WorldWideScience

Sample records for met2 ura3-52 ptdh3-6myc-hmg2

  1. MET-2-Dependent H3K9 Methylation Suppresses Transgenerational Small RNA Inheritance.

    Lev, Itamar; Seroussi, Uri; Gingold, Hila; Bril, Roberta; Anava, Sarit; Rechavi, Oded

    2017-04-24

    In C. elegans, alterations to chromatin produce transgenerational effects, such as inherited increase in lifespan and gradual loss of fertility. Inheritance of histone modifications can be induced by double-stranded RNA-derived heritable small RNAs. Here, we show that the mortal germline phenotype, which is typical of met-2 mutants, defective in H3K9 methylation, depends on HRDE-1, an argonaute that carries small RNAs across generations, and is accompanied by accumulated transgenerational misexpression of heritable small RNAs. We discovered that MET-2 inhibits small RNA inheritance, and, as a consequence, induction of RNAi in met-2 mutants leads to permanent RNAi responses that do not terminate even after more than 30 generations. We found that potentiation of heritable RNAi in met-2 animals results from global hyperactivation of the small RNA inheritance machinery. Thus, changes in histone modifications can give rise to drastic transgenerational epigenetic effects, by controlling the overall potency of small RNA inheritance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Caenorhabditis elegans histone methyltransferase MET-2 shields the male X chromosome from checkpoint machinery and mediates meiotic sex chromosome inactivation.

    Paula M Checchi

    2011-09-01

    Full Text Available Meiosis is a specialized form of cellular division that results in the precise halving of the genome to produce gametes for sexual reproduction. Checkpoints function during meiosis to detect errors and subsequently to activate a signaling cascade that prevents the formation of aneuploid gametes. Indeed, asynapsis of a homologous chromosome pair elicits a checkpoint response that can in turn trigger germline apoptosis. In a heterogametic germ line, however, sex chromosomes proceed through meiosis with unsynapsed regions and are not recognized by checkpoint machinery. We conducted a directed RNAi screen in Caenorhabditis elegans to identify regulatory factors that prevent recognition of heteromorphic sex chromosomes as unpaired and uncovered a role for the SET domain histone H3 lysine 9 histone methyltransferase (HMTase MET-2 and two additional HMTases in shielding the male X from checkpoint machinery. We found that MET-2 also mediates the transcriptional silencing program of meiotic sex chromosome inactivation (MSCI but not meiotic silencing of unsynapsed chromatin (MSUC, suggesting that these processes are distinct. Further, MSCI and checkpoint shielding can be uncoupled, as double-strand breaks targeted to an unpaired, transcriptionally silenced extra-chromosomal array induce checkpoint activation in germ lines depleted for met-2. In summary, our data uncover a mechanism by which repressive chromatin architecture enables checkpoint proteins to distinguish between the partnerless male X chromosome and asynapsed chromosomes thereby shielding the lone X from inappropriate activation of an apoptotic program.

  3. The MeteoMet2 project—highlights and results

    Merlone, A.; Sanna, F.; Beges, G.; Bell, S.; Beltramino, G.; Bojkovski, J.; Brunet, M.; del Campo, D.; Castrillo, A.; Chiodo, N.; Colli, M.; Coppa, G.; Cuccaro, R.; Dobre, M.; Drnovsek, J.; Ebert, V.; Fernicola, V.; Garcia-Benadí, A.; Garcia-Izquierdo, C.; Gardiner, T.; Georgin, E.; Gonzalez, A.; Groselj, D.; Heinonen, M.; Hernandez, S.; Högström, R.; Hudoklin, D.; Kalemci, M.; Kowal, A.; Lanza, L.; Miao, P.; Musacchio, C.; Nielsen, J.; Nogueras-Cervera, M.; Oguz Aytekin, S.; Pavlasek, P.; de Podesta, M.; Rasmussen, M. K.; del-Río-Fernández, J.; Rosso, L.; Sairanen, H.; Salminen, J.; Sestan, D.; Šindelářová, L.; Smorgon, D.; Sparasci, F.; Strnad, R.; Underwood, R.; Uytun, A.; Voldan, M.

    2018-02-01

    Launched in 2011 within the European Metrology Research Programme (EMRP) of EURAMET, the joint research project ‘MeteoMet’—Metrology for Meteorology—is the largest EMRP consortium; national metrology institutes, universities, meteorological and climate agencies, research institutes, collaborators and manufacturers are working together, developing new metrological techniques, as well as improving existing ones, for use in meteorological observations and climate records. The project focuses on humidity in the upper and surface atmosphere, air temperature, surface and deep-sea temperatures, soil moisture, salinity, permafrost temperature, precipitation, and the snow albedo effect on air temperature. All tasks are performed using a rigorous metrological approach and include the design and study of new sensors, new calibration facilities, the investigation of sensor characteristics, improved techniques for measurements of essential climate variables with uncertainty evaluation, traceability, laboratory proficiency and the inclusion of field influencing parameters, long-lasting measurements, and campaigns in remote and extreme areas. The vision for MeteoMet is to take a step further towards establishing full data comparability, coherency, consistency, and long-term continuity, through a comprehensive evaluation of the measurement uncertainties for the quantities involved in the global climate observing systems and the derived observations. The improvement in quality of essential climate variables records, through the inclusion of measurement uncertainty budgets, will also highlight possible strategies for the reduction of the uncertainty. This contribution presents selected highlights of the MeteoMet project and reviews the main ongoing activities, tasks and deliverables, with a view to its possible future evolution and extended impact.

  4. KM3MeT 2.0 Letter of intent for ARCA and ORCA

    Adrián-Martínez, S.; van Haren, H.; KM3NeT Collaboration

    2016-01-01

    S Adrián-Martínez, M Ageron, F Aharonian, S Aiello, A Albert, F Ameli, E Anassontzis, M Andre, G Androulakis, M Anghinolfi, G Anton, M Ardid, T Avgitas, G Barbarino, E Barbarito, B Baret, J Barrios-Martí, B Belhorma, A Belias, E Berbee, A van den Berg, V Bertin, S Beurthey, V van Beveren, N

  5. Functional pyruvate formate lyase pathway expressed with two different electron donors in Saccharomyces cerevisiae at aerobic growth

    Zhang, Yiming; Dai, Zongjie; Krivoruchko, Anastasia

    2015-01-01

    pyruvate decarboxylase and having a reduced glucose uptake rate due to a mutation in the transcriptional regulator Mth1, IMI076 (Pdc-MTH1-ΔT ura3-52). PFL was expressed with two different electron donors, reduced ferredoxin or reduced flavodoxin, respectively, and it was found that the coexpression...

  6. Begeleid rijden: wie doet mee met 2toDrive en waarom? : een vragenlijstonderzoek onder 16- en 17-jarigen in Nederland.

    Schagen, I.N.L.G. van Wijlhuizen, G.J. & Craen, S. de

    2013-01-01

    Accompanied driving: who participate in 2toDrive and why? : a questionnaire study among 16 and 17-year-olds in the Netherlands. On 1 November 2011, 2toDrive, a six-year pilot of accompanied driving, commenced in the Netherlands. In 2toDrive youths can start their driver training and take the theory

  7. Functional co-operation between the nuclei of Saccharomyces cerevisiae and mitochondria from other yeast species

    Spirek, M.; Horvath, A.; Piskur, Jure

    2000-01-01

    We elaborated a simple method that allows the transfer of mitochondria from collection yeasts to Saccharomyces cerevisiae. Protoplasts prepared from different yeasts were fused to the protoplasts of the ade2-1, ura3-52, kar1-1, rho (0) strain of S. cerevisiae and were selected for respiring cybrids....... italicus, S, oviformis, S. capensis and S. chevalieri) exhibited complete compatibility with S. cerevisiae nuclei. The closely related S. douglasii mitochondrial genome could also partially restore respiration-deficiency in rho (0) S. cerevisiae, whereas mitochondrial genomes from phylogenetically less...

  8. Reply to Jongschaap et al.: The water footprint of Jatropha curcas under poor growing conditions

    Hoekstra, Arjen Y.; Gerbens-Leenes, Winnie; van der Meer, Theo H.

    2009-01-01

    The water footprint (WF) of a product refers to freshwater onsumed during production (1). We calculated bioenergy WFs assuming crop water requirements are met (2); Jongschaap et al. (3) correctly point out that this is not always true, giving an example for jatropha grown under poor, rainfed

  9. Characterizing the microstructural basis of “unidentified bright objects” in neurofibromatosis type 1 : A combined in vivo multicomponent T2 relaxation and multi-shell diffusion MRI analysis

    Billiet, T.; Mädler, B.; D'Arco, F.; Deprez, S.; Plasschaert, E.; Leemans, A.; Zhang, H.; Van Den Bergh, B.R.H.; Vandenbulcke, M.; Legius, E.; Sunaert, S.; Emsell, L.

    2014-01-01

    Introduction The histopathological basis of “unidentified bright objects” (UBOs) (hyperintense regions seen on T2-weighted magnetic resonance (MR) brain scans in neurofibromatosis-1 (NF1)) remains unclear. New in vivo MRI-based techniques (multi-exponential T2 relaxation (MET2) and diffusion MR

  10. Stuurlicht bij anjer - Consultancy: Vergelijking van LED lampen en gloeilampen

    Helm, van der F.P.M.

    2013-01-01

    Als gevolg van nieuwe wetgeving zullen gloeilampen vervangen moeten worden. De kwekers moeten nu kiezen tussen de alternatieven; LED lampen of spaarlampen. In een onderzoek in de praktijk in 2012 zijn op twee bedrijven proeven aangelegd. Op 1 bedrijf bij 2 rassen en op een ander bedrijf met 2

  11. New hybrids between Saccharomyces sensu stricto yeast species found among wine and cider production strains

    Masneuf, I; Hansen, J.; Groth, C

    1998-01-01

    Two yeast isolates, a wine-making yeast first identified as a Mel(+) strain (ex. S. uvarum) and a cider-making yeast, were characterized for their nuclear and mitochondrial genomes, Electrophoretic karyotyping analyses, restriction fragment length polymorphism maps of PCR-amplified MET2 gene...

  12. Economic regimes for fission--fusion energy systems

    Deonigi, D.E.

    1974-01-01

    The objectives of this hybrid fusion-fission economic regimes study are to: (1) define the target costs to be met, (2) define the optimum fissile/electrical production ratio for hybrid blankets, (3) discover synergistic configurations, and (4) define the windows of economic hybrid design having desirable cost/benefit ratios. (U.S.)

  13. 46 CFR 199.620 - Alternatives for all vessels in a specified service.

    2010-10-01

    ... that are readily accessible to each watch or work station, the requirement in § 199.70(b)(2)(iv) to have lifejackets at each watch or work station need not be met. (2) If the vessel carries lifejackets... may use lights for lifejackets and immersions suits approved under series 161.012. However, lifejacket...

