PAX3 mutations and clinical characteristics in Chinese patients with Waardenburg syndrome type 1

Science.gov (United States)

Wang, Juan; Li, Shiqiang; Xiao, Xueshan; Wang, Panfeng; Guo, Xiangming

2010-01-01

Purpose To detect paired box gene 3 (PAX3) mutations and associated phenotypes in Chinese patients with Waardenburg syndrome type 1 (WS1). Methods Five unrelated families with suspected WS1 were selected from our Genomic DNA Repository for Hereditary Eye Diseases. The coding and adjacent intronic regions of PAX3 were amplified by polymerase chain reaction and the amplicons were then analyzed by cycle sequencing. Variations detected were further evaluated in available family members as well as one hundred controls with heteroduplex-single strand conformational polymorphism (heteroduplex-SSCP) analysis and/or clone sequencing. Results Three novel and two known mutations in PAX3 were detected in five patients, respectively: c.567_586+17del (p.Asp189_Gln505delinsGluGlyGlyAlaLeuAlaGly), c.456_459dupTTCC (p.Ile154PhefsX162), c.795_800delCTGGTT (p.Trp266_Phe267del), c.799T>A (p.Phe267Ile), and c.667C>T (p.Arg223X). Two novel mutations proved to be de novo as their parents did not carry the mutations. All five patients with PAX3 mutations had dystopia canthorum and different iris color and fundi between their two eyes. However, none had white forelock, skin hypopigmentation, and deafness. Conclusions Our findings expand the frequency and spectrum of PAX3 mutations and ethnic-related phenotypes in Chinese patients with WS1. De novo mutations in PAX3 have not been reported before. PMID:20664692

Digenic mutations involving both the BSND and GJB2 genes detected in Bartter syndrome type IV.

Science.gov (United States)

Wang, Hong-Han; Feng, Yong; Li, Hai-Bo; Wu, Hong; Mei, Ling-Yun; Wang, Xing-Wei; Jiang, Lu; He, Chu-Feng

2017-01-01

Bartter syndrome type IV, characterized by salt-losing nephropathies and sensorineural deafness, is caused by mutations of BSND or simultaneous mutations of both CLCNKA and CLCNKB. GJB2 is the primary causative gene for non-syndromic sensorineural deafness and associated with several syndromic sensorineural deafness. Owing to the rarity of Bartter syndrome, only a few mutations have been reported in the abovementioned causative genes. To investigate the underlying mutations in a Chinese patient with Bartter syndrome type IV, genetic analysis of BSND, CLCNKA, CLCNKB and GJB2 were performed by polymerase chain reaction and direct sequencing. Finally, double homozygous mutations c.22C > T (p.Arg8Trp) and c.127G > A (Val43Ile) were detected in exon 1 of BSND. Intriguingly, compound heterozygous mutations c.235delC (p.Leu79CysfsX3) and c.109G > A (p.Val37Ile) were also revealed in exon 2 of GJB2 in the same patient. No pathogenic mutations were found in CLCNKA and CLCNKB. Our results indicated that the homozygous mutation c.22C > T was the key genetic reason for the proband, and a digenic effect of BSND and GJB2 might contributed to sensorineural deafness. To our knowledge, it was the first report showing that the GJB2 gene mutations were detected in Bartter syndrome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PAX3 mutations and clinical characteristics in Chinese patients with Waardenburg syndrome type 1.

Science.gov (United States)

Wang, Juan; Li, Shiqiang; Xiao, Xueshan; Wang, Panfeng; Guo, Xiangming; Zhang, Qingjiong

2010-06-22

To detect paired box gene 3 (PAX3) mutations and associated phenotypes in Chinese patients with Waardenburg syndrome type 1 (WS1). Five unrelated families with suspected WS1 were selected from our Genomic DNA Repository for Hereditary Eye Diseases. The coding and adjacent intronic regions of PAX3 were amplified by polymerase chain reaction and the amplicons were then analyzed by cycle sequencing. Variations detected were further evaluated in available family members as well as one hundred controls with heteroduplex-single strand conformational polymorphism (heteroduplex-SSCP) analysis and/or clone sequencing. Three novel and two known mutations in PAX3 were detected in five patients, respectively: c.567_586+17del (p.Asp189_Gln505delinsGluGlyGlyAlaLeuAlaGly), c.456_459dupTTCC (p.Ile154PhefsX162), c.795_800delCTGGTT (p.Trp266_Phe267del), c.799T>A (p.Phe267Ile), and c.667C>T (p.Arg223X). Two novel mutations proved to be de novo as their parents did not carry the mutations. All five patients with PAX3 mutations had dystopia canthorum and different iris color and fundi between their two eyes. However, none had white forelock, skin hypopigmentation, and deafness. Our findings expand the frequency and spectrum of PAX3 mutations and ethnic-related phenotypes in Chinese patients with WS1. De novo mutations in PAX3 have not been reported before.

Research progress on distribution, migration, transformation of antibiotics and antibiotic resistance genes (ARGs) in aquatic environment.

Science.gov (United States)

Shao, Sicheng; Hu, Yongyou; Cheng, Jianhua; Chen, Yuancai

2018-05-28

Antimicrobial and antibiotics resistance caused by misuse or overuse of antibiotics exposure is a growing and significant threat to global public health. The spread and horizontal transfer of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) by the selective pressure of antibiotics in an aquatic environment is a major public health issue. To develop a better understanding of potential ecological risks die to antibiotics and ARGs, this study mainly summarizes research progress about: (i) the occurrence, concentration, fate, and potential ecological effects of antibiotics and ARGs in various aquatic environments, (ii) the threat, spread, and horizontal gene transfer (HGT) of ARGs, and (iii) the relationship between antibiotics, ARGs, and ARB. Finally, this review also proposes future research direction on antibiotics and ARGs.

Fine mapping of the sunflower resistance locus Pl(ARG) introduced from the wild species Helianthus argophyllus.

Science.gov (United States)

Wieckhorst, S; Bachlava, E; Dussle, C M; Tang, S; Gao, W; Saski, C; Knapp, S J; Schön, C-C; Hahn, V; Bauer, E

2010-11-01

Downy mildew, caused by Plasmopara halstedii, is one of the most destructive diseases in cultivated sunflower (Helianthus annuus L.). The dominant resistance locus Pl(ARG) originates from silverleaf sunflower (H. argophyllus Torrey and Gray) and confers resistance to all known races of P. halstedii. We mapped Pl(ARG) on linkage group (LG) 1 of (cms)HA342 × ARG1575-2, a population consisting of 2,145 F(2) individuals. Further, we identified resistance gene candidates (RGCs) that cosegregated with Pl(ARG) as well as closely linked flanking markers. Markers from the target region were mapped with higher resolution in NDBLOS(sel) × KWS04, a population consisting of 2,780 F(2) individuals that does not segregate for Pl(ARG). A large-insert sunflower bacterial artificial chromosome (BAC) library was screened with overgo probes designed for markers RGC52 and RGC151, which cosegregated with Pl(ARG). Two RGC-containing BAC contigs were anchored to the Pl(ARG) region on LG 1.

Evaluation of new Tc-99m-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone peptides for melanoma imaging.

Science.gov (United States)

Flook, Adam M; Yang, Jianquan; Miao, Yubin

2013-09-03

The purpose of this study was to examine the melanoma targeting and imaging properties of two new (99m)Tc-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg(11))CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg(11))CCMSH peptides were synthesized, and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution and melanoma imaging properties of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The IC50 values of RTD-Lys-(Arg(11))CCMSH and RVD-Lys-(Arg(11))CCMSH were 0.7 ± 0.07 and 1.0 ± 0.3 nM in B16/F1 melanoma cells. Both (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH displayed high melanoma uptake. (99m)Tc-RTD-Lys-(Arg(11))CCMSH exhibited the highest tumor uptake of 18.77 ± 5.13% ID/g at 2 h postinjection, whereas (99m)Tc-RVD-Lys-(Arg(11))CCMSH reached the highest tumor uptake of 19.63 ± 4.68% ID/g at 4 h postinjection. Both (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH showed low accumulation in normal organs (<1.7% ID/g) except for the kidneys at 2 h postinjection. The renal uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH was 135.14 ± 23.62 and 94.01 ± 18.31% ID/g at 2 h postinjection, respectively. The melanoma lesions were clearly visualized by single-photon emission computed tomography (SPECT)/CT using either (99m)Tc-RTD-Lys-(Arg(11))CCMSH or (99m)Tc-RVD-Lys-(Arg(11))CCMSH as an imaging probe at 2 h postinjection. Overall, the introduction of Thr or Val residue retained high melanoma uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH. However, high renal uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH need to be reduced to facilitate their future applications.

Evaluation of New Tc-99m-Labeled Arg-X-Asp-Conjugated Alpha-Melanocyte Stimulating Hormone Peptides for Melanoma Imaging

Science.gov (United States)

Flook, Adam M.; Yang, Jianquan; Miao, Yubin

2013-01-01

The purpose of this study was to examine the melanoma targeting and imaging properties of two new 99mTc-labeled Arg-X-Asp-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg11)CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg11)CCMSH peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution and melanoma imaging properties of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The IC50 values of RTD-Lys-(Arg11)CCMSH and RVD-Lys-(Arg11)CCMSH were 0.7 ± 0.07 and 1.0 ± 0.3 nM in B16/F1 melanoma cells. Both 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH displayed high melanoma uptake. 99mTc-RTD-Lys-(Arg11)CCMSH exhibited the peak tumor uptake of 18.77 ± 5.13% ID/g at 2 h post-injection, whereas 99mTc-RVD-Lys-(Arg11)CCMSH reached the peak tumor uptake of 19.63 ± 4.68% ID/g at 4 h post-injection. Both 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH showed low accumulation in normal organs (<1.7% ID/g) except for the kidneys at 2 h post-injection. The renal uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH was 135.14 ± 23.62 and 94.01 ± 18.31% ID/g at 2 h post-injection, respectively. The melanoma lesions were clearly visualized by SPECT/CT using either 99mTc-RTD-Lys-(Arg11)CCMSH or 99mTc-RVD-Lys-(Arg11)CCMSH as an imaging probe at 2 h post-injection. Overall, the introduction of Thr or Val residue retained high melanoma uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH. However, high renal uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH need to be reduced to facilitate their future applications. PMID:23885640

An ARGS-aggrecan assay for analysis in blood and synovial fluid

DEFF Research Database (Denmark)

Larsson, S; Lohmander, Stefan; Struglics, A

2014-01-01

OBJECTIVE: To validate a modified ligand-binding assay for the detection of aggrecanase generated aggrecan fragments with the ARGS neoepitope in synovial fluid (SF) and blood, and to verify the identity of aggrecan fragments found in blood. DESIGN: An enzyme-linked immunosorbent assay (ELISA....... Aggrecan was purified from serum and plasma pools and analysed by Western blot. RESULTS: The limits of quantification for the ARGS-aggrecan assay was between 0.2 and 0.025 pmol ARGS/ml, and the sensitivity of the assay was improved two-fold compared to when using a standard purified from human donors...... similar, and correlated (r(S) = 0.773, P assay is highly sensitive and suited for analysis...

Human migration activities drive the fluctuation of ARGs: Case study of landfills in Nanjing, eastern China.

Science.gov (United States)

Sun, Mingming; Ye, Mao; Schwab, Arthur P; Li, Xu; Wan, Jinzhong; Wei, Zhong; Wu, Jun; Friman, Ville-Petri; Liu, Kuan; Tian, Da; Liu, Manqiang; Li, Huixin; Hu, Feng; Jiang, Xin

2016-09-05

Landfills are perfect sites to study the effect of human migration on fluctuation of antibiotic resistance genes (ARGs) as they are the final destination of municipal waste. For example, large-scale human migration during the holidays is often accompanied by changes in waste dumping having potential effects on ARG abundance. Three landfills were selected to examine fluctuation in the abundance of fifteen ARGs and Intl1 genes for 14 months in Nanjing, eastern China. Mass human migration, the amount of dumped waste and temperature exerted the most significant effects on bimonthly fluctuations of ARG levels in landfill sites. As a middle-sized cosmopolitan city in China, millions of college students and workers migrate during holidays, contributing to the dramatic increases in waste production and fluctuation in ARG abundances. In line with this, mass migration explained most of the variation in waste dumping. The waste dumping also affected the bioaccessibility of mixed-compound pollutants that further positively impacted the level of ARGs. The influence of various bioaccessible compounds on ARG abundance followed the order: antibiotics>nutrients>metals>organic pollutants. Concentrations of bioaccessible compounds were more strongly correlated with ARG levels compared to total compound concentrations. Improved waste classification and management strategies could thus help to decrease the amount of bioaccessible pollutants leading to more effective control for urban ARG dissemination. Copyright © 2016 Elsevier B.V. All rights reserved.

A three-step programmed method for the identification of causative gene mutations of maturity onset diabetes of the young (MODY).

Science.gov (United States)

Li, Qian; Cao, Xi; Qiu, Hai-Yan; Lu, Jing; Gao, Rui; Liu, Chao; Yuan, Ming-Xia; Yang, Guang-Ran; Yang, Jin-Kui

2016-08-22

To establish a three-step programmed method to find gene mutations related to maturity onset diabetes of the young (MODY). Target region capture and next-generation sequencing (NGS) were performed using customized oligonucleotide probes designed to capture suspected genes for MODY in 11 probands with clinically diagnosed MODY. The suspected associations of certain genes with MODY were then confirmed by Sanger sequencing in the probands and their family members. Finally, to validate variants of one of the genes of interest (glucokinase, GCK) as pathogenic mutations, protein function editing by the variant genes was assessed. In the target region capture and NGS phase, a total of nine variants of seven genes (GCK, WFS1, SLC19A2, SH2B1, SERPINB4, RFX6, and GATA6) were identified in eight probands. Two heterozygous GCK mutations located on the same allele (p.Leu77Arg and p.Val101Met) were identified in a MODY family. Sanger sequencing was used to confirm the variants identified by NGS to be present in probands and their diabetic family members, but not in non-diabetic family members. Finally, enzyme kinetic and thermal stability analyses revealed that the p.Leu77Arg mutation or the p.Leu77Arg mutation in combination with the p.Val101Met mutation inactivates GCK function and stability, while mutation of p.Val101Met alone does not. The p.Leu77Arg but not p.Val101Met GCK mutation is therefore considered a pathogenic mutation associated with MODY. Genetic screening coupled with gene-editing protein function testing is an effective and reliable method by which causative gene mutations of MODY can be identified. Copyright © 2016 Elsevier B.V. All rights reserved.

Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity

DEFF Research Database (Denmark)

Andersen, Kirstine Lynge; Echwald, Søren Morgenthaler; Larsen, Lesli Hingstrup

2005-01-01

was identified in two families and showed partial cosegregation with obesity. The Pro(39)Pro, Ile(178)Ile, and Arg(517)Cys variants are in complete linkage disequilibrium and defined a prevalent haplotype. In a case-control study, the Arg(517)Cys polymorphism allele prevalence was 11.4% [95% confidence interval...... (CI), 9.7-13.0] among 744 men with juvenile-onset obesity and 9.3% (CI, 7.9-10.7) among 867 control subjects (P = 0.048). However, among middle-aged men the allelic prevalence was 9.7% (CI, 7.9-11.4) among 523 obese men and 12.2% (CI, 10.8-13.6) among 1051 lean men (P = 0.037). In conclusion...

Structural motifs of importance for the constitutive activity of the orphan 7TM receptor EBI2: analysis of receptor activation in the absence of an agonist

DEFF Research Database (Denmark)

Benned-Jensen, Tau; Rosenkilde, Mette M

2008-01-01

were identified by a systematic mutational analysis of 29 residues in EBI2. The cAMP response element-binding protein transcription factor was used as a measure of receptor activity and was correlated to the receptor surface expression. PheVI:13 (Phe257), and the neighboring CysVI:12 (Cys256......, but not to Lys, decreased the constitutive activity more than 7-fold compared with wt EBI2. IleIII:03 (Ile106) is located only 4 A from ArgII:20, and a favorable electrostatic interaction with ArgII:20 was created by introduction of Glu in III:03, given that the activity increased to 4.4-fold of that wt EBI2...

Calculation of mixed HEU-LEU cores for the HOR research reactor with the scale code system

International Nuclear Information System (INIS)

Leege, P.F.A. de; Gibcus, H.P.M.; Hoogenboom, J.E.; Vries, J.W. de

1997-01-01

The HOR reactor of Interfaculty Reactor Institute (IRI), Delft, The Netherlands, will be converted to use low enriched fuel (LEU) assemblies. As there are still many usable high enriched (HEU) fuel assemblies present, there will be a considerable reactor operation time with mixed cores with both HEU and LEU fuel assemblies. At IRI a comprehensive reactor physics code system and evaluated nuclear data is implemented for detailed core calculations. One of the backbones of the IRI code system is the well-known SCALE code system package. Full core calculations are performed with the diffusion theory code BOLD VENTURE, the nodal code SILWER, and the Monte Carlo code KENO Va. Results are displayed of a strategy from a HEU core to a mixed HEU-LEU core and eventually a LEU core. (author)

ANL progress in developing a target and process for converting CNEA Mo-99 production to LEU

International Nuclear Information System (INIS)

Vandegrift, G.F.; Gelis, A.; Aase, S.; Bakel, A.; Freiberg, E.; Conner, C.

2002-01-01

The primary mission of the Reduced Enrichment in Research and Test Reactors (RERTR) Program is to facilitate the conversion of research and test reactor fuel and targets from high-enriched uranium (HEU) to low-enriched uranium (LEU). One of the current goals at Argonne National Laboratory (ANL) is to convert 99 Mo production at Argentine Commission Nacional de Energia Atomica (CNEA) from HEU to LEU targets. Specifically addressed in this paper is ANL R and D related to this conversion: (1) designing a prototype production vessel for digesting irradiated LEU foils in alkaline solutions, (2) developing means to improve digestion efficiency, and (3) modifying ion-exchange processes used in the CNEA recovery and purification of 99 Mo to deal with the lower volumes generated from LEU-foil digestion. (author)

Simple and rapid analytical method for detection of amino acids in blood using blood spot on filter paper, fast-GC/MS and isotope dilution technique.

Science.gov (United States)

Kawana, Shuichi; Nakagawa, Katsuhiro; Hasegawa, Yuki; Yamaguchi, Seiji

2010-11-15

A simple and rapid method for quantitative analysis of amino acids, including valine (Val), leucine (Leu), isoleucine (Ile), methionine (Met) and phenylalanine (Phe), in whole blood has been developed using GC/MS. In this method, whole blood was collected using a filter paper technique, and a 1/8 in. blood spot punch was used for sample preparation. Amino acids were extracted from the sample, and the extracts were purified using cation-exchange resins. The isotope dilution method using ²H₈-Val, ²H₃-Leu, ²H₃-Met and ²H₅-Phe as internal standards was applied. Following propyl chloroformate derivatization, the derivatives were analyzed using fast-GC/MS. The extraction recoveries using these techniques ranged from 69.8% to 87.9%, and analysis time for each sample was approximately 26 min. Calibration curves at concentrations from 0.0 to 1666.7 μmol/l for Val, Leu, Ile and Phe and from 0.0 to 333.3 μmol/l for Met showed good linearity with regression coefficients=1. The method detection limits for Val, Leu, Ile, Met and Phe were 24.2, 16.7, 8.7, 1.5 and 12.9 μmol/l, respectively. This method was applied to blood spot samples obtained from patients with phenylketonuria (PKU), maple syrup urine disease (MSUD), hypermethionine and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), and the analysis results showed that the concentrations of amino acids that characterize these diseases were increased. These results indicate that this method provides a simple and rapid procedure for precise determination of amino acids in whole blood. Copyright © 2010 Elsevier B.V. All rights reserved.

De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms.

Science.gov (United States)

Weiss, Karin; Terhal, Paulien A; Cohen, Lior; Bruccoleri, Michael; Irving, Melita; Martinez, Ariel F; Rosenfeld, Jill A; Machol, Keren; Yang, Yaping; Liu, Pengfei; Walkiewicz, Magdalena; Beuten, Joke; Gomez-Ospina, Natalia; Haude, Katrina; Fong, Chin-To; Enns, Gregory M; Bernstein, Jonathan A; Fan, Judith; Gotway, Garrett; Ghorbani, Mohammad; van Gassen, Koen; Monroe, Glen R; van Haaften, Gijs; Basel-Vanagaite, Lina; Yang, Xiang-Jiao; Campeau, Philippe M; Muenke, Maximilian

2016-10-06

Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATP-dependent chromatin remodeler involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression. Also known as Mi2β, CHD4 is an integral subunit of a well-characterized histone deacetylase complex. Here we report five individuals with de novo missense substitutions in CHD4 identified through whole-exome sequencing and web-based gene matching. These individuals have overlapping phenotypes including developmental delay, intellectual disability, hearing loss, macrocephaly, distinct facial dysmorphisms, palatal abnormalities, ventriculomegaly, and hypogonadism as well as additional findings such as bone fusions. The variants, c.3380G>A (p.Arg1127Gln), c.3443G>T (p.Trp1148Leu), c.3518G>T (p.Arg1173Leu), and c.3008G>A, (p.Gly1003Asp) (GenBank: NM_001273.3), affect evolutionarily highly conserved residues and are predicted to be deleterious. Previous studies in yeast showed the equivalent Arg1127 and Trp1148 residues to be crucial for SNF2 function. Furthermore, mutations in the same positions were reported in malignant tumors, and a de novo missense substitution in an equivalent arginine residue in the C-terminal helicase domain of SMARCA4 is associated with Coffin Siris syndrome. Cell-based studies of the p.Arg1127Gln and p.Arg1173Leu mutants demonstrate normal localization to the nucleus and HDAC1 interaction. Based on these findings, the mutations potentially alter the complex activity but not its formation. This report provides evidence for the role of CHD4 in human development and expands an increasingly recognized group of Mendelian disorders involving chromatin remodeling and modification. Published by Elsevier Inc.

Identification of a breast cancer family double heterozygote for RAD51C and BRCA2 gene mutations

DEFF Research Database (Denmark)

Ahlborn, Lise B; Steffensen, Ane Y; Jønson, Lars

2015-01-01

for mutations in the RAD51C and BRCA2 genes. The RAD51C missense mutation p.Arg258His has previously been identified in a homozygous state in a patient with Fanconi anemia. This mutation is known to affect the DNA repair function of the RAD51C protein. The BRCA2 p.Leu3216Leu synonymous mutation has not been...

Metagenomic profiles of antibiotic resistance genes (ARGs) between human impacted estuary and deep ocean sediments.

Science.gov (United States)

Chen, Baowei; Yang, Ying; Liang, Ximei; Yu, Ke; Zhang, Tong; Li, Xiangdong

2013-11-19

Knowledge of the origins and dissemination of antibiotic resistance genes (ARGs) is essential for understanding modern resistomes in the environment. The mechanisms of the dissemination of ARGs can be revealed through comparative studies on the metagenomic profiling of ARGs between relatively pristine and human-impacted environments. The deep ocean bed of the South China Sea (SCS) is considered to be largely devoid of anthropogenic impacts, while the Pearl River Estuary (PRE) in south China has been highly impacted by intensive human activities. Commonly used antibiotics (sulfamethazine, norfloxacin, ofloxacin, tetracycline, and erythromycin) have been detected through chemical analysis in the PRE sediments, but not in the SCS sediments. In the relatively pristine SCS sediments, the most prevalent and abundant ARGs are those related to resistance to macrolides and polypeptides, with efflux pumps as the predominant mechanism. In the contaminated PRE sediments, the typical ARG profiles suggest a prevailing resistance to antibiotics commonly used in human health and animal farming (including sulfonamides, fluoroquinolones, and aminoglycosides), and higher diversity in both genotype and resistance mechanism than those in the SCS. In particular, antibiotic inactivation significantly contributed to the resistance to aminoglycosides, β-lactams, and macrolides observed in the PRE sediments. There was a significant correlation in the levels of abundance of ARGs and those of mobile genetic elements (including integrons and plasmids), which serve as carriers in the dissemination of ARGs in the aquatic environment. The metagenomic results from the current study support the view that ARGs naturally originate in pristine environments, while human activities accelerate the dissemination of ARGs so that microbes would be able to tolerate selective environmental stress in response to anthropogenic impacts.

Enkephalin, dynorphin and substance P in postmortem substantia nigra from normals and schizophrenic patients

International Nuclear Information System (INIS)

Iadarola, M.J.; Ofri, D.; Kleinman, J.E.

1991-01-01

Three peptide neuromodulators that are found in high concentration in the subtantia nigra: dynorphin A 1,8-met5-enkephalin-arg6-gly7-leu8 and substance P, were measured by specific radioimmunoassays in nigral tissue from normals and schizophrenics postmortem. Substance P and dynorphin were unchanged between the two groups. However, the proenkephalin-derived peptide was significantly elevated in the schizophrenic group. The immunoreactivity was identified as authentic met5-enkephalin-arg6-gly7-leu8 by high pressure liquid chromatography. The data suggest that a different set of regulatory controls exists for nigral enkephalin peptides as compared to dynorphin and substance P, and that the former system may be disordered in schizophrenia

Enkephalin, dynorphin and substance P in postmortem substantia nigra from normals and schizophrenic patients

Energy Technology Data Exchange (ETDEWEB)

Iadarola, M.J.; Ofri, D.; Kleinman, J.E. (National Institute of Dental Research, Bethesda, MD (USA) National Institute of Mental Health, Washington, DC (USA))

1991-01-01

Three peptide neuromodulators that are found in high concentration in the subtantia nigra: dynorphin A 1,8-met5-enkephalin-arg6-gly7-leu8 and substance P, were measured by specific radioimmunoassays in nigral tissue from normals and schizophrenics postmortem. Substance P and dynorphin were unchanged between the two groups. However, the proenkephalin-derived peptide was significantly elevated in the schizophrenic group. The immunoreactivity was identified as authentic met5-enkephalin-arg6-gly7-leu8 by high pressure liquid chromatography. The data suggest that a different set of regulatory controls exists for nigral enkephalin peptides as compared to dynorphin and substance P, and that the former system may be disordered in schizophrenia.

Neutronic feasibility studies for LEU conversion of the HFR Petten reactor

International Nuclear Information System (INIS)

Hanan, N.A.; Deen, J.R.; Matos, J.E.; Hendriks, J.A.; Thijssen, P.J.M.; Wijtsma, F.J.

2000-01-01

Design and safety analyses to determine an optimum LEU fuel assembly design using U 3 Si 2 -Al fuel with up to 4.8 g/cm 3 for conversion of the HFR Petten reactor were performed by the RERTR program in cooperation with the Joint Research Centre and NRG. Credibility of the calculational methods and models were established by comparing calculations with recent measurements by NRG for a core configuration set up for this purpose. This model and methodology were then used to study various LEU fissile loading and burnable poison options that would satisfy specific design criteria. (author)

Neutronic performance of a 14 MW TRIGA reactor: LEU vs HEU fuel

International Nuclear Information System (INIS)

Bretscher, M.M.; Snelgrove, J.L.; Cornella, R.J.

