible dissociation of GDP-bound enzyme dimer to monomer, which further reversibly dissociates to give the product. Denaturation studies of different catalytic complexes show that unlike other complexes the free energy of GDP-bound hGBP1 decreases significantly at lower temperature. GDP formation is found to be dependent on the free energy of the GDP-bound enzyme complex. The decrease in the free energy of this complex at low temperature compared to at high is the reason for higher GDP formation at low temperature. Thermal denaturation studies also suggest that the difference in the free energy of the GTP-bound enzyme dimer compared to its monomer plays a crucial role in the product formation; higher stability favours GMP but lower favours GDP. Thus, this study provides the first thermodynamic insight into the effect of temperature in the product formation of hGBP1. PMID:22859948

An example of slip instability resulting from displacement-varying strength

USGS Publications Warehouse

Lockner, D.; Byerlee, J.

1990-01-01

A rock cylinder, containing a clay-filled sawcut making an angle of 30?? to the sample axis, was deformed at constant confining and pore pressures and constant remote shortening rate. The sawcut surfaces contained a series of regularly spaced ridges and grooves oriented perpendicular to the direction of shear. The interaction of these grooved surfaces resulted in a sliding strength which varied periodically with displacement. By varying the effective machine stiffness through the use of an electronic feedback circuit, a range of stable and unstable slip behavior was achieved. In this way, we examined fault slip behavior which was dominated by displacement-dependent strength. ?? 1990 Birkha??user Verlag.

Skyrmion dynamics in width-varying nanotracks and implications for skyrmionic applications

NASA Astrophysics Data System (ADS)

Chen, Xing; Kang, Wang; Zhu, Daoqian; Zhang, Xichao; Lei, Na; Zhang, Youguang; Zhou, Yan; Zhao, Weisheng

2017-11-01

A comprehensive study of the magnetic skyrmion dynamics in terms of size, velocity, energy, and stability in width-varying nanotracks is reported by micromagnetic simulations. We find that the diameter of a skyrmion reduces with the decrease in the nanotrack width in the spin Hall effect (SHE)-induced skyrmion motion. Accordingly, the skyrmion energy increases giving rise to the growing instability of the skyrmion. It is also numerically demonstrated that the velocity of the skyrmion varies during the motion, since the repulsive force of the nanotrack edges acting on the skyrmion as well as the driving force created by the SHE associated with the size of the skyrmion have a joint impact on the skyrmion motion dynamics in the width-varying nanotrack. In addition, one interesting finding reveals that skyrmions with small sizes, which may be inaccessible to typical approaches by means of directly injecting a spin-polarized current, could be obtained by utilizing this structure. This finding is potential for generating nanoscale skyrmions in skyrmionic applications with ultra-dense density. Finally, inspired by the skyrmion dynamics in the width-varying nanotrack, a general summary on the tradeoff between the nanotrack width (storage density) and the skyrmion velocity (data access speed) is given by further analyzing the skyrmion dynamics in parallel nanotracks with different widths, which may provide guidelines in designing racetrack-type skyrmionic applications.

Opinion formation in time-varying social networks: The case of the naming game

NASA Astrophysics Data System (ADS)

Maity, Suman Kalyan; Manoj, T. Venkat; Mukherjee, Animesh

2012-09-01

We study the dynamics of the naming game as an opinion formation model on time-varying social networks. This agent-based model captures the essential features of the agreement dynamics by means of a memory-based negotiation process. Our study focuses on the impact of time-varying properties of the social network of the agents on the naming game dynamics. In particular, we perform a computational exploration of this model using simulations on top of real networks. We investigate the outcomes of the dynamics on two different types of time-varying data: (1) the networks vary on a day-to-day basis and (2) the networks vary within very short intervals of time (20 sec). In the first case, we find that networks with strong community structure hinder the system from reaching global agreement; the evolution of the naming game in these networks maintains clusters of coexisting opinions indefinitely leading to metastability. In the second case, we investigate the evolution of the naming game in perfect synchronization with the time evolution of the underlying social network shedding new light on the traditional emergent properties of the game that differ largely from what has been reported in the existing literature.

Dynamic Stability Analysis of Linear Time-varying Systems via an Extended Modal Identification Approach

NASA Astrophysics Data System (ADS)

Ma, Zhisai; Liu, Li; Zhou, Sida; Naets, Frank; Heylen, Ward; Desmet, Wim

2017-03-01

The problem of linear time-varying(LTV) system modal analysis is considered based on time-dependent state space representations, as classical modal analysis of linear time-invariant systems and current LTV system modal analysis under the "frozen-time" assumption are not able to determine the dynamic stability of LTV systems. Time-dependent state space representations of LTV systems are first introduced, and the corresponding modal analysis theories are subsequently presented via a stability-preserving state transformation. The time-varying modes of LTV systems are extended in terms of uniqueness, and are further interpreted to determine the system's stability. An extended modal identification is proposed to estimate the time-varying modes, consisting of the estimation of the state transition matrix via a subspace-based method and the extraction of the time-varying modes by the QR decomposition. The proposed approach is numerically validated by three numerical cases, and is experimentally validated by a coupled moving-mass simply supported beam experimental case. The proposed approach is capable of accurately estimating the time-varying modes, and provides a new way to determine the dynamic stability of LTV systems by using the estimated time-varying modes.

Time-varying nonstationary multivariate risk analysis using a dynamic Bayesian copula

NASA Astrophysics Data System (ADS)

Sarhadi, Ali; Burn, Donald H.; Concepción Ausín, María.; Wiper, Michael P.

2016-03-01

A time-varying risk analysis is proposed for an adaptive design framework in nonstationary conditions arising from climate change. A Bayesian, dynamic conditional copula is developed for modeling the time-varying dependence structure between mixed continuous and discrete multiattributes of multidimensional hydrometeorological phenomena. Joint Bayesian inference is carried out to fit the marginals and copula in an illustrative example using an adaptive, Gibbs Markov Chain Monte Carlo (MCMC) sampler. Posterior mean estimates and credible intervals are provided for the model parameters and the Deviance Information Criterion (DIC) is used to select the model that best captures different forms of nonstationarity over time. This study also introduces a fully Bayesian, time-varying joint return period for multivariate time-dependent risk analysis in nonstationary environments. The results demonstrate that the nature and the risk of extreme-climate multidimensional processes are changed over time under the impact of climate change, and accordingly the long-term decision making strategies should be updated based on the anomalies of the nonstationary environment.

Time varying default barrier as an agreement rules on bond contract

NASA Astrophysics Data System (ADS)

Maruddani, Di Asih I.; Safitri, Diah; Hoyyi, Abdul

2018-05-01

There are some default time rules on contract agreement of a bond. The classical default time is known as Merton Model. The most important characteristic of Merton’s model is the restriction of default time to the maturity of the debt, not taking into consideration the possibility of an early default. If the firm’s value falls down to minimal level before the maturity of the debt, but it is able to recover and meet the debt’s payment at maturity, the default would be avoided in Merton’ s approach. Merton model has been expanded by Hull & White [6] and Avellaneda & Zhu [1]. They introduced time-varying default barrier for modelling distance to default process. This model use time-varying variable as a barrier. In this paper, we give a valuation of a bond with time-varying default barrier agreement. We use straight forward integration for obtaining equity and liability equation. This theory is applied in Indonesian corporate bond.

From calls to communities: a model for time-varying social networks

NASA Astrophysics Data System (ADS)

Laurent, Guillaume; Saramäki, Jari; Karsai, Márton

2015-11-01

Social interactions vary in time and appear to be driven by intrinsic mechanisms that shape the emergent structure of social networks. Large-scale empirical observations of social interaction structure have become possible only recently, and modelling their dynamics is an actual challenge. Here we propose a temporal network model which builds on the framework of activity-driven time-varying networks with memory. The model integrates key mechanisms that drive the formation of social ties - social reinforcement, focal closure and cyclic closure, which have been shown to give rise to community structure and small-world connectedness in social networks. We compare the proposed model with a real-world time-varying network of mobile phone communication, and show that they share several characteristics from heterogeneous degrees and weights to rich community structure. Further, the strong and weak ties that emerge from the model follow similar weight-topology correlations as real-world social networks, including the role of weak ties.