  14. The development of youth business as the direction of new innovative regional economy formation

    V. Chugunova; S. Pryadko; O. Lomovtseva

    2013-01-01

    Artikel geschreven door een Russische student. Drie Russische studenten zijn samen met 2 docenten in november 2013 op bezoek geweest bij de Hanzehogeschool in het kader van internationalisering. Gepubliceerd op verzoek van de Russische universiteit (Belgorod University). "According to the submitted

  15. Electron Transfer Dissociation and Collision-Induced Dissociation of Underivatized Metallated Oligosaccharides

    Schaller-Duke, Ranelle M.; Bogala, Mallikharjuna R.; Cassady, Carolyn J.

    2018-05-01

    Electron transfer dissociation (ETD) and collision-induced dissociation (CID) were used to investigate underivatized, metal-cationized oligosaccharides formed via electrospray ionization (ESI). Reducing and non-reducing sugars were studied including the tetrasaccharides maltotetraose, 3α,4β,3α-galactotetraose, stachyose, nystose, and a heptasaccharide, maltoheptaose. Univalent alkali, divalent alkaline earth, divalent and trivalent transition metal ions, and a boron group trivalent metal ion were adducted to the non-permethylated oligosaccharides. ESI generated [M + Met]+, [M + 2Met]2+, [M + Met]2+, [M + Met - H]+, and [M + Met - 2H]+ most intensely along with low intensity nitrate adducts, depending on the metal and sugar ionized. The ability of these metal ions to produce oligosaccharide adduct ions by ESI had the general trend: Ca(II) > Mg(II) > Ni(II) > Co(II) > Zn(II) > Cu(II) > Na(I) > K(I) > Al(III) ≈ Fe(III) ≈ Cr(III). Although trivalent metals were utilized, no triply charged ions were formed. Metal cations allowed for high ESI signal intensity without permethylation. ETD and CID on [M + Met]2+ produced various glycosidic and cross-ring cleavages, with ETD producing more cross-ring and internal ions, which are useful for structural analysis. Product ion intensities varied based on glycosidic-bond linkage and identity of monosaccharide sub-unit, and metal adducts. ETD and CID showed high fragmentation efficiency, often with complete precursor dissociation, depending on the identity of the adducted metal ion. Loss of water was occasionally observed, but elimination of small neutral molecules was not prevalent. For both ETD and CID, [M + Co]2+ produced the most uniform structurally informative dissociation with all oligosaccharides studied. The ETD and CID spectra were complementary. [Figure not available: see fulltext.

  16. Electron Transfer Dissociation and Collision-Induced Dissociation of Underivatized Metallated Oligosaccharides

    Schaller-Duke, Ranelle M.; Bogala, Mallikharjuna R.; Cassady, Carolyn J.

    2018-02-01

    Electron transfer dissociation (ETD) and collision-induced dissociation (CID) were used to investigate underivatized, metal-cationized oligosaccharides formed via electrospray ionization (ESI). Reducing and non-reducing sugars were studied including the tetrasaccharides maltotetraose, 3α,4β,3α-galactotetraose, stachyose, nystose, and a heptasaccharide, maltoheptaose. Univalent alkali, divalent alkaline earth, divalent and trivalent transition metal ions, and a boron group trivalent metal ion were adducted to the non-permethylated oligosaccharides. ESI generated [M + Met]+, [M + 2Met]2+, [M + Met]2+, [M + Met - H]+, and [M + Met - 2H]+ most intensely along with low intensity nitrate adducts, depending on the metal and sugar ionized. The ability of these metal ions to produce oligosaccharide adduct ions by ESI had the general trend: Ca(II) > Mg(II) > Ni(II) > Co(II) > Zn(II) > Cu(II) > Na(I) > K(I) > Al(III) ≈ Fe(III) ≈ Cr(III). Although trivalent metals were utilized, no triply charged ions were formed. Metal cations allowed for high ESI signal intensity without permethylation. ETD and CID on [M + Met]2+ produced various glycosidic and cross-ring cleavages, with ETD producing more cross-ring and internal ions, which are useful for structural analysis. Product ion intensities varied based on glycosidic-bond linkage and identity of monosaccharide sub-unit, and metal adducts. ETD and CID showed high fragmentation efficiency, often with complete precursor dissociation, depending on the identity of the adducted metal ion. Loss of water was occasionally observed, but elimination of small neutral molecules was not prevalent. For both ETD and CID, [M + Co]2+ produced the most uniform structurally informative dissociation with all oligosaccharides studied. The ETD and CID spectra were complementary. [Figure not available: see fulltext.

  17. Investigation into dimethyl cadmium decomposition proceeding in form of deflagration combustion

    Mikheev, V.S.; Orlov, A.S.

    1987-01-01

    Results of measuring the maximum explosion pressure of dimethyl cadmium CdMet 2 at 0.1 MPa initial pressure and ∼378 K temperature are presented. The investigation was conducted using the method of constant volume bomb-reactor with central ignition. Experimental value of the pressure increase, equalling to 0.46 MPa, agrees with evaluation, based on reaction adiabatic temperature thrmodynamic calculation. The normal burning rate, determined by the pressure increase, equals to 25±8 cm/s

  18. Information Management: Army Information Management

    2002-05-31

    funds or personnel to produce free programming solely for the benefit of a commercial CATV company. (6) The Army will require that the CATV franchisee ...provided, future customer requirements, and emerging IT capabilities which can benefit the customer. The Army’s increasing employment of IT dictates a...proactive oversight/insight system is operational and ensures mission benefit , cost, and schedule goals are met. (2) IT performance measures at the

  19. Characterizing the microstructural basis of "unidentified bright objects" in neurofibromatosis type 1: A combined in vivo multicomponent T2 relaxation and multi-shell diffusion MRI analysis.

    Billiet, Thibo; Mädler, Burkhard; D'Arco, Felice; Peeters, Ronald; Deprez, Sabine; Plasschaert, Ellen; Leemans, Alexander; Zhang, Hui; den Bergh, Bea Van; Vandenbulcke, Mathieu; Legius, Eric; Sunaert, Stefan; Emsell, Louise

    2014-01-01

    The histopathological basis of "unidentified bright objects" (UBOs) (hyperintense regions seen on T2-weighted magnetic resonance (MR) brain scans in neurofibromatosis-1 (NF1)) remains unclear. New in vivo MRI-based techniques (multi-exponential T2 relaxation (MET2) and diffusion MR imaging (dMRI)) provide measures relating to microstructural change. We combined these methods and present previously unreported data on in vivo UBO microstructure in NF1. 3-Tesla dMRI data were acquired on 17 NF1 patients, covering 30 white matter UBOs. Diffusion tensor, kurtosis and neurite orientation and dispersion density imaging parameters were calculated within UBO sites and in contralateral normal appearing white matter (cNAWM). Analysis of MET2 parameters was performed on 24 UBO-cNAWM pairs. No significant alterations in the myelin water fraction and intra- and extracellular (IE) water fraction were found. Mean T2 time of IE water was significantly higher in UBOs. UBOs furthermore showed increased axial, radial and mean diffusivity, and decreased fractional anisotropy, mean kurtosis and neurite density index compared to cNAWM. Neurite orientation dispersion and isotropic fluid fraction were unaltered. Our results suggest that demyelination and axonal degeneration are unlikely to be present in UBOs, which appear to be mainly caused by a shift towards a higher T2-value of the intra- and extracellular water pool. This may arise from altered microstructural compartmentalization, and an increase in 'extracellular-like', intracellular water, possibly due to intramyelinic edema. These findings confirm the added value of combining dMRI and MET2 to characterize the microstructural basis of T2 hyperintensities in vivo.

  20. Characterizing the microstructural basis of “unidentified bright objects” in neurofibromatosis type 1: A combined in vivo multicomponent T2 relaxation and multi-shell diffusion MRI analysis

    Thibo Billiet

    2014-01-01

    Conclusion: Our results suggest that demyelination and axonal degeneration are unlikely to be present in UBOs, which appear to be mainly caused by a shift towards a higher T2-value of the intra- and extracellular water pool. This may arise from altered microstructural compartmentalization, and an increase in ‘extracellular-like’, intracellular water, possibly due to intramyelinic edema. These findings confirm the added value of combining dMRI and MET2 to characterize the microstructural basis of T2 hyperintensities in vivo.

  1. Efeito da hiperprolactinemia induzida pela metoclopramida na córnea de camundongas Effects of metoclopramide-induced hyperprolactinemia on the murine corneal

    Carina Verna

    2006-10-01

    Full Text Available OBJETIVO: Avaliar as alterações morfológicas promovidas pela hiperprolactinemia induzida pela metoclopramida na córnea de camundongas durante a fase de proestro e na gestação. MÉTODOS: Quarenta camundongas adultas foram divididas, aleatoriamente, em dois grupos, a saber: controle (CTR1 e metoclopramida (MET1. Após 50 dias metade dos animais de cada grupo foram sacrificados. O restante dos animais foi acasalado, constituindo dois grupos: controle prenhe (CTR2 e o metoclopramida prenhe (MET2, que foi sacrificado no 6º dia de gestação. Após decapitação dos animais coletou-se sangue para dosagens de estradiol, progesterona e prolactina, em seguida removidos os globos oculares para estudo histomorfométrico da córnea. RESULTADOS: As espessuras do epitélio, estroma, endotélio e a espessura total das córneas dos grupos experimentais: MET1 e MET2 mostraram-se mais espessados quando comparados com os grupos controles: CTR1 e CTR2, respectivamente. Houve redução dos níveis hormonais do estrogênio e da progesterona nos animais que receberam metoclopramida em comparação com os respectivos controles (CTR1: estradiol = 156,6±42,2 pg/ml; progesterona = 39,4±5,1 ng/ml; prolactina = 130,4±26,2 ng/ml; MET1: estradiol = 108,0±33,1 pg/ml; progesterona = 28,0±6,4 ng/ml; prolactina = 551,5± 23,3 ng/ml; CTR2: estradiol = 354,0±56,0 pg/ml; progesterona = 251,0± 56,0 ng/ml; prolactina = 423,2±28,1 ng/ml; MET2: estradiol = 293,0± 43,0 pg/ml; progesterona = 184,0±33,0 ng/ml; prolactina = 823,1±51,1 ng/ml. CONCLUSÃO: A hiperprolactinemia induzida pela metoclopramida produziu espessamento da córnea, sobretudo, em camundongas prenhes. Possivelmente este efeito está relacionado com a redução da produção hormonal de estrogênio e de progesterona.PURPOSE: To evaluate the morphological changes in murine cornea upon metoclopramide-induced hyperprolactinemia during the proestrous phase or pregnancy. METHODS: Forty adult mice were divided

  2. Estimation of terrorist attack resistibility of dual-purpose cask TP-117 with DU (depleted uranium) gamma shield

    Alekseev, O.G.; Matveev, V.Z.; Morenko, A.I.; Il'kaev, R.I.; Shapovalov, V.I.