1983-01-01

A primary objective of the US Reduced Enrichment Research and Test Reactor (RERTR) Program is to develop means for replacing, wherever possible, currently used highly-enriched uranium (HEU) fuel ( 235 U enrichment > 90%) with low-enriched uranium (LEU) fuel ( 235 U enrichment < 20%) without significantly degrading the performance of research and test reactors. The General Atomic Company has developed a low-enriched but high uranium content Er-U-ZrH/sub 1.6/ fuel to enable the conversion of TRIGA reactors (and others) from HEU to LEU. One possible application is to the water-moderated 14 MW TRIGA Steady State Reactor (SSR) at the Romanian Institute for Nuclear Power Reactors. The work reported here was undertaken for the purpose of comparing the neutronic performance of the SSR for HEU fuel with that for LEU fuel. In order to make these relative comparisons as valid as possible, identical methods and models were used for the neutronic calculations

Extruder ile Pişirme Yönteminin Gıda Bileşim Öğeleri

Directory of Open Access Journals (Sweden)

Nevzat Artık

2015-02-01

Full Text Available Gıdalara uygulanan diğer ısıl işlemler gibi extruder ile pişirme yönteminde yararlı ve zararlı etkileri birlikte söz konusudur. Bu yöntemin yararlı etkisi; gıdanın özelliklerini olumsuz etkileyen faktörlerin elemine edilmesi; olumsuz etkisi ise, proteinler ile şekerler arasında oluşan Maillard tepkimesidir. Anılan tepkime ile proteinlerin besleyici niteliği azalmaktadır. Ayrıca ısıl işlem nedeniyle vitamin kayıpları söz konusu olmaktadır (Bjorck ve Asp, 1982.

Modeling of pollution aerosols in Ile-de-France

International Nuclear Information System (INIS)

Hodzic, A.

2005-10-01

The modeling of aerosols is a major stake in the understanding of the emission processes and evolution of particulates in the atmosphere. However, the parameterizations used in today's aerosol models still comprise many uncertainties. This work has been motivated by the need of better identifying the weaknesses of aerosols modeling tools and by the necessity of having new validation methods for a 3D evaluation of models. The studies have been carried out using the CHIMERE chemistry-transport model, which allows to simulate the concentrations and physico-chemical characteristics of pollution aerosols at the European scale and in Ile-de-France region. The validation approach used is based on the complementarity of the measurements performed on the ground by monitoring networks with those acquired during the ESQUIF campaign (study and simulation of air quality in Ile-de-France), with lidar and photometric measurements and with satellite observations. The comparison between the observations and the simulations has permitted to identify and reduce the modeling errors, and to characterize the aerosol properties in the vicinity of an urban area. (J.S.)

Conceptual designs parameters for MURR LEU U-Mo fuel conversion design demonstration experiment. Revision 1

International Nuclear Information System (INIS)

Stillman, J.; Feldman, E.; Stevens, J.

2013-01-01

The design parameters for the conceptual design of a fuel assembly containing U-10Mo fuel foils with low-enriched uranium (LEU) for the University of Missouri Research Reactor (MURR) are described. The Design Demonstration Experiment (MURR-DDE) will use a prototypic MURR-LEU element manufactured according to the parameters specified here. Also provided are calculated performance parameters for the LEU element in the MURR, and a set of goals for the MURR-DDE related to those parameters. The conversion objectives are to develop a fuel element design that will ensure safe reactor operations, as well as maintaining existing performance. The element was designed by staff members of the Global Threat Reduction Initiative (GTRI) Reactor Conversion Program at the Argonne National Laboratory (ANL) and the MURR Facility. A set of manufacturing assumptions were provided by the Fuel Development (FD) and Fuel Fabrication Capability (FFC) pillars of the GTRI Reduced Enrichment for Research and Test Reactors (RERTR) program to reliably manufacture the fuel plates. The proposed LEU fuel element has an overall design and exterior dimensions that are similar to those of the current highly-enriched uranium (HEU) fuel elements. There are 23 fuel plates in the LEU design. The overall thickness of each plate is 44 mil, except for the exterior plate that is furthest from the center flux trap (plate 23), which is 49 mil thick. The proposed LEU fuel plates have U-10Mo monolithic fuel foils with a 235U enrichment of 19.75% varying from 9 mil to 20 mil thick, and clad with Al-6061 aluminum. A thin layer of zirconium exists between the fuel foils and the aluminum as a diffusion barrier. The thinnest nominal combined zirconium and aluminum clad thickness on each side of the fuel plates is 12 mil. The LEU U-10Mo monolithic fuel is not yet qualified as driver fuel in research reactors, but is under intense development under the auspices of the GTRI FD and FFC programs.

Homology modeling, molecular docking and DNA binding studies of nucleotide excision repair UvrC protein from M. tuberculosis.

Science.gov (United States)

Parulekar, Rishikesh S; Barage, Sagar H; Jalkute, Chidambar B; Dhanavade, Maruti J; Fandilolu, Prayagraj M; Sonawane, Kailas D

2013-08-01

Mycobacterium tuberculosis is a Gram positive, acid-fast bacteria belonging to genus Mycobacterium, is the leading causative agent of most cases of tuberculosis. The pathogenicity of the bacteria is enhanced by its developed DNA repair mechanism which consists of machineries such as nucleotide excision repair. Nucleotide excision repair consists of excinuclease protein UvrABC endonuclease, multi-enzymatic complex which carries out repair of damaged DNA in sequential manner. UvrC protein is a part of this complex and thus helps to repair the damaged DNA of M. tuberculosis. Hence, structural bioinformatics study of UvrC protein from M. tuberculosis was carried out using homology modeling and molecular docking techniques. Assessment of the reliability of the homology model was carried out by predicting its secondary structure along with its model validation. The predicted structure was docked with the ATP and the interacting amino acid residues of UvrC protein with the ATP were found to be TRP539, PHE89, GLU536, ILE402 and ARG575. The binding of UvrC protein with the DNA showed two different domains. The residues from domain I of the protein VAL526, THR524 and LEU521 interact with the DNA whereas, amino acids interacting from the domain II of the UvrC protein included ARG597, GLU595, GLY594 and GLY592 residues. This predicted model could be useful to design new inhibitors of UvrC enzyme to prevent pathogenesis of Mycobacterium and so the tuberculosis.

The ClpS-like N-domain is essential for the functioning of Ubr11, an N-recognin in Schizosaccharomyces pombe.

Science.gov (United States)

Kitamura, Kenji

2014-01-01

Several Ubr ubiquitin ligases recognize the N-terminal amino acid of substrate proteins and promote their degradation via the Arg/N-end rule pathway. The primary destabilizing N-terminal amino acids in yeast are classified into type 1 (Arg, Lys, and His) and type 2 (Phe, Trp, Tyr, Leu, Ile, and Met-Ф) residues. The type 1 and type 2 residues bind to the UBR box and the ClpS/N-domain, respectively, in canonical Ubr ubiquitin ligases that act as N-recognins. In this study, the requirement for type 1 and type 2 amino acid recognition by Schizosaccharomyces pombe Ubr11 was examined in vivo. Consistent with the results of previous studies, the ubr11∆ null mutant was found to be defective in oligopeptide uptake and resistant to ergosterol synthesis inhibitors. Furthermore, the ubr11∆ mutant was also less sensitive to some protein synthesis inhibitors. A ubr11 ClpS/N-domain mutant, which retained ubiquitin ligase activity but could not recognize type 2 amino acids, phenocopied all known defects of the ubr11∆ mutant. However, the recognition of type 1 residues by Ubr11 was not required for its functioning, and no severe physiological abnormalities were observed in a ubr11 mutant defective in the recognition of type 1 residues. These results reinforce the fundamental importance of the ClpS/N-domain for the functioning of the N-recognin, Ubr11.

Development of a chromosomally integrated metabolite-inducible Leu3p-alpha-IPM "off-on" gene switch.

Directory of Open Access Journals (Sweden)

Maria Poulou

2010-08-01

Full Text Available Present technology uses mostly chimeric proteins as regulators and hormones or antibiotics as signals to induce spatial and temporal gene expression.Here, we show that a chromosomally integrated yeast 'Leu3p-alpha-IotaRhoMu' system constitutes a ligand-inducible regulatory "off-on" genetic switch with an extensively dynamic action area. We find that Leu3p acts as an active transcriptional repressor in the absence and as an activator in the presence of alpha-isopropylmalate (alpha-IotaRhoMu in primary fibroblasts isolated from double transgenic mouse embryos bearing ubiquitously expressing Leu3p and a Leu3p regulated GFP reporter. In the absence of the branched amino acid biosynthetic pathway in animals, metabolically stable alpha-IPM presents an EC(50 equal to 0.8837 mM and fast "OFF-ON" kinetics (t(50ON = 43 min, t(50OFF = 2.18 h, it enters the cells via passive diffusion, while it is non-toxic to mammalian cells and to fertilized mouse eggs cultured ex vivo.Our results demonstrate that the 'Leu3p-alpha-IotaRhoMu' constitutes a simpler and safer system for inducible gene expression in biomedical applications.

Neutronics analysis of the proposed 25-MW leu TRIGA Multipurpose Research Reactor

International Nuclear Information System (INIS)

Nurdin, M.; Bretscher, M.M.; Snelgrove, J.L.

1982-01-01

More than two years ago the government of Indonesia announced plans to purchase a research reactor for the Puspiptek Research Center in Serpong Indonesia to be used for isotope production, materials testing, neutron physics measurements, and reactor operator training. Reactors using low-enriched uranium (LEU) plate-type and rod-type fuel elements were considered. This paper deals with the neutronic evaluation of the rod-type 25-MW LEU TRIGA Multipurpose Research Reactor (MPRR) proposed by the General Atomic Company of the United States of America

Milles Iles River : study of solutions to address critically low water levels; Riviere des Milles Iles : etude des solutions de soutien des etiages critiques

Energy Technology Data Exchange (ETDEWEB)

Cyr, J F; Fontin, M [Centre d' Expertise Hydrique du Quebec, Quebec, PQ (Canada). Service de la Securite des Barrages

2006-07-01

Water management for the Mille Iles River, which supplies drinking water to 400,000 people, was discussed with reference to solutions for critically low water flow which was experienced in 2001 and 2002. The river is part of the Lac des Deux Montagnes watershed in the region of Montreal which is characterized as a high population growth area. In the summer of 2001, municipalities served by the Mille Iles River were faced with problems in the supply of drinking water when the river flow reached only 13 cubic metres per second. The minimal values of flow observed for this time of year have rarely been under 20 cubic metres per second since 1970. The quality of water was reduced under such conditions of flow because the dilution of wastewater discharged into the river became so weak that the aging water treatment facilities had to work beyond their capacity. Quebec's Center of Water Expertise (CEHQ) intervened in an emergency measure to ensure water quality. This study investigated the following 3 possible scenarios for a solution to this problem: (1) to increase the Mille Iles River capacity at the Lac des Deux Montagnes outlet, (2) to reduce the flow discharged by the 3 other outlets of Lac des Deux Montagnes, and (3) to increase the inflow to Lac des Deux Montagnes from reservoirs located in the Ottawa River watershed. The first solution was favoured. 2 refs., 1 tab., 8 figs.

Milles Iles River : study of solutions to address critically low water levels; Riviere des Milles Iles : etude des solutions de soutien des etiages critiques

Energy Technology Data Exchange (ETDEWEB)

Cyr, J.F.; Fontin, M. [Centre d' Expertise Hydrique du Quebec, Quebec, PQ (Canada). Service de la Securite des Barrages

2006-07-01

Water management for the Mille Iles River, which supplies drinking water to 400,000 people, was discussed with reference to solutions for critically low water flow which was experienced in 2001 and 2002. The river is part of the Lac des Deux Montagnes watershed in the region of Montreal which is characterized as a high population growth area. In the summer of 2001, municipalities served by the Mille Iles River were faced with problems in the supply of drinking water when the river flow reached only 13 cubic metres per second. The minimal values of flow observed for this time of year have rarely been under 20 cubic metres per second since 1970. The quality of water was reduced under such conditions of flow because the dilution of wastewater discharged into the river became so weak that the aging water treatment facilities had to work beyond their capacity. Quebec's Center of Water Expertise (CEHQ) intervened in an emergency measure to ensure water quality. This study investigated the following 3 possible scenarios for a solution to this problem: (1) to increase the Mille Iles River capacity at the Lac des Deux Montagnes outlet, (2) to reduce the flow discharged by the 3 other outlets of Lac des Deux Montagnes, and (3) to increase the inflow to Lac des Deux Montagnes from reservoirs located in the Ottawa River watershed. The first solution was favoured. 2 refs., 1 tab., 8 figs.

Neutronics Study on LEU Nuclear Thermal Rocket Fuel Options

Energy Technology Data Exchange (ETDEWEB)

Venneri, Paolo; Kim, Yong Hee [KAIST, Daejeon (Korea, Republic of); Howe, Steven [CSNR, Idaho (United States)

2014-10-15

This has resulted in a non-trivial simplification of the tasks needed to develop such an engine and the quick initial development of the concept. There are, however, a series of key core-design choices that are currently under scrutiny in the field that have to be resolved in order for the LEU-NTR to be fully developed. The most important of these is the choice of fuel: carbide composite or tungsten cermet. This study presents a first comparison of the two fuel types specifically in the neutronic application to the LEU-NTR, keeping in mind the unique neutronic environment and the system requirements of the system. The scope of the study itself is limited to a neutronics study of the two fuels and only a cursory overview of the material properties of the fuels themselves... The results of this study have led to two major conclusions. First of all is that the carbide composite fuel is, from a neutronics standpoint, a much better fuel. It has a low absorption cross-section, is inherently a strong moderator, is able to achieve a higher reactivity using smaller amounts of fissile material, and can potentially enable a smaller reactor. Second is that despite its neutronic difficulties (high absorption, inferior moderating abilities, and lower k-infinity values) the tungsten cermet fuel is still able to perform satisfactorily in an LEU-NTR, largely due to its ability to have an extremely high fuel loading.

Flexibility of the myosin heavy chain: direct evidence that the region containing SH/sub 1/ and SH/sub 2/ can move 10 /Angstrom/ under the influence of nucleotide binding

Energy Technology Data Exchange (ETDEWEB)

Huston, E.E.; Grammer, J.C.; Yount, R.G.

1988-12-13

Previous experiments demonstrated that two thiols of skeletal myosin subfragment 1 (SF/sub 1/) could be oxidized to a disulfide bond by treatment with a 2-fold excess of 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) in the presence of MgADP. The resulting characteristic changes in the ATPase activities of SF/sub 1/ and the fact that MgADP was stably trapped at the active site, suggested that the two thiols cross-linked were SH/sub 1/ (Cys-707) and SH/sub 2/ (Cys-697) from the myosin heavy chain. To verify this suggestion, SF/sub 1/, after DTNB treatment as above, was treated with an excess of N-ethylmaleimide to block all accessible thiols. The single protein disulfide produced by DTNB oxidation was reduced with dithioerythritol and the modified SF/sub 1/ internally cross-linked with equimolar (/sup 14/C)p-phenylenedimaleimide (pPDM) in the presence of MgADP. After extensive trypsinization, the major /sup 14/C-labeled peptide was isolated, characterized, and shown to be Cys-Asn-Gly-Val-Leu-Gly-Ile-Arg-Ile-Cys-Arg, in which the two cysteines were cross-linked by pPDM. This peptide is known to contain SH/sub 2/ and SH/sub 1/ in this order and to come from residues 697-708 in the rabbit skeletal myosin heavy chain. Parallel experiments with (/sup 14/C)pPDM and unmodified SF/sub 1/ similar to those above gave an identical SH/sub 1/, SH/sub 2/ tryptic peptide, verifying earlier labeling results. These combined results demonstrate that SH/sub 1/ and SH/sub 2/ cross-linked by pPDM (12-13 /Angstrom/, S to S) or by oxidation with DTNB (2 /Angstrom/, S to S) can move a minimum of 10 /Angstrom/ under the influence of nucleotide binding. Because these residues are separated by only nine amino acids in the primary sequence, this small section of the heavy chain must possess extraordinary flexibility.

Molecular and clinical characterization of a series of patients with childhood-onset lysosomal acid lipase deficiency. Retrospective investigations, follow-up and detection of two novel LIPA pathogenic variants.

Science.gov (United States)

Pisciotta, Livia; Tozzi, Giulia; Travaglini, Lorena; Taurisano, Roberta; Lucchi, Tiziano; Indolfi, Giuseppe; Papadia, Francesco; Di Rocco, Maja; D'Antiga, Lorenzo; Crock, Patricia; Vora, Komal; Nightingale, Scott; Michelakakis, Helen; Garoufi, Anastasia; Lykopoulou, Lilia; Bertolini, Stefano; Calandra, Sebastiano

2017-10-01

Childhood/Adult-onset Lysosomal Acid Lipase Deficiency (LAL-D) is a recessive disorder due to loss of function variants of LAL, the enzyme which hydrolyses cholesteryl esters, derived from internalized apoB containing lipoproteins. The disease is characterized by multi-organ involvement including the liver, spleen, intestine and cardiovascular system. The aim of this study was the clinical and molecular characterization of 14 (13 unrelated) previously unreported patients with childhood-onset LAL-D. Data collected included clinical and laboratory investigations, liver imaging, liver biopsy and LIPA gene analysis. The response to lipid-lowering medications, liver transplantation and enzyme replacement therapy (ERT) was reported for some patients. LAL-D was suspected at 4.4 ± 3.3 years of age for the presence of hepatomegaly, elevated serum transaminases and hypercholesterolemia, and was confirmed by liver biopsy/imaging and LAL assay. The follow up period ranged from 3 to 40 years (mean 7.8 ± 4.0 years in 13 cases). Patients treated with statins with or without ezetimibe showed 28% reduction of plasma LDL-cholesterol without a tangible effect on liver enzymes; some patients receiving ERT showed normalized lipoprotein profile and transaminase levels. The common c.894G > A variant was observed in homozygosity or compound heterozygosity in 10 patients. We found seven previously reported variants: p.(Trp140*), p.(Arg218*), p.(Gly266*), p.(Thr288Ile), p.(Leu294Ser), p.(His295Tyr) and p.(Gly342Arg) and two novel variants: p.(Asp345Asn), affecting the LAL catalytic triad, and c.229+3A > C, affecting splicing. Homozygosity for p.(Thr288Ile) or c.229+3A > C was associated with a severe phenotype. This study provides additional data on the features of childhood-onset LAL-D and describes two novel pathogenic variants of the LIPA gene. Copyright © 2017. Published by Elsevier B.V.

CYP1A1 Ile462Val polymorphism contributes to lung cancer susceptibility among lung squamous carcinoma and smokers: a meta-analysis.

Directory of Open Access Journals (Sweden)

Ya-Nan Ji

Full Text Available Many studies have examined the association between the CYP1A1 Ile462Val gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. Ultimately, 43 case-control studies, comprising 19,228 subjects were included. A significantly elevated lung cancer risk was associated with 2 Ile462Val genotype variants (for Val/Val vs Ile/Ile: OR = 1.22, 95% CI = 1.08-1.40; for (Ile/Val +Val/Val vs Ile/Ile: OR = 1.15, 95% CI = 1.07-1.23 in overall population. In the stratified analysis, a significant association was found in Asians, Caucasians and lung SCC, not lung AC and lung SCLC. Additionally, a significant association was found in smoker population and not found in non-smoker populations. This meta-analysis suggests that the Ile462Val polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility in Asian and Caucasian populations and there is an interaction with smoking status, but these associations vary in different histological types of lung caner.

Escherichia coli ArgR mutants defective in cer/Xer recombination, but not in DNA binding.

Science.gov (United States)

Sénéchal, Hélène; Delesques, Jérémy; Szatmari, George

2010-04-01

The Escherichia coli arginine repressor (ArgR) is an L-arginine-dependent DNA-binding protein that controls the expression of the arginine biosynthetic genes and is required as an accessory factor for Xer site-specific recombination at cer and related recombination sites in plasmids. We used the technique of pentapeptide scanning mutagenesis to isolate a series of ArgR mutants that were considerably reduced in cer recombination, but were still able to repress an argA::lacZ fusion. DNA sequence analysis showed that all of the mutants mapped to the same nucleotide, resulting in a five amino acid insertion between residues 149 and 150 of ArgR, corresponding to the end of the alpha6 helix. A truncated ArgR containing a stop codon at residue 150 displayed the same phenotype as the protein with the five amino acid insertion, and both mutants displayed sequence-specific DNA-binding activity that was L-arginine dependent. These results show that the C-terminus of ArgR is more important in cer/Xer site-specific recombination than in DNA binding.

The Polymorphism of DNA Repair Gene ERCC2/XPD Arg156Arg and Susceptibility to Breast Cancer in a Chinese Population

DEFF Research Database (Denmark)

Yin, J. Y.; Liang, D. H.; Vogel, Ulla Birgitte

2009-01-01

Polymorphisms in DNA repair genes are good candidates for modifying cancer risk. ERCC2/XPD, a gene involved in nucleotide excision repair and basal transcription, may influence individual DNA repair capacity, particularly of bulky adducts. This is implicated in cancer susceptibility. To detect...... found between ERCC2/XPD Arg156Arg and risk of breast cancer (AA/AC versus CC: OR = 0.79, 95% CI = 0.49-1.28, P = 0.33; AA versus CC: OR = 0.89, 95% CI = 0.49-1.63, P = 0.72; AC versus CC: OR = 0.74, 95% CI = 0.44-1.24, P = 0.25). Breast cancer cases with the variant AA genotype were marginally younger...

Polymorphism Glu389Arg of β1-adrenoreceptor gene and cardiovascular complications of hyperthyroidism

Directory of Open Access Journals (Sweden)

A Yu Babenko

2010-06-01

Full Text Available Gly389Arg polymorphism β1-adrenoreceptors can influence the cardio-vascular prognosis. Human heart β1-adrenoreceptors perform a crucial role in mediating the cardiostimulant effects of norepinephrine. Understanding the significance of Gly389Arg polymorphism in the human heart is beginning to emerge, but not in adult patients with thyrotoxicosis. We've studied the Gly389Arg polymorphism of β1-adrenoreceptors gene in relation to Echo-cardiography parameters in 136 normotensive patients with a thyrotoxicosis without any CVD. Echo-CG was performed according to standard protocol before and during the thyreostatic treatment. The genotype distribution was as following: Gly/Gly – 25% (1 group (1 gr., Arg/Gly – 75% (2 group (2 gr., Arg/Arg – 0%. There was significant difference between 1 and 2 gr. by relative left ventricle wall thickness, left ventricular mass index, isovolumic relaxation time, Е/А ratio. The frequency of diastolic dysfunction (DD was in gr. 1–10%, in gr. 2–30%, р <0.001. After treatment during a year this damages were saved. These data demonstrate, that Gly/Gly genotype of β1-adrenoreceptors gene can have cardioprotective effect leading to less of LV hypertrophy and diastolic dysfunction in patients with thyrotoxicosis.

Continuing investigations for technology assessment of 99Mo production from LEU [low enriched uranium] targets

International Nuclear Information System (INIS)

Vandegrift, G.F.; Kwok, J.D.; Marshall, S.L.; Vissers, D.R.; Matos, J.E.

1987-01-01

Currently much of the world's supply of 99m Tc for medical purposes is produced from 99 Mo derived from the fissioning of high enriched uranium (HEU). This paper presents the results of our continuing studies on the effects of substituting low enriched uranium (LEU) for HEU in targets for the production of fission product 99 Mo. Improvements in the electrodeposition of thin films of uranium metal continue to increase the appeal for the substitution of LEU metal for HEU oxide films in cylindrical targets. The process is effective for targets fabricated from stainless steel or zircaloy. Included is a cost estimate for setting up the necessary equipment to electrodeposit uranium metal on cylindrical targets. Further investigations on the effect of LEU substitution on processing of these targets are also reported. Substitution of uranium silicides for the uranium-aluminium alloy or uranium aluminide dispersed fuel used in current target designs will allow the substitution of LEU for HEU in these targets with equivalent 99 Mo-yield per target and no change in target geometries. However, this substitution will require modifications in current processing steps due to 1) the insolubility of uranium silicides in alkaline solutions and 2) the presence of significant quantities of silicate in solution. Results to date suggest that substitution of LEU for HEU can be achieved. (Author)

Progress in the neutronic core conversion (HEU-LEU) analysis of Ghana research reactor-1.

Energy Technology Data Exchange (ETDEWEB)

Anim-Sampong, S.; Maakuu, B. T.; Akaho, E. H. K.; Andam, A.; Liaw, J. J. R.; Matos, J. E.; Nuclear Engineering Division; Ghana Atomic Energy Commission; Kwame Nkrumah Univ. of Science and Technology

2006-01-01

The Ghana Research Reactor-1 (GHARR-1) is a commercial version of the Miniature Neutron Source Reactor (MNSR) and has operated at different power levels since its commissioning in March 1995. As required for all nuclear reactors, neutronic and thermal hydraulic analysis are being performed for the HEU-LEU core conversion studies of the Ghana Research Reactor-1 (GHARR-1) facility, which is a commercial version of the Miniature Neutron Source Reactor (MNSR). Stochastic Monte Carlo particle transport methods and tools (MCNP4c/MCNP5) were used to fine-tune a previously developed 3-D MCNP model of the GHARR-1 facility and perform neutronic analysis of the 90.2% HEU reference and candidate LEU (UO{sub 2}, U{sub 3}Si{sub 2}, U-9Mo) fresh cores with varying enrichments from 12.6%-19.75%. In this paper, the results of the progress made in the Monte Carlo neutronic analysis of the HEU reference and candidate LEU fuels are presented. In particular, a comparative performance assessment of the LEU with respect to neutron flux variations in the fission chamber and experimental irradiation channels are highlighted.

Technetium-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptides for human melanoma imaging

Energy Technology Data Exchange (ETDEWEB)

Yang Jianquan; Guo Haixun [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin, E-mail: ymiao@salud.unm.ed [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Dermatology, University of New Mexico, Albuquerque, NM 87131 (United States)

2010-11-15

Introduction: The purpose of this study was to examine whether {sup 99m}Tc-labeled Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone ({alpha}-MSH) hybrid peptide targeting both melanocortin-1 (MC1) and {alpha}{sub v{beta}3} integrin receptors was superior in melanoma targeting to {sup 99m}Tc-labeled {alpha}-MSH or RGD peptide targeting only the MC1 or {alpha}{sub v{beta}3} integrin receptor. Methods: RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were designed to target both MC1 and {alpha}{sub v{beta}3} integrin receptors, MC1 receptor only and {alpha}{sub v{beta}3} integrin receptor only, respectively. The MC1 or {alpha}{sub v{beta}3} integrin receptor binding affinities of three peptides were determined in M21 human melanoma cells. The melanoma targeting properties of {sup 99m}Tc-labeled RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were determined in M21 human melanoma-xenografted nude mice. Meanwhile, the melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was blocked with various non-radiolabeled peptides in M21 melanoma xenografts. Results: RGD-Lys-(Arg{sup 11})CCMSH displayed 2.0 and 403 nM binding affinities to both MC1 and {alpha}{sub v{beta}3} integrin receptors, whereas RAD-Lys-(Arg{sup 11})CCMSH or RGD-Lys-(Arg{sup 11})CCMSHscramble lost their {alpha}{sub v{beta}3} integrin receptor binding affinity by greater than 248-fold or MC1 receptor binding affinity by more than 100-fold, respectively. The melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was 2.49 and 2.24 times (P < .05) the melanoma uptakes of {sup 99m}Tc-RAD-Lys-(Arg{sup 11})CCMSH and {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSHscramble at 2 h post-injection, respectively. Either RGD or (Arg{sup 11})CCMSH peptide co-injection could block 42% and 57% of the tumor uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH, whereas the coinjection of RGD+(Arg{sup 11})CCMSH peptide mixture

Thermal analysis of LEU modified Cintichem target irradiated in TRIGA reactor

International Nuclear Information System (INIS)

Catana, A; Toma, C.