Hierarchical classification of dynamically varying radar pulse repetition interval modulation patterns.

PubMed

Kauppi, Jukka-Pekka; Martikainen, Kalle; Ruotsalainen, Ulla

2010-12-01

The central purpose of passive signal intercept receivers is to perform automatic categorization of unknown radar signals. Currently, there is an urgent need to develop intelligent classification algorithms for these devices due to emerging complexity of radar waveforms. Especially multifunction radars (MFRs) capable of performing several simultaneous tasks by utilizing complex, dynamically varying scheduled waveforms are a major challenge for automatic pattern classification systems. To assist recognition of complex radar emissions in modern intercept receivers, we have developed a novel method to recognize dynamically varying pulse repetition interval (PRI) modulation patterns emitted by MFRs. We use robust feature extraction and classifier design techniques to assist recognition in unpredictable real-world signal environments. We classify received pulse trains hierarchically which allows unambiguous detection of the subpatterns using a sliding window. Accuracy, robustness and reliability of the technique are demonstrated with extensive simulations using both static and dynamically varying PRI modulation patterns. Copyright © 2010 Elsevier Ltd. All rights reserved.

Electron dynamics in solid state via time varying wavevectors

NASA Astrophysics Data System (ADS)

Khaneja, Navin

2018-06-01

In this paper, we study electron wavepacket dynamics in electric and magnetic fields. We rigorously derive the semiclassical equations of electron dynamics in electric and magnetic fields. We do it both for free electron and electron in a periodic potential. We do this by introducing time varying wavevectors k(t). In the presence of magnetic field, our wavepacket reproduces the classical cyclotron orbits once the origin of the Schröedinger equation is correctly chosen to be center of cyclotron orbit. In the presence of both electric and magnetic fields, our equations for wavepacket dynamics differ from classical Lorentz force equations. We show that in a periodic potential, on application of electric field, the electron wave function adiabatically follows the wavefunction of a time varying Bloch wavevector k(t), with its energies suitably shifted with time. We derive the effective mass equation and discuss conduction in conductors and insulators.

Time-varying effect moderation using the structural nested mean model: estimation using inverse-weighted regression with residuals

PubMed Central

Almirall, Daniel; Griffin, Beth Ann; McCaffrey, Daniel F.; Ramchand, Rajeev; Yuen, Robert A.; Murphy, Susan A.

2014-01-01

This article considers the problem of examining time-varying causal effect moderation using observational, longitudinal data in which treatment, candidate moderators, and possible confounders are time varying. The structural nested mean model (SNMM) is used to specify the moderated time-varying causal effects of interest in a conditional mean model for a continuous response given time-varying treatments and moderators. We present an easy-to-use estimator of the SNMM that combines an existing regression-with-residuals (RR) approach with an inverse-probability-of-treatment weighting (IPTW) strategy. The RR approach has been shown to identify the moderated time-varying causal effects if the time-varying moderators are also the sole time-varying confounders. The proposed IPTW+RR approach provides estimators of the moderated time-varying causal effects in the SNMM in the presence of an additional, auxiliary set of known and measured time-varying confounders. We use a small simulation experiment to compare IPTW+RR versus the traditional regression approach and to compare small and large sample properties of asymptotic versus bootstrap estimators of the standard errors for the IPTW+RR approach. This article clarifies the distinction between time-varying moderators and time-varying confounders. We illustrate the methodology in a case study to assess if time-varying substance use moderates treatment effects on future substance use. PMID:23873437

Synthesis fidelity and time-varying spectral change in vowels

NASA Astrophysics Data System (ADS)

Assmann, Peter F.; Katz, William F.

2005-02-01

Recent studies have shown that synthesized versions of American English vowels are less accurately identified when the natural time-varying spectral changes are eliminated by holding the formant frequencies constant over the duration of the vowel. A limitation of these experiments has been that vowels produced by formant synthesis are generally less accurately identified than the natural vowels after which they are modeled. To overcome this limitation, a high-quality speech analysis-synthesis system (STRAIGHT) was used to synthesize versions of 12 American English vowels spoken by adults and children. Vowels synthesized with STRAIGHT were identified as accurately as the natural versions, in contrast with previous results from our laboratory showing identification rates 9%-12% lower for the same vowels synthesized using the cascade formant model. Consistent with earlier studies, identification accuracy was not reduced when the fundamental frequency was held constant across the vowel. However, elimination of time-varying changes in the spectral envelope using STRAIGHT led to a greater reduction in accuracy (23%) than was previously found with cascade formant synthesis (11%). A statistical pattern recognition model, applied to acoustic measurements of the natural and synthesized vowels, predicted both the higher identification accuracy for vowels synthesized using STRAIGHT compared to formant synthesis, and the greater effects of holding the formant frequencies constant over time with STRAIGHT synthesis. Taken together, the experiment and modeling results suggest that formant estimation errors and incorrect rendering of spectral and temporal cues by cascade formant synthesis contribute to lower identification accuracy and underestimation of the role of time-varying spectral change in vowels. .

Allelic Variation in Paralogs of GDP-l-Galactose Phosphorylase Is a Major Determinant of Vitamin C Concentrations in Apple Fruit1[C][W][OA

PubMed Central

Mellidou, Ifigeneia; Chagné, David; Laing, William A.; Keulemans, Johan; Davey, Mark W.

2012-01-01

To identify the genetic factors underlying the regulation of fruit vitamin C (l-ascorbic acid [AsA]) concentrations, quantitative trait loci (QTL) studies were carried out in an F1 progeny derived from a cross between the apple (Malus × domestica) cultivars Telamon and Braeburn over three years. QTL were identified for AsA, glutathione, total antioxidant activity in both flesh and skin tissues, and various quality traits, including flesh browning. Four regions on chromosomes 10, 11, 16, and 17 contained stable fruit AsA-QTL clusters. Mapping of AsA metabolic genes identified colocations between orthologs of GDP-l-galactose phosphorylase (GGP), dehydroascorbate reductase (DHAR), and nucleobase-ascorbate transporter within these QTL clusters. Of particular interest are the three paralogs of MdGGP, which all colocated within AsA-QTL clusters. Allelic variants of MdGGP1 and MdGGP3 derived from the cultivar Braeburn parent were also consistently associated with higher fruit total AsA concentrations both within the mapping population (up to 10-fold) and across a range of commercial apple germplasm (up to 6-fold). Striking differences in the expression of the cv Braeburn MdGGP1 allele between fruit from high- and low-AsA genotypes clearly indicate a key role for MdGGP1 in the regulation of fruit AsA concentrations, and this MdGGP allele-specific single-nucleotide polymorphism marker represents an excellent candidate for directed breeding for enhanced fruit AsA concentrations. Interestingly, colocations were also found between MdDHAR3-3 and a stable QTL for browning in the cv Telamon parent, highlighting links between the redox status of the AsA pool and susceptibility to flesh browning. PMID:23001142

The health benefits of secondary education in adolescents and young adults: An international analysis in 186 low-, middle- and high-income countries from 1990 to 2013.

PubMed

Viner, Russell M; Hargreaves, Dougal S; Ward, Joseph; Bonell, Chris; Mokdad, Ali H; Patton, George

2017-12-01

The health benefits of secondary education have been little studied. We undertook country-level longitudinal analyses of the impact of lengthening secondary education on health outcomes amongst 15-24 year olds. Exposures: average length of secondary and primary education from 1980 to 2013.Data/Outcomes: Country level adolescent fertility rate (AFR), HIV prevalence and mortality rate from 1989/90 to 2013 across 186 low-, middle- and high-income countries.Analysis: Longitudinal mixed effects models, entering secondary and primary education together, adjusted for time varying GDP and country income status. Longitudinal structural marginal models using inverse probability weighting (IPW) to take account of time varying confounding by primary education and GDP. Counterfactual scenarios of no change in secondary education since 1980/1990 were estimated from model coefficients for each outcome. Each additional year of secondary education decreased AFR by 8.4% in mixed effects models and 14.6% in IPW models independent of primary education and GDP. Counterfactual analyses showed the proportion of the reduction in adolescent fertility rate over the study period independently attributable to secondary education was 28% in low income countries. Each additional year of secondary education reduced mortality by 16.9% for 15-19 year and 14.8% for 20-24 year old young women and 11.4% for 15-19 year and 8.8% for 20-24 year old young men. Counterfactual scenarios suggested 12% and 23% of the mortality reduction for 15-19 and 20-24 year old young men was attributable to secondary education in low income countries. Each additional year of secondary education was associated with a 24.5% and 43.1% reduction in HIV prevalence amongst young men and women. The health benefits associated with secondary education were greater than those of primary education and were greatest amongst young women and those from low income countries. Secondary education has the potential to be a social vaccine

An adaptive bit synchronization algorithm under time-varying environment.