    2004-01-01

    Report is devoted to numerical research of dual-purpose unified cask (used for SFA transportation and storage) resistance to terrorist attacks. High resistance of dual-purpose unified cask has been achieved due to the unique design-technological solutions and implementation of depleted uranium in cask construction. In suggested variant of construction depleted uranium fulfils functions of shielding and constructional material. It is used both in metallic and cermet form (basing on steel and depleted uranium dioxide). Implementation of depleted uranium in cask construction allows maximal load in existing overall dimensions of the cask. At the same time: 1) all safety requirements (IAEA) are met, 2) dual-purpose cask with SFA has high resistance to terrorist attacks

  3. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters

    Carolina L. Haass-Koffler

    2017-12-01

    Full Text Available The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled “Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers” (Haass-Koffler et al., 2017 [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73. Keywords: Glutamate receptor subtype 5 (mGlu5, Allosteric modulator, GET 73, Safety, Tolerability

  4. Scalable Data Management, Analysis, and Visualization

    Shen, Han-Wei [The Ohio State Univ., Columbus, OH (United States)

    2017-10-31

    This report is the entire final report for the SciDAC project authored by the whole team. OSU is part of the contributors to the report. This report is organized into sections and subsections, each covering an area of development and deployment of technologies applied to scientific applications of interest to the Department of Energy. Each sub-section includes: 1) a summary description of the research, development, and deployment carried out, the results and the extent to which the stated project objectives were met; 2) significant results, including major findings, developments, or conclusions; 3) products, such as publications and presentations, software developed, project website(s), technologies or techniques, inventions, awards, etc., and 4) conclusions of the projects and future directions for research, development, and deployment in this technology area.

  5. Estimation of terrorist attack resistibility of dual-purpose cask TP-117 with DU (depleted uranium) gamma shield

    Alekseev, O.G.; Matveev, V.Z.; Morenko, A.I.; Il' kaev, R.I.; Shapovalov, V.I. [Russian Federal Nuclear Center - All-Russian Research Inst. of Experimental Physics, Sarov (Russian Federation)

    2004-07-01

    Report is devoted to numerical research of dual-purpose unified cask (used for SFA transportation and storage) resistance to terrorist attacks. High resistance of dual-purpose unified cask has been achieved due to the unique design-technological solutions and implementation of depleted uranium in cask construction. In suggested variant of construction depleted uranium fulfils functions of shielding and constructional material. It is used both in metallic and cermet form (basing on steel and depleted uranium dioxide). Implementation of depleted uranium in cask construction allows maximal load in existing overall dimensions of the cask. At the same time: 1) all safety requirements (IAEA) are met, 2) dual-purpose cask with SFA has high resistance to terrorist attacks.

  6. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters.

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-12-01

    The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled "Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers" (Haass-Koffler et al., 2017) [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK) parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73.

  7. Antibacterial activity of Pd(II) complexes with salicylaldehyde-amino acids Schiff bases ligands.

    Rîmbu, Cristina; Danac, Ramona; Pui, Aurel

    2014-01-01

    Palladium(II) complexes with Schiff bases ligands derived from salicylaldehyde and amino acids (Ala, Gly, Met, Ser, Val) have been synthesized and characterized by Fourier transform (FT)-IR, UV-Vis and (1)H-NMR spectroscopy. The electrospray mass spectrometry (ES-MS) spectrometry confirms the formation of palladium(II) complexes in 1/2 (M/L) molar ratio. All the Pd(II) complexes 1, [Pd(SalAla)2]Cl2; 2, [Pd(SalGly)2]Cl2; 3, [Pd(SalMet)2]Cl2; 4, [Pd(SalSer)2]Cl2; 5, [Pd(SalVal)2]Cl2; have shown antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli.

  8. Evidence that morphine and opioid peptides do not share a common pathway with adenosine in inhibiting acetylcholine release from isolated intestine.

    Vizi, E S; Somogyi, G T; Magyar, K

    1981-12-01

    1 The release of acetylcholine from guinea-pig ileal isolated longitudinal muscle strip with intact Auerbach's plexus was measured by bioassay and by a radioisotope technique. 2 Normorphine (5 x 10(-7)M) and D-Met2, Pro5-enkephalinamide (D-Met, Pro-EA) reduced the release of acetylcholine. Theophylline, an adenosine antagonist, failed to prevent the inhibitory effect of normorphine or D-Met, Pro-EA. 3 Theophylline (1.7 x 10(-4)M) by itself enhanced the twitch responses to field stimulation (0.1 Hz) but did not prevent the inhibitory effect of normorphine and D-Met, Pro-EA. 4 From the results it can be concluded that morphine and opioid peptides do not share a common pathway with adenosine in inhibiting acetylcholine release from axon terminals of Auerbach's plexus.

  9. N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content

    Viquez, Olga M.; Lai, Barry; Ahn, Jae Hee; Does, Mark D.; Valentine, Holly L.; Valentine, William M.

    2009-01-01

    Dithiocarbamates are a commercially important class of compounds that can produce peripheral neuropathy in humans and experimental animals. Previous studies have supported a requirement for copper accumulation and enhanced lipid peroxidation in dithiocarbamate-mediated myelinopathy. The study presented here extends previous investigations in two areas. Firstly, although total copper levels have been shown to increase within the nerve it has not been determined whether copper is increased within the myelin compartment, the primary site of lesion development. Therefore, the distribution of copper in sciatic nerve was characterized using synchrotron X-ray fluorescence microscopy to determine whether the neurotoxic dithiocarbamate, N,N-diethyldithiocarbamate, increases copper levels in myelin. Secondly, because lipid peroxidation is an ongoing process in normal nerve and the levels of lipid peroxidation products produced by dithiocarbamate exposure demonstrated an unusual cumulative dose response in previous studies the biological impact of dithiocarbamate-mediated lipid peroxidation was evaluated. Experiments were performed to determine whether dithiocarbamate-mediated lipid peroxidation products elicit an antioxidant response through measuring the protein expression levels of three enzymes, superoxide dismutase 1, heme oxygenase 1, and glutathione transferase α, that are linked to the antioxidant response element promoter. To establish the potential of oxidative injury to contribute to myelin injury the temporal relationship of the antioxidant response to myelin injury was determined. Myelin structure in peripheral nerve was assessed using multi-exponential transverse relaxation measurements (MET 2 ) as a function of exposure duration, and the temporal relationship of protein expression changes relative to the onset of changes in myelin integrity were determined. Initial assessments were also performed to explore the potential contribution of dithiocarbamate

  10. Age, gender, and socioeconomic gradients in metabolic syndrome: biomarker evidence from a large sample in Taiwan, 2005-2013.

    Wu, Hania F; Tam, Tony; Jin, Lei; Lao, Xiang Q; Chung, Roger Yat-Nork; Su, Xue F; Zee, Benny

    2017-05-01

    To examine the age and gender heterogeneities in the association between socioeconomic status (SES) and the risk of metabolic syndrome (MetS) with biomarker data from Taiwan. Subjects included 102,201 men and 112,015 women aged 25 and above, from the 2005-2013 MJ Health Survey in Taiwan. SES was measured by education and family income. MetS was defined by the Adult Treatment Panel III criteria for Asian population. Logistic regression analyses were performed by age and gender groups. (1) Higher education level was associated with significantly lower risk of MetS. (2) Higher income was associated with lower MetS risk among women aged under 65, but no association among men of all ages. (3) SES gradients were generally much stronger among women than among men of the same age group. (4) SES gradients reduced over the life course with the exception that income gradient remains flat among men of all ages. Among Chinese in Taiwan, the gender and age heterogeneities in the SES gradients in MetS are similar to those reported for Western societies. This cross-cultural convergence is broadly consistent with the general hypothesis that social conditions are fundamental causes of diseases and health disparities. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients.

    Kiwata, J L; Dorff, T B; Schroeder, E T; Gross, M E; Dieli-Conwright, C M

    2016-12-01

    Androgen deprivation therapy (ADT), a primary treatment for locally advanced or metastatic prostate cancer, is associated with the adverse effects on numerous physiologic parameters, including alterations in cardiometabolic variables that overlap with components of the metabolic syndrome (MetS). As MetS is an established risk factor for cardiovascular mortality and treatment for prostate cancer has been associated with the development of MetS, interventions targeting cardiometabolic factors have been investigated in prostate cancer patients to attenuate the detrimental effects of ADT. Much support exists for exercise interventions in improving MetS variables in insulin-resistant adults, but less evidence is available in men with prostate cancer. Regular exercise, when performed at appropriate intensities and volumes, can elicit improvements in ADT-related adverse effects, including MetS, and contributes to the growing body of literature supporting the role of exercise in cancer survivorship. This review (1) discusses the biologic inter-relationship between prostate cancer, ADT and MetS, (2) evaluates the current literature in support of exercise in targeting MetS and (3) describes the physiological mechanisms by which exercise may favorably alter MetS risk factors in prostate cancer patients on ADT.

  12. Mediator, TATA-binding Protein, and RNA Polymerase II Contribute to Low Histone Occupancy at Active Gene Promoters in Yeast*

    Ansari, Suraiya A.; Paul, Emily; Sommer, Sebastian; Lieleg, Corinna; He, Qiye; Daly, Alexandre Z.; Rode, Kara A.; Barber, Wesley T.; Ellis, Laura C.; LaPorta, Erika; Orzechowski, Amanda M.; Taylor, Emily; Reeb, Tanner; Wong, Jason; Korber, Philipp; Morse, Randall H.

    2014-01-01

    Transcription by RNA polymerase II (Pol II) in eukaryotes requires the Mediator complex, and often involves chromatin remodeling and histone eviction at active promoters. Here we address the role of Mediator in recruitment of the Swi/Snf chromatin remodeling complex and its role, along with components of the preinitiation complex (PIC), in histone eviction at inducible and constitutively active promoters in the budding yeast Saccharomyces cerevisiae. We show that recruitment of the Swi/Snf chromatin remodeling complex to the induced CHA1 promoter, as well as its association with several constitutively active promoters, depends on the Mediator complex but is independent of Mediator at the induced MET2 and MET6 genes. Although transcriptional activation and histone eviction at CHA1 depends on Swi/Snf, Swi/Snf recruitment is not sufficient for histone eviction at the induced CHA1 promoter. Loss of Swi/Snf activity does not affect histone occupancy of several constitutively active promoters; in contrast, higher histone occupancy is seen at these promoters in Mediator and PIC component mutants. We propose that an initial activator-dependent, nucleosome remodeling step allows PIC components to outcompete histones for occupancy of promoter sequences. We also observe reduced promoter association of Mediator and TATA-binding protein in a Pol II (rpb1-1) mutant, indicating mutually cooperative binding of these components of the transcription machinery and indicating that it is the PIC as a whole whose binding results in stable histone eviction. PMID:24727477

  13. Identification of auxotrophic mutants of the yeast Kluyveromyces marxianus by non-homologous end joining-mediated integrative transformation with genes from Saccharomyces cerevisiae.