2009-01-01

Actions conceived during last years at international level for conversion of Molybdenum fabrication process from HEU to LEU targets utilization created opportunities for INR to get access to information and participating to international discussions under IAEA auspices. Concrete steps for developing fission Molybdenum technology were facilitated. Institute of Nuclear Research bringing together a number of conditions like suitable irradiation possibilities, direct communication between reactor and hot cell facility, handling capacity of high radioactive sources, and simultaneously the existence of an expanding internal market, decided to undertake the necessary steps in order to produce fission molybdenum. Over the course of last years of efforts in this direction we developed the steps for fission Molybdenum technology development based on modified Cintichem process in accordance with the Argonne National Laboratory proved methodology. Progress made by INR to heat transfer computations of annular target using is presented. An advanced thermal-hydraulic analysis was performed to estimate the heat removal capability for an enriched uranium (LEU) foil annular target irradiated in TRIGA reactor core. As a result, the present analysis provides an upper limit estimate of the LEU-foil and external target surface temperatures during irradiation in TRIGA 14 MW reactor. (authors)

Mixed core conversion study with HEU and LEU fuels

International Nuclear Information System (INIS)

Matos, J.E.; Freese, K.E.

1984-01-01

The results of a mixed core study are presented for gradual replacement of HEU fuel with LEU fuel using the IAEA generic 10 MW reactor as an example. The key parameters show that the transition can be accomplished safely and economically

Fine mapping of the sunflower resistance locus PlARG introduced from the wild species Helianthus argophyllus

Science.gov (United States)

Wieckhorst, S.; Bachlava, E.; Dußle, C. M.; Tang, S.; Gao, W.; Saski, C.; Knapp, S. J.; Schön, C.-C.; Hahn, V.

2010-01-01

Downy mildew, caused by Plasmopara halstedii, is one of the most destructive diseases in cultivated sunflower (Helianthus annuus L.). The dominant resistance locus PlARG originates from silverleaf sunflower (H. argophyllus Torrey and Gray) and confers resistance to all known races of P. halstedii. We mapped PlARG on linkage group (LG) 1 of (cms)HA342 × ARG1575-2, a population consisting of 2,145 F2 individuals. Further, we identified resistance gene candidates (RGCs) that cosegregated with PlARG as well as closely linked flanking markers. Markers from the target region were mapped with higher resolution in NDBLOSsel × KWS04, a population consisting of 2,780 F2 individuals that does not segregate for PlARG. A large-insert sunflower bacterial artificial chromosome (BAC) library was screened with overgo probes designed for markers RGC52 and RGC151, which cosegregated with PlARG. Two RGC-containing BAC contigs were anchored to the PlARG region on LG 1. Electronic supplementary material The online version of this article (doi:10.1007/s00122-010-1416-4) contains supplementary material, which is available to authorized users. PMID:20700574

A neutronics study of LEU fuel options for the HFR-Petten

International Nuclear Information System (INIS)

Deen, J.R.; Snelgrove, J.L.

1985-01-01

The standard HEU fuel cycle characteristics are compared with those of several different LEU fuel cycles in the new vessel configuration. The primary design goals were to provide similar reactivity performance and neutron flux profiles with a minimal increase in 235 U loading. The fuel cycle advantages of Cd burnable absorbers over 10 B are presented. The LEU fuel cycle requirements were calculated also for an extended 32-day cycle and for a reload batch size reduction from six to five standard elements for the standard 26-day cycle. The effects of typical in-core experiments upon neutron flux profiles and fuel loading requirements are also presented. (author)

Preliminary Assessment of Heavy Metal Pollution of Opa Reservoir, Ile

African Journals Online (AJOL)

big timmy

Awolowo University (OAU), Ile-Ife, Nigeria, with a view to assessing its pollution level. ... Heavy metals are not biodegradable, but are assimilated .... samples were filtered (with Whatman filter paper. No 42) and ..... acidity,Water, Air Soil Pollut.

Evaluation of a novel Arg-Gly-Asp-conjugated α-melanocyte stimulating hormone hybrid peptide for potential melanoma therapy.

Science.gov (United States)

Yang, Jianquan; Guo, Haixun; Gallazzi, Fabio; Berwick, Marianne; Padilla, R Steven; Miao, Yubin

2009-08-19

The purpose of this study was to determine whether Arg-Gly-Asp (RGD)-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptide could be employed to target melanocortin-1 (MC1) receptor for potential melanoma therapy. The RGD motif {cyclic(Arg-Gly-Asp-DTyr-Asp)} was coupled to [Cys(3,4,10), DPhe(7), Arg(11)]α-MSH(3-13) {(Arg(11))CCMSH} to generate RGD-Lys-(Arg(11))CCMSH hybrid peptide. The MC1 receptor binding affinity of RGD-Lys-(Arg(11))CCMSH was determined in B16/F1 melanoma cells. The internalization and efflux, melanoma targeting and pharmacokinetic properties and single photon emission computed tomography/CT (SPECT/CT) imaging of (99m)Tc-RGD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma cells and melanoma-bearing C57 mice. Clonogenic cytotoxic effect of RGD-Lys-(Arg(11))CCMSH was examined in B16/F1 melanoma cells. RGD-Lys-(Arg(11))CCMSH displayed 2.1 nM MC1 receptor binding affinity. (99m)Tc-RGD-Lys-(Arg(11))CCMSH showed rapid internalization and extended retention in B16/F1 cells. The cellular uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was MC1 receptor-mediated. (99m)Tc-RGD-Lys-(Arg(11))CCMSH exhibited high tumor uptake (14.83 ± 2.94% ID/g 2 h postinjection) and prolonged tumor retention (7.59 ± 2.04% ID/g 24 h postinjection) in B16/F1 melanoma-bearing mice. Nontarget organ uptakes were generally low except for the kidneys. Whole-body clearance of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was rapid, with approximately 62% of the injected radioactivity cleared through the urinary system by 2 h postinjection. Flank melanoma tumors were clearly imaged by small animal SPECT/CT using (99m)Tc-RGD-Lys-(Arg(11))CCMSH as an imaging probe 2 h postinjection. Single treatment (3 h incubation) with 100 nM of RGD-Lys-(Arg(11))CCMSH significantly (p < 0.05) decreased the clonogenic survival of B16/F1 cells by 65% compared to the untreated control cells. Favorable melanoma targeting property of (99m)Tc-RGD-Lys-(Arg(11))CCMSH and remarkable cytotoxic effect of RGD-Lys-(Arg

LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation.

Science.gov (United States)

Milkereit, Ruth; Persaud, Avinash; Vanoaica, Liviu; Guetg, Adriano; Verrey, Francois; Rotin, Daniela

2015-05-22

Mammalian target of rapamycin 1 (mTORC1), a master regulator of cellular growth, is activated downstream of growth factors, energy signalling and intracellular essential amino acids (EAAs) such as Leu. mTORC1 activation occurs at the lysosomal membrane, and involves V-ATPase stimulation by intra-lysosomal EAA (inside-out activation), leading to activation of the Ragulator, RagA/B-GTP and mTORC1 via Rheb-GTP. How Leu enters the lysosomes is unknown. Here we identified the lysosomal protein LAPTM4b as a binding partner for the Leu transporter, LAT1-4F2hc (SLC7A5-SLAC3A2). We show that LAPTM4b recruits LAT1-4F2hc to lysosomes, leading to uptake of Leu into lysosomes, and is required for mTORC1 activation via V-ATPase following EAA or Leu stimulation. These results demonstrate a functional Leu transporter at the lysosome, and help explain the inside-out lysosomal activation of mTORC1 by Leu/EAA.

Origami ile Matematik Öğretimi/Teaching Mathematic With Origami

OpenAIRE

Polat, Seyat

2013-01-01

Özet Bu çalışmada; origami etkinliklerinin matematik dersinde kullanılması ile ilgili olarak, origaminin ilişkili olduğu konular, origami uygulamaları ile ilgili öğrenci görüşleri, origami yapılırken en çok zorlanılan şekiller ve origami uygulamaları sürecinde öğrenciler için görselleşen terimler incelenmiştir. Nitel olarak desenlenen çalışma ilköğretim 4 ve 5. sınıfa devam eden 17 öğrenciyle gerçekleştirilmiştir. Veriler yarı yapılandırılmış görüşme yöntemiyle toplanmıştır. Elde edilen bulgu...

Preliminary investigations for technology assessment of 99Mo production from LEU [low enriched uranium] targets

International Nuclear Information System (INIS)

Vandegrift, G.F.; Chaiko, D.J.; Heinrich, R.R.; Kucera, E.T.; Jensen, K.J.; Poa, D.S.; Varma, R.; Vissers, D.R.

1986-11-01

This paper presents the results of preliminary studies on the effects of substituting low enriched uranium (LEU) for highly enriched uranium (HEU) in targets for the production of fission product 99 Mo. Issues that were addressed are: (1) purity and yield of the 99 Mo//sup 99m/Tc product, (2) fabrication of LEU targets and related concerns, and (3) radioactive waste. Laboratory experimentation was part of the efforts for issues (1) and (2); thus far, radioactive waste disposal has only been addressed in a paper study. Although the reported results are still preliminary, there is reason to be optimistic about the feasibility of utilizing LEU targets for 99 Mo production. 37 refs., 1 fig., 5 tabs

Performance and economic penalties of some LEU [low enriched uranium] conversion options for the Australian Reactor HIFAR

International Nuclear Information System (INIS)

McCulloch, D.B.; Robinson, G.S.

1987-01-01

Performance calculations for the conversion of HIFAR to low enriched uranium (LEU) fuel have been extended to a wide range of 235 U loadings per fuel element. Using a simple approximate algorithm for the likely costs of LEU compared with highly enriched uranium (HEU) fuel elements, the increases in annual fuelling costs for LEU compared with HEU fuel are examined for a range of conversion options involving different performance penalties. No significant operational/safety problems were found for any of the options canvassed. (Author)

Assessment of the effectiveness of the LEU Reform Rule and its implementation

International Nuclear Information System (INIS)

Moran, B.W.; Nations, J.O.; Hammond, G.A.

1993-11-01

The US Nuclear Regulatory Commission (NRC) amended its material control and accounting (MC ampersand A) requirements in 1985 for licensees possessing and using special nuclear material (SNM) of low strategic significance in quantities larger than one effective kilogram (kg). The goal of the Low-Enriched Uranium (LEU) Reform Rule (i.e., 10CFR 74.31) was to establish MC ampersand A requirements for the LEU licensees at a level consistent with the safeguards risk associated with the relatively low strategic importance of such material. The amended requirements were written in a performance-oriented manner, rather than a prescriptive one, in an effort to allow the licensees the opportunity to choose the most cost-effective means of satisfying the requirements. The LEU Reform Rule was implemented in January 1988 and the fuel cycle facilities have had sufficient experience in implementing the rule to allow a meaningful review of its effectiveness. This document provides technical analysis and recommendations to assist the NRC in making a determination if the rule is achieving its intended purpose, and if not, to make the necessary changes to accomplish this

THE PRIVATISATION AND THE ECONOMICAL ENVIRONMENT OF ARGES COUNTY

Directory of Open Access Journals (Sweden)

Cristina, CHIRIAC

2014-11-01

Full Text Available The privatisation process has generated over time a lot of controversial opinions of the specialists. The lack of a complete analysis of the privatisation process, even now, after more than 20 years from its beginning, has raised questions regarding the accomplishment of the goals of the macro-economic policy. This paper aims to enclose the analysis and evaluation function of the privatisation process in Arges County. Based on the information gathered, we will analyse individually the privatised companies in Arges County, we will try to estimate the success rate of the privatisation process but also what were the effects of the privatisation process with regards to employment. The purpose of this paper is the improvement of the evaluation frame of the privatisation process by creating an inventory of problems and techniques, establishing the success rate and the percent of failed privatisations. This is a complex subject whose causes and effects are connected in the Romanian context, sometimes in the European and even geopolitical one, as we will try to prove by analysing the most important privatised companies from Arges County: Automobile Dacia SA and ARO SA.

Sample summary report for ARG 1 pressure tube sample

International Nuclear Information System (INIS)

Belinco, C.

2006-01-01

The ARG 1 sample is made from an un-irradiated Zr-2.5% Nb pressure tube. The sample has 103.4 mm ID, 112 mm OD and approximately 500 mm length. A punch mark was made very close to one end of the sample. The punch mark indicates the 12 O'clock position and also identifies the face of the tube for making all the measurements. ARG 1 sample contains flaws on ID and OD surface. There was no intentional flaw within the wall of the pressure tube sample. Once the flaws are machined the pressure tube sample was covered from outside to hide the OD flaws. Approximately 50 mm length of pressure tube was left open at both the ends to facilitate the holding of sample in the fixtures for inspection. No flaw was machined in this zone of 50 mm on either end of the pressure tube sample. A total of 20 flaws were machined in ARG 1 sample. Out of these, 16 flaws were on the OD surface and the remaining 4 on the ID surface of the pressure tube. The flaws were characterized in to various groups like axial flaws, circumferential flaws, etc

Structures of LeuT in bicelles define conformation and substrate binding in a membrane-like context

Energy Technology Data Exchange (ETDEWEB)

Wang, Hui; Elferich, Johannes; Gouaux, Eric (Oregon HSU)

2012-02-13

Neurotransmitter sodium symporters (NSSs) catalyze the uptake of neurotransmitters into cells, terminating neurotransmission at chemical synapses. Consistent with the role of NSSs in the central nervous system, they are implicated in multiple diseases and disorders. LeuT, from Aquifex aeolicus, is a prokaryotic ortholog of the NSS family and has contributed to our understanding of the structure, mechanism and pharmacology of NSSs. At present, however, the functional state of LeuT in crystals grown in the presence of n-octyl-{beta}-D-glucopyranoside ({beta}-OG) and the number of substrate binding sites are controversial issues. Here we present crystal structures of LeuT grown in DMPC-CHAPSO bicelles and demonstrate that the conformations of LeuT-substrate complexes in lipid bicelles and in {beta}-OG detergent micelles are nearly identical. Furthermore, using crystals grown in bicelles and the substrate leucine or the substrate analog selenomethionine, we find only a single substrate molecule in the primary binding site.

Polyester kumaşların indigo boyar maddeleri ile boyanabilirliğinin geliştirilmesi için poli(Vinil Alkol) ve modifiye poli(Vinil Alkol) polimerleri ile modifiye edilmesi

OpenAIRE

KALKAN ERDOĞAN, Meryem

2017-01-01

Bu çalışmada, tekstil sanayiinde önemli sentetik liflerden olan poli(etilen teraftalat) (PET) esaslı polyester (PES) kumaşların, indigo boyarmaddesi ile pamuklu denim (kot) kumaşlara benzer şekilde yüzeysel ve kesintisiz olarak soğukta boyanabilmesi amacıyla, poli(vinil alkol) (PVA) ve farklı bileşimlerde sentezlenen modifiye PVA (M-PVA) polimerlerini kullanarak fiziksel ve kimyasal yöntemler ile modifikasyonu gerçekleştirildi. M-PVA polimerleri, PVA varlığında glisidil metakrilat (G...

Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the mouse melanocortin receptors. Part 3: modifications at the Arg position.

Science.gov (United States)

Holder, Jerry Ryan; Xiang, Zhimin; Bauzo, Rayna M; Haskell-Luevano, Carrie

2003-01-01

The melanocortin pathway is involved in the regulation of several physiological functions including skin pigmentation, steroidogenesis, obesity, energy homeostasis, and exocrine gland function. This melanocortin pathway consists of five known G-protein coupled receptors, endogenous agonists derived from the proopiomelanocortin (POMC) gene transcript, the endogenous antagonists Agouti and the Agouti-related protein (AGRP) and signals through the intracellular cAMP signal transduction pathway. The melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) located in the brain are implicated as participating in the metabolic and food intake aspects of energy homeostasis and are stimulated by melanocortin agonists such as alpha-melanocyte stimulation hormone (alpha-MSH). All the endogenous (POMC-derived) melanocortin agonists contain the putative message sequence "His-Phe-Arg-Trp." Herein, we report 12 tetrapeptides, based upon the template Ac-His(6)-DPhe(7)-Arg(8)-Trp(9)-NH(2) (alpha-MSH numbering) that have been modified at the Arg(8) position by neutral, basic, or acidic amino acid side chains. These peptides have been pharmacologically characterized for agonist activity at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R. The most notable results of this study include the observation that removal of the guanidinyl side chain moiety results in decreased melanocortin receptor potency, but that this Arg(8) side chain is not critical for melanocortin receptor agonist activity. Additionally, incorporation of the homoArg(8) residue results in 56-fold MC4R versus MC3R selectivity, and the Orn(8) residue results in 123-fold MC4R versus MC5R and 63-fold MC5R versus MC3R selectivity. Copyright 2002 Elsevier Science Inc.

Specific fluorogenic substrates for neprilysin (neutral endopeptidase, EC 3.4.24.11 which are highly resistant to serine- and metalloproteases

Directory of Open Access Journals (Sweden)

M.A.S. Medeiros

1997-10-01

Full Text Available Two intramolecularly quenched fluorogenic peptides containing o-aminobenzoyl (Abz and ethylenediamine 2,4-dinitrophenyl (EDDnp groups at amino- and carboxyl-terminal amino acid residues, Abz-DArg-Arg-Leu-EDDnp (Abz-DRRL-EDDnp and Abz-DArg-Arg-Phe-EDDnp (Abz-DRRF-EDDnp, were selectively hydrolyzed by neutral endopeptidase (NEP, enkephalinase, neprilysin, EC 3.4.24.11 at the Arg-Leu and Arg-Phe bonds, respectively. The kinetic parameters for the NEP-catalyzed hydrolysis of Abz-DRRL-EDDnp and Abz-DRRF-EDDnp were Km = 2.8 µM, kcat = 5.3 min-1, kcat/Km = 2 min-1 µM-1 and Km = 5.0 µM, kcat = 7.0 min-1, kcat/Km = 1.4 min-1 µM-1, respectively. The high specificity of these substrates was demonstrated by their resistance to hydrolysis by metalloproteases [thermolysin (EC 3.4.24.2, angiotensin-converting enzyme (ACE; EC 3.4.24.15], serineproteases [trypsin (EC 3.4.21.4, a-chymotrypsin (EC 3.4.21.1] and proteases present in tissue homogenates from kidney, lung, brain and testis. The blocked amino- and carboxyl-terminal amino acids protected these substrates against the action of aminopeptidases, carboxypeptidases and ACE. Furthermore, DR amino acids ensured total protection of Abz-DRRL-EDDnp and Abz-DRRF-EDDnp against the action of thermolysin and trypsin. Leu-EDDnp and Phe-EDDnp were resistant to hydrolysis by a-chymotrypsin. The high specifity of these substrates suggests their use for specific NEP assays in crude enzyme preparations

Functional analysis of four naturally occurring variants of human constitutive androstane receptor.

Science.gov (United States)

Ikeda, Shinobu; Kurose, Kouichi; Jinno, Hideto; Sai, Kimie; Ozawa, Shogo; Hasegawa, Ryuichi; Komamura, Kazuo; Kotake, Takeshi; Morishita, Hideki; Kamakura, Shiro; Kitakaze, Masafumi; Tomoike, Hitonobu; Tamura, Tomohide; Yamamoto, Noboru; Kunitoh, Hideo; Yamada, Yasuhide; Ohe, Yuichiro; Shimada, Yasuhiro; Shirao, Kuniaki; Kubota, Kaoru; Minami, Hironobu; Ohtsu, Atsushi; Yoshida, Teruhiko; Saijo, Nagahiro; Saito, Yoshiro; Sawada, Jun-ichi

2005-01-01

The human constitutive androstane receptor (CAR, NR1I3) is a member of the orphan nuclear receptor superfamily that plays an important role in the control of drug metabolism and disposition. In this study, we sequenced all the coding exons of the NR1I3 gene for 334 Japanese subjects. We identified three novel single nucleotide polymorphisms (SNPs) that induce non-synonymous alterations of amino acids (His246Arg, Leu308Pro, and Asn323Ser) residing in the ligand-binding domain of CAR, in addition to the Val133Gly variant, which was another CAR variant identified in our previous study. We performed functional analysis of these four naturally occurring CAR variants in COS-7 cells using a CYP3A4 promoter/enhancer reporter gene that includes the CAR responsive elements. The His246Arg variant caused marked reductions in both transactivation of the reporter gene and in the response to 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO), which is a human CAR-specific agonist. The transactivation ability of the Leu308Pro variant was also significantly decreased, but its responsiveness to CITCO was not abrogated. The transactivation ability and CITCO response of the Val133Gly and Asn323Ser variants did not change as compared to the wild-type CAR. These data suggest that the His246Arg and Leu308Pro variants, especially His246Arg, may influence the expression of drug-metabolizing enzymes and transporters that are transactivated by CAR.

A conformational switch in the inhibitory gamma-subunit of PDE6 upon enzyme activation by transducin.

Science.gov (United States)

Granovsky, A E; Artemyev, N O

2001-11-06

In response to light, a photoreceptor G protein, transducin, activates cGMP-phosphodiesterase (PDE6) by displacing the inhibitory gamma-subunits (Pgamma) from the enzyme's catalytic sites. Evidence suggests that the activation of PDE6 involves a conformational change of the key inhibitory C-terminal domain of Pgamma. In this study, the C-terminal region of Pgamma, Pgamma-73-85, has been targeted for Ala-scanning mutagenesis to identify the point-to-point interactions between Pgamma and the PDE6 catalytic subunits and to probe the nature of the conformational change. Pgamma mutants were tested for their ability to inhibit PDE6 and a chimeric PDE5-conePDE6 enzyme containing the Pgamma C-terminus-binding site of cone PDE. This analysis has revealed that in addition to previously characterized Ile86 and Ile87, important inhibitory contact residues of Pgamma include Asn74, His75, and Leu78. The patterns of mutant PDE5-conePDE6 enzyme inhibition suggest the interaction between the PgammaAsn74/His75 sequence and Met758 of the cone PDE6alpha' catalytic subunit. This interaction, and the interaction between the PgammaIle86/Ile87 and PDE6alpha'Phe777/Phe781 residues, is most consistent with an alpha-helical structure of the Pgamma C-terminus. The analysis of activation of PDE6 enzymes containing Pgamma mutants with Ala-substituted transducin-contact residues demonstrated the critical role of PgammaLeu76. Accordingly, we hypothesize that the initial step in PDE6 activation involves an interaction of transducin-alpha with PgammaLeu76. This interaction introduces a bend into the alpha-helical structure of the Pgamma C-terminus, allowing transducin-alpha to further twist the C-terminus thereby uncovering the catalytic pocket of PDE6.

Statistical Characterization of the Charge State and Residue Dependence of Low-Energy CID Peptide Dissociation Patterns

International Nuclear Information System (INIS)

Huang, Yingying; Triscari, Joseph M.; Tseng, George C.; Pasa-Tolic, Ljiljana; Lipton, Mary S.; Smith, Richard D.; Wysocki, Vicki H.

2005-01-01

Data mining was performed on 28 330 unique peptide tandem mass spectra for which sequences were assigned with high confidence. By dividing the spectra into different sets based on structural features and charge states of the corresponding peptides, chemical interactions involved in promoting specific cleavage patterns in gas-phase peptides were characterized. Pairwise fragmentation maps describing cleavages at all Xxx-Zzz residue combinations for b and y ions reveal that the difference in basicity between Arg and Lys results in different dissociation patterns for singly charged Arg- and Lys-ending tryptic peptides. While one dominant protonation form (proton localized) exists for Arg-ending peptides, a heterogeneous population of different protonated forms or more facile interconversion of protonated forms (proton partially mobile) exists for Lys-ending peptides. Cleavage C-terminal to acidic residues dominates spectra from peptides that have a localized proton and cleavage N-terminal to Pro dominates those that have a mobile or partially mobile proton. When Pro is absent from peptides that have a mobile or partially mobile proton, cleavage at each peptide bond becomes much more prominent. Whether the above patterns can be found in b ions, y ions, or both depends on the location of the proton holder(s). Enhanced cleavages C-terminal to branched aliphatic residues (Ile, Val, Leu) are observed in both b and y ions from peptides that have a mobile proton, as well as in y ions from peptides that have a partially mobile proton; enhanced cleavages N-terminal to these residues are observed in b ions from peptides that have a partially mobile proton. Statistical tools have been designed to visualize the fragmentation maps and measure the similarity between them. The pairwise cleavage patterns observed expand our knowledge of peptide gas-phase fragmentation behaviors and should be useful in algorithm development that employs improved models to predict fragment ion

Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis PotosÍ and León, México.

Science.gov (United States)

Aradillas-Garc X Cd, Celia; Cruz, Miguel; Pérez-Luque, Elva; Garay-Sevilla, María E; Malacara, Juan M; R, Aduna; Peralta, Jesús; Burguete-García, Ana; Alegría-Torres, Jorge A

2016-10-17

This research was designed to analyze the possible associations of Arg389Gly ADRB1 and Trp64Arg ADRB3 polymorphisms in children with obesity. A cross-sectional study included 1,046 school-age Mexican participants (6-12 years old) from the cities of San Luis PotosÍ and León. Children were classified as non-obese or obese according to their body mass index (BMI) percentile; obese children had a BMI≥95th percentile for sex and age. Biochemical data were collected. Polymorphisms were detected using TaqMan qPCR assay. A logistic regression analysis was used to calculate the risk of obesity based on genotypes. Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, LDL-cholesterol, triglycerides, and lower HDL-cholesterol compared with the normal weight group (P<0.05). The distribution of allele frequency in the population was Arg= 87.4 and Gly= 12.6 (Hardy Weinberg equilibrium c 2 = 3.16 , P = 0.07 ); Trp= 81.5 and Arg= 18.5 (Hardy Weinberg equilibrium c 2 = 2.2, P = 0.14 ) for ADRB1 and ADRB3, respectively. Even though no different frequencies of Arg389Gly polymorphism between groups were found (P = 0.08), children carriers of one Gly389 ADRB1 allele had a risk for obesity of OR=1.40 (95%CI, 1.03-1.90, P = 0.03) after adjustment for age and gender. No other association was found for Trp64Arg ADRB3 polymorphism. Only the Arg389Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

A neutronic feasibility study for LEU conversion of the IR-8 research reactor

International Nuclear Information System (INIS)

Deen, J.R.; Hanan, N.A.; Matos, J.E.; Egorenkov, P.M.; Nasonov, V.A.

1998-01-01

Equilibrium fuel cycle comparisons for the IR-8 research reactor were made for HEU (90%), HEU (36%), and LEU (19.75%) fuel assembly (FA) designs using three dimensional multi-group diffusion theory models benchmarked to detailed Monte Carlo models of the reactor. Comparisons were made of changes in reactivity, cycle length, average 235 U discharge burnup, thermal neutron flux, and control rod worths for the 90% and 36% enriched IRT-3M fuel assembly and the 19.75% enriched IRT-4M fuel assembly with the same fuel management strategy. The results of these comparisons showed that a uranium density of 3.5 g/cm 3 in the fuel meat would be required in the LEU IRT-4M fuel assembly to match the cycle length of the HEU (90%) IRT-3M FA and an LEU density of 3.7 g/cm 3 is needed to match the cycle length of the HEU (36%) IRT-3M FA. (author)

Arg deficiency does not influence the course of Myelin Oligodendrocyte Glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis

DEFF Research Database (Denmark)

Jacobsen, Freja Aksel; Hulst, Camilla; Bäckström, Thomas

2016-01-01

Background: Inhibition of Abl kinases has an ameliorating effect on the rodent model for multiple sclerosis, experimental autoimmune encephalomyelitis, and arrests lymphocyte activation. The family of Abl kinases consists of the Abl1/Abl and Abl2/Arg tyrosine kinases. While the Abl kinase has bee...... encephalomyelitis is not dependent on Arg, but Arg plays a role for the number of B cells in immunized mice. This might suggest a novel role for the Arg kinase in B-cell trafficking or regulation. Furthermore, the results suggest that Arg is important for normal embryonic development....