NASA Technical Reports Server (NTRS)

Chow, L. R.; Owen, H. A., Jr.; Wang, P. P.

1973-01-01

This paper presents an adaptive estimation algorithm for bit synchronization, assuming that the parameters of the incoming data process are time-varying. Experiment results have proved that this synchronizer is workable either judged by the amount of data required or the speed of convergence.

Failure Modes in Capacitors When Tested Under a Time-Varying Stress

NASA Technical Reports Server (NTRS)

Liu, David (Donhang)

2011-01-01

Steady step surge testing (SSST) is widely applied to screen out potential power-on failures in solid tantalum capacitors. The test simulates the power supply's on and off characteristics. Power-on failure has been the prevalent failure mechanism for solid tantalum capacitors for decoupling applications. On the other hand, the SSST can also be reviewed as an electrically destructive test under a time-varying stress. It consists of rapidly charging the capacitor with incremental voltage increases, through a low resistance in series, until the capacitor under test is electrically shorted. Highly accelerated life testing (HALT) is usually a time-efficient method for determining the failure mechanism in capacitors; however, a destructive test under a time-varying stress like SSST is even more effective. It normally takes days to complete a HALT test, but it only takes minutes for a time-varying stress test to produce failures. The advantage of incorporating specific time-varying stress into a statistical model is significant in providing an alternative life test method for quickly revealing the failure modes in capacitors. In this paper, a time-varying stress has been incorporated into the Weibull model to characterize the failure modes. The SSST circuit and transient conditions to correctly test the capacitors is discussed. Finally, the SSST was applied for testing polymer aluminum capacitors (PA capacitors), Ta capacitors, and multi-layer ceramic capacitors with both precious metal electrode (PME) and base-metal-electrodes (BME). It appears that testing results are directly associated to the dielectric layer breakdown in PA and Ta capacitors and are independent on the capacitor values, the way the capacitors being built, and the manufactures. The testing results also reveal that ceramic capacitors exhibit breakdown voltages more than 20 times the rated voltage, and the breakdown voltages are inverse proportional to the dielectric layer thickness. The possibility of

JPRS Report:. Soviet Union, Political Affairs.

DTIC Science & Technology

1990-07-26

the subject of social studies. Thus, 20 percent of Latvians and 59 percent of representatives of other nationalities fear losing their jobs in the...schools; and 2.2 times as many clinics. To all this we must add the actual current unemploy- ment. The increase in jobs does not meet the popula...tion’s employment requirements. In addition, there are today more than 7,000 unfilled jobs , which speaks to poor job training and orientation for young

JPRS Report, Science & Technology, USSR: Life Sciences

DTIC Science & Technology

1990-12-10

Kostyuchenko; VECHERNYAYA MOSKVA, 29 Aug 90] 16 First Results and Objectives of Investigation of Lyme Disease in the USSR [ E . I. Korenberg, V . N...89) pp 993-996 [Article by M. A. Bundule, V . V . Bychko, Yu. B. Saulitis, E . E . Liyepinsh, G. P. Borisova, I. A. Petrovskiy, V . V . Tsibinogin, P. P...Pushko, V . P. Ose, D. E . Dreylinya, P. P. Pumpen, and E . Ya. Gren, corresponding member, Organic Synthesis Institute, Latvian SSR Academy of JPRS-ULS

Simple Model with Time-Varying Fine-Structure ``Constant''

NASA Astrophysics Data System (ADS)

Berman, M. S.

2009-10-01

Extending the original version written in colaboration with L.A. Trevisan, we study the generalisation of Dirac's LNH, so that time-variation of the fine-structure constant, due to varying electrical and magnetic permittivities is included along with other variations (cosmological and gravitational ``constants''), etc. We consider the present Universe, and also an inflationary scenario. Rotation of the Universe is a given possibility in this model.

Lagrange constraint neural network for audio varying BSS

NASA Astrophysics Data System (ADS)

Szu, Harold H.; Hsu, Charles C.

2002-03-01

Lagrange Constraint Neural Network (LCNN) is a statistical-mechanical ab-initio model without assuming the artificial neural network (ANN) model at all but derived it from the first principle of Hamilton and Lagrange Methodology: H(S,A)= f(S)- (lambda) C(s,A(x,t)) that incorporates measurement constraint C(S,A(x,t))= (lambda) ([A]S-X)+((lambda) 0-1)((Sigma) isi -1) using the vector Lagrange multiplier-(lambda) and a- priori Shannon Entropy f(S) = -(Sigma) i si log si as the Contrast function of unknown number of independent sources si. Szu et al. have first solved in 1997 the general Blind Source Separation (BSS) problem for spatial-temporal varying mixing matrix for the real world remote sensing where a large pixel footprint implies the mixing matrix [A(x,t)] necessarily fill with diurnal and seasonal variations. Because the ground truth is difficult to be ascertained in the remote sensing, we have thus illustrated in this paper, each step of the LCNN algorithm for the simulated spatial-temporal varying BSS in speech, music audio mixing. We review and compare LCNN with other popular a-posteriori Maximum Entropy methodologies defined by ANN weight matrix-[W] sigmoid-(sigma) post processing H(Y=(sigma) ([W]X)) by Bell-Sejnowski, Amari and Oja (BSAO) called Independent Component Analysis (ICA). Both are mirror symmetric of the MaxEnt methodologies and work for a constant unknown mixing matrix [A], but the major difference is whether the ensemble average is taken at neighborhood pixel data X's in BASO or at the a priori sources S variables in LCNN that dictates which method works for spatial-temporal varying [A(x,t)] that would not allow the neighborhood pixel average. We expected the success of sharper de-mixing by the LCNN method in terms of a controlled ground truth experiment in the simulation of variant mixture of two music of similar Kurtosis (15 seconds composed of Saint-Saens Swan and Rachmaninov cello concerto).

Transforming Universities: National Conditions of Their Varied Organisational Actorhood

ERIC Educational Resources Information Center

Whitley, Richard

2012-01-01

Despite major changes in the governance of universities overtly intended to transform them into authoritatively integrated collectivities, the extent of their organisational actorhood remains quite limited and varied between OECD countries. This is because of inherent limitations to the managerial direction and control of research and teaching…

Time-varying economic dominance in financial markets: A bistable dynamics approach

NASA Astrophysics Data System (ADS)

He, Xue-Zhong; Li, Kai; Wang, Chuncheng

2018-05-01

By developing a continuous-time heterogeneous agent financial market model of multi-assets traded by fundamental and momentum investors, we provide a potential mechanism for generating time-varying dominance between fundamental and non-fundamental in financial markets. We show that investment constraints lead to the coexistence of a locally stable fundamental steady state and a locally stable limit cycle around the fundamental, characterized by a Bautin bifurcation. This provides a mechanism for market prices to switch stochastically between the two persistent but very different market states, leading to the coexistence and time-varying dominance of seemingly controversial efficient market and price momentum over different time periods. The model also generates other financial market stylized facts, such as spillover effects in both momentum and volatility, market booms, crashes, and correlation reduction due to cross-sectional momentum trading. Empirical evidence based on the U.S. market supports the main findings. The mechanism developed in this paper can be used to characterize time-varying economic dominance in economics and finance in general.

Varying irrelevant phonetic features hinders learning of the feature being trained.