    Yarimizu, Tohru; Nonklang, Sanom; Nakamura, Junpei; Tokuda, Shuya; Nakagawa, Takaaki; Lorreungsil, Sasithorn; Sutthikhumpha, Surasit; Pukahuta, Charida; Kitagawa, Takao; Nakamura, Mikiko; Cha-Aim, Kamonchai; Limtong, Savitree; Hoshida, Hisashi; Akada, Rinji

    2013-12-01

    The isolation and application of auxotrophic mutants for gene manipulations, such as genetic transformation, mating selection and tetrad analysis, form the basis of yeast genetics. For the development of these genetic methods in the thermotolerant fermentative yeast Kluyveromyces marxianus, we isolated a series of auxotrophic mutants with defects in amino acid or nucleic acid metabolism. To identify the mutated genes, linear DNA fragments of nutrient biosynthetic pathway genes were amplified from Saccharomyces cerevisiae chromosomal DNA and used to directly transform the K. marxianus auxotrophic mutants by random integration into chromosomes through non-homologous end joining (NHEJ). The appearance of transformant colonies indicated that the specific S. cerevisiae gene complemented the K. marxianus mutant. Using this interspecific complementation approach with linear PCR-amplified DNA, we identified auxotrophic mutations of ADE2, ADE5,7, ADE6, HIS2, HIS3, HIS4, HIS5, HIS6, HIS7, LYS1, LYS2, LYS4, LYS9, LEU1, LEU2, MET2, MET6, MET17, TRP3, TRP4 and TRP5 without the labour-intensive requirement of plasmid construction. Mating, sporulation and tetrad analysis techniques for K. marxianus were also established. With the identified auxotrophic mutant strains and S. cerevisiae genes as selective markers, NHEJ-mediated integrative transformation with PCR-amplified DNA is an attractive system for facilitating genetic analyses in the yeast K. marxianus. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Characterization of acetanilide herbicides degrading bacteria isolated from tea garden soil.

    Wang, Yei-Shung; Liu, Jian-Chang; Chen, Wen-Ching; Yen, Jui-Hung

    2008-04-01

    Three different green manures were added to the tea garden soils separately and incubated for 40 days. After, incubation, acetanilide herbicides alachlor and metolachlor were spiked into the soils, separately, followed by the isolation of bacteria in each soil at designed intervals. Several bacterial strains were isolated from the soils and identified as Bacillus silvestris, B. niacini, B. pseudomycoides, B. cereus, B. thuringiensis, B. simplex, B. megaterium, and two other Bacillus sp. (Met1 and Met2). Three unique strains with different morphologies were chosen for further investigation. They were B. megaterium, B. niacini, and B. silvestris. The isolated herbicide-degrading bacteria showed optimal performance among three incubation temperatures of 30 degrees C and the best activity in the 10 to 50 microg/ml concentration of the herbicide. Each bacterial strain was able to degrade more than one kind of test herbicides. After incubation for 119 days, B. cereus showed the highest activity to degrade alachlor and propachlor, and B. thuringiensis to degrade metolachlor.

  15. Derivation and validation of the automated search algorithms to identify cognitive impairment and dementia in electronic health records.

    Amra, Sakusic; O'Horo, John C; Singh, Tarun D; Wilson, Gregory A; Kashyap, Rahul; Petersen, Ronald; Roberts, Rosebud O; Fryer, John D; Rabinstein, Alejandro A; Gajic, Ognjen

    2017-02-01

    Long-term cognitive impairment is a common and important problem in survivors of critical illness. We developed electronic search algorithms to identify cognitive impairment and dementia from the electronic medical records (EMRs) that provide opportunity for big data analysis. Eligible patients met 2 criteria. First, they had a formal cognitive evaluation by The Mayo Clinic Study of Aging. Second, they were hospitalized in intensive care unit at our institution between 2006 and 2014. The "criterion standard" for diagnosis was formal cognitive evaluation supplemented by input from an expert neurologist. Using all available EMR data, we developed and improved our algorithms in the derivation cohort and validated them in the independent validation cohort. Of 993 participants who underwent formal cognitive testing and were hospitalized in intensive care unit, we selected 151 participants at random to form the derivation and validation cohorts. The automated electronic search algorithm for cognitive impairment was 94.3% sensitive and 93.0% specific. The search algorithms for dementia achieved respective sensitivity and specificity of 97% and 99%. EMR search algorithms significantly outperformed International Classification of Diseases codes. Automated EMR data extractions for cognitive impairment and dementia are reliable and accurate and can serve as acceptable and efficient alternatives to time-consuming manual data review. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. The Information Needs of Women Who Have Undergone Breast Cancer Surgery in the West of Turkey.

    Findik, Ummu Yildiz

    2017-09-01

    This descriptive study aimed to evaluate the information needs of breast cancer patients who have undergone surgery, and the level to which those information needs are met in the west of Turkey. It was conducted in 55 women who had undergone surgical intervention between March 2013 and March 2014 in a university hospital in the west of Turkey. A personal information form and the Patient Information Needs Scale were used to gather data. Descriptive statistics, the Chi-square test, and the Wilcoxon signed-rank test were used to analyze the data. It was found that the information need of the patients (3.9 +/- 0.6) was near the "very important" level, and that this need was "somewhat met" (2.4 +/- 0.9). When the information needs of the patients and the level to which those needs were fulfilled were compared, the level of fulfillment was statistically significantly lower (p < 0.001). Among the different subscales evaluated, information relating to medication was the most needed, and the information needs pertaining to this subscale were met to a greater degree (p < 0.05) than the remaining subscales. The results showed that the information needs, primarily the medication-related information needs, of the patients were high, but that the level of meeting these needs was low. It should be considered important for patients who have undergone breast cancer surgery to be kept informed and provided with information regarding their medication.

  17. Selenium inhibits the phytotoxicity of mercury in garlic (Allium sativum)

    Zhao, Jiating; Gao, Yuxi; Li, Yu-Feng; Hu, Yi; Peng, Xiaomin; Dong, Yuanxing; Li, Bai; Chen, Chunying; Chai, Zhifang

    2013-01-01

    To investigate the influence of selenium on mercury phytotoxicity, the levels of selenium and mercury were analyzed with inductively coupled plasma-mass spectrometry (ICP-MS) in garlic tissues upon exposure to different dosages of inorganic mercury (Hg 2+ ) and selenite (SeO 3 2− ) or selenate (SeO 4 2− ). The distributions of selenium and mercury were examined with micro-synchrotron radiation X-ray fluorescence (μ-SRXRF), and the mercury speciation was investigated with micro-X-ray absorption near edge structure (μ-XANES). The results show that Se at higher exposure levels (>1 mg/L of SeO 3 2− or SeO 4 2− ) would significantly inhibit the absorption and transportation of Hg when Hg 2+ levels are higher than 1 mg/L in culture media. SeO 3 2− and SeO 4 2− were found to be equally effective in reducing Hg accumulation in garlic. The inhibition of Hg uptake by Se correlates well with the influence of Se on Hg phytotoxicity as indicated by the growth inhibition factor. Elemental imaging using μ-SRXRF also shows that Se could inhibit the accumulation and translocation of Hg in garlic. μ-XANES analysis shows that Hg is mainly present in the forms of Hg–S bonding as Hg(GSH) 2 and Hg(Met) 2 . Se exposure elicited decrease of Hg–S bonding in the form of Hg(GSH) 2 , together with Se-mediated alteration of Hg absorption, transportation and accumulation, may account for attenuated Hg phytotoxicity by Se in garlic. -- Highlights: ► Hg phytotoxicity can be mitigated by Se supplement in garlic growth. ► Se can inhibit the accumulation and transportation of Hg in garlic tissues. ► Localization and speciation of Hg in garlic can be modified by Se

  18. S-type and P-type habitability in stellar binary systems: A comprehensive approach. I. Method and applications

    Cuntz, M., E-mail: cuntz@uta.edu [Department of Physics, University of Texas at Arlington, Arlington, TX 76019-0059 (United States)

    2014-01-01

    A comprehensive approach is provided for the study of both S-type and P-type habitability in stellar binary systems, which in principle can also be expanded to systems of higher order. P-type orbits occur when the planet orbits both binary components, whereas in the case of S-type orbits, the planet orbits only one of the binary components with the second component considered a perturbator. The selected approach encapsulates a variety of different aspects, which include: (1) the consideration of a joint constraint, including orbital stability and a habitable region for a putative system planet through the stellar radiative energy fluxes ({sup r}adiative habitable zone{sup ;} RHZ), needs to be met; (2) the treatment of conservative, general, and extended zones of habitability for the various systems as defined for the solar system and beyond; (3) the provision of a combined formalism for the assessment of both S-type and P-type habitability; in particular, mathematical criteria are presented for the kind of system in which S-type and P-type habitability is realized; (4) applications of the attained theoretical approach to standard (theoretical) main-sequence stars. In principle, five different cases of habitability are identified, which are S-type and P-type habitability provided by the full extent of the RHZs; habitability, where the RHZs are truncated by the additional constraint of planetary orbital stability (referred to as ST- and PT-type, respectively); and cases of no habitability at all. Regarding the treatment of planetary orbital stability, we utilize the formulae of Holman and Wiegert as also used in previous studies. In this work, we focus on binary systems in circular orbits. Future applications will also consider binary systems in elliptical orbits and provide thorough comparisons to other methods and results given in the literature.

  19. Environmentally Sustainable Transport. Implementation and Impacts for the Netherlands for 2030

    Van Wee, G.P.; Geurs, K.T.

    2000-02-01

    Dutch transport scenarios for the OECD project on Environmental Sustainable Transport (EST) are described in this Phase 3 report of the project. The EST project contains a business-as-usual scenario (BAU) and three EST scenarios which attain the EST criteria (i.e. a reduction of CO2 by 80%, NOx by 90%, VOC by 90%, PM10 by 90%): (1) a 'high-technology' scenario containing only technological changes, (2) a 'mobility-management' scenario containing only mobility changes, (3) a combination scenario containing a combination of technological and mobility changes. Furthermore, the report describes possible instrument packages for the implementation of EST and the social and economic impacts of EST. The main conclusions are: (1) only if a high increase in technological developments and/or very stringent behaviour adaptations and changes in spatial and economic structures at the national and international level are assumed, the EST criteria can be met, (2) if EST is to be realised, measures will have to be taken in the short term and innovative policy instruments must be developed and implemented. The implementation of the tradeable CO2 emission permit system for passenger and freight transport is crucial for the attainment of EST, (3) a timely implementation of the policy instruments for the attainment of EST means that the current policy life cycle must radically change, (4) the level of material wealth (expressed in GDP) and employment will be somewhat slower in EST compared to BAU, but several social factors will improve. Firstly, differences between societal groups in (a) travel behaviour, (b) the level of accessibility of economic and social opportunities and (c) (perceived) environmental quality will decrease. Secondly, the level of motorised transport will be strongly reduced which will improve traffic safety and reduce health problems caused by local air pollution and noise nuisance from road traffic and aviation

  20. A calibration facility to provide traceable calibration to upper air humidity measuring sensors

    Cuccaro, Rugiada; Rosso, Lucia; Smorgon, Denis; Beltramino, Giulio; Fernicola, Vito

    2017-04-01

    Accurate knowledge and high quality measurement of the upper air humidity and of its profile in atmosphere is essential in many areas of the atmospheric research, for example in weather forecasting, environmental pollution studies and research in meteorology and climatology. Moving from the troposphere to the stratosphere, the water vapour amount varies between some percent to few part per million. For this reason, through the years, several methods and instruments have been developed for the measurement of the humidity in atmosphere. Among the instruments used for atmospheric sounding, radiosondes, airborne and balloon-borne chilled mirror hygrometer (CMH) and tunable diode laser absorption spectrometers (TDLAS) play a key role. To avoid the presence of unknown biases and systematic errors and to obtain accurate and reliable humidity measurements, these instruments need a SI-traceable calibration, preferably carried out in conditions similar to those expected in the field. To satisfy such a need, a new calibration facility has been developed at INRIM. The facility is based on a thermodynamic-based frost-point generator designed to achieve a complete saturation of the carrier gas with a single passage through an isothermal saturator. The humidity generator covers the frost point temperature range between -98 °C and -20 °C and is able to work at any controlled pressure between 200 hPa and 1000 hPa (corresponding to a barometric altitude between ground level and approximately 12000 m). The paper reports the work carried out to test the generator performances, discusses the results and presents the evaluation of the measurement uncertainty. The present work was carried out within the European Joint Research Project "MeteoMet 2 - Metrology for Essential Climate Variables" co-funded by the European Metrology Research Programme (EMRP). The EMRP is jointly funded by the EMRP participating countries within EURAMET and the European Union.