A neutronic feasibility study for LEU conversion of the WWR-M reactor at Gatchina

International Nuclear Information System (INIS)

Petrov, Yu. V.; Erykalov, A.N.; Onegin, M.S.

2000-01-01

In this report we present the results of computations of the full scale reactor core with HEU (90%), MEU (36%) and LEU (19.75%) fuel. The reactor computer model for the MCU RFFI Monte Carlo code includes all peculiarities of the core. Calculations show that a uranium density of 3.3gU/cm 3 of MEU (36%) fuel and 8/25gU/cm 3 of LEU (19.75%) in WWR-M5 fuel assembly (FA) geometry is required to match the fuel cycle length of the HEU (90%) case with the same end of cycle (EOEC) excess reactivity. For the equilibrium fuel cycle the fuel burnup and poisoning, the fast and thermal neutron fluxes, the reactivity worth of control rods were calculated for the reference case with HEU (90%) FA and for the MEU and LEU FA. The relative accuracy of this neutronic feasibility study of fuel enrichment reduction of the WWR-M reactor in Gatchina is sufficient to start the fabrication feasibility study of MEU (36%) WWR-M5 fuel assemblies. At the present stage of technology it seems hardly possible to manufacture LEU (19.75%) fuel elements in WWR-M5 geometry due to too high uranium density. Only a future R and D can solve the problem. (author)

Molecular evolution of the lysine biosynthetic pathways.

Science.gov (United States)

Velasco, A M; Leguina, J I; Lazcano, A

2002-10-01

Among the different biosynthetic pathways found in extant organisms, lysine biosynthesis is peculiar because it has two different anabolic routes. One is the diaminopimelic acid pathway (DAP), and the other over the a-aminoadipic acid route (AAA). A variant of the AAA route that includes some enzymes involved in arginine and leucine biosyntheses has been recently reported in Thermus thermophilus (Nishida et al. 1999). Here we describe the results of a detailed genomic analysis of each of the sequences involved in the two lysine anabolic routes, as well as of genes from other routes related to them. No evidence was found of an evolutionary relationship between the DAP and AAA enzymes. Our results suggest that the DAP pathway is related to arginine metabolism, since the lysC, asd, dapC, dapE, and lysA genes from lysine biosynthesis are related to the argB, argC, argD, argE, and speAC genes, respectively, whose products catalyze different steps in arginine metabolism. This work supports previous reports on the relationship between AAA gene products and some enzymes involved in leucine biosynthesis and the tricarboxylic acid cycle (Irvin and Bhattacharjee 1998; Miyazaki et al. 2001). Here we discuss the significance of the recent finding that several genes involved in the arginine (Arg) and leucine (Leu) biosynthesis participate in a new alternative route of the AAA pathway (Miyazaki et al. 2001). Our results demonstrate a clear relationship between the DAP and Arg routes, and between the AAA and Leu pathways.

ARG1 (altered response to gravity) encodes a DnaJ-like protein that potentially interacts with the cytoskeleton

Science.gov (United States)

Sedbrook, J. C.; Chen, R.; Masson, P. H.

1999-01-01

Gravitropism allows plant organs to direct their growth at a specific angle from the gravity vector, promoting upward growth for shoots and downward growth for roots. Little is known about the mechanisms underlying gravitropic signal transduction. We found that mutations in the ARG1 locus of Arabidopsis thaliana alter root and hypocotyl gravitropism without affecting phototropism, root growth responses to phytohormones or inhibitors of auxin transport, or starch accumulation. The positional cloning of ARG1 revealed a DnaJ-like protein containing a coiled-coil region homologous to coiled coils found in cytoskeleton-interacting proteins. These data suggest that ARG1 participates in a gravity-signaling process involving the cytoskeleton. A combination of Northern blot studies and analysis of ARG1-GUS fusion-reporter expression in transgenic plants demonstrated that ARG1 is expressed in all organs. Ubiquitous ARG1 expression in Arabidopsis and the identification of an ortholog in Caenorhabditis elegans suggest that ARG1 is involved in other essential processes.

Status of core conversion with LEU silicide fuel in JRR-4

Energy Technology Data Exchange (ETDEWEB)

Nakajima, Teruo; Ohnishi, Nobuaki; Shirai, Eiji [Japan Atomic Energy Research Institute, Ibaraki-ken (Japan)

1997-08-01

Japan Research Reactor No.4 (JRR-4) is a light water moderated and cooled, 93% enriched uranium ETR-type fuel used and swimming pool type reactor with thermal output of 3.5MW. Since the first criticality was achieved on January 28, 1965, JRR-4 has been used for shielding experiments, radioisotope production, neutron activation analyses, training for reactor engineers and so on for about 30 years. Within the framework of the RERTR Program, the works for conversion to LEU fuel are now under way, and neutronic and thermal-hydraulic calculations emphasizing on safety and performance aspects are being carried out. The design and evaluation for the core conversion are based on the Guides for Safety Design and Evaluation of research and testing reactor facilities in Japan. These results show that the JRR-4 will be able to convert to use LEU fuel without any major design change of core and size of fuel element. LEU silicide fuel (19.75%) will be used and maximum neutron flux in irradiation hole would be slightly decreased from present neutron flux value of 7x10{sup 13}(n/cm{sup 2}/s). The conversion works are scheduled to complete in 1998, including with upgrade of the reactor building and utilization facilities.

Status of core conversion with LEU silicide fuel in JRR-4

International Nuclear Information System (INIS)

Nakajima, Teruo; Ohnishi, Nobuaki; Shirai, Eiji

1997-01-01

Japan Research Reactor No.4 (JRR-4) is a light water moderated and cooled, 93% enriched uranium ETR-type fuel used and swimming pool type reactor with thermal output of 3.5MW. Since the first criticality was achieved on January 28, 1965, JRR-4 has been used for shielding experiments, radioisotope production, neutron activation analyses, training for reactor engineers and so on for about 30 years. Within the framework of the RERTR Program, the works for conversion to LEU fuel are now under way, and neutronic and thermal-hydraulic calculations emphasizing on safety and performance aspects are being carried out. The design and evaluation for the core conversion are based on the Guides for Safety Design and Evaluation of research and testing reactor facilities in Japan. These results show that the JRR-4 will be able to convert to use LEU fuel without any major design change of core and size of fuel element. LEU silicide fuel (19.75%) will be used and maximum neutron flux in irradiation hole would be slightly decreased from present neutron flux value of 7x10 13 (n/cm 2 /s). The conversion works are scheduled to complete in 1998, including with upgrade of the reactor building and utilization facilities

Contribution of Arg288 of Escherichia coli elongation factor Tu to translational functionality

DEFF Research Database (Denmark)

Rattenborg, Thomas; Nautrup-Pedersen, Gitte; Clark, Brian F. C.

1997-01-01

. This network is disrupted upon formation of the ternary complex. Arg288 was replaced by alanine, isoleucine, lysine or glutamic acid, and the resulting mutants have been subjected to an in vitro characterisation with the aim of clarifying the function of Arg288. Unexpectedly, the mutants behaved like the wild...

Enhancement of the thermostability of Hydrogenobacter thermophilus cytochrome c(552) through introduction of an extra methylene group into its hydrophobic protein interior.

Science.gov (United States)

Tai, Hulin; Irie, Kiyofumi; Mikami, Shin-ichi; Yamamoto, Yasuhiko

2011-04-19

Careful scrutiny of the protein interior of Hydrogenobacter thermophilus cytochrome c(552) (HT) on the basis of its X-ray structure [Travaglini-Allocatelli, C., Gianni, S., Dubey, V. K., Borgia, A., Di Matteo, A., Bonivento, D., Cutruzzola, F., Bren, K. L., and Brunori, M. (2005) J. Biol. Chem. 280, 25729-25734] indicated that a void space, which is large enough to accommodate a methyl group, exists in the hydrophobic protein interior near the heme. We tried to reduce the void space through the replacement of a Val by Ile or Leu (Val/Ile or Val/Leu mutation), and then the structural and functional consequences of these two mutations were characterized in order to elucidate the relationship between the nature of the packing of hydrophobic residues and the functional properties of the protein. The study demonstrated striking differences in the structural and functional consequences between the two mutations. The Val/Ile mutation was found to cause further enhancement of the thermostability of the oxidized HT, as reflected in the increase of the denaturation temperature (T(m)) value by ∼ 3 deg, whereas the thermostability of the reduced form was essentially unaffected. As a result, the redox potential (E(m)) of the Val/Ile mutant exhibited a negative shift of ∼ 50 mV relative to that of the wild-type protein in an enthalpic manner, this being consistent with our previous finding that a protein with higher stability in its oxidized form exhibits a lower E(m) value [Terui, N., Tachiiri, N., Matsuo, H., Hasegawa, J., Uchiyama, S., Kobayashi, Y., Igarashi, Y., Sambongi, Y., and Yamamoto, Y. (2003) J. Am. Chem. Soc. 125, 13650-13651]. In contrast, the Val/Leu mutation led to a decrease in thermostability of both the redox forms of the protein, as reflected in the decreases of the T(m) values of the oxidized and reduced proteins by ∼ 3 and ∼ 5 deg, respectively, and the E(m) value of the Val/Leu mutant happened to be similar to that of the Val/Ile one. The E

Male Involvement in Family Planning Decision Making in Ile-Ife ...

African Journals Online (AJOL)

This study assessed men's awareness, attitude, and practice of modern contraceptive methods, determined the level of spousal communication, and investigated the correlates of men's opinion in family planning decision making in Ile-Ife, Nigeria. Quantitative methodology was employed in this cross-sectional descriptive ...

Continuing investigations for technology assessment of 99Mo production from LEU [low enriched Uranium] targets

International Nuclear Information System (INIS)

Vandergrift, G.F.; Kwok, J.D.; Marshall, S.L.; Vissers, D.R.; Matos, J.E.

1987-01-01

Currently much of the world's supply of /sup 99m/Tc for medical purposes is produced from 99 Mo derived from the fissioning of high enriched uranium (HEU). The need for /sup 99m/Tc is continuing to grow, especially in developing countries, where needs and national priorities call for internal production of 99 Mo. This paper presents the results of our continuing studies on the effects of substituting low enriched Uranium (LEU) for HEU in targets for the production of fission product 99 Mo. Improvements in the electrodeposition of thin films of uranium metal are reported. These improvements continue to increase the appeal for the substitution of LEU metal for HEU oxide films in cylindrical targets. The process is effective for targets fabricated from stainless steel or hastaloy. A cost estimate for setting up the necessary equipment to electrodeposit uranium metal on cylindrical targets is reported. Further investigations on the effect of LEU substitution on processing of these targets are also reported. Substitution of uranium silicides for the uranium-aluminum alloy or uranium aluminide dispersed fuel used in other current target designs will allow the substitution of LEU for HEU in these targets with equivalent 99 Mo-yield per target and no change in target geometries. However, this substitution will require modifications in current processing steps due to (1) the insolubility of uranium silicides in alkaline solutions and (2) the presence of significant quantities of silicate in solution. Results to date suggest that both concerns can be handled and that substitution of LEU for HEU can be achieved

The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.

Science.gov (United States)

Zhuang, Langen; Li, Ming; Yu, Changhua; Li, Can; Zhao, Mingming; Lu, Ming; Zheng, Taishan; Zhang, Rong; Zhao, Weijing; Bao, Yuqian; Xiang, Kunsan; Jia, Weiping; Wang, Niansong; Liu, Limei

2014-02-01

The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case-control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.

Identification of a Histidine Metal Ligand in the argE-Encoded N-Acetyl-L-Ornithine Deacetylase from Escherichia coli.

Science.gov (United States)

McGregor, Wade C; Gillner, Danuta M; Swierczek, Sabina I; Liu, Dali; Holz, Richard C

2013-01-01

The H355A, H355K, H80A, and H80K mutant enzymes of the argE-encoded N-acetyl-L-ornithine deacetylase (ArgE) from Escherichia coli were prepared, however, only the H355A enzyme was found to be soluble. Kinetic analysis of the Co(II)-loaded H355A exhibited activity levels that were 380-fold less than Co(II)-loaded WT ArgE. Electronic absorption spectra of Co(II)-loaded H355A-ArgE indicate that the bound Co(II) ion resides in a distorted, five-coordinate environment and Isothermal Titration Calorimetry (ITC) data for Zn(II) binding to the H355A enzyme provided a dissociation constant (K d) of 39 μM. A three-dimensional homology model of ArgE was generated using the X-ray crystal structure of the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) from Haemophilus influenzae confirming the assignment of H355 as well as H80 as active site ligands.

SMOPY, a new NDA tool for safeguards of LEU and MOX spent fuel

International Nuclear Information System (INIS)

Lebrun, A.; Merelli, M.; Szabo, J.-L.; Huver, M.; Arenas-Carrasco, J.

2001-01-01

Upon IAEA request, the French support program to IAEA Safeguards has developed a new device for control of the irradiated LEU and MOX fuels. The Safeguards Mox Python (SMOPY) is the achievement of a 4 years R and D program supported by CEA and COGEMA in partnership with Eurisys Mesures. The SMOPY system is based on the combination of 2 NDA techniques (passive neutron and room temperature gamma spectrometry) and on line interpretation tools (automatic gamma spectrum interpretation, depletion code EVO). Through the measurement managing software, all this contributes to the fully automatic measurement, interpretation and characterization of any kind of spent fuel. The device is transportable (50 kg, 60 cm) and is composed of four parts: 1. the measurement head with one high efficiency fission chamber and a micro room temperature gamma spectrometric probe; 2. the carrier which carries the measurement head. The carrier bottom fits the racks for accurate positioning and its top fits operator's fuel moving tool; 3. the portable electronic cabinet which includes both neutron and gamma electronic cards; 4. the portable PC which gets inspectors data, controls the measurement, get measured values, interprets them and immediately provides the inspector with worthwhile info for appropriate on the field decisions. Main features of SMOPY are: Discrimination of MOX versus LEU irradiated fuels in any case (conservative case is one cycle MOX versus three cycles LEU after short cooling time); Full characterization of irradiated LEU (burnup, cooling time, Pu amounts ...); Partial Defect Test on LEU fuels. A first version of SMOPY has been tested in industrial condition during summer 2000. This tests shown a need of shielding improvement around the gamma detector. A new version has been build a will be qualified during a new field test and then the system will be ready for routine operation in IAEA and commercial delivery. After giving details about the system itself, this paper

Study on Al-alloy or silicide LEU for DR3 in Denmark

Energy Technology Data Exchange (ETDEWEB)

Haack, Karsten [Riso National Laboratory, DK 4000 Roskilde (Germany)

1985-07-01

The 10 MW D{sub 2}0-moderated and -cooled research reactor DR3 has at present HEU fuel available for continued operation till early 19. This report presents the status of a feasibility study prepared for selection of the best suited candidate LEU fuel type for DR3 at a potential conversion in 1988. At the moment two alternatives are evaluated: UAl-alloy with modified geometry and U{sub 3}Si{sub 2} with unchanged geometry. A decision on the type selected for further investigation is expected late 1984. The investigation should comprise development, in- and out-of-pile--testing and licensing activities on the potential LEU option. (author)

A synthetic peptide blocking TRPV1 activation inhibits UV-induced skin responses.

Science.gov (United States)

Kang, So Min; Han, Sangbum; Oh, Jang-Hee; Lee, Young Mee; Park, Chi-Hyun; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

2017-10-01

Transient receptor potential type 1 (TRPV1) can be activated by ultraviolet (UV) irradiation, and mediates UV-induced matrix metalloproteinase (MMP)-1 and proinflammatory cytokines in keratinocytes. Various chemicals and compounds targeting TRPV1 activation have been developed, but are not in clinical use mostly due to their safety issues. We aimed to develop a novel TRPV1-targeting peptide to inhibit UV-induced responses in human skin. We designed and generated a novel TRPV1 inhibitory peptide (TIP) which mimics the specific site in TRPV1 (aa 701-709: Gln-Arg-Ala-Ile-Thr-Ile-Leu-Asp-Thr, QRAITILDT), Thr 705 , and tested its efficacy of blocking UV-induced responses in HaCaT, mouse, and human skin. TIP effectively inhibited capsaicin-induced calcium influx and TRPV1 activation. Treatment of HaCaT with TIP prevented UV-induced increases of MMP-1 and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-α. In mouse skin in vivo, TIP inhibited UV-induced skin thickening and prevented UV-induced expression of MMP-13 and MMP-9. Moreover, TIP attenuated UV-induced erythema and the expression of MMP-1, MMP-2, IL-6, and IL-8 in human skin in vivo. The novel synthetic peptide targeting TRPV1 can ameliorate UV-induced skin responses in vitro and in vivo, providing a promising therapeutic approach against UV-induced inflammation and photoaging. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Isoleucine requirement of pigs weighing 8 to 18 kg fed blood cell–free diets1

DEFF Research Database (Denmark)

Nørgaard, Jan Værum; Shresta, Aruna; Krogh, Uffe

2013-01-01

The aim of the present study was to determine the minimum requirement of Ile in young pigs, enabling feeding of balanced low-CP diets. Most previous studies have used experimental diets that included blood cells, which are particularly high in Leu and known to antagonize the use of Ile. One week....... In conclusion, the average estimation of requirement in this dose-response study using blood cell–free diets was 0.52 SID Ile:Lys during a 21-d experimental period from 8 kg BW....... after weaning at d 28, 100 crossbred female pigs weighing 7.9 ± 0.7 kg were allocated to 1 of 5 dietary treatments. Diets were formulated to contain 1.15 g standardized ileal digestible (SID) Lys/MJ NE and were free of blood cells. The SID Ile was 0.42, 0.47, 0.53, 0.58, and 0.62 relative to Lys...

Professor Jüri Talvetist sai Ida-Lääne akadeemia liige / intervjueerinud Rein Veidemann

Index Scriptorium Estoniae

Talvet, Jüri, 1945-

2011-01-01

Intervjuu Tartu ülikooli maailmakirjanduse professori Jüri Talvetiga luulefestivalist Curtea de Argeş ("Nopţile de Poezie de la Curtea de Argeş") ja tema rumeenia keelde tõlgitud luulekogust „Unest, lumest” ("De din somn, de din zăpadă" - tõlkija Dumitru M. Ion), mida autor seal esitlemas käis ning Ida-Lääne akadeemiast (Academia Internationala Orient-Occident), mille tegevliikmeks ta valiti

Butterfly diversity in Obafemi Awolowo University, Ile Ife, South-west ...

African Journals Online (AJOL)

Butterfly diversity on Obafemi Awolowo University, Ile Ife, was investigated by the use of sweep nets along transects in different sites. The sites include; Parks and Gardens, Zoological Garden, Oxidation Pond, Botanical Garden, Teaching and Research Farm, New Bukkateria and open fields. Data was analyzed with ...

Expression and mutagenesis of the sea anemone toxin Av2 reveals key amino acid residues important for activity on voltage-gated sodium channels.

Science.gov (United States)

Moran, Yehu; Cohen, Lior; Kahn, Roy; Karbat, Izhar; Gordon, Dalia; Gurevitz, Michael

2006-07-25

Type I sea anemone toxins are highly potent modulators of voltage-gated Na-channels (Na(v)s) and compete with the structurally dissimilar scorpion alpha-toxins on binding to receptor site-3. Although these features provide two structurally different probes for studying receptor site-3 and channel fast inactivation, the bioactive surface of sea anemone toxins has not been fully resolved. We established an efficient expression system for Av2 (known as ATX II), a highly insecticidal sea anemone toxin from Anemonia viridis (previously named A. sulcata), and mutagenized it throughout. Each toxin mutant was analyzed in toxicity and binding assays as well as by circular dichroism spectroscopy to discern the effects derived from structural perturbation from those related to bioactivity. Six residues were found to constitute the anti-insect bioactive surface of Av2 (Val-2, Leu-5, Asn-16, Leu-18, and Ile-41). Further analysis of nine Av2 mutants on the human heart channel Na(v)1.5 expressed in Xenopus oocytes indicated that the bioactive surfaces toward insects and mammals practically coincide but differ from the bioactive surface of a structurally similar sea anemone toxin, Anthopleurin B, from Anthopleura xanthogrammica. Hence, our results not only demonstrate clear differences in the bioactive surfaces of Av2 and scorpion alpha-toxins but also indicate that despite the general conservation in structure and importance of the Arg-14 loop and its flanking residues Gly-10 and Gly-20 for function, the surface of interaction between different sea anemone toxins and Na(v)s varies.

Affinity labeling of Escherichia coli phenylalanyl-tRNA synthetase at the binding site for tRNA

International Nuclear Information System (INIS)

Hountondji, C.; Schmitter, J.M.; Beauvallet, C.; Blanquet, S.

1987-01-01

Periodate-oxidized tRNA/sup Phe/ (tRNA/sub ox//sup Phe/) behaves as a specific affinity label of tetrameric Escherichia coli phenylalanyl-tRNA synthetase (PheRS). Reaction of the α 2 β 2 enzyme with tRNA/sub ox//sup Phe/ results in the loss of tRNA/sup Phe/ aminoacylation activity with covalent attachment of 2 mol of tRNA dialdehyde/mol of enzyme, in agreement with the stoichiometry of tRNA binding. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the PheRS-[ 14 C]tRNA/sub ox//sup Phe/ covalent complex indicates that the large (α, M/sub r/ 87K) subunit of the enzyme interacts with the 3'-adenosine of tRNA/sub ox//sup Phe/. The [ 14 C]tRNA-labeled chymotryptic peptides of PheRS were purified by both gel filtration and reverse-phase high-performance liquid chromatography. The radioactivity was almost equally distributed among three peptides: Met-Lys[Ado]-Phe, Ala-Asp-Lys[Ado]-Leu, and Lys-Ile-Lys[Ado]-Ala. These sequences correspond to residues 1-3, 59-62, and 104-107, respectively, in the N-terminal region of the 795 amino acid sequence of the α subunit. It is noticeable that the labeled peptide Ala-Asp-Lys-Leu is adjacent to residues 63-66 (Arg-Val-Thr-Lys). The latter sequence was just predicted to resemble the proposed consensus tRNA CCA binding region Lys-Met-Ser-Lys-Ser, as deduced from previous affinity labeling studies on E. coli methionyl- and tyrosyl-tRNA synthetases

A 19-kDa C-terminal tryptic fragment of the α chain of Na/K-ATPase is essential for occlusion and transport of cations

International Nuclear Information System (INIS)

Karlish, S.J.D.; Goldshleger, R.; Stein, W.D.

1990-01-01

Tryptic digestion of pig renal Na/K-ATPase in the presence of Rb and absence of Ca ions removes about half of the protein but leaves a stable 19-kDa membrane-embedded fragment derived from the α chain, a largely intact β chain, and essentially normal Rb- and Na-occlusion capacity. Subsequent digestion with trypsin in the presence of Ca or absence of Rb ions leads to rapid loss of the 19-kDa fragment and a parallel loss of Rb occlusion, demonstrating that the fragment is essential for occlusion. The N-terminal sequence of the 19-kDa fragment is Asn-Pro-Lys-Thr-Asp-Lys-Leu-Val-Asn-Glu-Arg-Leu-Ile-Ser-Met-Ala, beginning at residue 830 and extending toward the C terminus. Membranes containing the 19-kDa fragment have the following functional properties. (i) ATP-dependent functions are absent. (ii) The apparent affinity for occluding Rb is unchanged, the affinity for Na is lower than in the control enzyme, and activation is now strongly sigmoidal rather than hyperbolic. (iii) Membranes containing the 19-kDa fragment can be reconstituted into phospholipid vesicles and sustain slow Rb-Rb exchange. Thus the transport pathway is retained. The authors conclude that cation occlusion sites and the transport pathway within transmembrane segments are quite separate from the ATP binding sites, located on the cytoplasmic domain of the α chain. Interactions between cation and ATP sites, the heart of active transport, must be indirect - mediated, presumably, by conformational changes of the protein

A 19-kDa C-terminal tryptic fragment of the. alpha. chain of Na/K-ATPase is essential for occlusion and transport of cations

Energy Technology Data Exchange (ETDEWEB)

Karlish, S.J.D.; Goldshleger, R. (Weizmann Institute of Science, Rehovot (Israel)); Stein, W.D. (Hebrew Univ. Jerusalem (Israel))

1990-06-01

Tryptic digestion of pig renal Na/K-ATPase in the presence of Rb and absence of Ca ions removes about half of the protein but leaves a stable 19-kDa membrane-embedded fragment derived from the {alpha} chain, a largely intact {beta} chain, and essentially normal Rb- and Na-occlusion capacity. Subsequent digestion with trypsin in the presence of Ca or absence of Rb ions leads to rapid loss of the 19-kDa fragment and a parallel loss of Rb occlusion, demonstrating that the fragment is essential for occlusion. The N-terminal sequence of the 19-kDa fragment is Asn-Pro-Lys-Thr-Asp-Lys-Leu-Val-Asn-Glu-Arg-Leu-Ile-Ser-Met-Ala, beginning at residue 830 and extending toward the C terminus. Membranes containing the 19-kDa fragment have the following functional properties. (i) ATP-dependent functions are absent. (ii) The apparent affinity for occluding Rb is unchanged, the affinity for Na is lower than in the control enzyme, and activation is now strongly sigmoidal rather than hyperbolic. (iii) Membranes containing the 19-kDa fragment can be reconstituted into phospholipid vesicles and sustain slow Rb-Rb exchange. Thus the transport pathway is retained. The authors conclude that cation occlusion sites and the transport pathway within transmembrane segments are quite separate from the ATP binding sites, located on the cytoplasmic domain of the {alpha} chain. Interactions between cation and ATP sites, the heart of active transport, must be indirect - mediated, presumably, by conformational changes of the protein.

Radioactive Waste Issues related to Production of Fission-based Mo-99 by using Low Enriched Uranium (LEU)

Energy Technology Data Exchange (ETDEWEB)

Hassan, Muhmood ul; Ryu, Ho Jin [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2014-10-15

In order to produce fission-based Mo-99 from research reactors, two types of targets are being used and they are highly enriched uranium (HEU) targets with {sup 235}U enrichment more than 90wt% of {sup 235}U and low enriched uranium (LEU) targets with {sup 235}U enrichment less than 20wt% of {sup 235}U. It is worth noting that medium enriched uranium i.e. 36wt% of {sup 235}U as being used in South Africa is also regarded as non-LEU from a nuclear security point of view. In order to cope with the proliferation issues, international nuclear security policy is promoting the use of LEU targets in order to minimize the civilian use of HEU. It is noteworthy that Mo-99 yield of the LEU target is less than 20% of the HEU target, which requires approximately five times more LEU targets to be irradiated and consequently results in increased volume of waste. The waste generated from fission Mo-99 production can be mainly due to: target fabrication, assembling of target, irradiation in reactor and processing of irradiated targets. During the fission of U-235 in a reactor, a large number of radionuclides with different chemical and physical properties are formed. The waste produced from these practices may be a combination of low level waste (LLW) and intermediate level waste (ILW) comprised of all three types, i.e., solid, liquid and gas. Handling and treatment of the generated waste are dependent on its form and activity. In case of the large production facility, waste storage facility should be constructed in order to limit the radiation exposures of the workers and the environment. In this study, we discuss and compare mainly the radioactive waste generated by alkaline digestion of both HEU and LEU targets to assist in planning and deciding the choice of the technology with better arrangements for proper handling and disposal of generated waste. With the use of the LEU targets in Mo-99 production facility, significant increase in liquid and solid waste has been expected.