PubMed

Antoniou, Mark; Wong, Patrick C M

2016-01-01

Learning to distinguish nonnative words that differ in a critical phonetic feature can be difficult. Speech training studies typically employ methods that explicitly direct the learner's attention to the relevant nonnative feature to be learned. However, studies on vision have demonstrated that perceptual learning may occur implicitly, by exposing learners to stimulus features, even if they are irrelevant to the task, and it has recently been suggested that this task-irrelevant perceptual learning framework also applies to speech. In this study, subjects took part in a seven-day training regimen to learn to distinguish one of two nonnative features, namely, voice onset time or lexical tone, using explicit training methods consistent with most speech training studies. Critically, half of the subjects were exposed to stimuli that varied not only in the relevant feature, but in the irrelevant feature as well. The results showed that subjects who were trained with stimuli that varied in the relevant feature and held the irrelevant feature constant achieved the best learning outcomes. Varying both features hindered learning and generalization to new stimuli.

Time-varying economic dominance in financial markets: A bistable dynamics approach.

PubMed

He, Xue-Zhong; Li, Kai; Wang, Chuncheng

2018-05-01

By developing a continuous-time heterogeneous agent financial market model of multi-assets traded by fundamental and momentum investors, we provide a potential mechanism for generating time-varying dominance between fundamental and non-fundamental in financial markets. We show that investment constraints lead to the coexistence of a locally stable fundamental steady state and a locally stable limit cycle around the fundamental, characterized by a Bautin bifurcation. This provides a mechanism for market prices to switch stochastically between the two persistent but very different market states, leading to the coexistence and time-varying dominance of seemingly controversial efficient market and price momentum over different time periods. The model also generates other financial market stylized facts, such as spillover effects in both momentum and volatility, market booms, crashes, and correlation reduction due to cross-sectional momentum trading. Empirical evidence based on the U.S. market supports the main findings. The mechanism developed in this paper can be used to characterize time-varying economic dominance in economics and finance in general.

Hemolymph drop impact outcomes on surfaces with varying wettability

NASA Astrophysics Data System (ADS)

Milionis, Athanasios; Ghokulla Krishnan, K.; Loth, Eric

2015-08-01

Insect fouling from coagulated hemolymph and exoskeleton parts is a major challenge in the aerospace industry for the next generation of aerodynamic surfaces, which will employ laminar flow that requires extremely smooth surfaces. However, the wetting physics and dynamics of hemolymph (insect blood) on surfaces are not well understood. The present study seeks to gain a fundamental insight on the effect of surface wetting characteristics and dynamics resulting from a hemolymph drop impact, the first such study. In particular, hemolymph drops extracted from Acheta domesticus were dispensed from a range of heights to vary the kinetic impact on surfaces, which had widely varying water wetting behavior (from superhydrophilic to superhydrophobic). The impact dynamics were investigated with high-speed imaging while the dried residues were studied with optical microscopy. It was found that a superhydrophobic surface (based on thermoplastic with silica nano-particles) was able to significantly reduce hemolymph drop spreading, and even provide complete rebound when impacting on inclined surfaces.

The role of periodically varying discharge on river plume structure and transport

NASA Astrophysics Data System (ADS)

Yuan, Yeping; Horner-Devine, Alexander R.; Avener, Margaret; Bevan, Shaun

2018-04-01

We present results from laboratory experiments that simulate the effects of periodically varying discharge on buoyant coastal plumes. Freshwater is discharged into a two meter diameter tank filled with saltwater on a rotating table. The mean inflow rate, tank rotation period and density of the ambient salt water are varied to simulate a range of inflow Froude and Rossby numbers. The amplitude and the period of the inflow modulation are varied across a range that simulates variability due to tides and storms. Using the optical thickness method, we measure the width and depth of the plume, plume volume and freshwater retention rate in the plume. With constant discharge, freshwater is retained in a growing anticyclonic bulge circulation near the river mouth, as observed in previous studies. When the discharge is varied, the bulge geometry oscillates between a circular plume structure that extends mainly in the offshore direction, and a compressed plume structure that extends mainly in the alongshore direction. The oscillations result in periodic variations in the width and depth of the bulge and the incidence angle formed where the bulge flow re-attaches with the coastal wall. The oscillations are more pronounced for longer modulation periods, but are relatively insensitive to the modulation amplitude. A phase difference between the time varying transport within the bulge and bulge geometry determines the fraction of the bulge flow discharged into the coastal current. As a result, the modulation period determines the variations in amount of freshwater that returns to the bulge. Freshwater retention in the bulge is increased in longer modulation periods and more pronounced for larger modulation amplitudes.

Surface Wave Tomography with Spatially Varying Smoothing Based on Continuous Model Regionalization

NASA Astrophysics Data System (ADS)

Liu, Chuanming; Yao, Huajian

2017-03-01

Surface wave tomography based on continuous regionalization of model parameters is widely used to invert for 2-D phase or group velocity maps. An inevitable problem is that the distribution of ray paths is far from homogeneous due to the spatially uneven distribution of stations and seismic events, which often affects the spatial resolution of the tomographic model. We present an improved tomographic method with a spatially varying smoothing scheme that is based on the continuous regionalization approach. The smoothness of the inverted model is constrained by the Gaussian a priori model covariance function with spatially varying correlation lengths based on ray path density. In addition, a two-step inversion procedure is used to suppress the effects of data outliers on tomographic models. Both synthetic and real data are used to evaluate this newly developed tomographic algorithm. In the synthetic tests, when the contrived model has different scales of anomalies but with uneven ray path distribution, we compare the performance of our spatially varying smoothing method with the traditional inversion method, and show that the new method is capable of improving the recovery in regions of dense ray sampling. For real data applications, the resulting phase velocity maps of Rayleigh waves in SE Tibet produced using the spatially varying smoothing method show similar features to the results with the traditional method. However, the new results contain more detailed structures and appears to better resolve the amplitude of anomalies. From both synthetic and real data tests we demonstrate that our new approach is useful to achieve spatially varying resolution when used in regions with heterogeneous ray path distribution.

Sense of Community and Interethnic Relations: Comparing Local Communities Varying in Ethnic Heterogeneity

ERIC Educational Resources Information Center

Castellini, Federica; Colombo, Monica; Maffeis, Daniele; Montali, Lorenzo

2011-01-01

This study investigates the sense of community and interethnic relations in two different metropolitan areas that vary in ethnic heterogeneity. The study was conducted in Milan, Italy using a sample of 318 participants living in different city districts that vary in ethnic heterogeneity (low vs. high). The participants completed a questionnaire…

Limited generalization with varied, as compared to specific, practice in short-term motor learning.

PubMed

Willey, Chéla R; Liu, Zili

2018-01-01

The schema theory of learning predicts that varied training in motor learning should give rise to better transfer than specific training. For example, throwing beanbags during practice to targets 5 and 9ft away should better generalize to targets 7 and 11ft away, as compared to only throwing to a target 7ft away. In this study, we tested this prediction in a throwing task, when the pretest, practice, and posttest were all completed within an hour. Participants in the varied group practiced throwing at 5 and 9ft targets, while participants in the specific group practiced throwing at 7ft only. All participants reliably reduced errors from pretest to posttest. The varied group never outperformed the specific group at the 7ft target (the trained target for the specific group). They did not reliably outperform the specific group at 11ft, either. The numerically better performance at 11ft by the varied group was due, as it turned out in a subsequent experiment, to the fact that 11ft was closer to 9ft (one of the two training targets for the varied group) than to 7ft (the training target for the specific group). We conclude that varied training played a very limited role in short-term motor learning. Copyright © 2017 Elsevier B.V. All rights reserved.

Emotions in freely varying and mono-pitched vowels, acoustic and EGG analyses.