  1. Partial protection from organophosphate-induced cholinesterase inhibition by metyrapone treatment

    Radosław Świercz

    2013-08-01

    Full Text Available Background: Organophosphates are cholinesterase (ChE inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP poisoning symptomatology. In rodents, corticosterone (CORT is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentraion (the CORT response and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET [2-methyl-1,2-di(pyridin-3-ylpropan-1-one] blocks CORT synthesis by inhibiting steoid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP [2-chloro-1-(2,4-dichlorophenyl ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. Material and Methods: The purose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. Conclusion: The following was observed in the MET-treated rats: i no rise in plasma CORT concentration after the CVP administration, ii a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.

  2. Regarding fuel prices and automobility. A brief analysis of price and cost elasticities; Over brandstofprijzen en automobiliteit. Een beknopte analyse van prijs- en kostenelasticiteit

    Groot, W.

    2012-01-15

    Car drivers do not drive significantly less when fuel prices at the pump rise. If fuel prices increase by approximately 12.5 percent, the long-term decrease in car kilometres travelled is just 2.5 percent. Higher fuel prices have also not resulted in a more fuel-efficient 'car fleet' (i.e. the range of available car model types). The fuel consumption rate per kilometre remained relatively constant from the late 1980s to 2009, although recent years have seen a marked improvement in the per kilometre fuel consumption rate, as measured in CO2 emissions of new passenger cars. These were the findings of the title study, conducted by the KiM Netherlands Institute for Transport Policy Analysis. This study was based on data covering the period 1980 to 2009. The majority of the definitive effects of higher fuel prices revealed in this study were less pronounced than the effects previously cited in available literature, especially with regard to the long-term effects [Dutch] Uit de titel studie blijkt dat automobilisten in beperkte mate minder gaan rijden als de brandstofprijzen aan de pomp stijgen. Een stijging van de benzineprijs met ongeveer 12,5 procent leidt op langere termijn tot een vermindering van de hoeveelheid afgelegde kilometers met 2,5 procent. De hoge brandstofprijzen hebben ook niet geleid tot een zuiniger wagenpark. Het benzineverbruik per kilometer is tussen het eind van de jaren tachtig en 2009 vrijwel gelijk gebleven. Met als kanttekening dat in de meest recente jaren sprake is van een zichtbare verbetering van het verbruik per kilometer, afgemeten aan de CO2-uitstoot van nieuwe personenauto's. Het KiM heeft zich in de studie gebaseerd op cijfers over de periode 1980-2009. De meeste in het onderzoek vastgestelde effecten van hogere benzineprijzen zijn kleiner dan de effecten die in de beschikbare literatuur zijn aangetroffen. Dit geldt vooral voor de effecten op de lange termijn.

  3. Relationship between thyroid stimulating hormone and various components of metabolic syndrome

    Majeed, S.; Hashim, R.

    2015-01-01

    To determine the relation between thyroid stimulating hormone and various components of metabolic syndrome. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Pathology department, Army Medical College of National University of Sciences and Technology (NUST) Islamabad and Military Hospital (MH), Rawalpindi, Pakistan; from January to March 2013. Material and Methods: Hundred adult inhabitants (30-60 years) of Rawalpindi participated in this study. Subjects who fulfilled the WHO criteria for metabolic syndrome (MetS) were included and those who had any thyroid illness, or were using any thyroid medications were excluded from this study. For thyroid function tests (TFT's), serum thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), free throxine (FT4) were estimated. Insulin resistance (IR) was measured by Homeostasis Model Assessment for IR (HOMA-IR). Data was analyzed by SPSS-18. Results: Out of 50 subjects of control group, 26 (52%) were male and 24 (48%) were female. Basal metabolic rate (BMI), serum triglyceride (TG), HOMA-IR were higher and serum high density lipoprotein cholesterol (HDL-c) was lower in MetS patients. There was no significant difference in serum TT3 and FT4 between MetS patients and control group, however, mean serum TSH levels were higher in MetS (2.622 + 0.924 vs 5.002 + 1.074 mIU/l, p<0.001). In correlation analysis, serum TSH was positively and significantly correlated with BMI (r=0.344, p=0.014) and HOMA-IR (r=0.419, p<0.002). Conclusion: These results suggest that serum TSH correlates with various components of metabolic syndrome patients. Analysis of serum TSH levels in metabolic syndrome patients may prove beneficial in preventing the various cardiometabolic complications in such patients. (author)

  4. 18F-FDG imaging with a coincidence dual-headed gamma camera (Co-PET) in the diagnosis, staging and management of lung cancer

    Lin, P.; Chu, J.; Pocock, N.; Quach, T.; Sorensen, B.

    1999-01-01

    Full text: FDG-PET has an established role in the management of lung cancer, while the experience with FDG-Co-PET is limited. Our study aims to demonstrate the feasibility of Co-PET in staging and management of lung cancer. Thirty-nine Co-PET studies were performed on our first 36 patients (pts) with primary lung cancer between November 1997 and October 1998. Tomography of brain and torso with an ADAC Solus MCD gamma camera was performed (60 min after 200 MBq of 18 FFDG and > 6 h fasting). Histology subgroups included squamous (14 pts), small cell (1), adeno-carcinoma (11), broncho-alveolar (1), large cell (8), carcinoid (1). CT/clinical staging subgroups included 18 pts in stage 1, 4 in stage 2, 7 in stage 3a, 2 in stage 3b, 8 in stage 4. Compared with CT/clinical staging, FDG upstaged 5 pts (14%) with regional nodal metastases (mets) and 8 pts (22%) with distant mets (cervical = 2, lung = 1, brain = 3, bone = 3, abdomen = 4). FDG under-staged 2 pts in 3 sites (all < 15 mm). Surgical nodal staging was performed in 14 pts: false-positives occurred in 3 CT and 1 Co-PET studies, and false-negatives in one CT/Co-PET. Site sensitivities for primary (smallest 7 mm) and regional lymph nodes are 100% and 88% respectively. Specificities for primary and regional nodes are 100% and 96% respectively. Co-PET also has impact on management: treatment intent (6 pts), radiotherapy fields (1), diagnosis of lung mets (2) and radiation pneumonitis (1). In conclusion, our initial data demonstrate FDG-Co-PET scanning could provide a valuable addition to conventional imaging studies in diagnosis, staging and management of lung cancer

  5. Effects of 1-Methylnicotinamide (MNA) on Exercise Capacity and Endothelial Response in Diabetic Mice.

    Przyborowski, Kamil; Wojewoda, Marta; Sitek, Barbara; Zakrzewska, Agnieszka; Kij, Agnieszka; Wandzel, Krystyna; Zoladz, Jerzy Andrzej; Chlopicki, Stefan

    2015-01-01

    1-Methylnicotinamide (MNA), which was initially considered to be a biologically inactive endogenous metabolite of nicotinamide, has emerged as an anti-thrombotic and anti-inflammatory agent with the capacity to release prostacyclin (PGI2). In the present study, we characterized the effects of MNA on exercise capacity and the endothelial response to exercise in diabetic mice. Eight-week-old db/db mice were untreated or treated with MNA for 4 weeks (100 mg·kg-1), and their exercise capacity as well as NO- and PGI2-dependent response to endurance running were subsequently assessed. MNA treatment of db/db mice resulted in four-fold and three-fold elevation of urine concentrations of MNA and its metabolites (Met-2PY + Met-4PY), respectively (P<0.01), but did not affect HbA1c concentration, fasting glucose concentration or lipid profile. However, insulin sensitivity was improved (P<0.01). In MNA-treated db/db mice, the time to fatigue for endurance exercise was significantly prolonged (P<0.05). Post-exercise Δ6-keto-PGF1α (difference between mean concentration in the sedentary and exercised groups) tended to increase, and post-exercise leukocytosis was substantially reduced in MNA-treated animals. In turn, the post-exercise fall in plasma concentration of nitrate was not affected by MNA. In conclusion, we demonstrated for the first time that MNA improves endurance exercise capacity in mice with diabetes, and may also decrease the cardiovascular risk of exercise.

  6. Effects of 1-Methylnicotinamide (MNA on Exercise Capacity and Endothelial Response in Diabetic Mice.

    Kamil Przyborowski

    Full Text Available 1-Methylnicotinamide (MNA, which was initially considered to be a biologically inactive endogenous metabolite of nicotinamide, has emerged as an anti-thrombotic and anti-inflammatory agent with the capacity to release prostacyclin (PGI2. In the present study, we characterized the effects of MNA on exercise capacity and the endothelial response to exercise in diabetic mice. Eight-week-old db/db mice were untreated or treated with MNA for 4 weeks (100 mg·kg-1, and their exercise capacity as well as NO- and PGI2-dependent response to endurance running were subsequently assessed. MNA treatment of db/db mice resulted in four-fold and three-fold elevation of urine concentrations of MNA and its metabolites (Met-2PY + Met-4PY, respectively (P<0.01, but did not affect HbA1c concentration, fasting glucose concentration or lipid profile. However, insulin sensitivity was improved (P<0.01. In MNA-treated db/db mice, the time to fatigue for endurance exercise was significantly prolonged (P<0.05. Post-exercise Δ6-keto-PGF1α (difference between mean concentration in the sedentary and exercised groups tended to increase, and post-exercise leukocytosis was substantially reduced in MNA-treated animals. In turn, the post-exercise fall in plasma concentration of nitrate was not affected by MNA. In conclusion, we demonstrated for the first time that MNA improves endurance exercise capacity in mice with diabetes, and may also decrease the cardiovascular risk of exercise.