Enterovirus infections in hospitals of Ile de France region over 2013.

Science.gov (United States)

Molet, Lucie; Saloum, Kenda; Marque-Juillet, Stéphanie; Garbarg-Chenon, Antoine; Henquell, Cécile; Schuffenecker, Isabelle; Peigue-Lafeuille, Hélène; Rozenberg, Flore; Mirand, Audrey

2016-01-01

The monitoring and genotyping of Enterovirus (EV) infections can help to associate particular or severe clinical manifestations with specific EV types and to identify the aetiology of infectious outbreaks. To describe the epidemiological features of EV infections diagnosed during the year 2013 in the Greater Paris area (Ile de France). During 2013, 2497 samples taken from 470 patients in 33 hospitals of Ile-de France were tested for EV genome by RT-PCR. EV genotyping was performed by the National Reference Centre (NRC) laboratories. EV infections were retrospectively reviewed by retrieving clinical and genotyping data from the NRC database. Of the 2497 samples, 490 (19.6%) was positive for EV genome detection. These EV infections represented 88.7% and 24.1%, respectively, of all reported regional and national infections. Twenty-seven different genotypes were identified. Echovirus 30 (E-30) accounted for 54.1% of all characterized strains and caused a large outbreak. Four severe neonatal infections were reported, of which two were caused by EV-A71. Respiratory infections involving EV-D68 were observed in two adults. One fatal case of Coxsackievirus A2-associated myocarditis was reported. Monitoring EV infections in combination with EV genotyping via the French EV network characterized the epidemiology of EV infections in the Ile de France region in 2013 and documented severe EV infections associated with EV-A71 or CV-A2. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of thermohydraulic and nuclear aspects in a standard HEU core and a typical LEU core for the HFR Petten. A case study

International Nuclear Information System (INIS)

Pruimboom, H.; Tas, A.

1985-01-01

Within the framework of the RERTR program various HEU-LEU core calculations have been performed by ANL in a cooperative effort with ECN and JRC Petten. The main purpose of this work has been to gain competence in analysing HEU-LEU core conversion for high power Materials Testing Reactors and to assist in a possible HEU-LEU conversion of the HFR Petten. For reference purposes the present HFR standard core (HEU) in the 'old' vessel geometry was calculated at first. As a next step the new vessel geometry and the increased fuel weights were taken into account. Subsequently various LEU HFR core options have been analysed. Main parameters in the LEU study were the uranium loading in the meat, the fuel type, the thickness of the meat, the number of fuel plates per element and the type of burnable poison applied. Though the study has not yet been completed, one of its striking preliminary results concerns the increased power peaking in the LEU fuel elements as compared with the HEU situation. A preliminary analysis of the thermal characteristics of a typical LEU core as compared with a standard HEU core has been made and is presented in the paper. A short survey of the various HEU and LEU calculations is given. The thermal safety analysis procedure for the HFR, as based on the flow instability criterion, is clarified. Finally, the thermal comparison HEU versus LEU and the resulting conclusions are presented. (author)

Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids.

Science.gov (United States)

Ji, L L; Miller, R H; Nagle, F J; Lardy, H A; Stratman, F W

1987-08-01

The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.

A mixed core conversion study with HEU and LEU fuels

International Nuclear Information System (INIS)

Matos, J.E.; Freese, K.E.

1985-01-01

The results of a mixed core study are presented for gradual replacement of HEU fuel with LEU fuel using the IAEA generic 10 MW reactor as an example. The key parameters show that the transition can be accomplished safely and economically. (author)

Microchidia protein 2, MORC2, downregulates the cytoskeleton adapter protein, ArgBP2, via histone methylation in gastric cancer cells

Energy Technology Data Exchange (ETDEWEB)

Tong, Yuxin; Li, Yan [Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122 (China); Gu, Hui [Department of Key Laboratory of Health Ministry for Congenital Malformation Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004 (China); Wang, Chunyu [Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122 (China); Liu, Funan [Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001 (China); Shao, Yangguang; Li, Jiabin; Cao, Liu [Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122 (China); Li, Feng, E-mail: fli@mail.cmu.edu.cn [Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122 (China)

2015-11-27

ArgBP2 is an adapter protein that plays an important role in actin-dependent processes such as cell adhesion and migration. However, its function and regulation mechanisms in gastric cancer have not yet been investigated. Here, we showed the low expression of ArgBP2 mRNA level in gastric tumor samples and its repressive function in the proliferation, migration, and invasion of gastric cancer cells. Then, we cloned and identified ArgBP2 promoter and verified that MORC2 bound to the promoter. Moreover, we demonstrated that MORC2 enhanced the recruitment of EZH2, which promoted the tri-methylation of H3K27, leading to the transcriptional repression of ArgBP2. Our results might thus contribute to understanding the molecular mechanisms of ArgBP2 regulation and suggesting ArgBP2 as a potential therapeutic target for gastric cancer. - Highlights: • ArgBP2 inhibits proliferation, migration, and invasion of gastric cancer cells. • Identification of ArgBP2 promoter and its transcription factor MORC2. • EZH2 is required in MORC2 down-regulating ArgBP2 via histone methylation.

Microchidia protein 2, MORC2, downregulates the cytoskeleton adapter protein, ArgBP2, via histone methylation in gastric cancer cells

International Nuclear Information System (INIS)

Tong, Yuxin; Li, Yan; Gu, Hui; Wang, Chunyu; Liu, Funan; Shao, Yangguang; Li, Jiabin; Cao, Liu; Li, Feng

2015-01-01

ArgBP2 is an adapter protein that plays an important role in actin-dependent processes such as cell adhesion and migration. However, its function and regulation mechanisms in gastric cancer have not yet been investigated. Here, we showed the low expression of ArgBP2 mRNA level in gastric tumor samples and its repressive function in the proliferation, migration, and invasion of gastric cancer cells. Then, we cloned and identified ArgBP2 promoter and verified that MORC2 bound to the promoter. Moreover, we demonstrated that MORC2 enhanced the recruitment of EZH2, which promoted the tri-methylation of H3K27, leading to the transcriptional repression of ArgBP2. Our results might thus contribute to understanding the molecular mechanisms of ArgBP2 regulation and suggesting ArgBP2 as a potential therapeutic target for gastric cancer. - Highlights: • ArgBP2 inhibits proliferation, migration, and invasion of gastric cancer cells. • Identification of ArgBP2 promoter and its transcription factor MORC2. • EZH2 is required in MORC2 down-regulating ArgBP2 via histone methylation.

Development of LEU targets for 99Mo production and their chemical processing status 1989

International Nuclear Information System (INIS)

Vandegrift, G.F.; Kwok, J.D.; Chamberlain, D.B.; Hoh, J.C.; Streets, E.W.; Vogler, S.; Thresh, H.R.; Domagala, R.F.; Wiencek, T.C.; Matos, J.E.

1991-01-01

Most of the world's supply of Tc-99m for medical purposes is currently produced from Mo-99 derived from the fissioning of high enriched uranium (HEU). Substitution of low enriched uranium (LEU) silicide fuel for the HEU alloy and aluminide fuels used in current target designs will allow equivalent Mo-99 yields with no change in target geometries. Substitution of uranium metal will also allow the substitution of LEU for HEU. Efforts performed in 1989 focused on (1) fabrication of a uranium metal target by Hot Isostatic Pressing uranium metal foil to zirconium, (2) experimental investigation of the dissolution step for U 3 Si 2 targets, allowing us to present a conceptual design for the dissolution process and equipment, and (3) investigation of the procedures used to reclaim irradiated uranium from Mo-production targets, allowing us to further analyze the waste and by-product problems associated with the substitution of LEU for HEU. (orig.)

Quantitation of underivatized branched-chain amino acids in sport nutritional supplements by capillary electrophoresis with direct or indirect UV absorbance detection.

Science.gov (United States)

Qiu, Jun; Wang, Jinhao; Xu, Zhongqi; Liu, Huiqing; Ren, Jie

2017-01-01

The branched-chain amino acids (BCAAs) including leucine (Leu), isoleucine (Ile) and valine (Val) play a pivotal role in the human body. Herein, we developed capillary electrophoresis (CE) coupled with conventional UV detector to quantify underivatized BCAAs in two kinds of sport nutritional supplements. For direct UV detection at 195 nm, the BCAAs (Leu, two enantiomers of Ile and Val) were separated in a background electrolyte (BGE) consisting of 40.0 mmol/L sodium tetraborate, and 40.0 mmol/L β-cyclodextrin (β-CD) at pH 10.2. In addition, the indirect UV detection at 264 nm was achieved in a BGE of 2.0 mmol/L Na2HPO4, 10.0 mmol/L p-aminosalicylic acid (PAS) as UV absorbing probe, and 40.0 mmol/L β-CD at pH 12.2. The β-CD significantly benefited the isomeric separation of Leu, L- and D-Ile. The optimal conditions allowed the LODs (limit of detections) of direct and indirect UV absorption detection to be tens μmol/L level, which was comparable to the reported CE inline derivatization method. The RSDs (relative standard deviations) of migration time and peak area were less than 0.91% and 3.66% (n = 6). Finally, CE with indirect UV detection method was applied for the quantitation of BCAAs in two commercial sport nutritional supplements, and good recovery and precision were obtained. Such simple CE method without tedious derivatization process is feasible of quality control and efficacy evaluation of the supplemental proteins.

Quantitation of underivatized branched-chain amino acids in sport nutritional supplements by capillary electrophoresis with direct or indirect UV absorbance detection.

Directory of Open Access Journals (Sweden)

Jun Qiu

Full Text Available The branched-chain amino acids (BCAAs including leucine (Leu, isoleucine (Ile and valine (Val play a pivotal role in the human body. Herein, we developed capillary electrophoresis (CE coupled with conventional UV detector to quantify underivatized BCAAs in two kinds of sport nutritional supplements. For direct UV detection at 195 nm, the BCAAs (Leu, two enantiomers of Ile and Val were separated in a background electrolyte (BGE consisting of 40.0 mmol/L sodium tetraborate, and 40.0 mmol/L β-cyclodextrin (β-CD at pH 10.2. In addition, the indirect UV detection at 264 nm was achieved in a BGE of 2.0 mmol/L Na2HPO4, 10.0 mmol/L p-aminosalicylic acid (PAS as UV absorbing probe, and 40.0 mmol/L β-CD at pH 12.2. The β-CD significantly benefited the isomeric separation of Leu, L- and D-Ile. The optimal conditions allowed the LODs (limit of detections of direct and indirect UV absorption detection to be tens μmol/L level, which was comparable to the reported CE inline derivatization method. The RSDs (relative standard deviations of migration time and peak area were less than 0.91% and 3.66% (n = 6. Finally, CE with indirect UV detection method was applied for the quantitation of BCAAs in two commercial sport nutritional supplements, and good recovery and precision were obtained. Such simple CE method without tedious derivatization process is feasible of quality control and efficacy evaluation of the supplemental proteins.

Heat-transfer analysis of the existing HEU and proposed LEU cores of Pakistan research reactor

International Nuclear Information System (INIS)

Khan, L.A.; Nabbi, R.

1987-02-01

In connection with conversion of Pakistan Research Reactor (PARR) from the use of Highly Enriched Uranium (HEU) fuel to the use of Low Enriched Uranium (LEU) fuel, steady-state thermal hydraulic analysis of both existing HEU and proposed LEU cores has been carried out. Keeping in mind the possibility of power upgrading, the performance of proposed LEU core, under 10 MW operating conditions, has also been evaluated. Computer code HEATHYD has been used for this purpose. In order to verify the reliability of the code, IAEA benchmark 2 MW reactor was analyzed. The cooling parameters evaluated include: coolant velocity, critical velocity, pressure drop, temperature distribution in the core, heat fluxes at onset of nucleate boiling, flow instability and burnout and corresponding safety margins. From the results of the study it can be concluded that the conversion of the core to LEU fuel will result in higher safety margins, as compared to existing HEU core, mainly because the increased number of fuel plates in the proposed design will reduce the average heat flux significantly. Anyhow upgrading of the reactor power to 10 MW will need the flow rate to be adjusted between 850 to 900 m 3 /hr, to achieve reasonable safety margins, at least, comparable with the existing HEU core. (orig.)

A conversion development program to LEU targets for medical isotope production in the MAPLE Facilities

International Nuclear Information System (INIS)

Malkoske, G.R.

2000-01-01

Historically, the production of molybdenum-99 in the NRU research reactors at Chalk River, Canada has been extracted from reactor targets employing highly enriched uranium (HEU). The molybdenum extraction process from the HEU targets provided predictable, consistent yields for our high-volume molybdenum production process. A reliable supply of HEU for the NRU research reactor targets has enabled MDS Nordion to develop a secure chain of medical isotope supply for the international nuclear medicine community. Each link of the isotope supply chain, from isotope production to patient application, has been established on a proven method of HEU target irradiation and processing. To ensure a continued reliable and timely supply of medical isotopes, the design of the MAPLE facilities was based on our established process - extraction of isotopes from HEU target material. However, in concert with the global trend to utilize low enriched uranium (LEU) in research reactors, MDS Nordion has launched a program to convert the MAPLE facilities to LEU targets. An initial feasibility study was initiated to identify the technical issues to convert the MAPLE targets from HEU to LEU. This paper will present the results of the feasibility study. It will also describe future challenges and opportunities in converting the MAPLE facilities to LEU targets for large scale, commercial medical isotope production. (author)

Processing of LEU targets for 99Mo production--testing and modification of the Cintichem process

International Nuclear Information System (INIS)

Wu, D.; Landsberger, S.; Buchholz, B.

1995-09-01

Recent experimental results on testing and modification of the Cintichem process to allow substitution of low enriched uranium (LEU) for high enriched uranium (HEU) targets are presented in this report. The main focus is on 99 Mo recovery and purification by its precipitation with α-benzoin oxime. Parameters that were studied include concentrations of nitric and sulfuric acids, partial neutralization of the acids, molybdenum and uranium concentrations, and the ratio of α-benzoin oxime to molybdenum. Decontamination factors for uranium, neptunium, and various fission products were measured. Experiments with tracer levels of irradiated LEU were conducted for testing the 99 Mo recovery and purification during each step of the Cintichem process. Improving the process with additional processing steps was also attempted. The results indicate that the conversion of molybdenum chemical processing from HEU to LEU targets is possible

Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4.

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Byoung-Kuk Na

2010-10-01

Full Text Available Multiple cysteine proteases of malaria parasites are required for maintenance of parasite metabolic homeostasis and egress from the host erythrocyte. In Plasmodium falciparum these proteases appear to mediate the processing of hemoglobin and aspartic proteases (plasmepsins in the acidic food vacuole and the hydrolysis of erythrocyte structural proteins at neutral pH. Two cysteine proteases, vivapain (VX-2 and VX-3 have been characterized in P. vivax, but comprehensive studies of P. vivax cysteine proteases remain elusive.We characterized a novel cysteine protease of P. vivax, VX-4, of which orthologs appears to have evolved differentially in primate plasmodia with strong cladistic affinity toward those of rodent Plasmodium. Recombinant VX-4 demonstrated dual substrate specificity depending on the surrounding micro-environmental pH. Its hydrolyzing activity against benzyloxycarbonyl-Leu-Arg-4-methyl-coumaryl-7-amide (Z-Leu-Arg-MCA and Z-Phe-Arg-MCA was highest at acidic pH (5.5, whereas that against Z-Arg-Arg-MCA was maximal at neutral pH (6.5-7.5. VX-4 preferred positively charged amino acids and Gln at the P1 position, with less strict specificity at P3 and P4. P2 preferences depended on pH (Leu at pH 5.5 and Arg at pH 7.5. Three amino acids that delineate the S2 pocket were substituted in VX-4 compared to VX-2 and VX-3 (Ala90, Gly157 and Glu180. Replacement of Glu180 abolished activity against Z-Arg-Arg-MCA at neutral pH, indicating the importance of this amino acid in the pH-dependent substrate preference. VX-4 was localized in the food vacuoles and cytoplasm of the erythrocytic stage of P. vivax. VX-4 showed maximal activity against actin at neutral pH, and that against P. vivax plasmepsin 4 and hemoglobin was detected at neutral/acidic and acidic pH, respectively.VX-4 demonstrates pH-dependent substrate switching, which might offer an efficient mechanism for the specific cleavage of different substrates in different intracellular

HEU to LEU conversion experience at the UMass-Lowell research reactor

International Nuclear Information System (INIS)

White, John R.; Bobek, Leo M.

2005-01-01

The UMass-Lowell Research Reactor (UMLRR) operated safely with high-enriched uranium (HEU) fuel for over 25 years. Having reached the end of core lifetime and due to proliferation concerns, the reactor was recently converted to low-enriched uranium silicide (LEU) fuel. The actual process for converting the UMLRR from HEU to LEU fuel covered a period of over 15 years. The conversion effort - from the initial conceptual design studies in the late 1980s to the final offsite shipment of the spent HEU fuel in August 2004 - was a unique experience for the faculty and staff of a small university research reactor. This paper gives a historical view of the process and it highlights several key milestones along the road to successful completion of this project. (author)

The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

Science.gov (United States)

Ramos-Araque, Maria E; Rodriguez, Cristina; Vecino, Rebeca; Cortijo Garcia, Elisa; de Lera Alfonso, Mercedes; Sanchez Barba, Mercedes; Colàs-Campàs, Laura; Purroy, Francisco; Arenillas, Juan F; Almeida, Angeles; Delgado-Esteban, Maria

2018-04-23

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

Amino acid substitutions in the thymidine kinase gene of induced acyclovir-resistant herpes simplex virus type 1

Science.gov (United States)

Hussin, Ainulkhir; Nor, Norefrina Shafinaz Md; Ibrahim, Nazlina

2013-11-01

Acyclovir (ACV) is an antiviral drug of choice in healthcare setting to treat infections caused by herpes viruses, including, but not limited to genital herpes, cold sores, shingles and chicken pox. Acyclovir resistance has emerged significantly due to extensive use and misuse of this antiviral in human, especially in immunocompromised patients. However, it remains unclear about the amino acid substitutions in thymidine (TK) gene, which specifically confer the resistance-associated mutation in herpes simplex virus. Hence, acyclovir-resistant HSV-1 was selected at high concentration (2.0 - 4.5 μg/mL), and the TK-gene was subjected to sequencing and genotypic characterization. Genotypic sequences comparison was done using HSV-1 17 (GenBank Accesion no. X14112) for resistance-associated mutation determination whereas HSV-1 KOS, HSV-1 473/08 and HSV clinical isolates sequences were used for polymorphism-associated mutation. The result showed that amino acid substitutions at the non-conserved region (UKM-1: Gln34Lys, UKM-2: Arg32Ser & UKM-5: Arg32Cys) and ATP-binding site (UKM-3: Tyr53End & UKM-4: Ile54Leu) of the TK-gene. These discoveries play an important role to extend another dimension to the evolution of acyclovir-resistant HSV-1 and suggest that selection at high ACV concentration induced ACV-resistant HSV-1 evolution. These findings also expand the knowledge on the type of mutations among acyclovir-resistant HSV-1. In conclusion, HSV-1 showed multiple strategies to exhibit acyclovir resistance, including amino acid substitutions in the TK gene.

Cardiovascular and vasoconstrictive actions of skate bradykinin in the little skate, Leucoraja erinacea (Elasmobranchii).

Science.gov (United States)

Dasiewicz, Patricia J; Conlon, J Michael; Anderson, W Gary

2011-11-01

The vasoconstrictive and cardiovascular actions of a recently identified bradykinin (BK)-related peptide (Gly-Ile-Thr-Ser-Trp-Leu-Pro-Phe) from the little skate, Leucoraja erinacea were examined in the unanesthetised little skate. Intra-arterial administration of a skate BK (0.1-1 nmolkg(-1)) produced a hypertensive response with a rise in blood pressure reaching a maximum elevation of 28.7±4.8% over baseline (Pskate BK. Further, in vivo administration of 1 nmolkg(-1) skate BK induced a significant delayed increase in stroke volume (reaching a maximum of 54.4±14.7% above baseline) without significant effect on either cardiac output or heart rate. In vitro, skate BK constricted the 1st branchial, mesenteric (EC(50) 2.7×10(-9)M) and coeliac (EC(50) 3.1×10(-9)M) arterial preparations of the skate. In contrast, skate [Arg(9)]BK, the mammalian B(1) receptor agonist des-[Arg(9)]BK, and the mammalian B(2) receptor antagonist HOE-140 failed to induce vasoconstriction in these isolated arterial preparations. The vasoconstrictor actions of skate BK in the isolated mesenteric, coeliac and branchial arterial preparations were significantly inhibited when co-administrated with esculetin and phentolamine. Indomethacin also inhibited the vasoconstrictor actions of skate BK in the isolated branchial artery. We conclude that, as in mammals and teleost fish, multiple pathways involving at least the alpha adrenergic and leukotriene synthesis pathway are involved in mediating the vasoconstrictive actions of BK in vascular smooth muscle of the little skate. Copyright © 2011 Elsevier Inc. All rights reserved.

Eight novel F13A1 gene missense mutations in patients with mild FXIII deficiency: in silico analysis suggests changes in FXIII-A subunit structure/function.

Science.gov (United States)

Biswas, Arijit; Ivaskevicius, Vytautas; Thomas, Anne; Varvenne, Michael; Brand, Brigitte; Rott, Hannelore; Haussels, Iris; Ruehl, Heiko; Scholz, Ute; Klamroth, Robert; Oldenburg, Johannes

2014-10-01

Mild FXIII deficiency is an under-diagnosed disorder because the carriers of this deficiency are often asymptomatic and reveal a phenotype only under special circumstances like surgery or induced trauma. Mutational reports from this type of deficiency have been rare. In this study, we present the phenotypic and genotypic data of nine patients showing mild FXIII-A deficiency caused by eight novel heterozygous missense mutations (Pro166Leu, Arg171Gln, His342Tyr, Gln415Arg, Leu529Pro, Gln601Lys, Arg703Gln and Arg715Gly) in the F13A1 gene. None of these variants were seen in 200 healthy controls. In silico structural analysis of the local wild-type protein structures (activated and non-activated) from X-ray crystallographic models downloaded from the protein databank identified potential structural/functional effects for the identified mutations. The missense mutations in the core domain are suggested to be directly influencing the catalytic triad. Mutations on other domains might influence other critical factors such as activation peptide cleavage or the barrel domain integrity. In vitro expression and subsequent biochemical studies in the future will be able to confirm the pathophysiological mechanisms proposed for the mutations in this article.

As formações em bolas argênticas do sistema nervoso simpático

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José Fernandez

1957-09-01

Full Text Available Foram estudados, histològicamente, gânglios simpáticos provenientes de 40 pacientes portadores de enfermidades variadas e 40 gânglios tidos como normais, para pesquisar as formações cm bolas argênticas. As impregnações foram feitas pelos métodos de Cajal, Arteta, Castro, Gros, Bielschowsky e Agduhr. Foi verificado que a presença de bolas argênticas é mais constante nas doenças circulatórias periféricas; nestas afecções, foi verificada, também, a presença de um pigmento corável pelos tricrômios de Gomori e de Goldner e que, possìvelmente, tem o mesmo significado que os descritos por Fedorow 12 corados pelo vermelho neutro; tais pigmentos foram relacionados com as formações em bolas argênticas, levando em consideração os trabalhos experimentais dos autores da escola russa. A presença das formações em bolas argênticas, tanto nos casos normais como nos patológicos, é atribuída a uma hiperfunção, por excitação, do simpático, por serem mais numerosas nos casos de transtornos periféricos. Foi observado que os neurônios em íntimo contacto com as formações em bolas argênticas, apresentam sempre alterações que vão desde o grau mais leve (tumefação do soma celular, retificação dos prolongamentos, neurofibrilas mais fortemente impregnadas, até o mais grave (hiperplasia e hipertrofia dos dendritos, degeneração retrátil, degeneração pigmentar. Foi notado que as terminações das fibras pré-ganglionares e as próprias fibras apresentam, muitas vêzes, alterações (hipertrofia, sinuosidade e grande poder de impregnação; as bolas argênticas foram observadas tanto no final dos dendritos como no das fibras pré-ganglionares. Foram encontradas formações de bolas argênticas em rosário, concluindo-se que elas têm a mesma significação que as alterações claviformes. Conclui-se, finalmente, que as bolas argênticas são produtos patológicos.

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

Science.gov (United States)

Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

2006-07-01

Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

Status of LEU fuel development and conversion of NRU

International Nuclear Information System (INIS)

Sears, D.F.; Herbert, L.N.; Vaillancourt, K.D.

1991-01-01

This paper reviews the status of the LEU conversion program and the progress made in the fuel development program over the last year. The results from post-irradiation examinations of prototype NRU fuel rods containing Al-U 3 Si dispersion fuel, and of mini-elements containing Al-U 3 Si 2 dispersion fuel, are presented. (orig.)

Assessment Of School Library Services In Ile-Luji/Okeigbo Local ...

African Journals Online (AJOL)

The paper carried out the analysis of the library collection, staffing, building space and furniture of Ile-oluji/Okeigbo Local Government Area, Ondo State. The evaluation was based on the “Ondo State Library Board for Schools Standard”. Findings from the research showed that these school libraries were yet to achieve any ...

The LEU target development and conversion program for the MAPLE reactors and new processing facility

International Nuclear Information System (INIS)

Malkoske, G.R.

2002-01-01

Historically, the production of molybdenum-99 in the NRU research reactors at Chalk River, Canada has been extracted from reactor targets employing highly enriched uranium (HEU). A reliable supply of HEU metal from the United States used in the manufacture of targets for the NRU research reactor has been a key factor to enable MDS Nordion to develop a secure supply of medical isotopes for the international nuclear medicine community. The molybdenum extraction process from HEU targets provides predictable, consistent yields for our high-volume molybdenum production process. Each link of the isotope supply chain, from isotope production to ultimate use by the physician, has been established using this proven and established method of HEU target irradiation and processing to extract molybdenum-99. To ensure a continued reliable and timely supply of medical isotopes, MDS Nordion is completing the construction of two MAPLE reactors and a New Processing Facility. The design of the MAPLE facilities was based on an established process developed by Atomic Energy of Canada Ltd. (AECL) - extraction of isotopes from HEU target material. However, in concert with the global trend to utilize low enriched uranium (LEU) in research reactors, MDS Nordion has launched a three phase LEU Target Development and Conversion Program for the MAPLE facilities. Phase 1, the Initial Feasibility Study, which identified the technical issues to convert the MAPLE reactor targets from HEU to LEU for large scale commercial production was reported on at the RERTR- 2000 conference. The second phase of the LEU Target Development and Conversion Program was developed with extensive consultation and involvement of experts knowledgeable in target development, process system design, enriched uranium conversion chemistry and commercial scale reactor operations and molybdenum production. This paper will provide an overview of the Phase 2 Conversion Development Program, report on progress to date, and further

Human migration activities drive the fluctuation of ARGs : Case study of landfills in Nanjing, eastern China

OpenAIRE

Sun, Mingming; Ye, Mao; Schwab, Arthur P; Li, Xu; Wan, Jinzhong; Wei, Zhong; Wu, Jun; Friman, Ville-Petri; Liu, Kuan; Tian, Da; Liu, Manqiang; Li, Huixin; Hu, Feng; Jiang, Xin

2016-01-01

Landfills are perfect sites to study the effect of human migration on fluctuation of antibiotic resistance genes (ARGs) as they are the final destination of municipal waste. For example, large-scale human migration during the holidays is often accompanied by changes in waste dumping having potential effects on ARG abundance. Three landfills were selected to examine fluctuation in the abundance of fifteen ARGs and Intl1 genes for 14 months in Nanjing, eastern China. Mass human migration, the a...