PubMed

Waaramaa, Teija; Palo, Pertti; Kankare, Elina

2015-12-01

Vocal emotions are expressed either by speech or singing. The difference is that in singing the pitch is predetermined while in speech it may vary freely. It was of interest to study whether there were voice quality differences between freely varying and mono-pitched vowels expressed by professional actors. Given their profession, actors have to be able to express emotions both by speech and singing. Electroglottogram and acoustic analyses of emotional utterances embedded in expressions of freely varying vowels [a:], [i:], [u:] (96 samples) and mono-pitched protracted vowels (96 samples) were studied. Contact quotient (CQEGG) was calculated using 35%, 55%, and 80% threshold levels. Three different threshold levels were used in order to evaluate their effects on emotions. Genders were studied separately. The results suggested significant gender differences for CQEGG 80% threshold level. SPL, CQEGG, and F4 were used to convey emotions, but to a lesser degree, when F0 was predetermined. Moreover, females showed fewer significant variations than males. Both genders used more hypofunctional phonation type in mono-pitched utterances than in the expressions with freely varying pitch. The present material warrants further study of the interplay between CQEGG threshold levels and formant frequencies, and listening tests to investigate the perceptual value of the mono-pitched vowels in the communication of emotions.

Tuning Structural Properties of Biocompatible Block Copolymer Micelles by Varying Solvent Composition

NASA Astrophysics Data System (ADS)

Cooksey, Tyler; Singh, Avantika; Mai Le, Kim; Wang, Shu; Kelley, Elizabeth; He, Lilin; Vajjala Kesava, Sameer; Gomez, Enrique; Kidd, Bryce; Madsen, Louis; Robertson, Megan

The self-assembly of block copolymers into micelles when introduced to selective solvents enables a wide array of applications, ranging from drug delivery to personal care products to nanoreactors. In order to probe the assembly and dynamics of micellar systems, the structural properties and solvent uptake of biocompatible poly(ethylene oxide-b- ɛ-caprolactone) (PEO-PCL) diblock copolymers in deuterated water (D2O) / tetrahydrofuran (THFd8) mixtures were investigated using small-angle neutron scattering in combination with nuclear magnetic resonance. PEO-PCL block copolymers, of varying molecular weight yet constant block ratio, formed spherical micelles through a wide range of solvent compositions. Varying the composition from 10 to 60 % by volume THFd8\\ in D2O / THFd8 mixtures was a means of varying the core-corona interfacial tension in the micelle system. An increase in THFd8 content in the bulk solvent increased the solvent uptake within the micelle core, which was comparable for the two series, irrespective of the polymer molecular weight. Differences in the behaviors of the micelle size parameters as the solvent composition varied originated from the differing trends in aggregation number for the two micelle series. Incorporation of the known unimer content determined from NMR allowed refinement of extracted micelle parameters.

Influence of postnatal glucocorticoids on hippocampal-dependent learning varies with elevation patterns and administration methods

DTIC Science & Technology

2017-05-22

Influence of postnatal glucocorticoids on hippocampal-dependent learning varies with elevation patterns and administration methods 5b. GRANT NUMBER...of these effects varies with the elevation patterns (level, duration, temporal fluctuation) achieved by different administration methods . In general...learning varies with elevation patterns and administration methods Dragana I. Claflin a, Kevin D. Schmidt a, Zachary D. Vallandingham b, Michal

A VARI-Based Relative Greenness from MODIS Data for Computing the Fire Potential Index

NASA Technical Reports Server (NTRS)

Schneider, P.; Roberts, D. A.; Kyriakidis, P. C.

2008-01-01

The Fire Potential Index (FPI) relies on relative greenness (RG) estimates from remote sensing data. The Normalized Difference Vegetation index (NDVI), derived from NOAA Advanced Very High Resolution Radiometer (AVHRR) imagery is currently used to calculate RG operationally. Here we evaluated an alternate measure of RG using the Visible Atmospheric Resistant Index (VARI) derived from Moderate Resolution Imaging Spectrometer (MODIS) data. VARI was chosen because it has previously been shown to have the strongest relationship with Live Fuel Moisture (LFM) out of a wide selection of MODIS-derived indices in southern California shrublands. To compare MODIS-based NDVI-FPI and VARI-FPI, RG was calculated from a 6-year time series of MODIS composites and validated against in-situ observations of LFM as a surrogate for vegetation greenness. RG from both indices was then compared in terms of its performance for computing the FPI using historical wildfire data. Computed RG values were regressed against ground-sampled LFM at 14 sites within Los Angeles County. The results indicate the VARI-based RG consistently shows a stronger relationship with observed LFM than NDVI-based RG. With an average R2 of 0.727 compared to a value of only 0.622 for NDVI-RG, VARI-RG showed stronger relationships at 13 out of 14 sites. Based on these results, daily FPI maps were computed for the years 2001 through 2005 using both NDVI-RG and VARI-RG. These were then validated against 12,490 fire detections from the MODIS active fire product using logistic regression. Deviance of the logistic regression model was 408.8 for NDVI-FPI and 176.2 for VARI-FPI. The c-index was found to be 0.69 and 0.78, respectively. The results show that VARI-FP outperforms NDVI-FPI in distinguishing between fire and no-fire events for historical wildfire data in southern California for the given time period.

Spectral analysis and markov switching model of Indonesia business cycle

NASA Astrophysics Data System (ADS)

Fajar, Muhammad; Darwis, Sutawanir; Darmawan, Gumgum

2017-03-01

This study aims to investigate the Indonesia business cycle encompassing the determination of smoothing parameter (λ) on Hodrick-Prescott filter. Subsequently, the components of the filter output cycles were analyzed using a spectral method useful to know its characteristics, and Markov switching regime modeling is made to forecast the probability recession and expansion regimes. The data used in the study is real GDP (1983Q1 - 2016Q2). The results of the study are: a) Hodrick-Prescott filter on real GDP of Indonesia to be optimal when the value of the smoothing parameter is 988.474, b) Indonesia business cycle has amplitude varies between±0.0071 to±0.01024, and the duration is between 4 to 22 quarters, c) the business cycle can be modelled by MSIV-AR (2) but regime periodization is generated this model not perfect exactly with real regime periodzation, and d) Based on the model MSIV-AR (2) obtained long-term probabilities in the expansion regime: 0.4858 and in the recession regime: 0.5142.

Time-varying long term memory in the European Union stock markets

NASA Astrophysics Data System (ADS)

Sensoy, Ahmet; Tabak, Benjamin M.

2015-10-01

This paper proposes a new efficiency index to model time-varying inefficiency in stock markets. We focus on European stock markets and show that they have different degrees of time-varying efficiency. We observe that the 2008 global financial crisis has an adverse effect on almost all EU stock markets. However, the Eurozone sovereign debt crisis has a significant adverse effect only on the markets in France, Spain and Greece. For the late members, joining EU does not have a uniform effect on stock market efficiency. Our results have important implications for policy makers, investors, risk managers and academics.

Legionella pneumophila Seropositivity-Associated Factors in Latvian Blood Donors

PubMed Central

Valciņa, Olga; Pūle, Daina; Lucenko, Irina; Krastiņa, Dita; Šteingolde, Žanete; Krūmiņa, Angelika; Bērziņš, Aivars

2015-01-01

Continuous environmental exposure of humans to Legionella may induce immune responses and generation of antibodies. The aim of this study was to investigate the seroprevalence of Legionella pneumophila serogroups (SG) 1–6 in the general healthy population and identify the associated host-related and environmental risk factors. L. pneumophila SG 1–6 seroprevalence among a total of 2007 blood samples collected from healthy donors was 4.8%. Seroprevalence was higher in women (5.9%) than men (3.3%) and in areas with a larger number of inhabitants, ranging from 3.5% in rural regions to 6.8% in the capital, Riga. Blood samples from inhabitants of apartment buildings tested positive for L. pneumophila in more cases (5.8%) compared to those from inhabitants of single-family homes (2.7%). Residents of buildings with a municipal hot water supply system were more likely to be seropositive for L. pneumophila (OR = 3.16, 95% CI 1.26–7.91). Previous episodes of fever were additionally identified as a risk factor (OR = 2.42, 95% CI 1.43–4.1). In conclusion, centralized hot water supply, female gender and previous episodes of fever were determined as the main factors associated with L. pneumophila seropositivity in our study population. PMID:26703696

Linear-parameter-varying gain-scheduled control of aerospace systems

NASA Astrophysics Data System (ADS)