  7. Short-term therapy with combination dipeptidyl peptidase-4 inhibitor saxagliptin/metformin extended release (XR) is superior to saxagliptin or metformin XR monotherapy in prediabetic women with polycystic ovary syndrome: a single-blind, randomized, pilot study.

    Elkind-Hirsch, Karen E; Paterson, Martha S; Seidemann, Ericka L; Gutowski, Hanh C

    2017-01-01

    To evaluate efficacy with the dipeptidyl peptidase-4 inhibitor saxagliptin (SAXA), metformin extended release (MET), and combination (SAXA-MET) in patients with polycystic ovary syndrome (PCOS) and impaired glucose regulation. Prospective, randomized, single-blind drug study. Outpatient clinic. Patients (n = 38) with PCOS (aged 18-42 years) and prediabetic hyperglycemia determined by a 75-gram oral glucose tolerance test. Patients were randomized to SAXA-MET (5 mg/2,000 mg), SAXA (5 mg), or MET (2,000 mg) for 16 weeks. Fasting and mean blood glucose, insulin sensitivity, insulin secretion, and insulin secretion-sensitivity index (IS-SI) by oral glucose tolerance tests. Free androgen index and lipid levels, average menstrual interval, and anthropometric measurements (body mass index, waist circumference, and waist/height ratio). The study was completed by 34 patients. Nineteen patients had normal glucose tolerance: 3 of 12 (25%) on MET; 6 of 11 (55%) on SAXA; and 10 of 11 (91%) on SAXA-MET (SAXA-MET statistically superior to MET) at study completion. Body mass index, waist circumference, waist/height ratio, free androgen index, insulin sensitivity, IS-SI, and menses improved in all groups; however, IS-SI and menstrual regularity were significantly better with SAXA-MET vs. MET treatment. Triglyceride, triglyceride/high-density lipoprotein cholesterol ratio and mean blood glucose significantly declined in the SAXA-MET and SAXA groups only. This pilot work provides the first evidence regarding the effects of a dipeptidyl peptidase-4 inhibitor alone and in combination with MET in this patient population. Treatment with SAXA-MET was superior to either drug alone in terms of clinical and metabolic benefits in prediabetic patients with PCOS. NCT02022007. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Mediator, TATA-binding protein, and RNA polymerase II contribute to low histone occupancy at active gene promoters in yeast.

    Ansari, Suraiya A; Paul, Emily; Sommer, Sebastian; Lieleg, Corinna; He, Qiye; Daly, Alexandre Z; Rode, Kara A; Barber, Wesley T; Ellis, Laura C; LaPorta, Erika; Orzechowski, Amanda M; Taylor, Emily; Reeb, Tanner; Wong, Jason; Korber, Philipp; Morse, Randall H

    2014-05-23

    Transcription by RNA polymerase II (Pol II) in eukaryotes requires the Mediator complex, and often involves chromatin remodeling and histone eviction at active promoters. Here we address the role of Mediator in recruitment of the Swi/Snf chromatin remodeling complex and its role, along with components of the preinitiation complex (PIC), in histone eviction at inducible and constitutively active promoters in the budding yeast Saccharomyces cerevisiae. We show that recruitment of the Swi/Snf chromatin remodeling complex to the induced CHA1 promoter, as well as its association with several constitutively active promoters, depends on the Mediator complex but is independent of Mediator at the induced MET2 and MET6 genes. Although transcriptional activation and histone eviction at CHA1 depends on Swi/Snf, Swi/Snf recruitment is not sufficient for histone eviction at the induced CHA1 promoter. Loss of Swi/Snf activity does not affect histone occupancy of several constitutively active promoters; in contrast, higher histone occupancy is seen at these promoters in Mediator and PIC component mutants. We propose that an initial activator-dependent, nucleosome remodeling step allows PIC components to outcompete histones for occupancy of promoter sequences. We also observe reduced promoter association of Mediator and TATA-binding protein in a Pol II (rpb1-1) mutant, indicating mutually cooperative binding of these components of the transcription machinery and indicating that it is the PIC as a whole whose binding results in stable histone eviction. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Could piracetam potentiate behavioural effects of psychostimulants?

    Slais, Karel; Machalova, Alena; Landa, Leos; Vrskova, Dagmar; Sulcova, Alexandra

    2012-08-01

    Press and internet reports mention abuse of nootropic drug piracetam (PIR) in combination with psychostimulants methamphetamine (MET) or 4-methylenedioxymethamphetamine (MDMA). These combinations are believed to produce more profound desirable effects, while decreasing hangover. However, there is a lack of valid experimental studies on such drug-drug interactions in the scientific literature available. Our hypothesis proposes that a functional interaction exists between PIR and amphetamine psychostimulants (MET and MDMA) which can potentiate psychostimulant behavioural effects. Our hypothesis is supported by the results of our pilot experiment testing acute effects of drugs given to mice intraperitoneally (Vehicle, n=12; MET 2.5mg/kg, n=10; MDMA 2.5mg/kg, n=11; PIR 300 mg/kg, n=12; PIR+MET, n=12; PIR+MDMA, n=11) in the Open Field Test (Actitrack, Panlab, Spain). PIR given alone caused no significant changes in mouse locomotor/exploratory behaviour, whereas the same dose combined with either MET or MDMA significantly enhanced their stimulatory effects. Different possible neurobiological mechanism underlying drug-drug interaction of PIR with MET or MDMA are discussed, as modulation of dopaminergic, glutamatergic or cholinergic brain systems. However, the interaction with membrane phospholipids seems as the most plausible mechanism explaining PIR action on activities of neurotransmitter systems. Despite that our behavioural experiment cannot serve for explanation of the pharmacological mechanisms of these functional interactions, it shows that PIR effects can increase behavioural stimulation of amphetamine drugs. Thus, the reported combining of PIR with MET or MDMA by human abusers is not perhaps a coincidental phenomenon and may be based on existing PIR potential to intensify acute psychostimulant effects of these drugs of abuse. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Workload of official contests, net cost of transport, and metabolic power of Mangalarga Marchador horses of marcha batida or picada gaits.

    Lage, J; Fonseca, M G; de Barros, G G M; Feringer-Júnior, W H; Pereira, G T; Ferraz, G C

    2017-06-01

    This study aimed to characterize the maximum heart rate (HR) and the intensity of official marcha contests (OMC) and to compare the cost of transport (COT) and metabolic power (Pmet) of Mangalarga Marchador (MM) horses of marcha batida (MB) and marcha picada (MP) gaits. Twenty-two MM horses participated in this study. The experiment was conducted in 3 phases: 1) maximum effort test (MET), 2) OMC, and 3) standardized marcha test (SMT). To characterize the HR, 19 horses (14 MB and 5 MP) underwent a MET. Of those, 13 (9 MB and 4 MP) were monitored during the OMC, which consisted of 4 stages: marcha, walk, functional trial, and rest. The average heart rate (HR) in each stage of the OMC was related to the HR to determine their relative intensity. The SMT was performed with 14 horses (9 MB and 5 MP), of which 11 had already participated in the previous stages. The COT and Pmet were calculated from the HR values obtained during the SMT. Blood samples were collected to analyze plasma lactate concentration ([Lac]). One-way ANOVA or 1-way repeated-measures ANOVA followed by the Tukey's test ( 0.05). This indicated that horses of both groups had the same physical fitness levels. The OMC stages defined in our study differed ( < 0.05) regarding the relative intensity of the HR, except for the walk and standing stages, which were similar ( = 0.0875). The MP group presented greater COT ( = 0.0247) and Pmet ( = 0.0193). It can be concluded that the mean HR of MM horses (MB and MP) is 212 ± 11 bpm. The OMC of the MM breed can be characterized as an effort of intermittent and submaximal intensity. In addition, the locomotion of the MB horses is probably more energetically efficient than that of MP horses.

  11. Advantages of integrated and sustainability based assessment for metabolism based strategic planning of urban water systems.

    Behzadian, Kourosh; Kapelan, Zoran

    2015-09-15

    Despite providing water-related services as the primary purpose of urban water system (UWS), all relevant activities require capital investments and operational expenditures, consume resources (e.g. materials and chemicals), and may increase negative environmental impacts (e.g. contaminant discharge, emissions to water and air). Performance assessment of such a metabolic system may require developing a holistic approach which encompasses various system elements and criteria. This paper analyses the impact of integration of UWS components on the metabolism based performance assessment for future planning using a number of intervention strategies. It also explores the importance of sustainability based criteria in the assessment of long-term planning. Two assessment approaches analysed here are: (1) planning for only water supply system (WSS) as a part of the UWS and (2) planning for an integrated UWS including potable water, stormwater, wastewater and water recycling. WaterMet(2) model is used to simulate metabolic type processes in the UWS and calculate quantitative performance indicators. The analysis is demonstrated on the problem of strategic level planning of a real-world UWS to where optional intervention strategies are applied. The resulting performance is assessed using the multiple criteria of both conventional and sustainability type; and optional intervention strategies are then ranked using the Compromise Programming method. The results obtained show that the high ranked intervention strategies in the integrated UWS are those supporting both water supply and stormwater/wastewater subsystems (e.g. rainwater harvesting and greywater recycling schemes) whilst these strategies are ranked low in the WSS and those targeting improvement of water supply components only (e.g. rehabilitation of clean water pipes and addition of new water resources) are preferred instead. Results also demonstrate that both conventional and sustainability type performance indicators

  12. A Phase I randomized clinical trial testing the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy volunteers.

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-11-15

    Preclinical work suggests that the metabotropic glutamate receptor subtype 5 (mGlu5) may represent a novel target to treat neuropsychiatric disorders, including alcohol use disorder and obesity. The goal of this first-in-man study was to evaluate the safety, tolerability and pharmacokinetics (PK) of GET 73 (PubChem SID: 329974174), a novel mGluR5 negative allosteric modulator. This was a double-blind, placebo-controlled, ascending dose, Phase I study conducted in healthy male volunteers in two experiments. GET 73 was administered as single ascending doses (N=48; Experiment 1; 10, 30, 100, 300, 450, 600-mg) or multiple ascending doses (N=32; Experiment 2; 100, 300, 450, 450-mg twice a day). Primary endpoints were the incidence of adverse events (AEs) among drug conditions and drug tolerability. The secondary endpoints were the PK parameters of GET 73 and its metabolite MET 2. Single GET 73 doses of up to 600-mg and repeated ascending doses of up to 450-mg twice/day were safe and well-tolerated. There were no serious or severe AEs. All AEs were mild or moderate in severity. Total GET 73 exposure increased with each increased GET 73 dose. A dose-related increase in mean maximum plasma drug concentration was observed after repeated dosing. Maximum plasma drug concentrations occurred between 0.5 and 2.05h after administration in all groups for both single and repeated doses. This first-in-human study indicates that GET 73, as single or multiple ascending doses, is safe and well-tolerated when administered to healthy male volunteers. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Regarding fuel prices and automobility. A brief analysis of price and cost elasticities; Over brandstofprijzen en automobiliteit. Een beknopte analyse van prijs- en kostenelasticiteit

    Groot, W.