Criticality Calculations of Fresh LEU and MOX Assemblies for Transport and Storage at the Balakovo Nuclear Power Plant

Energy Technology Data Exchange (ETDEWEB)

Goluoglu, S.

2001-01-11

Transportation of low-enriched uranium (LEU) and mixed-oxide (MOX) assemblies to and within the VVER-1000-type Balakovo Nuclear Power Plant is investigated. Effective multiplication factors for fresh fuel assemblies on the railroad platform, fresh fuel assemblies in the fuel transportation vehicle, and fresh fuel assemblies in the spent fuel storage pool are calculated. If there is no absorber between the units, the configurations with all MOX assemblies result in higher effective multiplication factors than the configurations with all LEU assemblies when the system is dry. When the system is flooded, the configurations with all LEU assemblies result in higher effective multiplication factors. For normal operating conditions, effective multiplication factors for all configurations are below the presumed upper subcritical limit of 0.95. For an accident condition of a fully loaded fuel transportation vehicle that is flooded with low-density water (possibly from a fire suppression system), the presumed upper subcritical limit is exceeded by configurations containing LEU assemblies.

Associations of Leu72Met Polymorphism of Preproghrelin with Ratios of Plasma Lipids Are Diversified by a High-Carbohydrate Diet in Healthy Chinese Adolescents.

Science.gov (United States)

Su, Mi; Qiu, Li; Wang, Qian; Jiang, Zhen; Liu, Xiao Juan; Lin, Jia; Fang, Ding Zhi

2015-01-01

The association of preproghrelin Leu72Met polymorphism with plasma lipids profile was inconsistently reported and needs more studies to be confirmed. Our study was to investigate the changes of plasma lipids ratios after a high-carbohydrate (high-CHO) diet in healthy Chinese adolescents with different genotypes of this polymorphism. Fifty-three healthy university students were given a washout diet of 54.1% carbohydrate for 7 days, followed by a high-CHO diet of 70.1% carbohydrate for 6 days. The anthropometric and biological parameters were analyzed at baseline and before and after the high-CHO diet. When compared with those before the high-CHO diet, body mass index (BMI) decreased in the male and female Met72 allele carriers. Decreased low-/high-density lipoprotein cholesterol (LDL-C/HDL-C) was observed in all participants except the female subjects with the Leu72Leu genotype. TG/HDL-C and log (TG/HDL-C) were increased only in the female subjects with the Leu72Leu genotype. These results suggest that the Met72 allele of preproghrelin Leu72Met polymorphism may be associated with decreased BMI induced by the high-CHO diet in male and female adolescents, while the Leu72 allele with increased TG/HDL-C and log (TG/HDL-C) in the female adolescents only. Furthermore, the decreasing effect of the high-CHO diet on LDL/HDL-C may be eliminated in the female Leu72Leu homozygotes. © 2015 S. Karger AG, Basel.

Fuel cycle flexibility in Advanced Heavy Water Reactor (AHWR) with the use of Th-LEU fuel

International Nuclear Information System (INIS)

Thakur, A.; Singh, B.; Pushpam, N.P.; Bharti, V.; Kannan, U.; Krishnani, P.D.; Sinha, R.K.

2011-01-01

The Advanced Heavy Water Reactor (AHWR) is being designed for large scale commercial utilization of thorium (Th) and integrated technological demonstration of the thorium cycle in India. The AHWR is a 920 MW(th), vertical pressure tube type cooled by boiling light water and moderated by heavy water. Heat removal through natural circulation and on-line fuelling are some of the salient features of AHWR design. The physics design of AHWR offers considerable flexibility to accommodate different kinds of fuel cycles. Our recent efforts have been directed towards a case study for the use of Th-LEU fuel cycle in a once-through mode. The discharged Uranium from Th-LEU cycle has proliferation resistant characteristics. This paper gives the initial core, fuel cycle characteristics and online refueling strategy of Th-LEU fuel in AHWR. (author)

Establishing a LEU MTR fuel manufacturing facility in South Africa

International Nuclear Information System (INIS)

Jamie, R.W.; Kocher, A.

2010-01-01

The South African MTR Fuel Manufacturing Facility was established in the 1970's to supply SAFARI-1 with Fuel Elements and Control Rods. South African capability was developed in parallel with the uranium enrichment program to meet the needs of the Reactor. Further to the July 2005 decision by the South African Governmnent to convert both SAFARI-1 and the Fuel Plant to LEU, the SAFARI-1 phase has been successfully completed and Necsa has commenced with the conversion of the MTR Fuel Manufacturing Facility. In order to establish, validate and qualify the facility, Necsa has entered into a co-operation and technology transfer agreement with AREVA CERCA, the French manufacturer of Research Reactor fuel elements. Past experiences, conversion challenges and the status of the MTR Fuel Facility Project are discussed. On-going co-operation with AREVA CERCA to implement the local manufacture of LEU fuel is explained and elaborated on. (author)

Tracking and Monitoring with Dosimeter-Enabled ARG-US RFID System - 12009

Energy Technology Data Exchange (ETDEWEB)

Anderson, J.; Lee, H.; De Lurgio, P.; Kearney, C.M.; Craig, B.; Soos, I.H.; Tsai, H.; Liu, Y. [Argonne National Laboratory, Argonne, IL 60439 (United States); Shuler, J. [U.S. Department of Energy, Washington, D.C. 20585 (United States)

2012-07-01

Automated monitoring and tracking of materials with radio frequency identification (RFID) technology can significantly improve both the operating efficiency of radiological facilities and the application of the ALARA (as low as reasonably achievable) principle in them. One such system, called ARG-US, has been developed by Argonne National Laboratory for the U.S. Department of Energy (DOE) Packaging and Certification Program to use in managing sensitive nuclear and radioactive materials. Several ARG-US systems are in various stages of deployment and advanced testing across DOE sites. ARG-US utilizes sensors in the tags to continuously monitor the state of health of the packaging and promptly disseminates alarms to authorized users. In conjunction with global positioning system (GPS) tracking provided by TRANSCOM, the system can also monitor and track packages during transport. A compact dosimeter has been incorporated in the ARG-US tags via an onboard universal asynchronous receiver/transmitter interface. The detector has a wide measurement range for gamma radiation - from 0.1 mSv/h to 8 Sv/h. The detector is able to generate alarms for both high and low radiation and for a high cumulative dose. In a large installation, strategically located dosimeter-enabled tags can yield an accurate, real-time, 2D or 3D dose field map that can be used to enhance facility safety, security, and safeguards. This implementation can also lead to a reduced need for manned surveillance and reduced exposure of personnel to radiation, consistent with the ALARA principle at workplaces. (authors)

Glucosinolate diversity within a phylogenetic framework of the tribe Cardamineae (Brassicaceae) unraveled with HPLC-MS/MS and NMR-based analytical distinction of 70 desulfoglucosinolates

DEFF Research Database (Denmark)

Olsen, Carl Erik; Huang, Xiao-Chen; Hansen, Cecilie Ida Cetti

2016-01-01

. This included glucosinolates apparently derived from Met, Phe, Trp, Val/Leu, Ile and higher homologues. Normal side chain elongation and side chain decoration by oxidation or methylation was observed, as well as rare abnormal side chain decoration (hydroxylation of aliphatics at the δ rather than β...

The Active Jasmonate JA-Ile Regulates a Specific Subset of Plant Jasmonate-Mediated Resistance to Herbivores in Nature

Directory of Open Access Journals (Sweden)

Meredith C. Schuman

2018-06-01

Full Text Available The jasmonate hormones are essential regulators of plant defense against herbivores and include several dozen derivatives of the oxylipin jasmonic acid (JA. Among these, the conjugate jasmonoyl isoleucine (JA-Ile has been shown to interact directly with the jasmonate co-receptor complex to regulate responses to jasmonate signaling. However, functional studies indicate that some aspects of jasmonate-mediated defense are not regulated by JA-Ile. Thus, it is not clear whether JA-Ile is best characterized as the master jasmonate regulator of defense, or if it regulates more specific aspects. We investigated possible functions of JA-Ile in anti-herbivore resistance of the wild tobacco Nicotiana attenuata, a model system for plant-herbivore interactions. We first analyzed the soluble and volatile secondary metabolomes of irJAR4xirJAR6, asLOX3, and WT plants, as well as an RNAi line targeting the jasmonate co-receptor CORONATINE INSENSITIVE 1 (irCOI1, following a standardized herbivory treatment. irJAR4xirJAR6 were the most similar to WT plants, having a ca. 60% overlap in differentially regulated metabolites with either asLOX3 or irCOI1. In contrast, while at least 25 volatiles differed between irCOI1 or asLOX3 and WT plants, there were few or no differences in herbivore-induced volatile emission between irJAR4xirJAR6 and WT plants, in glasshouse- or field-collected samples. We then measured the susceptibility of jasmonate-deficient vs. JA-Ile-deficient plants in nature, in comparison to wild-type (WT controls, and found that JA-Ile-deficient plants (irJAR4xirJAR6 are much better defended even than a mildly jasmonate-deficient line (asLOX3. The differences among lines could be attributed to differences in damage from specific herbivores, which appeared to prefer either one or the other jasmonate-deficient phenotype. We further investigated the elicitation of one herbivore-induced volatile known to be jasmonate-regulated and to mediate resistance to

Modeling and experimental assessment of a buried Leu–Ile mutation in dengue envelope domain III

Energy Technology Data Exchange (ETDEWEB)

Kulkarni, Manjiri R. [Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16, Nakamachi, Koganei-shi, Tokyo, 184-8588 (Japan); Numoto, Nobutaka; Ito, Nobutoshi [Department of Structural Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima Bunkyo-ku, Tokyo, 113-8510 (Japan); Kuroda, Yutaka, E-mail: ykuroda@cc.tuat.ac.jp [Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16, Nakamachi, Koganei-shi, Tokyo, 184-8588 (Japan)

2016-02-26

Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4-L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile{sup 387} conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype’s ED3 is used as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile{sup 387} confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4-L387I at 2 Å resolution. Ile{sup 387} indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task. - Highlights: • We mutated L387I of DEN4 ED3 and examined its effects on structure and stability. • We modeled the side-chain of Ile{sup 387} using DEN4 ED3's structure as a template. • We determined the crystal structure of DEN4-L387I and confirmed the modeling. • Side-chain repacking occurring around Ile{sup 387} involved >3 inter-connected residues. • These results explained why L387I mutation in DEN4 ED3 conserves thermostability.

Modeling and experimental assessment of a buried Leu–Ile mutation in dengue envelope domain III

International Nuclear Information System (INIS)

Kulkarni, Manjiri R.; Numoto, Nobutaka; Ito, Nobutoshi; Kuroda, Yutaka

2016-01-01

Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4-L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile"3"8"7 conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype’s ED3 is used as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile"3"8"7 confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4-L387I at 2 Å resolution. Ile"3"8"7 indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task. - Highlights: • We mutated L387I of DEN4 ED3 and examined its effects on structure and stability. • We modeled the side-chain of Ile"3"8"7 using DEN4 ED3's structure as a template. • We determined the crystal structure of DEN4-L387I and confirmed the modeling. • Side-chain repacking occurring around Ile"3"8"7 involved >3 inter-connected residues. • These results explained why L387I mutation in DEN4 ED3 conserves thermostability.

Feasibility study for LEU conversion of the WWR-K reactor at the Institute of Nuclear Physics in Kazakhstan using a 5-tube fuel assembly

International Nuclear Information System (INIS)

Hanan, N.A.; Liaw, J.R.; Matos, J.E.

2005-01-01

A feasibility study by the RERTR program for possible LEU conversion of the 6 MW WWR-K reactor concludes that conversion is feasible using an LEU 5-tube Russian fuel assembly design. This 5-tube design is one of several LEU fuel assembly designs being studied (Ref. 1) for possible use in this reactor. The 5-tube assembly contains 200 g 235 U with an enrichment of 19.7% in four cylindrical inner tubes and an outer hexagonal tube with the same external dimensions as the current HEU (36%) 5-tube fuel assembly, which contains 112.5 g 235 U. The fuel meat material, LEU UO 2 -Al dispersion fuel with ∼ 2.5 g U/cm 3 , has been extensively irradiation tested in a number of reactors with uranium enrichments of 36% and 19.7%. Since the 235 U loading of the LEU assemblies is much larger than the HEU assemblies, a smaller LEU core with five rows of fuel assemblies is possible (instead of six rows of fuel assemblies in the HEU core). This smaller LEU core would consume about 60% as many fuel assemblies per year as the current HEU core and provide thermal neutron fluxes in the inner irradiation channels that are ∼ 17% larger than with the present HEU core. The current 21 day cycle length would be maintained and the average discharge burnup would be ∼ 42%. Neutron fluxes in the five outer irradiation channels would be smaller in the LEU core unless these channels can be moved closer to the LEU fuel assemblies. Results show that the smaller LEU core would meet the reactor's shutdown margin requirements and would have an adequate thermal-hydraulic safety margin to onset of nucleate boiling. (author)

Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in Ureaplasma species.

Science.gov (United States)

Song, Jingjuan; Qiao, Yingli; Kong, Yingying; Ruan, Zhi; Huang, Jun; Song, Tiejun; Zhang, Jun; Xie, Xinyou

2015-11-01

This study aimed to investigate the role of quinolone resistance-determining regions (QRDRs) of DNA gyrase (encoded by gyrA and gyrB) and topoisomerase IV (encoded by parC and parE) associated with fluoroquinolone resistance. A total of 114 Ureaplasma spp. strains, isolated from clinical female patients with symptomatic infection, were tested for species distribution and susceptibility to four fluoroquinolones. Moreover, we analysed the QRDRs and compared these with 14 ATCC reference strains of Ureaplasma spp. serovars to identify mutations that caused antimicrobial resistance. Our study indicated that moxifloxacin was the most effective fluoroquinolone against Ureaplasma spp. (MIC range: 0.125-32 μg ml⁻¹). However, extremely high MICs were estimated for ciprofloxacin (MIC range: 1-256 μg ml⁻¹) and ofloxacin (MIC range: 0.5-128 μg ml⁻¹), followed by levofloxacin (MIC range: 0.5-64 μg ml⁻¹). Seven amino acid substitutions were discovered in GyrB, ParC and ParE, but not in GyrA. Ser-83 → Leu/Trp (C248T/G) in ParC and Arg-448 → Lys (G1343A) in ParE, which were potentially responsible for fluoroquinolone resistance, were observed in 89 (77.2 %) and three (2.6 %) strains, respectively. Pro-462 → Ser (C1384T), Asn-481 → Ser (A1442G) and Ala-493 → Val (C1478T) in GyrB and Met-105 → Ile (G315T) in ParC seemed to be neutral polymorphisms, and were observed and occurred along with the amino acid change of Ser-83 → Leu (C248T) in ParC. Interestingly, two novel mutations of ParC and ParE were independently found in four strains. These observations suggest that amino acid mutation in topoisomerase IV appears to be the leading cause of fluoroquinolone resistance, especially the mutation of Ser-83 → Leu (C248T) in ParC. Moxifloxacin had the best activity against strains with Ser-83 → Leu mutation.

Phosphorylation-induced conformational changes in short peptides probed by fluorescence resonance energy transfer in the 10A domain.

Science.gov (United States)

Sahoo, Harekrushna; Nau, Werner M

2007-03-26

Phosphorylation-induced conformational changes in short polypeptides were probed by a fluorescence resonance energy transfer (FRET) method by employing a short-distance FRET pair (R(0) approximately 10 A) based on tryptophan as natural donor and a 2,3-diazabicyclo[2.2.2]oct-2-ene-labeled asparagine (Dbo) as synthetic acceptor. Two substrates for kinases, LeuArgArgTrpSerLeuGly-Dbo (peptide I) and TrpLysArgThrLeuArgArg-Dbo (peptide II), were investigated, with serine and threonine, respectively, as phosphorylation sites. Steady-state and time-resolved fluorescence experiments in H(2)O revealed a decrease in FRET efficiency for peptide I and an increase for peptide II; this suggested that the effective distances between donor and acceptor increased and decreased, respectively. The same trends and similar absolute variations in effective donor-acceptor distances were observed in propylene glycol, a less polar and highly viscous solvent; this suggested that the variations are due to intrinsic structural preferences. Fitting of the time-resolved decay traces according to a distribution function model (Gaussian distribution) provided the mean donor-acceptor distances, which showed an increase upon phosphorylation for peptide I (from 9.7 to 10.5 A) and a decrease for peptide II (from 10.9 to 9.3 A) in H(2)O. The broadness (half-width) of the distributions, which provides a measure of the rigidity of the peptides, remained similar upon phosphorylation of peptide I (3.0 versus 3.1 A), but decreased for peptide II (from 3.1 to 0.73 A in H(2)O); this suggests a more compact, structured conformation upon phosphorylation of the latter peptide. The elongation of the peptide backbone (by ca. 0.7 A) for peptide I is attributed to an increase in steric demand upon phosphorylation, which favors an extended conformation. The contraction (by ca. 1.4 A) and structural rigidification of peptide II is attributed to attractive Coulombic interactions and hydrogen bonding between the

Analytical analyses of startup measurements associated with the first use of LEU fuel in Romania's 14-MW TRIGA reactor

International Nuclear Information System (INIS)

Bretscher, M.M.; Snelgrove, J.L.; Ciocanescu, M.

1992-01-01

The 14-MW TRIGA steady state reactor (SSR) is located in Pitesti, Romania. Beginning with an HEU core (10 wt% U), the reactor first went critical in November 1979 but was shut down ten years later because of insufficient excess reactivity. Last November the Institute for Nuclear Research (INR), which operates the SSR, received from the ANL RERTR program a shipment of 125 LEU pins fabricated by General Atomics and of the same geometry as the original fuel but with an enrichment of 19.7% 235U and a loading of 45 wt% U. Using 100 of these pins, four LEU clusters, each containing a 5 x 5 square array of fuel rods, were assembled. These four LEU clusters replaced the four most highly burned HEU elements in the SSR. The reactor resumed operations last February with a 35-element mixed HEU/LEU core configuration. In preparation for full power operation of the SSR with this mixed HEU/LEU core, a number of measurements were made. These included control rod calibrations, excess reactivity determinations, worths of experiment facilities, reaction rate distributions, and themocouple measurements of fuel temperatures as a function of reactor power. This paper deals with a comparison of some of these measured reactor parameters with corresponding analytical calculations

Kültür ve Sanat Ekonomisi Kapsamında Talep Analizleri Yardımı ile Kültür Politikasına Teorik Yaklaşım: Türkiye Örneği

Directory of Open Access Journals (Sweden)

Duygu BÜYÜKYAZICI

2016-08-01

Full Text Available Kültür-sanat ekonomisinin bağımsız bir disiplin olarak ortaya çıkmasını sağlayantemel tez, devletin sanatı desteklemesi gerektiği önermesidir. Gösteri sanatı formlarınıniktisadi araçlarla incelenmesi sonucunda ortaya konan maliyet hastalığı argümanı, devletsanatları desteklemezse sanatların yok olacağı öngörüsünü içerir. Söz konusu analizlerdenönce devlet-sanat ilişkisi farklı disiplinlerin gözlem alanında iken, bu değişkenlerin yanınaekonomi teriminin eklenmesi tartışmaları bilimsel zemine çekmiş ve engin incelemeleriberaberinde getirmiştir. Devletin finansal ve kurumsal anlamda sanatı desteklemesi politikayapıcıların nezdinde erdemli mallar varsayımı ile gerçekleşirken, literatürdekitemellendirmeler büyük ölçüde piyasa başarısızlıkları ekseninde olmuş ve maliyet hastalığıargümanı çürütülmüştür. Devletin sanatı destekleme formu ve miktarına yönelik tercihlerkültür politikasının önemli payını oluştururken, söz konusu politikaların edinilmiş başarısıancak talep analizleri ile tartılabilir. Türkiye’nin kültür politikasına hem teorik biryaklaşımda bulunmayı hem de ulaşılmış başarısını araştırmayı amaçlayan buçalışmada, kültür-sanat ekonomisindeki mikroekonomik talep analizlerinden yola çıkarak,talep profilinin kültür politikasındaki önemi vurgulanmakta ve devletin kültür-sanata olandesteği kadar biçiminin öneminin de altı çizilmektedir. Talep analizlerinin gelişmesidoğrultusunda, talebin profiline yönelik farklı kültür politikaları gerekecek, kültür-sanatayönelik çoğunlukla yetersiz veri ve analiz ile tespit edilen destek, üretim vesübvansiyonların içerik ve miktarı farklılaşarak optimal düzeye yakınsanacaktır. Piyasabaşarısızlıklar da kültür politikasının temellendiği teorik faz olarak analize eklenmiş, pozitifdışsallıklar özelinde devletin sanatı desteklemesinin sebepleri

LEU-fueled SLOWPOKE-2 modelling with MCNP4A

International Nuclear Information System (INIS)

Pierre, J.R.M.; Bonin, H.W.J.

1996-01-01

Following the commissioning of the Low Enrichment Uranium (LEU) Fueled SLOWPOKE-2 research reactor at Royal Military College,excess reactivity measurements were conducted over a range of temperature and power. Given the advance in computer technology, the use of Monte Carlo N-Particle Transport Code System MCNP 4A appeared possible for the simulation of the LEU-fueled SLOWPOKE-2 reactor core, and this work demonstrates that this is indeed the case. MCNP 4A is a full three dimensional program allowing the user to enter a large amount of complexity. The limit on the geometry complexity is the computing time required to achieve a reasonable standard deviation. To this point several models of the SLOWPOKE-2 have been developed giving some insight on the sensitivity of the code. MCNP4A can use various cross section libraries. The aim of this work is to calculate accurately the reactivity of the core and reproduce The temperature trend of the reactivity. The model preserved as much as possible the details of the core and facility in order to allow further study in the flux mapping

ArgR of Streptomyces coelicolor Is a Pleiotropic Transcriptional Regulator: Effect on the Transcriptome, Antibiotic Production, and Differentiation in Liquid Cultures

Science.gov (United States)

Botas, Alma; Pérez-Redondo, Rosario; Rodríguez-García, Antonio; Álvarez-Álvarez, Rubén; Yagüe, Paula; Manteca, Angel; Liras, Paloma

2018-01-01

ArgR is a well-characterized transcriptional repressor controlling the expression of arginine and pyrimidine biosynthetic genes in bacteria. In this work, the biological role of Streptomyces coelicolor ArgR was analyzed by comparing the transcriptomes of S. coelicolor ΔargR and its parental strain, S. coelicolor M145, at five different times over a 66-h period. The effect of S. coelicolor ArgR was more widespread than that of the orthologous protein of Escherichia coli, affecting the expression of 1544 genes along the microarray time series. This S. coelicolor regulator repressed the expression of arginine and pyrimidine biosynthetic genes, but it also modulated the expression of genes not previously described to be regulated by ArgR: genes involved in nitrogen metabolism and nitrate utilization; the act, red, and cpk genes for antibiotic production; genes for the synthesis of the osmotic stress protector ectoine; genes related to hydrophobic cover formation and sporulation (chaplins, rodlins, ramR, and whi genes); all the cwg genes encoding proteins for glycan cell wall biosynthesis; and genes involved in gas vesicle formation. Many of these genes contain ARG boxes for ArgR binding. ArgR binding to seven new ARG boxes, located upstream or near the ectA-ectB, afsS, afsR, glnR, and redH genes, was tested by DNA band-shift assays. These data and those of previously assayed fragments permitted the construction of an improved model of the ArgR binding site. Interestingly, the overexpression of sporulation genes observed in the ΔargR mutant in our culture conditions correlated with a sporulation-like process, an uncommon phenotype. PMID:29545785

Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer.

Directory of Open Access Journals (Sweden)

Rakhshan Ihsan

Full Text Available Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR, classification and regression tree (CART and multifactor dimensionality reduction (MDR, was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11-2.59,p = 0.01, whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25-0.65,p<0.001 and OR = 0.51;95%CI = 0.33-0.78,p = 0.002 respectively. In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His, SULT1A1 213GG (Arg/Arg or AA (His/His and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33-10.55,p = 0.006, whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15-7.51,p = 0.01. MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His with testing balance accuracy (TBA of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with

A novel FKRP-related muscular dystrophy founder mutation in South ...

African Journals Online (AJOL)

porphyria variegata, familial hypercholesterolaemia, Gaucher's dis- ease and autosomal recessive polycystic kidney disease.[7-11]. FKRP founder mutations have been described in a number of populations around the world, for example the c.826C>A. (p.Leu276Ile) FKRP mutation in 20 LGMD German patients[12].

Kinetic proofreading at single molecular level: aminoacylation of tRNA(Ile and the role of water as an editor.

Directory of Open Access Journals (Sweden)

Mantu Santra

Full Text Available Proofreading/editing in protein synthesis is essential for accurate translation of information from the genetic code. In this article we present a theoretical investigation of efficiency of a kinetic proofreading mechanism that employs hydrolysis of the wrong substrate as the discriminatory step in enzyme catalytic reactions. We consider aminoacylation of tRNA(Ile which is a crucial step in protein synthesis and for which experimental results are now available. We present an augmented kinetic scheme and then employ methods of stochastic simulation algorithm to obtain time dependent concentrations of different substances involved in the reaction and their rates of formation. We obtain the rates of product formation and ATP hydrolysis for both correct and wrong substrates (isoleucine and valine in our case, respectively, in single molecular enzyme as well as ensemble enzyme kinetics. The present theoretical scheme correctly reproduces (i the amplitude of the discrimination factor in the overall rates between isoleucine and valine which is obtained as (1.8×10(2.(4.33×10(2 = 7.8×10(4, (ii the rates of ATP hydrolysis for both Ile and Val at different substrate concentrations in the aminoacylation of tRNA(Ile. The present study shows a non-michaelis type dependence of rate of reaction on tRNA(Ile concentration in case of valine. The overall editing in steady state is found to be independent of amino acid concentration. Interestingly, the computed ATP hydrolysis rate for valine at high substrate concentration is same as the rate of formation of Ile-tRNA(Ile whereas at intermediate substrate concentration the ATP hydrolysis rate is relatively low. We find that the presence of additional editing domain in class I editing enzyme makes the kinetic proofreading more efficient through enhanced hydrolysis of wrong product at the editing CP1 domain.

Structural, Functional, and Clinical Characterization of a Novel PTPN11 Mutation Cluster Underlying Noonan Syndrome.