Barker, Jeffrey Michael

The dynamics of many aerospace systems vary significantly as a function of flight condition. Robust control provides methods of guaranteeing performance and stability goals across flight conditions. In mu-syntthesis, changes to the dynamical system are primarily treated as uncertainty. This method has been successfully applied to many control problems, and here is applied to flutter control. More recently, two techniques for generating robust gain-scheduled controller have been developed. Linear fractional transformation (LFT) gain-scheduled control is an extension of mu-synthesis in which the plant and controller are explicit functions of parameters measurable in real-time. This LFT gain-scheduled control technique is applied to the Benchmark Active Control Technology (BACT) wing, and compared with mu-synthesis control. Linear parameter-varying (LPV) gain-scheduled control is an extension of Hinfinity control to parameter varying systems. LPV gain-scheduled control directly incorporates bounds on the rate of change of the scheduling parameters, and often reduces conservatism inherent in LFT gain-scheduled control. Gain-scheduled LPV control of the BACT wing compares very favorably with the LFT controller. Gain-scheduled LPV controllers are generated for the lateral-directional and longitudinal axes of the Innovative Control Effectors (ICE) aircraft and implemented in nonlinear simulations and real-time piloted nonlinear simulations. Cooper-Harper and pilot-induced oscillation ratings were obtained for an initial design, a reference aircraft and a redesign. Piloted simulation results for the initial LPV gain-scheduled control of the ICE aircraft are compared with results for a conventional fighter aircraft in discrete pitch and roll angle tracking tasks. The results for the redesigned controller are significantly better than both the previous LPV controller and the conventional aircraft.

Time-varying SMART design and data analysis methods for evaluating adaptive intervention effects.

PubMed

Dai, Tianjiao; Shete, Sanjay

2016-08-30

In a standard two-stage SMART design, the intermediate response to the first-stage intervention is measured at a fixed time point for all participants. Subsequently, responders and non-responders are re-randomized and the final outcome of interest is measured at the end of the study. To reduce the side effects and costs associated with first-stage interventions in a SMART design, we proposed a novel time-varying SMART design in which individuals are re-randomized to the second-stage interventions as soon as a pre-fixed intermediate response is observed. With this strategy, the duration of the first-stage intervention will vary. We developed a time-varying mixed effects model and a joint model that allows for modeling the outcomes of interest (intermediate and final) and the random durations of the first-stage interventions simultaneously. The joint model borrows strength from the survival sub-model in which the duration of the first-stage intervention (i.e., time to response to the first-stage intervention) is modeled. We performed a simulation study to evaluate the statistical properties of these models. Our simulation results showed that the two modeling approaches were both able to provide good estimations of the means of the final outcomes of all the embedded interventions in a SMART. However, the joint modeling approach was more accurate for estimating the coefficients of first-stage interventions and time of the intervention. We conclude that the joint modeling approach provides more accurate parameter estimates and a higher estimated coverage probability than the single time-varying mixed effects model, and we recommend the joint model for analyzing data generated from time-varying SMART designs. In addition, we showed that the proposed time-varying SMART design is cost-efficient and equally effective in selecting the optimal embedded adaptive intervention as the standard SMART design.

The Effects of Constant versus Varied Reinforcers on Preference and Resistance to Change

ERIC Educational Resources Information Center

Milo, Jessie-Sue; Mace, F. Charles; Nevin, John A.

2010-01-01

Previous research has demonstrated that factors such as reinforcer frequency, amount, and delay have similar effects on resistance to change and preference. In the present study, 4 boys with autism made choices between a constant reinforcer (one that was the same food item every trial) and a varied food reinforcer (one that varied randomly between…

Modeling spatially-varying landscape change points in species occurrence thresholds

USGS Publications Warehouse

Wagner, Tyler; Midway, Stephen R.

2014-01-01

Predicting species distributions at scales of regions to continents is often necessary, as large-scale phenomena influence the distributions of spatially structured populations. Land use and land cover are important large-scale drivers of species distributions, and landscapes are known to create species occurrence thresholds, where small changes in a landscape characteristic results in abrupt changes in occurrence. The value of the landscape characteristic at which this change occurs is referred to as a change point. We present a hierarchical Bayesian threshold model (HBTM) that allows for estimating spatially varying parameters, including change points. Our model also allows for modeling estimated parameters in an effort to understand large-scale drivers of variability in land use and land cover on species occurrence thresholds. We use range-wide detection/nondetection data for the eastern brook trout (Salvelinus fontinalis), a stream-dwelling salmonid, to illustrate our HBTM for estimating and modeling spatially varying threshold parameters in species occurrence. We parameterized the model for investigating thresholds in landscape predictor variables that are measured as proportions, and which are therefore restricted to values between 0 and 1. Our HBTM estimated spatially varying thresholds in brook trout occurrence for both the proportion agricultural and urban land uses. There was relatively little spatial variation in change point estimates, although there was spatial variability in the overall shape of the threshold response and associated uncertainty. In addition, regional mean stream water temperature was correlated to the change point parameters for the proportion of urban land use, with the change point value increasing with increasing mean stream water temperature. We present a framework for quantify macrosystem variability in spatially varying threshold model parameters in relation to important large-scale drivers such as land use and land cover

Finite-time stability of neutral-type neural networks with random time-varying delays

NASA Astrophysics Data System (ADS)

Ali, M. Syed; Saravanan, S.; Zhu, Quanxin

2017-11-01

This paper is devoted to the finite-time stability analysis of neutral-type neural networks with random time-varying delays. The randomly time-varying delays are characterised by Bernoulli stochastic variable. This result can be extended to analysis and design for neutral-type neural networks with random time-varying delays. On the basis of this paper, we constructed suitable Lyapunov-Krasovskii functional together and established a set of sufficient linear matrix inequalities approach to guarantee the finite-time stability of the system concerned. By employing the Jensen's inequality, free-weighting matrix method and Wirtinger's double integral inequality, the proposed conditions are derived and two numerical examples are addressed for the effectiveness of the developed techniques.

Pike Esox Lucius Distribution and Feeding Comparisons in Natural and Historically Channelized River Sections

NASA Astrophysics Data System (ADS)

Ivanovs, Kaspars

2016-12-01

During the last century a large portion of small and medium-sized rivers in Latvia were channelized, hydroelectric power stations were also built, which led to changes in the hydrodynamic conditions, geomorphological structure, as well as a change in the fish fauna. Fish are an integral part of any community in natural or man-made bodies of water. They actively participate in maintaining the system, balancing/equilibrium, energy, substance transformation and biomass production. They are able to influence other organisms in the ecosystem in which they live. The aim of the paper "Pike distribution and feeding comparisons in natural and historically channelized river sections" is to find out what pike feed on in different environments in Latvian rivers, such as natural and straightened river sections, as well as what main factors determine the composition of their food. Several points were assessed during the course of the study: the impact of environmental conditions on the feeding habits and the distribution of pike; the general feeding habits of predators in Latvian rivers; the feeding differences of predators in natural and straightened river sections; and lastly, rhithral and pothamal habitats were compared. The study was based on data from 2014 and 2015 on fish fauna monitoring. During the study, 347 pike were collected from 136 plots using electrofishing method.

Introduction of Energy and Climate Mitigation Policy Issues in Energy - Environment Model of Latvia

NASA Astrophysics Data System (ADS)

Klavs, G.; Rekis, J.

2016-12-01

The present research is aimed at contributing to the Latvian national climate policy development by projecting total GHG emissions up to 2030, by evaluating the GHG emission reduction path in the non-ETS sector at different targets set for emissions reduction and by evaluating the obtained results within the context of the obligations defined by the EU 2030 policy framework for climate and energy. The method used in the research was bottom-up, linear programming optimisation model MARKAL code adapted as the MARKAL-Latvia model with improvements for perfecting the integrated assessment of climate policy. The modelling results in the baseline scenario, reflecting national economic development forecasts and comprising the existing GHG emissions reduction policies and measures, show that in 2030 emissions will increase by 19.1 % compared to 2005. GHG emissions stabilisation and reduction in 2030, compared to 2005, were researched in respective alternative scenarios. Detailed modelling and analysis of the Latvian situation according to the scenario of non-ETS sector GHG emissions stabilisation and reduction in 2030 compared to 2005 have revealed that to implement a cost effective strategy of GHG emissions reduction first of all a policy should be developed that ensures effective absorption of the available energy efficiency potential in all consumer sectors. The next group of emissions reduction measures includes all non-ETS sectors (industry, services, agriculture, transport, and waste management).