    2012-01-15

    Car drivers do not drive significantly less when fuel prices at the pump rise. If fuel prices increase by approximately 12.5 percent, the long-term decrease in car kilometres travelled is just 2.5 percent. Higher fuel prices have also not resulted in a more fuel-efficient 'car fleet' (i.e. the range of available car model types). The fuel consumption rate per kilometre remained relatively constant from the late 1980s to 2009, although recent years have seen a marked improvement in the per kilometre fuel consumption rate, as measured in CO2 emissions of new passenger cars. These were the findings of the title study, conducted by the KiM Netherlands Institute for Transport Policy Analysis. This study was based on data covering the period 1980 to 2009. The majority of the definitive effects of higher fuel prices revealed in this study were less pronounced than the effects previously cited in available literature, especially with regard to the long-term effects [Dutch] Uit de titel studie blijkt dat automobilisten in beperkte mate minder gaan rijden als de brandstofprijzen aan de pomp stijgen. Een stijging van de benzineprijs met ongeveer 12,5 procent leidt op langere termijn tot een vermindering van de hoeveelheid afgelegde kilometers met 2,5 procent. De hoge brandstofprijzen hebben ook niet geleid tot een zuiniger wagenpark. Het benzineverbruik per kilometer is tussen het eind van de jaren tachtig en 2009 vrijwel gelijk gebleven. Met als kanttekening dat in de meest recente jaren sprake is van een zichtbare verbetering van het verbruik per kilometer, afgemeten aan de CO2-uitstoot van nieuwe personenauto's. Het KiM heeft zich in de studie gebaseerd op cijfers over de periode 1980-2009. De meeste in het onderzoek vastgestelde effecten van hogere benzineprijzen zijn kleiner dan de effecten die in de beschikbare literatuur zijn aangetroffen. Dit geldt vooral voor de effecten op de lange termijn.

  14. AN ENVIRONMENTAL COMPARISON OF PLASTIC AND PAPER CONSUMER CARRIER BAGS IN SOUTH AFRICA: IMPLICATIONS FOR THE LOCAL MANUFACTURING INDUSTRY

    J. Sevitz

    2012-01-01

    Full Text Available

    ENGLISH ABSTRACT: The conventional consumer carrier bags have recently received considerable attention in South Africa. The choice of material for these bags, based on environmental preferences in the South African context, could significantly influence the local manufacturing industry. Life Cycle Assessment (LCA, an environmental management tool, has been applied to objectively evaluate and compare the overall environmental impacts of the complete life cycles (from raw material extraction to final disposal of consumer plastic and paper carrier bags in South Africa. Paper bags have a higher carrying capacity compared to plastic bags and different use ratios were subsequently evaluated. Plastic bags have a lower environmental impact for use ratios of up to 2.5 plastic bags to one paper bag. Above this ratio the conclusions are not reliable. Paper bags would need to increase its recycled content significantly to be competitive in terms of environmental impacts. The re-use of thicker plastic, as proposed by the new plastic bag legislation, has the potential to significantly lower the impact of plastic bags.

    AFRIKAANSE OPSOMMING: Die konvensionele gebruikersdrasakke het onlangs aansienlike aandag in Suid Afrika ontvang. Die keuse van materiaal vir hierdie sakke, wat gebaseer is op omgewingsvoorkeure in die Suid-Afrikaanse konteks, kan 'n wesenlike invloed uitoefen op die plaaslike vervaardigingsindustrie. Lewenssiklusanalise (LCA, 'n omgewingsbestuurgereedskap, is aangewend vir 'n objektiewe evaluasie en vergelyking van die algehele omgewingsimpakte van die totale lewenssiklus (vanaf grondstofekstraksie tot finale wegdoening van gebruikersplastiek- en papierdrasakke in Suid-Afrika. Aangesien papiersakke 'n hoër drakapasiteit het in vergelyking met plastieksakke, is verskillende gebruiksverhoudings evalueer. Plastieksakke het 'n laer omgewingsimpak vir gebruiksverhoudings tot en met 2.5 plastieksakke vir elke papiersak. Die gevolgtrekkings

  15. Antibacterial resistance and the success of tailored triple therapy in Helicobacter pylori strains isolated from Slovenian children.

    Butenko, Tita; Jeverica, Samo; Orel, Rok; Homan, Matjaž

    2017-10-01

    Primary Helicobacter pylori (H. pylori) infection occurs predominantly in childhood. Antimicrobial resistance is the leading cause for H. pylori eradication failure. The aims of this study were (i) to establish for the first time the antimicrobial resistance of H. pylori strains in infected Slovenian children not previously treated for H. pylori infection and (ii) to evaluate the effectiveness of tailored triple therapy, assuming that eradication rate with tailored triple therapy will be >90%. Data on all treatment-naive children 1-18 years old and treated for H. pylori infection according to susceptibility testing were retrospectively analyzed. All relevant clinical information and demographical information were retrospectively collected from the hospital information systems and/or patients' medical documentation. The inclusion criteria were met by 107 children (64.5% girls) with a median age of 12.0 years (range 2.0-17.6 years). Primary antimicrobial resistance rates of H. pylori were 1.0% to amoxicillin (AMO), 23.4% to clarithromycin (CLA), 20.2% to metronidazole (MET), 2.8% to levofloxacin (LEV), and 0.0% to tetracycline (TET). Dual resistances were detected to CLA and MET in 11.5% (n=12) of strains, to CLA and LEV in 2.8% (n=3), and to MET and LEV in 2.9% (n=3). Results of treatment success were available for 71 patients (66.2% girls). Eradication of H. pylori was evaluated using the 13C-urea breath test, monoclonal stool antigen test or in some cases with repeated upper GI endoscopy with histology and cultivation/molecular tests. Eradication was achieved in 61 of 71 (85.9%) patients. The primary resistance rates of H. pylori to CLA and MET in Slovenia are high. Our data strongly support the fact that in countries with high prevalence of resistant H. pylori strains susceptibility testing and tailored therapy is essential. © 2017 The Authors Helicobacter Published by John Wiley & Sons Ltd.

  16. Health effects of home energy efficiency interventions in England: a modelling study

    Milner, James; Chalabi, Zaid; Das, Payel; Jones, Benjamin; Shrubsole, Clive; Davies, Mike; Wilkinson, Paul

    2015-01-01

    Objective To assess potential public health impacts of changes to indoor air quality and temperature due to energy efficiency retrofits in English dwellings to meet 2030 carbon reduction targets. Design Health impact modelling study. Setting England. Participants English household population. Intervention Three retrofit scenarios were modelled: (1) fabric and ventilation retrofits installed assuming building regulations are met; (2) as with scenario (1) but with additional ventilation for homes at risk of poor ventilation; (3) as with scenario (1) but with no additional ventilation to illustrate the potential risk of weak regulations and non-compliance. Main outcome Primary outcomes were changes in quality adjusted life years (QALYs) over 50 years from cardiorespiratory diseases, lung cancer, asthma and common mental disorders due to changes in indoor air pollutants, including secondhand tobacco smoke, PM2.5 from indoor and outdoor sources, radon, mould, and indoor winter temperatures. Results The modelling study estimates showed that scenario (1) resulted in positive effects on net mortality and morbidity of 2241 (95% credible intervals (CI) 2085 to 2397) QALYs per 10 000 persons over 50 years follow-up due to improved temperatures and reduced exposure to indoor pollutants, despite an increase in exposure to outdoor-generated particulate matter with a diameter of 2.5 μm or less (PM2.5). Scenario (2) resulted in a negative impact of −728 (95% CI −864 to −592) QALYs per 10 000 persons over 50 years due to an overall increase in indoor pollutant exposures. Scenario (3) resulted in −539 (95% CI −678 to -399) QALYs per 10 000 persons over 50 years follow-up due to an increase in indoor exposures despite the targeting of pollutants. Conclusions If properly implemented alongside ventilation, energy efficiency retrofits in housing can improve health by reducing exposure to cold and air pollutants. Maximising the health benefits requires careful

  17. Supporting documentation for requested exceptions to standing orders 96-36 (East) and 96-34 (West)

    Schofield, J.S.

    1997-01-16

    On November 1, 1996 the U.S. Department of Energy (DOE), Richland Operations Office (RL) approved the Flammable Gas Unreviewed Safety Question (USQ) (Wagoner 1996). The Tank Waste Remediation System issued (Hall 1996) two standing orders (96-36 East; and 96-34 West) to implement the requirements and authorization for continued operations included in the RL letter (Wagoner 199E). These standing orders included several requirements for the control of ignition sources (Appendix B, Section 7.0 ``Ignition Source Controls``) that include requirements for the design and operation of ``...equipment and materials used in the conduct of work...`` in Tank Farms. A verbatim compliance review of these ignition source controls identified several pieces of equipment and materials which have been used routinely in Tanks Farms for many years in support of safe operation that either could not: meet the equivalent design or safety provisions included in the standing orders (Hall 1996), or 21. be modified in a timely manner to meet safety and programmatic commitments. When the standing order was prepared it was anticipated that there would be a need to approve temporary exceptions. Appendix B, Section 7.0 of the standing order (Hall 1996) reads in part as follows: ``For activities where compliance will require modification to equipment or new materials, any temporary exceptions specifically allowed by RL until full compliance with the standing order is accomplished, are listed in Table 3.`` This document provides a specific listing of the items of equipment or material that could not meet the above two criteria. Also included in a table for each item is the following information: 1. the applicable control in the standing orders that could not be met, 2. under what conditions (when) the control could not be met, 3. a discussion of the applicability of the standing order, 4. a discussion of the risk associated with continued use of the equipment or material, and 5. a discussion of the

  18. Age- and sex-specific prevalence and ten-year risk for cardiovascular disease of all 16 risk factor combinations of the metabolic syndrome - A cross-sectional study

    Moebus Susanne

    2010-08-01

    Full Text Available Abstract Background Based on the AHA/NHLBI-definition three out of five cardiometabolic traits must be present for the diagnosis of the metabolic syndrome (MetS, resulting in 16 different combination types. The associated cardiovascular risk may however be different and specific combination may be indicative of an increased risk, furthermore little is known to which extent these 16 combinations contribute to the overall prevalence of MetS. Here we assessed the prevalence of all 16 combination types of MetS, analyzed the impact of age and gender on prevalence rates, and estimated the 10-year risk of fatal and non-fatal myocardial infarction (MI of each MetS combination type. Methods We used data of the German Metabolic and Cardiovascular Risk Project (GEMCAS, a cross-sectional study, performed during October 2005, including 35,869 participants (aged 18-99 years, 61% women. Age-standardized prevalence and 10-year PROCAM and ESC risk scores for MI were calculated. Results In both men and women the combination with elevated waist-circumference, blood pressure and glucose (WC-BP-GL was the most frequent combination (28%, however a distinct unequal distribution was observed regarding age and sex. Any combination with GL was common in the elderly, whereas any combination with dyslipidemia and without GL was frequent in the younger. Men without MetS had an estimated mean 10-year risk of 4.7% (95%-CI: 4.5%-4.8% for MI (PROCAM, whereas the mean 10-year risk of men with MetS was clearly higher (age-standardized 7.9%; 7.8-8.0%. In women without MetS the mean 10-year risk for MI was 1.1%, in those with MetS 2.3%. The highest impact on an estimated 10-year risk for MI (PROCAM was observed with TG-HDL-GL-BP in both sexes (men 14.7%, women 3.9%. However, we could identify combinations with equal risks of non-fatal and fatal MI compared to participants without MetS. Conclusions We observed large variations in the prevalence of all 16 combination types and their association to cardiovascular risk. The importance of different combinations of MetS changes with age and between genders putting emphasis on a tailored approach towards very young or very old subjects. This knowledge may guide clinicians to effectively screen individuals and prioritize diagnostic procedures depending on age and gender.