Science.gov (United States)

Pannone, Luca; Bocchinfuso, Gianfranco; Flex, Elisabetta; Rossi, Cesare; Baldassarre, Giuseppina; Lissewski, Christina; Pantaleoni, Francesca; Consoli, Federica; Lepri, Francesca; Magliozzi, Monia; Anselmi, Massimiliano; Delle Vigne, Silvia; Sorge, Giovanni; Karaer, Kadri; Cuturilo, Goran; Sartorio, Alessandro; Tinschert, Sigrid; Accadia, Maria; Digilio, Maria C; Zampino, Giuseppe; De Luca, Alessandro; Cavé, Hélène; Zenker, Martin; Gelb, Bruce D; Dallapiccola, Bruno; Stella, Lorenzo; Ferrero, Giovanni B; Martinelli, Simone; Tartaglia, Marco

2017-04-01

Germline mutations in PTPN11, the gene encoding the Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on the identification of five different PTPN11 missense changes affecting residues Leu 261 , Leu 262 , and Arg 265 in 16 unrelated individuals with clinical diagnosis of NS or with features suggestive for this disorder, specifying a novel disease-causing mutation cluster. Expression of the mutant proteins in HEK293T cells documented their activating role on MAPK signaling. Structural data predicted a gain-of-function role of substitutions at residues Leu 262 and Arg 265 exerted by disruption of the N-SH2/PTP autoinhibitory interaction. Molecular dynamics simulations suggested a more complex behavior for changes affecting Leu 261 , with possible impact on SHP2's catalytic activity/selectivity and proper interaction of the PTP domain with the regulatory SH2 domains. Consistent with that, biochemical data indicated that substitutions at codons 262 and 265 increased the catalytic activity of the phosphatase, while those affecting codon 261 were only moderately activating but impacted substrate specificity. Remarkably, these mutations underlie a relatively mild form of NS characterized by low prevalence of cardiac defects, short stature, and cognitive and behavioral issues, as well as less evident typical facial features. © 2017 WILEY PERIODICALS, INC.

Novel nucleotide and amino acid covariation between the 5'UTR and the NS2/NS3 proteins of hepatitis C virus: bioinformatic and functional analyses.

Directory of Open Access Journals (Sweden)

Hung-Yu Sun

Full Text Available Molecular covariation of highly polymorphic viruses is thought to have crucial effects on viral replication and fitness. This study employs association rule data mining of hepatitis C virus (HCV sequences to search for specific evolutionary covariation and then tests functional relevance on HCV replication. Data mining is performed between nucleotides in the untranslated regions 5' and 3'UTR, and the amino acid residues in the non-structural proteins NS2, NS3 and NS5B. Results indicate covariance of the 243(rd nucleotide of the 5'UTR with the 14(th, 41(st, 76(th, 110(th, 211(th and 212(th residues of NS2 and with the 71(st, 175(th and 621(st residues of NS3. Real-time experiments using an HCV subgenomic system to quantify viral replication confirm replication regulation for each covariant pair between 5'UTR₂₄₃ and NS2-41, -76, -110, -211, and NS3-71, -175. The HCV subgenomic system with/without the NS2 region shows that regulatory effects vanish without NS2, so replicative modulation mediated by HCV 5'UTR₂₄₃ depends on NS2. Strong binding of the NS2 variants to HCV RNA correlates with reduced HCV replication whereas weak binding correlates with restoration of HCV replication efficiency, as determined by RNA-protein immunoprecipitation assay band intensity. The dominant haplotype 5'UTR₂₄₃-NS2-41-76-110-211-NS3-71-175 differs according to the HCV genotype: G-Ile-Ile-Ile-Gly-Ile-Met for genotype 1b and A-Leu-Val-Leu-Ser-Val-Leu for genotypes 1a, 2a and 2b. In conclusion, 5'UTR₂₄₃ co-varies with specific NS2/3 protein amino acid residues, which may have significant structural and functional consequences for HCV replication. This unreported mechanism involving HCV replication possibly can be exploited in the development of advanced anti-HCV medication.

Greek research reactor performance characteristics after addition of beryllium reflector and LEU fuel

International Nuclear Information System (INIS)

Deen, J.R.; Snelgrove, J.L.; Papastergiou, C.

1992-01-01

The GRR-1 is a 5-MW pool-type, light-water-moderated and-cooled reactor fueled with MTR-type fuel elements. Recently received Be reflector blocks will soon be added to the core to add additional reactivity until fresh LEU fuel arrives. REBUS-3 xy fuel cycle analyses, using burnup dependent cross sections, were performed to assist in fuel management decisions for the water- and Be-reflected HEU nonequilibrium cores. Cross sections generated by EPRI-CELL have been benchmarked to identical VIM Monte Carlo models. The size of the Be-reflected LEU core has been reduced to 30 elements compared to 35 for the HEU water-reflected core, and an equilibrium cycle calculation has been performed

One adenosine deaminase allele in a patient with severe combined immunodeficiency contains a point mutation abolishing enzyme activity.

OpenAIRE

Valerio, D; Dekker, B M; Duyvesteyn, M G; van der Voorn, L; Berkvens, T M; van Ormondt, H; van der Eb, A J

1986-01-01

We have cloned and sequenced an adenosine deaminase (ADA) gene from a patient with severe combined immunodeficiency (SCID) caused by inherited ADA deficiency. Two point mutations were found, resulting in amino acid substitutions at positions 80 (Lys to Arg) and 304 (Leu to Arg) of the protein. Hybridization experiments with synthetic oligonucleotide probes showed that the determined mutations are present in both DNA and RNA from the ADA-SCID patient. In addition, wild-type sequences could be ...

Fuel element burnup determination in HEU-LEU mixed TRIGA research reactor core

International Nuclear Information System (INIS)

Zagar, Tomaz; Ravnik, Matjaz

2000-01-01

This paper presents the results of a burnup calculations and burnup measurements for TRIGA FLIP HEU fuel elements and standard TRIGA LEU fuel elements used simultaneously in small TRIGA Mark II research reactor in Ljubljana, Slovenija. The fuel element burnup for approximately 15 years of operation was calculated with two different in house computer codes TRIGAP and TRIGLAV (both codes are available at OECD NEA Data Bank). The calculation is performed in one-dimensional radial geometry in TRIGAP and in two-dimensional (r,φ) geometry in TRIGLAV. Inter-comparison of results shows important influence of in-core water gaps, irradiation channels and mixed rings on burnup calculation accuracy. Burnup of 5 HEU and 27 LEU fuel elements was also measured with reactivity method. Measured and calculated burnup values are inter-compared for these elements (author)

Trafalgar Square'ile järjekordne teos valitud / Rael Artel

Index Scriptorium Estoniae

Artel, Rael, 1980-

2004-01-01

Järgmisel kevadel paigaldatakse Trafalgar Square'ile 18 kuuks Marc Quinni 4,5 m kõrgune valgest marmorist kuju "Alison Lapper Pregnant". A. Lapper (sünd. 1965) on raske füüsilise väärarenguga kunstnik. Seejärel paigaldatakse väljakule teine finaali jõudnud skulptuur - sakslase Thomas Schütte'i "Hotel for the Birds"

First inventory of the echinoderms from Juan de Nova (Iles Eparses ...

African Journals Online (AJOL)

Juan de Nova is one of the Iles Eparses, French islands scattered in the Mozambique Channel (Western India Ocean). They have been kept isolated of the anthropogenic influences which makes them rare areas to study biodiversity and provides elements of comparison with areas that are strongly impacted by urbanization ...

Waste Treatment of Acidic Solutions from the Dissolution of Irradiated LEU Targets for 99-Mo Production

Energy Technology Data Exchange (ETDEWEB)

Bakel, Allen J. [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Conner, Cliff [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Quigley, Kevin [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Vandegrift, George F. [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division

2016-10-01

One of the missions of the Reduced Enrichment for Research and Test Reactors (RERTR) program (and now the National Nuclear Security Administrations Material Management and Minimization program) is to facilitate the use of low enriched uranium (LEU) targets for ⁹⁹Mo production. The conversion from highly enriched uranium (HEU) to LEU targets will require five to six times more uranium to produce an equivalent amount of ⁹⁹Mo. The work discussed here addresses the technical challenges encountered in the treatment of uranyl nitrate hexahydrate (UNH)/nitric acid solutions remaining after the dissolution of LEU targets. Specifically, the focus of this work is the calcination of the uranium waste from ⁹⁹Mo production using LEU foil targets and the Modified Cintichem Process. Work with our calciner system showed that high furnace temperature, a large vent tube, and a mechanical shield are beneficial for calciner operation. One- and two-step direct calcination processes were evaluated. The high-temperature one-step process led to contamination of the calciner system. The two-step direct calcination process operated stably and resulted in a relatively large amount of material in the calciner cup. Chemically assisted calcination using peroxide was rejected for further work due to the difficulty in handling the products. Chemically assisted calcination using formic acid was rejected due to unstable operation. Chemically assisted calcination using oxalic acid was recommended, although a better understanding of its chemistry is needed. Overall, this work showed that the two-step direct calcination and the in-cup oxalic acid processes are the best approaches for the treatment of the UNH/nitric acid waste solutions remaining from dissolution of LEU targets for ⁹⁹Mo production.

Meta-analyses of KIF6 Trp719Arg in coronary heart disease and statin therapeutic effect.

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Ping Peng

Full Text Available The goal of our study is to assess the contribution of KIF6 Trp719Arg to both the risk of CHD and the efficacy of statin therapy in CHD patients.Meta-analysis of 8 prospective studies among 77,400 Caucasians provides evidence that 719Arg increases the risk of CHD (P<0.001, HR = 1.27, 95% CI = 1.15-1.41. However, another meta-analysis of 7 case-control studies among 65,200 individuals fails to find a significant relationship between Trp719Arg and the risk of CHD (P = 0.642, OR = 1.02, 95% CI = 0.95-1.08. This suggests that the contribution of Trp719Arg to CHD varies in different ethnic groups. Additional meta-analysis also shows that statin therapy only benefit the vascular patients carry 719Arg allele (P<0.001, relative ratio (RR = 0.60, 95% CI = 0.54-0.67. To examine the role of this genetic variant in CHD risk in Han Chinese, we have conducted a case-control study with 289 CHD cases, 193 non-CHD controls, and 329 unrelated healthy volunteers as healthy controls. On post hoc analysis, significant allele frequency difference of 719Arg is observed between female CHD cases and female total controls under the dominant model (P = 0.04, χ(2 = 4.228, df = 1, odd ratio (OR = 1.979, 95% confidence interval (CI = 1.023-3.828. Similar trends are observed for post hoc analysis between female CHD cases and female healthy controls (dominant model: P = 0.04, χ(2 = 4.231, df = 1, OR = 2.015, 95% CI = 1.024-3.964. Non-genetic CHD risk factors are not controlled in these analyses.Our meta-analysis demonstrates the role of Trp719Arg of KIF6 gene in the risk of CHD in Caucasians. The meta-analysis also suggests the role of this variant in statin therapeutic response in vascular diseases. Our case-control study suggests that Trp719Arg of KIF6 gene is associated with CHD in female Han Chinese through a post hoc analysis.

Facility safeguards at an LEU fuel fabrication facility in Japan

International Nuclear Information System (INIS)

Kuroi, H.; Osabe, T.

1984-01-01

A facility description of a Japanese LEU BWR-type fuel fabrication plant focusing on safeguards viewpoints is presented. Procedures and practices of MC and A plan, measurement program, inventory taking, and the report and record system are described. Procedures and practices of safeguards inspection are discussed and lessons learned from past experiences are reviewed

Fission product release from TRIGA-LEU reactor fuels

International Nuclear Information System (INIS)

Baldwin, N.L.; Foushee, F.C.; Greenwood, J.S.

1980-01-01

Due to present international concerns over nuclear proliferation, TRIGA reactor fuels will utilize only low-enriched uranium (LEU) (enrichment <20%). This requires increased total uranium loading per unit volume of fuel in order to maintain the appropriate fissile loading. Tests were conducted to determine the fractional release of gaseous and metallic fission products from typical uranium-zirconium hydride TRIGA fuels containing up to 45 wt-% uranium. These tests, performed in late 1977 and early 1978, were similar to those conducted earlier on TRIGA fuels with 8.5 wt-% U. Fission gas release measurements were made on prototypic specimens from room temperature to 1100 deg. C in the TRIGA King Furnace Facility. The fuel specimens were irradiated in the TRIGA reactor at a low power level. The fractional releases of the gaseous nuclides of krypton and xenon were measured under steady-state operating conditions. Clean helium was used to sweep the fission gases released during irradiation from the furnace into a standard gas collection trap for gamma counting. The results of these tests on TRIGA-LEU fuel agree well with data from the similar, earlier tests on TRIGA fuel. The correlation used to calculate the release of fission products from 8.5 wt-% U TRIGA fuel applies equally well for U contents up to 45 wt-%. (author)

ARG1 Functions in the Physiological Adaptation of Undifferentiated Plant Cells to Spaceflight

Science.gov (United States)

Zupanska, Agata K.; Schultz, Eric R.; Yao, JiQiang; Sng, Natasha J.; Zhou, Mingqi; Callaham, Jordan B.; Ferl, Robert J.; Paul, Anna-Lisa

2017-11-01

Scientific access to spaceflight and especially the International Space Station has revealed that physiological adaptation to spaceflight is accompanied or enabled by changes in gene expression that significantly alter the transcriptome of cells in spaceflight. A wide range of experiments have shown that plant physiological adaptation to spaceflight involves gene expression changes that alter cell wall and other metabolisms. However, while transcriptome profiling aptly illuminates changes in gene expression that accompany spaceflight adaptation, mutation analysis is required to illuminate key elements required for that adaptation. Here we report how transcriptome profiling was used to gain insight into the spaceflight adaptation role of Altered response to gravity 1 (Arg1), a gene known to affect gravity responses in plants on Earth. The study compared expression profiles of cultured lines of Arabidopsis thaliana derived from wild-type (WT) cultivar Col-0 to profiles from a knock-out line deficient in the gene encoding ARG1 (ARG1 KO), both on the ground and in space. The cell lines were launched on SpaceX CRS-2 as part of the Cellular Expression Logic (CEL) experiment of the BRIC-17 spaceflight mission. The cultured cell lines were grown within 60 mm Petri plates in Petri Dish Fixation Units (PDFUs) that were housed within the Biological Research In Canisters (BRIC) hardware. Spaceflight samples were fixed on orbit. Differentially expressed genes were identified between the two environments (spaceflight and comparable ground controls) and the two genotypes (WT and ARG1 KO). Each genotype engaged unique genes during physiological adaptation to the spaceflight environment, with little overlap. Most of the genes altered in expression in spaceflight in WT cells were found to be Arg1-dependent, suggesting a major role for that gene in the physiological adaptation of undifferentiated cells to spaceflight.

Purification and partial characterization of Phaseolus vulgaris seed aminopeptidase

Directory of Open Access Journals (Sweden)

Abdala A.P.

1999-01-01

Full Text Available The aminopeptidase activity of Phaseolus vulgaris seeds was measured using L-Leu-p-nitroanilide and the L-aminoacyl-ß-naphthylamides of Leu, Ala, Arg and Met. A single peak of aminopeptidase activity on Leu-ß-naphthylamide was eluted at 750 µS after gradient elution chromatography on DEAE-cellulose of the supernatant of a crude seed extract. The effluent containing enzyme activity was applied to a Superdex 200 column and only one peak of aminopeptidase activity was obtained. SDS-polyacrylamide gel electrophoresis (10% presented only one protein band with molecular mass of 31 kDa under reducing and nonreducing conditions. The aminopeptidase has an optimum pH of 7.0 for activity on all substrates tested and the highest Vmax/KM ratio for L-Leu-ß-naphthylamide. The enzyme activity was increased 40% by 0.15 M NaCl, inhibited 94% by 2.0 mM Zn2+, inhibited 91% by sodium p-hydroxymercuribenzoate and inhibited 45% by 0.7 mM o-phenanthroline and 30 µM EDTA. Mercaptoethanol (3.3 mM, dithioerythritol (1.7 mM, Ala, Arg, Leu and Met (70 µM, p-nitroaniline (0.25 mM and ß-naphthylamine (0.53 mM had no effect on enzyme activity when assayed with 0.56 mM of substrate. Bestatin (20 µM inhibited 18% the enzyme activity. The aminopeptidase activity in the seeds decayed 50% after two months when stored at 4oC and room temperature. The enzyme is leucyl aminopeptidase metal- and thiol group-dependent.

Trp64Arg polymorphism of the ADRB3 gene associated with maximal fat oxidation and LDL-C levels in non-obese adolescents.

Science.gov (United States)

Jesus, Íncare Correa de; Alle, Lupe Furtado; Munhoz, Eva Cantalejo; Silva, Larissa Rosa da; Lopes, Wendell Arthur; Tureck, Luciane Viater; Purim, Katia Sheylla Malta; Titski, Ana Claudia Kapp; Leite, Neiva

2017-09-21

To analyze the association between the Trp64Arg polymorphism of the ADRB3 gene, maximal fat oxidation rates and the lipid profile levels in non-obese adolescents. 72 schoolchildren, of both genders, aged between 11 and 17 years, participated in the study. The anthropometric and body composition variables, in addition to total cholesterol, HDL-c, LDL-c, triglycerides, insulin, and basal glycemia, were evaluated. The sample was divided into two groups according to the presence or absence of the polymorphism: non-carriers of the Arg64 allele, i.e., homozygous (Trp64Trp: n=54), and carriers of the Arg64 allele (Trp64Arg+Arg64Arg: n=18), in which the frequency of the Arg64 allele was 15.2%. The maximal oxygen uptake and peak of oxygen uptake during exercise were obtained through the symptom-limited, submaximal treadmill test. Maximal fat oxidation was determined according to the ventilatory ratio proposed in Lusk's table. Adolescents carrying the less frequent allele (Trp64Arg and Arg64Arg) had higher LDL-c levels (p=0.031) and lower maximal fat oxidation rates (p=0.038) when compared with non-carriers (Trp64Trp). Although the physiological processes related to lipolysis and lipid metabolism are complex, the presence of the Arg 64 allele was associated with lower rates of FATMAX during aerobic exercise, as well as with higher levels of LDL-c in adolescents. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Management of Primary Dysmenorrhea by School Adolescents in ILE-IFE, Nigeria

Science.gov (United States)

Ogunfowokan, Adesola A.; Babatunde, Oluwayemisi A.

2010-01-01

Dysmenorrhea is a problem that girls and women face and often manage themselves with or without support from health professionals. A cross-sectional, descriptive study was conducted among adolescents with dysmenorrhea (N = 150) in Ile-Ife, Nigeria. The aims of the study were to determine their knowledge of menstruation and primary dysmenorrhea,…

Mutation analysis of pre-mRNA splicing genes in Chinese families with retinitis pigmentosa

Science.gov (United States)

Pan, Xinyuan; Chen, Xue; Liu, Xiaoxing; Gao, Xiang; Kang, Xiaoli; Xu, Qihua; Chen, Xuejuan; Zhao, Kanxing; Zhang, Xiumei; Chu, Qiaomei; Wang, Xiuying

2014-01-01

Purpose Seven genes involved in precursor mRNA (pre-mRNA) splicing have been implicated in autosomal dominant retinitis pigmentosa (adRP). We sought to detect mutations in all seven genes in Chinese families with RP, to characterize the relevant phenotypes, and to evaluate the prevalence of mutations in splicing genes in patients with adRP. Methods Six unrelated families from our adRP cohort (42 families) and two additional families with RP with uncertain inheritance mode were clinically characterized in the present study. Targeted sequence capture with next-generation massively parallel sequencing (NGS) was performed to screen mutations in 189 genes including all seven pre-mRNA splicing genes associated with adRP. Variants detected with NGS were filtered with bioinformatics analyses, validated with Sanger sequencing, and prioritized with pathogenicity analysis. Results Mutations in pre-mRNA splicing genes were identified in three individual families including one novel frameshift mutation in PRPF31 (p.Leu366fs*1) and two known mutations in SNRNP200 (p.Arg681His and p.Ser1087Leu). The patients carrying SNRNP200 p.R681H showed rapid disease progression, and the family carrying p.S1087L presented earlier onset ages and more severe phenotypes compared to another previously reported family with p.S1087L. In five other families, we identified mutations in other RP-related genes, including RP1 p. Ser781* (novel), RP2 p.Gln65* (novel) and p.Ile137del (novel), IMPDH1 p.Asp311Asn (recurrent), and RHO p.Pro347Leu (recurrent). Conclusions Mutations in splicing genes identified in the present and our previous study account for 9.5% in our adRP cohort, indicating the important role of pre-mRNA splicing deficiency in the etiology of adRP. Mutations in the same splicing gene, or even the same mutation, could correlate with different phenotypic severities, complicating the genotype–phenotype correlation and clinical prognosis. PMID:24940031

Effects of amino acids on melanoma targeting and clearance properties of Tc-99m-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone peptides.

Science.gov (United States)

Flook, Adam M; Yang, Jianquan; Miao, Yubin

2013-11-14

The purpose of this study was to examine the effects of amino acids on melanoma targeting and clearance properties of new (99m)Tc-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-Lys-(Arg(11))CCMSH {c[Arg-Ser-Asp-DTyr-Asp]-Lys-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RNleD-Lys-(Arg(11))CCMSH, RPheD-Lys-(Arg(11))CCMSH, and RdPheD-Lys-(Arg(11))CCMSH peptides were synthesized and evaluated for their melanocortin-1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of (99m)Tc-RSD-Lys-(Arg(11))CCMSH, (99m)Tc-RFD-Lys-(Arg(11))CCMSH, and (99m)Tc-RfD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The substitution of Gly with Ser, Phe, and dPhe increased the MC1 receptor binding affinities of the peptides, whereas the substitution of Gly with Nle decreased the MC1 receptor binding affinity of the peptide. (99m)Tc-RSD-Lys-(Arg(11))CCMSH exhibited the highest melanoma uptake (18.01 ± 4.22% ID/g) and the lowest kidney and liver uptake among these (99m)Tc-peptides. The B16/F1 melanoma lesions could be clearly visualized by SPECT/CT using (99m)Tc-RSD-Lys-(Arg(11))CCMSH as an imaging probe. It is desirable to reduce the renal uptake of (99m)Tc-RSD-Lys-(Arg(11))CCMSH to facilitate its potential therapeutic application.

Performance and Fabrication Status of TREAT LEU Conversion Conceptual Design Concepts

Energy Technology Data Exchange (ETDEWEB)

IJ van Rooyen; SR Morrell; AE Wright; E. P Luther; K Jamison; AL Crawford; HT III Hartman

2014-10-01

Resumption of transient testing at the TREAT facility was approved in February 2014 to meet U.S. Department of Energy (DOE) objectives. The National Nuclear Security Administration’s Global Threat Reduction Initiative Convert Program is evaluating conversion of TREAT from its existing highly enriched uranium (HEU) core to a new core containing low enriched uranium (LEU). This paper describes briefly the initial pre-conceptual designs screening decisions with more detailed discussions on current feasibility, qualification and fabrication approaches. Feasible fabrication will be shown for a LEU fuel element assembly that can meet TREAT design, performance, and safety requirements. The statement of feasibility recognizes that further development, analysis, and testing must be completed to refine the conceptual design. Engineering challenges such as cladding oxidation, high temperature material properties, and fuel block fabrication along with neutronics performance, will be highlighted. Preliminary engineering and supply chain evaluation provided confidence that the conceptual designs can be achieved.

Impaired 8-Hydroxyguanine Repair Activity of MUTYH Variant p.Arg109Trp Found in a Japanese Patient with Early-Onset Colorectal Cancer

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Kazuya Shinmura

2014-01-01

Full Text Available Purpose. The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP, which is characterized by colorectal multiple polyps and carcinoma(s. However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients. Methods. Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing. Results. Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19*  MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19* and p.Arg109Trp corresponded to p.Arg5* and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5* is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays. Conclusion. These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19* and p.Arg109Trp MUTYH variants are associated with functional impairments.

Neutronic design of a LEU [low enriched uranium] core for the Ohio State University research reactor

International Nuclear Information System (INIS)

Seshadri, M.D.; Aybar, H.S.; Aldemir, T.

1987-01-01

The 10 kw HEU fuelled Ohio State University Reactor (OSURR) will be upgraded to operate at 500 kW with standardized 125 g 235 U LEU U 3 Si 2 fuel plates. An earlier scoping study based on two-dimensional diffusion calculations has identified the potential LEU core configurations for the conversion/upgrade of OSURR using the standardized plates in a 16-plate (+ 2 dummy plates) standard and 10-scoping study is improved for a more precise determination of the excess reactivities and safety rod worths for these potential configurations. Comparison of the results obtained by the improved model to experimental results and to the results of full-core Monte Carlo simulations shows excellent agreement. The results also indicate that the conversion/upgrade of OSURR can be realized with three possible LEU core configurations while maintaining a cold, clean shutdown margin of 1.57-1.91 % Δ k/k, depending on the configuration used. (Author)

Verification of maximum radial power peaking factor due to insertion of FPM-LEU target in the core of RSG-GAS reactor

Energy Technology Data Exchange (ETDEWEB)

Setyawan, Daddy, E-mail: d.setyawan@bapeten.go.id [Center for Assessment of Regulatory System and Technology for Nuclear Installations and Materials, Indonesian Nuclear Energy Regulatory Agency (BAPETEN), Jl. Gajah Mada No. 8 Jakarta 10120 (Indonesia); Rohman, Budi [Licensing Directorate for Nuclear Installations and Materials, Indonesian Nuclear Energy Regulatory Agency (BAPETEN), Jl. Gajah Mada No. 8 Jakarta 10120 (Indonesia)

2014-09-30

Verification of Maximum Radial Power Peaking Factor due to insertion of FPM-LEU target in the core of RSG-GAS Reactor. Radial Power Peaking Factor in RSG-GAS Reactor is a very important parameter for the safety of RSG-GAS reactor during operation. Data of radial power peaking factor due to the insertion of Fission Product Molybdenum with Low Enriched Uranium (FPM-LEU) was reported by PRSG to BAPETEN through the Safety Analysis Report RSG-GAS for FPM-LEU target irradiation. In order to support the evaluation of the Safety Analysis Report incorporated in the submission, the assessment unit of BAPETEN is carrying out independent assessment in order to verify safety related parameters in the SAR including neutronic aspect. The work includes verification to the maximum radial power peaking factor change due to the insertion of FPM-LEU target in RSG-GAS Reactor by computational method using MCNP5and ORIGEN2. From the results of calculations, the new maximum value of the radial power peaking factor due to the insertion of FPM-LEU target is 1.27. The results of calculations in this study showed a smaller value than 1.4 the limit allowed in the SAR.

Receptor binding radiotracers for the angiotensin II receptor: radioiodinated [Sar1, Ile8]angiotensin II

International Nuclear Information System (INIS)

Gibson, R.E.; Beauchamp, H.T.; Fioravanti, C.; Brenner, N.; Burns, H.D.

1994-01-01

The potential for imaging the angiotensin II receptor was evaluated using the radioiodinated peptide antagonist [ 125 I][Sar 1 , Ile 8 ]angiotensin II. The radioligand provides a receptor-mediated signal in several tissues in rat (kidneys, adrenal and liver). The receptor-mediated signal of 3% ID/g kidney cortex should be sufficient to permit imaging, at least via SPECT. The radiotracer is sensitive to reductions in receptor concentration and can be used to define in vivo dose-occupancy curves of angiotensin II receptor ligands. Receptor-mediated images of [ 123 I][Sar 1 , Ile 8 ]angiotensin II were obtained in the rat kidney and Rhesus monkey liver. (author)

Conversion and start up of Tehran Research Reactor with LEU fuel

International Nuclear Information System (INIS)

Zaker, M.