Resolution Enhancement In Ultrasonic Imaging By A Time-Varying Filter

NASA Astrophysics Data System (ADS)

Ching, N. H.; Rosenfeld, D.; Braun, M.

1987-09-01

The study reported here investigates the use of a time-varying filter to compensate for the spreading of ultrasonic pulses due to the frequency dependence of attenuation by tissues. The effect of this pulse spreading is to degrade progressively the axial resolution with increasing depth. The form of compensation required to correct for this effect is impossible to realize exactly. A novel time-varying filter utilizing a bank of bandpass filters is proposed as a realizable approximation of the required compensation. The performance of this filter is evaluated by means of a computer simulation. The limits of its application are discussed. Apart from improving the axial resolution, and hence the accuracy of axial measurements, the compensating filter could be used in implementing tissue characterization algorithms based on attenuation data.

Structural nested mean models for assessing time-varying effect moderation.

PubMed

Almirall, Daniel; Ten Have, Thomas; Murphy, Susan A

2010-03-01

This article considers the problem of assessing causal effect moderation in longitudinal settings in which treatment (or exposure) is time varying and so are the covariates said to moderate its effect. Intermediate causal effects that describe time-varying causal effects of treatment conditional on past covariate history are introduced and considered as part of Robins' structural nested mean model. Two estimators of the intermediate causal effects, and their standard errors, are presented and discussed: The first is a proposed two-stage regression estimator. The second is Robins' G-estimator. The results of a small simulation study that begins to shed light on the small versus large sample performance of the estimators, and on the bias-variance trade-off between the two estimators are presented. The methodology is illustrated using longitudinal data from a depression study.

Design of crusher liner based on time - varying uncertainty theory

NASA Astrophysics Data System (ADS)

Tang, J. C.; Shi, B. Q.; Yu, H. J.; Wang, R. J.; Zhang, W. Y.

2017-09-01

This article puts forward the time-dependent design method considering the load fluctuation factors for the liner based on the time-varying uncertainty theory. In this method, the time-varying uncertainty design model of liner is constructed by introducing the parameters that affect the wear rate, the volatility and the drift rate. Based on the design example, the timevarying design outline of the moving cone liner is obtained. Based on the theory of minimum wear, the gap curve of wear resistant cavity is designed, and the optimized cavity is obtained by the combination of the thickness of the cone and the cavity gap. Taking the PYGB1821 multi cylinder hydraulic cone crusher as an example, it is proved that the service life of the new liner is improved by more than 14.3%.

Local inertial oscillations in the surface ocean generated by time-varying winds

NASA Astrophysics Data System (ADS)

Chen, Shengli; Polton, Jeff A.; Hu, Jianyu; Xing, Jiuxing

2015-12-01

A new relationship is presented to give a review study on the evolution of inertial oscillations in the surface ocean locally generated by time-varying wind stress. The inertial oscillation is expressed as the superposition of a previous oscillation and a newly generated oscillation, which depends upon the time-varying wind stress. This relationship is employed to investigate some idealized wind change events. For a wind series varying temporally with different rates, the induced inertial oscillation is dominated by the wind with the greatest variation. The resonant wind, which rotates anti-cyclonically at the local inertial frequency with time, produces maximal amplitude of inertial oscillations, which grows monotonically. For the wind rotating at non-inertial frequencies, the responses vary periodically, with wind injecting inertial energy when it is in phase with the currents, but removing inertial energy when it is out of phase. The wind rotating anti-cyclonically with time is much more favorable to generate inertial oscillations than the cyclonic rotating wind. The wind with a frequency closer to the inertial frequency generates stronger inertial oscillations. For a diurnal wind, the induced inertial oscillation is dependent on latitude and is most significant at 30 °. This relationship is also applied to examine idealized moving cyclones. The inertial oscillation is much stronger on the right-hand side of the cyclone path than on the left-hand side (in the northern hemisphere). This is due to the wind being anti-cyclonic with time on the right-hand side, but cyclonic on the other side. The inertial oscillation varies with the cyclone translation speed. The optimal translation speed generating the greatest inertial oscillations is 2 m/s at the latitude of 10 ° and gradually increases to 6 m/s at the latitude of 30 °.

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

2017-05-01

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), CO 2 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.

Two Site-Directed Mutations are Required for the Conversion of a Sugar Dehydratase into an Aminotransferase¶

PubMed Central

Cook, Paul D.; Kubiak, Rachel L.; Toomey, Daniel P.; Holden, Hazel M.

2009-01-01

l-colitose and d-perosamine are unusual sugars found in the O-antigens of some Gram-negative bacteria such as Escherichia coli, Vibrio cholerae, and Salmonella enterica, among others. The biosynthetic pathways for these two sugars begin with the formation of GDP-mannose from d-mannose-1-phosphate and GTP followed by the subsequent dehydration and oxidation of GDP-mannose to yield GDP-4-keto-6-deoxymannose. Following the production of GDP-4-keto-6-deoxymannose, the two pathways diverge. In the case of GDP-perosamine biosynthesis, the next step involves an amination reaction at the C-4′ position of the sugar, whereas in GDP-colitose production, the 3′-hydroxyl group is removed. The enzymes catalyzing these reactions are GDP-perosamine synthase and GDP-4-keto-6-deoxymannose-3-dehydratase (ColD), respectively. Both of these enzymes are pyridoxal-5′-phosphate (PLP)-dependent and their three-dimensional structures place them into the well-characterized aspartate aminotransferase superfamily. A comparison of the active site architecture of ColD from Escherichia coli (Strain 5a, type O55:H7) to that of GDP-perosamine synthase from Caulobacter crescentus CB15, suggested that only two mutations would be required to convert ColD into an aminotransferase. Here we present a combined structural and functional analysis of the ColD S187N/H188K mutant protein that, indeed, has been converted from a dehydratase into an aminotransferase. PMID:19402712

A comparison of the effects of oral glutamine dipeptide, glutamine, and alanine on blood amino acid availability in rats submitted to insulin-induced hypoglycemia.

PubMed

Minguetti-Câmara, Vania C; Marques, Any de C R; Schiavon, Fabiana P M; Vilela, Vanessa R; Bruschi, Marcos L; Bazotte, Roberto Barbosa

2014-10-21

We compared the effects of oral administration of high-dose or low-dose glutamine dipeptide (GDP), alanine (ALA), glutamine (GLN), and ALA + GLN on the blood availability of amino acids in rats submitted to insulin-induced hypoglycemia (IIH). Insulin detemir (1 U/kg) was intraperitoneally injected to produce IIH; this was followed by oral administration of GDP, GLN + ALA, GLN, or ALA. We observed higher blood levels of GLN, 30 min after oral administration of high-dose GDP (1000 mg/kg) than after administration of ALA (381 mg/kg) + GLN (619 mg/kg), GLN (619 mg/kg), or ALA (381 mg/kg). However, we did not observe the same differences after oral administration of low-dose GDP (100 mg/kg) compared with ALA (38.1 mg/kg) + GLN (61.9 mg/kg), GLN (61.9 mg/kg), or ALA (38.1 mg/kg). We also observed less liver catabolism of GDP compared to ALA and GLN. In conclusion, high-dose GDP promoted higher blood levels of GLN than oral ALA + GLN, GLN, or ALA. Moreover, the lower levels of liver catabolism of GDP, compared to ALA or GLN, contributed to the superior performance of high-dose GDP in terms of blood availability of GLN.