  19. A comparative study of the anorectic and behavioral effects of fenproporex on male and female rats.

    Mattei, R; Carlini, E A

    1996-08-01

    The anorectic and behavioral effects of fenproporex (Fenp, 10 mg/kg, ip) and methamphetamine (Met, 2.5 mg/kg, ip), a prototypical example of an amphetamine-like drug, were studied in male and female Wistar rats (5 and 3 months of age, respectively, at the beginning of the experiments) after acute (immediately after a single dose) or chronic treatment (after 60 days of administration). For the evaluation of the experimental parameters six groups of eight rats each were utilized for food intake and stereotyped behavior and six groups of nine rats each for body weight and motor activity. Similar anorectic effects (decreased food intake in grams: saline (Sal): 12.8 +/- 2.5, Met: 4.7 +/- 4.0, and Fenp: 4.4 +/- 20; decreased weight gain: Sal: 38 +/- 10, Met: 25 +/- 1.0, and Fenp: 27 +/- 3.0) were induced by both drugs in male rats. Female rats, however, required larger doses (20 mg/kg Fenp and 5.0 mg/kg Met) for a complete blockade of food intake. The behavioral tests were carried out 30, 60, 120, 180 and 300 min after drug administration and on day 1 and day 60 immediately after the treatment, for stereotypy and motor activity, respectively (male rats: Met: 3.8 +/- 0.3, Fenp: 6.0 +/- 0.9, and female rats: Met: 15.4 +/- 1.9, Fenp: 9.7 +/- 1.3). Though stereotyped behavior such as sniffing, continuous licking, and false bites was observed in all animals, this was more evident and prolonged in female rats. Both drugs also increased motor activity (male rats, acute treatment: Met: 608 +/- 419, Fenp: 677 +/- 354; chronic treatment: Met: 701 +/- 423, Fenp: 908 +/- 479; female rats, acute treatment: Met: 817 +/- 350, Fenp: 1177 +/- 282; chronic treatment: Met: 623 +/- 274, Fenp: 1511 +/- 573) with female rats once again showing greater sensitivity both after acute and chronic treatment. Our data indicate that fenproporex, like methamphetamine, has a stimulating effect on the central nervous system, indicating an action on the dopaminergic systems. These data further suggest

  20. Prevalence and characteristics of the metabolic syndrome among newly diagnosed hypertensive patients

    Osuji, Charles U.; Omejua, Emeka G.

    2012-01-01

    Background: Cardiovascular disease risk factors have a tendency to cluster. The presence of such a cluster in an individual has been designated the metabolic syndrome (MetS). There is a paucity of reports of the prevalence of MetS in hypertensive patients in south east Nigeria. This study was undertaken to determine the prevalence of the metabolic syndrome (MetS) among newly diagnosed hypertensive patients using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria in a tertiary healthcare centre in South East Nigeria. Materials and Methods: A population of 250 consecutive newly diagnosed adult hypertensive patients (126 males and 124 females) was evaluated. Blood pressure and anthropometric measurements were done using standardized techniques. After an overnight fast, blood samples were taken for glucose and lipid profile assays. The NCEP ATP III criteria were then applied for the diagnosis of MetS. Results: The prevalence of the MetS among the study population was 31.2%. The sex-specific prevalences were 15.1% and 47.6% among male and female patients respectively. A large number of the patients (40.4%) were at a high potential risk of developing the MetS as they already met 2 of the criteria. The MetS prevalence increased progressively from 14.3% through 23.8%, in the patients aged 24-33years and 34-43 years, respectively to a peak (40.4%) among those aged 44-53 years before declining in those aged 54-63 years (31.8%), 64-73 years (33.3%) and 74 years and above (20.6%). Central obesity was the most common component of the MetS being present in 50.4% of patients (28.6% of males and 72.6% of females). Of the other components, low HDL-C was present in 38.8% (26.2% of males and 51.6% of females), elevated FBS in 12.8% (6.3% of males and 19.4% of females) and elevated triglycerides in 8.8% (11.9% of males and 5.6% of females). Conclusion: The prevalence of the MetS is high among newly diagnosed hypertensive patients in Nnewi

  1. A hhase I/II trial to evaluate three-dimensional conformal radiation therapy confined to the region of the lumpectomy cavity for Stage I/II breast carcinoma: Initial report of feasibility and reproducibility of Radiation Therapy Oncology Group (RTOG) Study 0319

    Vicini, Frank; Winter, Kathryn M.S.; Straube, William; Wong, John; Pass, Helen; Rabinovitch, Rachel; Chafe, Susan; Arthur, Douglas; Petersen, Ivy; McCormick, Beryl

    2005-01-01

    Background: This prospective study (Radiation Therapy Oncology Group Study 0319) examines the use of three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Reproducibility, as measured by technical feasibility, was the primary end point with the goal of demonstrating whether the technique is widely applicable in a multicenter setting before a Phase III trial is undertaken. Methods and Materials: This study was designed such that if fewer than 5 cases out of the first 42 patients evaluable were scored as unacceptable, the treatment would be considered reproducible. Patients received 38.5 Gy in 3.85 Gy/fraction delivered twice daily. The clinical target volume included the lumpectomy cavity plus a 10-15-mm margin bounded by 5 mm within the skin surface and the lung-chest wall interface. The planning target volume (PTV) included the clinical target volume plus a 10-mm margin. Treatment plans were judged as follows: (1) No variations (total coverage), 95% isodose surface covers 100% of the PTV and all specified critical normal tissue dose-volume histogram (DVH) limits met. (2) Minor variation (marginal coverage), 95% isodose surface covers between ≥95% and <100% of the PTV. No portion of PTV receives <93% of prescription (isocenter) dose. All specified critical normal tissue DVH limits fall within 5% of the guidelines. (3) Major variation (miss), 95% isodose surface covers <95% of the PTV. Portion of PTV receives <93% of prescription isocenter dose. Any critical normal tissue DVH limit exceeds 5% of the specified value. Results: A total of 58 patients were enrolled on this study between 8/15/03 and 4/30/04, 5 of whom were ineligible or did not receive protocol treatment. Two additional patients were excluded, one because the on-study form was not submitted, and the other because no treatment planning material was submitted. This primary end point analysis is based on the first 42 (out of 51) evaluable patients

  2. EVALUASI PENGEMBANGAN EKOWISATA DI KAWASAN TAHURA NGURAH RAI

    PUTU IKA WAHYUNI

    2012-11-01

    Full Text Available Since January 1992 MIC has initiate Tahura Ngurah Rai are as a ecotourism area, offering programs such as :Mangrove Education Tour & Tracking, Bird Watching; Finishing; Mangrove Tree Plantation or Adoption, Canoeing, andBoating programs. However, its growth has not me the management’s targets in term of the number of visitors, improvedfacilities available, and the surrounding Tahura are – especially its cleanliness-these are far from expectation standard.The evaluation of eco-tourism area of Tahura is aimed at understanding the profile of the eco-tourism area and tounderstand to what extent the ecotourism has met criteria/principles issued in the national workshop. This ecotourism willoffer recommendations designed in relation to programs that has not been working so far after identifying obstacles oftheir implementation.The method used in the evaluation of this eco-tourism area I descriptive analysis by analyzing interview data,observations, and literature studies. These descriptive data then are measured against criteria and principles of nationaleco-tourism.Since March 12, 2007 Mangrove forest area is under the management of BPHM-wil-I continuing JICA ICprogram. Facilities available in the area are as follows; Wood Trails, 5 Huts along the trail, Floating Decks, 2 ViewingTowers; MIC/BPHM Office Building, Touch Pools, Seeding area, and a Monitor Pool. These facilities right now are stillin good condition and can be used to implement the eco-tourism programs.From the 6 programs offered, the Mangrove Education Tour & Tracking Program gets the most interests fromvisitors than the other 5 programs. From 9 criteria used to evaluate the programs, the outcome is as follows: 1 Beingsensitive to and respecting socio-cultural values and religious tradition of local community (88% met; 2 Showingconcern, commitment, and responsibility to natural conservation and cultural heritage (95,24% met; 3 Provideinterpretation that facilities visitors to enjoy

  3. Initiating change locally in bullying and aggression through the school environment (INCLUSIVE): a pilot randomised controlled trial.

    Bonell, Chris; Fletcher, Adam; Fitzgerald-Yau, Natasha; Hale, Daniel; Allen, Elizabeth; Elbourne, Diana; Jones, Rebecca; Bond, Lyndal; Wiggins, Meg; Miners, Alec; Legood, Rosa; Scott, Stephen; Christie, Deborah; Viner, Russell

    2015-07-01

    -up June-July 2012). A total of 1017 students surveyed at baseline remained in the study at follow-up (89%). Other quantitative data were collected via intervention provider checklists (n = 4) and action group surveys (n = 44); qualitative data were collected via interviews (n = 34), focus groups (n = 20) and observations of action group meetings (n = 16). (1) All prespecified feasibility and acceptability criteria were met. (2) Qualitative data indicated that all intervention components and the trial design were feasible and acceptable to students and staff, including in more disadvantaged school contexts. Qualitative data also suggested that student participation may be a core component in improving relationships and engagement across the school. The later-than-planned project start (July) and the timing of the baseline surveys (September), which needed to be completed pre allocation, caused delays in launching the intervention, staff training and other intervention outputs. (3) Three pilot primary outcomes were examined (completion rate at follow-up range: 91.7-94.2%) and the Gatehouse Bullying Scale and the Edinburgh Study of Youth Transitions and Crime school misbehaviour subscale were acceptable, discriminating and reliable measures of bullying and aggression in this context. Our pilot economic analyses support the use of the Child Health Utility 9D scale with this population and the feasibility of cost-utility analysis, although this should be supplemented with a cost-consequence analysis. There was no evidence of harm. It is feasible and acceptable to implement and trial the INCLUSIVE intervention in English secondary schools, although a longer lead-in time is required to enable timely intervention outputs to occur. A Phase III cluster randomised controlled trial is required to examine the effectiveness and cost-effectiveness over a 3-year period of implementation for reducing aggressive behaviours, promoting mental health and well-being, and