84. Mabry Mill. The varying roof lines and siding gives ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

84. Mabry Mill. The varying roof lines and siding gives the mill an interesting texture, increasing its photogenic value. Looking north. - Blue Ridge Parkway, Between Shenandoah National Park & Great Smoky Mountains, Asheville, Buncombe County, NC

253. Mabry Mill. The varying roof lines and siding gives ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

253. Mabry Mill. The varying roof lines and siding gives the mill an interesting texture, increasing its photogenic value. Looking north. - Blue Ridge Parkway, Between Shenandoah National Park & Great Smoky Mountains, Asheville, Buncombe County, NC

Linear Parameter Varying Control for Actuator Failure

NASA Technical Reports Server (NTRS)

Shin, Jong-Yeob; Wu, N. Eva; Belcastro, Christine; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

A robust linear parameter varying (LPV) control synthesis is carried out for an HiMAT vehicle subject to loss of control effectiveness. The scheduling parameter is selected to be a function of the estimates of the control effectiveness factors. The estimates are provided on-line by a two-stage Kalman estimator. The inherent conservatism of the LPV design is reducing through the use of a scaling factor on the uncertainty block that represents the estimation errors of the effectiveness factors. Simulations of the controlled system with the on-line estimator show that a superior fault-tolerance can be achieved.

Glow discharge plasma pretreatment enhances osteoclast differentiation and survival on titanium plates.

PubMed

Kawai, Hiroyuki; Shibata, Yo; Miyazaki, Takashi

2004-05-01

Despite the fact that several reports have demonstrated osteoclast activity on various bioactive ceramics, osteoclast functions on surface-modified titanium have not come under focus. This study aimed to examine whether the increasing surface energy of glow discharge plasma (GDP) involved in protein adhesion containing the RGD (Arg-Gly-Asp) sequence affects osteoclast responses on titanium plates. We examined osteoclast differentiation and survival rates on titanium plates with and without GDP. The amounts of osteoclasts on titanium plates were not increased by GDP after 1 week. However, osteoclast differentiation was greatly activated by GDP pretreatment, as tartrate-resistant acid phosphatase synthesis significantly increased on the titanium plates with GDP. Additionally, since the presence of osteoclasts was detected only on the titanium plates with GDP, even after 4h cultivation in a coculture test, the osteoclasts survival rate was increased by GDP pretreatment. As osteoclast responses were affected even on surface modified metallic materials, we concluded that novel approaches are needed not only for osteoclastic resorption on ceramic materials but also for osteoclast responses on surface-modified metallic materials.

Retinal specialization through spatially varying cell densities and opsin coexpression in cichlid fish.

PubMed

Dalton, Brian E; de Busserolles, Fanny; Marshall, N Justin; Carleton, Karen L

2017-01-15

The distinct behaviours of animals and the varied habitats in which animals live place different requirements on their visual systems. A trade-off exists between resolution and sensitivity, with these properties varying across the retina. Spectral sensitivity, which affects both achromatic and chromatic (colour) vision, also varies across the retina, though the function of this inhomogeneity is less clear. We previously demonstrated spatially varying spectral sensitivity of double cones in the cichlid fish Metriaclima zebra owing to coexpression of different opsins. Here, we map the distributions of ganglion cells and cone cells and quantify opsin coexpression in single cones to show these also vary across the retina. We identify an area centralis with peak acuity and infrequent coexpression, which may be suited for tasks such as foraging and detecting male signals. The peripheral retina has reduced ganglion cell densities and increased opsin coexpression. Modeling of cichlid visual tasks indicates that coexpression might hinder colour discrimination of foraging targets and some fish colours. But, coexpression might improve contrast detection of dark objects against bright backgrounds, which might be useful for detecting predators or zooplankton. This suggests a trade-off between acuity and colour discrimination in the central retina versus lower resolution but more sensitive contrast detection in the peripheral retina. Significant variation in the pattern of coexpression among individuals, however, raises interesting questions about the selective forces at work. © 2017. Published by The Company of Biologists Ltd.

Means for ultrasonic testing when material properties vary

DOEpatents

Beller, Laurence S.

1979-01-01

A device is provided for maintaining constant sensitivity in an ultrasonic testing device, despite varying attenuation due to the properties of the material being tested. The device includes a sensor transducer for transmitting and receiving a test signal and a monitor transducer positioned so as to receive ultrasonic energy transmitted through the material to be tested. The received signal of the monitor transducer is utilized in analyzing data obtained from the sensor transducer.

Operational Indistinguishably of Varying Speed of Light Theories

NASA Astrophysics Data System (ADS)

Jafari, Nosratollah; Shariati, Ahmad

The varying speed of light theories have been recently proposed to solve the standard model problems and anomalies in the ultra high energy cosmic rays. These theories try to formulate a new relativity with no assumptions about the constancy of the light speed. In this regard, we study two theories and want to show that these theories are not the new theories of relativity, but only re-descriptions of Einstein's special relativity.

Failure Modes in Capacitors When Tested Under a Time-Varying Stress

NASA Technical Reports Server (NTRS)

Liu, David (Donhang)

2011-01-01

Power-on failure has been the prevalent failure mechanism for solid tantalum capacitors in decoupling applications. A surge step stress test (SSST) has been previously applied to identify the critical stress level of a capacitor batch to give some predictability to the power-on failure mechanism [1]. But SSST can also be viewed as an electrically destructive test under a time-varying stress (voltage). It consists of rapidly charging the capacitor with incremental voltage increases, through a low resistance in series, until the capacitor under test is electrically shorted. When the reliability of capacitors is evaluated, a highly accelerated life test (HALT) is usually adopted since it is a time-efficient method of determining the failure mechanism; however, a destructive test under a time-varying stress such as SSST is even more time efficient. It usually takes days or weeks to complete a HALT test, but it only takes minutes for a time-varying stress test to produce failures. The advantage of incorporating a specific time-varying stress profile into a statistical model is significant in providing an alternative life test method for quickly revealing the failure mechanism in capacitors. In this paper, a time-varying stress that mimics a typical SSST has been incorporated into the Weibull model to characterize the failure mechanism in different types of capacitors. The SSST circuit and transient conditions for correctly surge testing capacitors are discussed. Finally, the SSST was applied for testing Ta capacitors, polymer aluminum capacitors (PA capacitors), and multi-layer ceramic (MLC) capacitors with both precious metal electrodes (PME) and base metal electrodes (BME). The test results are found to be directly associated with the dielectric layer breakdown in Ta and PA capacitors and are independent of the capacitor values, the way the capacitors were built, and the capacitors manufacturers. The test results also show that MLC capacitors exhibit surge breakdown

Hydraulic properties of fronds from palms of varying height and habitat.

PubMed

Renninger, Heidi J; Phillips, Nathan

2011-12-01

Because palms grow in highly varying climates and reach considerable heights, they present a unique opportunity to evaluate how environment and plant size impact hydraulic function. We studied hydraulic properties of petioles from palms of varying height from three species: Iriartea deltoidea, a tropical rainforest species; Mauritia flexuosa, a tropical rainforest, swamp species; and Washingtonia robusta, a subtropical species. We measured leaf areas, petiole cross-sectional areas, specific conductivity (K(S)), petiole anatomical properties, vulnerability to embolism and leaf water potentials and calculated petiole Huber values and leaf-specific conductivities (K(L)). Leaf and petiole cross-sectional areas varied widely with height. However, hydraulic properties including Huber values, K(S) and K(L), remained constant. The two palmate species, M. flexuosa and W. robusta, had larger Huber values than I. deltoidea, a pinnately-compound species which exhibited the highest K(S). Metaxylem vessel diameters and vascular bundle densities varied with height in opposing patterns to maintain petiole conductivities. I. deltoidea and W. robusta petioles had similar P(50) values (the point at which 50% of hydraulic conductivity is lost) averaged over all crown heights, but W. robusta exhibited more negative P(50) values in taller palms. Comparison of P (50) values with transpiring midday leaf water potentials, as well as a double-dye staining experiment in a 1-m-tall palm, suggested that a fairly significant amount of embolisms were occurring and refilled on a diurnal basis. Therefore, across palms differing widely in height and growing environments, we found convergence in water transport per unit leaf area (K(L)) with individuals exhibiting differing strategies for achieving this.