2004-01-01

The MW Tehran Research Reactor, Highly Enriched Uranium (HEU) fuel has been converted to Low Enriched Uranium (LEU) fuel using U 3 0 8 -Al with less than 20% enriched uranium. Measured value of excess reactivity, control rod worth and other parameters indicate good agreement with computational predictions. (author)

Human Islet Amyloid Polypeptide Fibril Binding to Catalase: A Transmission Electron Microscopy and Microplate Study

Directory of Open Access Journals (Sweden)

Nathaniel G. N. Milton

2010-01-01

Full Text Available The diabetes-associated human islet amyloid polypeptide (IAPP is a 37-amino-acid peptide that forms fibrils in vitro and in vivo. Human IAPP fibrils are toxic in a similar manner to Alzheimer's amyloid-β (Aβ and prion protein (PrP fibrils. Previous studies have shown that catalase binds to Aβ fibrils and appears to recognize a region containing the Gly-Ala-Ile-Ile sequence that is similar to the Gly-Ala-Ile-Leu sequence found in human IAPP residues 24-27. This study presents a transmission electron microscopy (TEM—based analysis of fibril formation and the binding of human erythrocyte catalase to IAPP fibrils. The results show that human IAPP 1-37, 8-37, and 20-29 peptides form fibrils with diverse and polymorphic structures. All three forms of IAPP bound catalase, and complexes of IAPP 1-37 or 8-37 with catalase were identified by immunoassay. The binding of biotinylated IAPP to catalase was high affinity with a KD of 0.77nM, and could be inhibited by either human or rat IAPP 1-37 and 8-37 forms. Fibrils formed by the PrP 118-135 peptide with a Gly-Ala-Val-Val sequence also bound catalase. These results suggest that catalase recognizes a Gly-Ala-Ile-Leu—like sequence in amyloid fibril-forming peptides. For IAPP 1-37 and 8-37, the catalase binding was primarily directed towards fibrillar rather than ribbon-like structures, suggesting differences in the accessibility of the human IAPP 24-27 Gly-Ala-Ile-Leu region. This suggests that catalase may be able to discriminate between different structural forms of IAPP fibrils. The ability of catalase to bind IAPP, Aβ, and PrP fibrils demonstrates the presence of similar accessible structural motifs that may be targets for antiamyloid therapeutic development.

Documentation Experiences for Jamaican SLOWPOKE-2 Conversion from HEU to LEU

International Nuclear Information System (INIS)

Warner, T.-A.; Dennis, H.; Antoine, J.

2015-01-01

The Jamaican SLOWPOKE–2 (JM–1) is a 20 kW research reactor manufactured by Atomic Energy of Canada Limited and has been operating since March 1984, in the department of the International Centre for Environmental and Nuclear Sciences (ICENS), at the University of the West Indies, Mona Campus in Kingston, Jamaica. The pool type reactor has been primarily used for Neutron Activation Analysis in environmental, agricultural, geochemical, health-related studies and mineral exploration. The University, assisted by the IAEA under the GTRI/RERTR program, is currently in the process of converting from HEU to LEU. Extensive documentation on policies, general requirements, elements of the conversion quality assurance (QA) system and conversion QA administrative procedures is required for the conversion. The core conversion activities are being carried out in accordance with current international standards and regulatory guidelines of the newly established Jamaican Radiation Safety Authority (RSA) with agreement between the RSA and IAEA or DOE related to Nuclear Safety and Control. The documentation structure has taken into consideration nuclear safety and licensing, LEU fuel design and conversion analysis, LEU fuel procurement and fabrication, removal of HEU fuel and reactor maintenance and conversion and commissioning, with the conversion QA manual at the apex of the structure. To a large extent, the documentation format will adhere to that of the IAEA applicable regulatory standards and guidance documents. The major challenge of the conversion activities, it is envisioned, will come from the absence of any previous regulatory framework in Jamaica; however, a timeline for the process, which includes training and equipping of regulators, will guide operation. (author)

Status of LEU fuel development and conversion of NRU

International Nuclear Information System (INIS)

Sears, D.F.; Herbert, L.N.; Vaillancourt, K.D.

1989-11-01

The status of the low-enrichment uranium (LEU) fuel development and NRU conversion program at Chalk River Nuclear Laboratories is reviewed. Construction of a new fuel fabrication facility is essentially completed and installation of LEW fuel manufacturing equipment has begun. The irradiation of 31 prototype Al-61 wt% U 3 Si dispersion fuel rods, approximately one third of a full NRU core, is continuing without incident. Recent post-irradiation examination of spent fuel rods revealed that the prototype LEU fuel achieved the design burnup (80 at%) in excellent condition, confirming that the Al-U 3 Si 2 dispersion fuel to complement out Al-U 3 Si capability. Three full-size NRU rods containing Al-U 3 Si 2 dispersion fuel have been fabricated for a qualification irradiation in NRU. Post-irradiation examinations of mini-elements containing Al-U 3 Si 2 fuel revealed that the U 3 Si 2 behaved similarly to U 3 Si 2 fuel revealed that the U 3 Si 2 particles and the aluminum matrix, and fission gas bubbles up to 10 μm in diameter, could be seen in the particles after 60 at% and 80 at% burnup. The mini-elements contained a variety of silicide particle sizes; however, no significant swelling dependence on particle size distribution was observed

Greenfield Alternative Study LEU-Mo Fuel Fabrication Facility

Energy Technology Data Exchange (ETDEWEB)

Washington Division of URS

2008-07-01

This report provides the initial “first look” of the design of the Greenfield Alternative of the Fuel Fabrication Capability (FFC); a facility to be built at a Greenfield DOE National Laboratory site. The FFC is designed to fabricate LEU-Mo monolithic fuel for the 5 US High Performance Research Reactors (HPRRs). This report provides a pre-conceptual design of the site, facility, process and equipment systems of the FFC; along with a preliminary hazards evaluation, risk assessment as well as the ROM cost and schedule estimate.

Key considerations in the conversion to LEU of a Mo-99 commercially producing reactor: SAFARI-1 of South Africa

International Nuclear Information System (INIS)

Stumpf, W.E.; Vermaak, A.P.; Ball, G.

2000-01-01

Apart from the technological demands and considerations associated with the conversion of a Mo-99 commercially producing reactor to LEU, a number of commercial challenges also need to be addressed. This is particularly the case when the reactor is primarily used as a source for the production, on an uninterrupted basis, of significant quantities of Mo-99 to satisfy long term commitments to a range of global customers. This paper highlights key business considerations which are applicable in the conversion process of firstly, reactor fuel to LEU and secondly target plates for Mo-99, also to LEU, using the SAFARI-1 reactor in South Africa as a typical example of such a commercially utilized reactor. (author)

Key considerations in the conversion to LEU of a Mo-99 commercially producing reactor: SAFARI-1 of South Africa

Energy Technology Data Exchange (ETDEWEB)

Stumpf, W E; Vermaak, A P; Ball, G [NECSA, PO Box 582, Pretoria (South Africa)

2000-10-01

Apart from the technological demands and considerations associated with the conversion of a Mo-99 commercially producing reactor to LEU, a number of commercial challenges also need to be addressed. This is particularly the case when the reactor is primarily used as a source for the production, on an uninterrupted basis, of significant quantities of Mo-99 to satisfy long term commitments to a range of global customers. This paper highlights key business considerations which are applicable in the conversion process of firstly, reactor fuel to LEU and secondly target plates for Mo-99, also to LEU, using the SAFARI-1 reactor in South Africa as a typical example of such a commercially utilized reactor. (author)

Association Between Genetic Polymorphisms in the XRCC1, XRCC3, XPD, GSTM1, GSTT1, MSH2, MLH1, MSH3, and MGMT Genes and Radiosensitivity in Breast Cancer Patients

International Nuclear Information System (INIS)

Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca; Sani, Cristina; Biti, Giampaolo; Livi, Lorenzo; Barletta, Emanuela; Costantini, Adele Seniori; Gorini, Giuseppe

2011-01-01

Purpose: Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Methods and Materials: Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results: Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR = 53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR = 38.26; 95% CI, 1.19-1232.52). Conclusions: To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be

Association of ghrelin polymorphisms with metabolic syndrome in Han Nationality Chinese.

Science.gov (United States)

Xu, Ling-Ling; Xiang, Hong-Ding; Qiu, Chang-Chun; Xu, Qun

2008-06-01

To investigate the association of ghrelin gene polymorphisms with metabolic syndrome in Han Nationality Chinese. A total of 240 patients with metabolic syndrome and 427 adults aged above forty years were recruited. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The allelic frequency of the Leu72Met polymorphism was 17.3% in the patient group and 11.9% in the control group (chi2 = 7.36, P = 0.007). Metabolic syndrome was more prevalent among carriers of the Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio = 1.57, P = 0.01). No Arg51Gln variants were found in our study subjects. Rather than being associated with its individual components, Leu72Met polymorphism is associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln polymorphism is rare in the Han Nationality Chinese.

Regional meetings on energy 2008. Ile-de-France facing the energy stakes. Conference proceedings

International Nuclear Information System (INIS)

Lamy, Marie-Laure; Rocher, Philippe; Falque-Masset, Marie-Laure; Cazas, Judith; Labrousse, Muriel; Gorges, Pascale; Boulet, Sophie; Petit-Tesson, Christophe

2009-01-01

This document proposes a synthesis of the conference. It presents an assessment of the regional plan for energy management and development of local and renewable energies. The first part gives an overview of regional actions (in the Ile de France region) performed by the ADEME, or within the regional plan. The second part presents ROSE (a network for the statistical survey of energy and of greenhouse gas emissions in Ile de France) and its activity. Some remarkable actions are briefly presented: energy management by the city of Montreuil, energy management and sensitisation in a secondary school, a zero-energy building (a school in Limeil-Brevannes), geothermal energy in Orly, solar energy in social dwelling, and wood-heat network in Cergy-Pontoise

“PESTEL Analizi” ile Türkiye-Almanya Ekonomik İlişkilerinin İncelenmesi

OpenAIRE

AKÇA, Hasan; ŞAHİN, Levent; KAYA, Zekayi

2016-01-01

Bu çalışmanın amacı; Türkiye ve Almanya arasındaki ekonomik ilişkileri PESTEL Analizi ile irdelemektir. Çalışmada ikincil veriler (1924-2015) kullanılmıştır. PESTEL Analizinden elde edilen bazı sonuçlar şu şekilde özetlenebilir. Almanya bir taraftan gelecekte enerji darboğazı çekmemek için enerji koridorunda bulunan Türkiye ile ilişkileri olumlu yönde tutmaya çalışırken; diğer yandan Türkiye’nin AB’ye üyeliğine mesafeli durmaktadır. 1954-2015/Ağustos döneminde Türkiye’ye yatırım yapan toplam ...

AVATAR: AdVanced Aerodynamic Tools for lArge Rotors

DEFF Research Database (Denmark)

Schepers, J.C.; Ceyhan, O.; Savenije, F.J.

2015-01-01

An EERA (European Energy Research Alliance) consortium started an ambitious EU FP7 project AVATAR (AdVanced Aerodynamic Tools of lArge Rotors) in November 2013. The project lasts 4 years and is carried out in a consortium with 11 research institutes and two industry partners. The motivation...

A new immunization procedure for the obtention of anti-leucine enkephalin antibodies. Part I. Immunization procedure and physicochemical characteristics of antibodies.

Science.gov (United States)

Cupo, A; Vion-Dury, J; Jarry, T

1986-10-01

We described here a new immunization procedure to obtain high titre and high specific antibodies against Leu-enkephalin (LE). The immunogen form is composed of one part of LE conjugate and one part of LE-Arg6 conjugate. We have observed an increase of titre, affinity and specificity of the antibodies in the coimmunization procedure compared to those obtained by conventional immunization involving only the LE conjugate. The Leu-enkephalin antibodies exhibit a high affinity (KD 8 X 10(-12) M) and we are able to detect the Leu-enkephalin at the 10(-15) mole level. These LE antibodies are highly specific of the C part of LE peptide and cross-react weakly with Met-enkephalin (1%).

The Leu72Met polymorphism of the ghrelin gene is associated with a decreased risk for type 2 diabetes.

Science.gov (United States)

Berthold, Heiner K; Giannakidou, Eleni; Krone, Wilhelm; Mantzoros, Christos S; Gouni-Berthold, Ioanna

2009-01-01

Ghrelin is involved in several metabolic and cardiovascular processes. The Leu72Met polymorphism of its gene was associated with an increased risk of type 2 diabetes (DM2) in some, but not all studies. Its association with atherosclerosis is not known. We investigated 420 Caucasian subjects with DM2 and 430 controls without diabetes (56.6% male, age 62+/-10 years). The Leu72Leu genotype frequencies were 89.76/84.65%, the Leu72Met 9.52/15.12% and the Met72Met 0.71/0.23% (P=0.029) in the DM2 and controls groups, respectively. In subjects with Met72+ genotypes the risk of DM2 was significantly decreased (univariate OR 0.63, 95% CI 0.42-0.95, P=0.026). In a logistic regression model, body mass index, hypertension and a positive family history for diabetes were predictors of diabetes while the polymorphism remained negatively associated with the disease (OR 0.62, 95% CI 0.40-0.97, P=0.036). After adjusting for known risk factors for atherosclerosis, the Met72+ variant was not associated with atherosclerotic disease (OR 1.41, 95% CI 0.78-2.54, P=0.25). Ghrelin concentrations were not associated with the polymorphism, DM2 or atherosclerotic disease. The Leu72Met polymorphism of the ghrelin gene is associated with a decreased risk for DM2. There is no association between the variant and atherosclerotic disease or ghrelin concentrations.

Contribution of Arginine 13 to the Catalytic Activity of Human Class Pi Glutathione Transferase P1-1

International Nuclear Information System (INIS)

Kong, Ji Na; Jo, Dong Hyeon; Do, Hyun Dong; Lee, Jin Ju; Kong, Kwang Hoon

2010-01-01

Arg13 is a conserved active-site residue in all known Pi class glutathione S-transferases (GSTs) and in most Alpha class GSTs. To evaluate its contribution to substrate binding and catalysis of this residue, three mutants (R13A, R13K, and R13L) were expressed in Escherichia coli and purified by GSH affinity chromatography. The substitutions of Arg13 significantly affected GSH-conjugation activity, while scarcely affecting glutathione peroxidase or steroid isomerase activities. Mutation of Arg13 into Ala largely reduced the GSH-conjugation activity by approximately 85 - 95%, whereas substitutions by Lys and Leu barely affected activity. These results suggest that, in the GSH-conjugation activity of hGST P1-1, the contribution of Arg13 toward catalytic activity is highly dependent on substrate specificities and the size of the side chain at position 13. From the kinetic parameters, introduction of larger side chains at position 13 results in stronger affinity (Leu > Lys, Arg > Ala) towards GSH. The substitutions of Arg13 with alanine and leucine significantly affected k cat , whereas substitution with Lys was similar to that of the wild type, indicating the significance of a positively charged residue at position 13. From the plots of log (k cat /K m CDNB ) against pH, the pK a values of the thiol group of GSH bound in R13A, R13K, and R13L were estimated to be 1.8, 1.4, and 1.8 pK units higher than the pK a value of the wildtype enzyme, demonstrating the contribution of the Arg13 guanidinium group to the electrostatic field in the active site. From these results, we suggest that contribution of Arg13 in substrate binding is highly dependent on the nature of the electrophilic substrates, while in the catalytic mechanism, it stabilizes the GSH thiolate through hydrogen bonding

A comparison of the radiological consequences of a HEU and LEU fueled research reactor

International Nuclear Information System (INIS)

Kollas, J.G.

1985-01-01

An analysis of the design basis accident radiological consequences of the HEU and LEU fueled Greek Research Reactor is presented. Doses and individual cancer risk from exposure to the passing radioactive cloud are estimated up to a distance of 20 km from the reactor site. Collective exposure and latent health effects are estimated for the total Athens area of 3081000 inhabitants. The results indicate that the plutonium isotopes buildup in the LEU fuel does not increase appreciably the consequences in respect to the HEU fueled reactor. The plutonium impact concerns mainly bone effects and secondly lung and whole body effects. The contribution to the limiting thyroid dose and the corresponding thyroid effects is insignificant. (author)

Data of evolutionary structure change: 1DFFA-3CPMA [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1DFFA-3CPMA 1DFF 3CPM A A -----SVLQVLHIPDERLRKVAKPVEEVNAEIQRIVDDM...line> 3CPM A 3CPMA THR CA 218 GLY CA 249 ILE CA 245 3CPM... A 3CPMA IKKYSDKLVPFILE CA 305 ARG CA 316 GLN CA 241 3CPM

Meta-analysis of the association between the Trp64Arg polymorphism of the beta-3 adrenergic receptor and susceptibility to gestational diabetes mellitus.

Science.gov (United States)

Guan, Lianyue; Cui, Xiaofeng; Zhou, Hui

2018-02-01

The study aimed to explore the associations between Trp64Arg polymorphism of Beta-3 Adrenergic receptor (ADRB3) and susceptibility to gestational diabetes mellitus (GDM). Relevant studies till December 2013 were identified through searching electronic databases. A meta-analysis was conducted on associations between Trp64Arg polymorphism in ADRB3 and susceptibility to GDM. We found no association between Trp64Arg polymorphism in ADRB3 and susceptibility to GDM in overall population (Arg vs. Trp: OR = 1.20, 95%CI = 0.99-1.47, p = .16; Trp/Arg + Arg/Arg vs. Trp/Trp: OR = 1.22, 95%CI = 0.99-1.50, p = .11). In subgroup analysis on European Caucasian population, Trp64Arg in ADRB3 was associated with susceptibility to GDM. Trp64Arg polymorphism in ADRB3 had certain association with susceptibility to GDM in the European Caucasian population. Impact statement What is already known on this subject: Gestational diabetes mellitus (GDM) is recognised as carbohydrate intolerance of varied severity that begins or is first recognised during pregnancy. A missense mutation in the codon 64 of the Beta-3 adrenergic receptor (ADRB3), Trp64Arg, leads to the substitution of tryptophan by arginine in the first intracellular loop of the ADRB3 receptor. Trp64Arg Polymorphism has also been reportedly associated with increased body weight, type 2 diabetes mellitus, insulin resistance and obesity. However, other investigators have found that the Trp64Arg polymorphism of ADRB3 has no effect on insulin resistance, obesity or type 2 diabetes mellitus. What the results of the study add: Our present meta-analysis demonstrated that Trp64Arg polymorphism in ADRB3 was associated with susceptibility to GDM in the European Caucasian population. Trp64Arg polymorphism in ADRB3 may be able to predict the occurrence of GDM and used for the diagnosis of it in clinic. What the implications are of these findings for clinical practice and future research: The findings in this study

Unstable argininosuccinate lyase in variant forms of the urea cycle disorder argininosuccinic aciduria.

Science.gov (United States)

Hu, Liyan; Pandey, Amit V; Balmer, Cécile; Eggimann, Sandra; Rüfenacht, Véronique; Nuoffer, Jean-Marc; Häberle, Johannes

2015-09-01

Loss of function of the urea cycle enzyme argininosuccinate lyase (ASL) is caused by mutations in the ASL gene leading to ASL deficiency (ASLD). ASLD has a broad clinical spectrum ranging from life-threatening severe neonatal to asymptomatic forms. Different levels of residual ASL activity probably contribute to the phenotypic variability but reliable expression systems allowing clinically useful conclusions are not yet available. In order to define the molecular characteristics underlying the phenotypic variability, we investigated all ASL mutations that were hitherto identified in patients with late onset or mild clinical and biochemical courses by ASL expression in human embryonic kidney 293 T cells. We found residual activities >3% of ASL wild type (WT) in nine of 11 ASL mutations. Six ASL mutations (p.Arg95Cys, p.Ile100Thr, p.Val178Met, p.Glu189Gly, p.Val335Leu, and p.Arg379Cys) with residual activities ≥16% of ASL WT showed no significant or less than twofold reduced Km values, but displayed thermal instability. Computational structural analysis supported the biochemical findings by revealing multiple effects including protein instability, disruption of ionic interactions and hydrogen bonds between residues in the monomeric form of the protein, and disruption of contacts between adjacent monomeric units in the ASL tetramer. These findings suggest that the clinical and biochemical course in variant forms of ASLD is associated with relevant residual levels of ASL activity as well as instability of mutant ASL proteins. Since about 30% of known ASLD genotypes are affected by mutations studied here, ASLD should be considered as a candidate for chaperone treatment to improve mutant protein stability.

Receptor-binding properties of modern human influenza viruses primarily isolated in Vero and MDCK cells and chicken embryonated eggs

International Nuclear Information System (INIS)

Mochalova, Larisa; Gambaryan, Alexandra; Romanova, Julia; Tuzikov, Alexander; Chinarev, Alexander; Katinger, Dietmar; Katinger, Herman; Egorov, Andrej; Bovin, Nicolai

2003-01-01

To study the receptor specificity of modern human influenza H1N1 and H3N2 viruses, the analogs of natural receptors, namely sialyloligosaccharides conjugated with high molecular weight (about 1500 kDa) polyacrylamide as biotinylated and label-free probes, have been used. Viruses isolated from clinical specimens were grown in African green monkey kidney (Vero) or Madin-Darby canine kidney (MDCK) cells and chicken embryonated eggs. All Vero-derived viruses had hemagglutinin (HA) sequences indistinguishable from original viruses present in clinical samples, but HAs of three of seven tested MDCK-derived isolates had one or two amino acid substitutions. Despite these host-dependent mutations and differences in the structure of HA molecules of individual strains, all studied Vero- and MDCK-isolated viruses bound to Neu5Ac α2-6Galβ1-4GlcNAc (6'SLN) essentially stronger than to Neu5Acα2-6Galβ1-4Glc (6'SL). Such receptor-binding specificity has been typical for earlier isolated H1N1 human influenza viruses, but there is a new property of H3N2 viruses that has been circulating in the human population during recent years. Propagation of human viruses in chicken embryonated eggs resulted in a selection of variants with amino acid substitutions near the HA receptor-binding site, namely Gln226Arg or Asp225Gly for H1N1 viruses and Leu194Ile and Arg220Ser for H3N2 viruses. These HA mutations disturb the observed strict 6'SLN specificity of recent human influenza viruses

Dysregulated autophagy in restrictive cardiomyopathy due to Pro209Leu mutation in BAG3.

Science.gov (United States)

Schänzer, A; Rupp, S; Gräf, S; Zengeler, D; Jux, C; Akintürk, H; Gulatz, L; Mazhari, N; Acker, T; Van Coster, R; Garvalov, B K; Hahn, A

2018-03-01

Myofibrillary myopathies (MFM) are hereditary myopathies histologically characterized by degeneration of myofibrils and aggregation of proteins in striated muscle. Cardiomyopathy is common in MFM but the pathophysiological mechanisms are not well understood. The BAG3-Pro209Leu mutation is associated with early onset MFM and severe restrictive cardiomyopathy (RCM), often necessitating heart transplantation during childhood. We report on a young male patient with a BAG3-Pro209Leu mutation who underwent heart transplantation at eight years of age. Detailed morphological analyses of the explanted heart tissue showed intracytoplasmic inclusions, aggregation of BAG3 and desmin, disintegration of myofibers and Z-disk alterations. The presence of undegraded autophagosomes, seen by electron microscopy, as well as increased levels of p62, LC3-I and WIPI1, detected by immunohistochemistry and western blot analyses, indicated a dysregulation of autophagy. Parkin and PINK1, proteins involved in mitophagy, were slightly increased whereas mitochondrial OXPHOS activities were not altered. These findings indicate that altered autophagy plays a role in the pathogenesis and rapid progression of RCM in MFM caused by the BAG3-Pro209Leu mutation, which could have implications for future therapeutic strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

Carcass and meat traits of Morada Nova, Santa Ines and ½ Ile de France ½ Texel lambs finished in feedlot

Directory of Open Access Journals (Sweden)

Juliano Issakowicz

2014-03-01

Full Text Available The aim of this study was to evaluate the carcass and meat traits of Morada Nova, Santa Ines and ½ Ile de France ½ Texel lambs finished in feedlot. Weight and proportion of meatcuts, measures of carcass size and color, tenderness, cooking loss and ultimate pH of meat from 10 Morada Nova, 6 Santa Ines and 10 ½ Ile de France ½ Texel were evaluated. The lambs were finished in collective pens, fed ad libitum with 50% corn silage and 50% concentrate and slaughtered at about six months old. Analysis of variance was performed by the procedure PROC GLM of SAS (SAS Inst., Inc., Cary, NC and means were compared by Tukey test at 5% significance. The Morada Nova lambs had values of 14.1 kg, 13.9 kg, 0.240 kg/cm, 56.2 cm and 35.8 cm for hot and cold carcass weight, compactness index, hip and leg circumference respectively and these values were lower (P <0.05 to values observed in Santa Ines (19.4 kg, 18.8 kg, 0.283 cm/kg, 64.6 cm and 40.0 cm and in ½ Ile de France ½ Texel (18.6 kg, 18.2 kg, 0.305 cm/kg; 65.4 cm and 41.6 cm lambs. The hot and cold carcass yield did not differ (P> 0.05 among genetic groups. The scores for conformation and fat cover were higher (P <0.05 in ½ Ile de France ½ Texel lambs (2.4 and 3.0 and the carcass length was greater in Santa Ines lambs (66.3 cm. The ½ Ile de France ½ Texel lambs had smaller (P<0.05 proportion of neck and greater of leg (9.10% and 33.1% compared to Morada Nova lambs (10.3% and 30.4% and Santa Inês (10.9% and 31.6%. The weight of shoulder, leg, rack, ribs and flank was lower (P<0.05 in Morada Nova (1.306, 2.127 kg, 0.999 kg, 0.775 kg and 0.433 kg respectively compared to Santa Inês (1.820 kg, 2.972 kg, 1.355 kg, 0.959 and 0.509 kg and ½ Ile de France ½ Texel (1.791 kg, 3.007 kg, 1.212 kg, 1.016 kg and 0.563 kg. The neck was heavier in Santa Ines (1.038 kg which differed (P <0.05 from the other genetic groups (0.725 kg for Morada Nova and 0.830 kg for ½ Ile de France x ½ Texel lambs. The ½ Ile de

Lys and Arg in UBI: A specific site for a stable Tc-99m complex?

International Nuclear Information System (INIS)

Melendez-Alafort, Laura; Ramirez, Flor de Maria; Ferro-Flores, Guillermina; Murphy, Consuelo Arteaga de; Pedraza-Lopez, Martha; Hnatowich, Donald J.

2003-01-01

The aim of this study was to help establish if ubiquicidin peptide 29-41 fragment (UBI) contains a specific site for 99m Tc labeling by a new direct method under alkaline conditions. Since this peptide does not have cysteine residues, it is possible that neighboring arginine and lysine in the peptide amino acid sequence (Thr-Gly-Arg-Ala-Lys-Arg-Arg-Met-Gln-Tyr-Asn-Arg-Arg) could be a specific coordination site to form a stable 99m Tc-UBI complex. Following direct labeling, the in vitro stability of 99m Tc-UBI was compared to UBI radiolabeled by one indirect method using HYNIC/tricine and HYNIC/tricine/EDDA. Radiochemical purity of 99m Tc-UBI averaged 97% compared to 88% for 99m Tc-HYNIC-UBI/tricine and 98% for 99m Tc-HYNIC-UBI/tricine/EDDA. Both 99m Tc-HYNIC-UBI (tricine or EDDA) and 99m Tc-UBI showed stability in human serum and solutions of cysteine. 99m Tc-UBI radiochemical purity 24 h after dilution in 0.9% NaCl was greater than 90% at pH 9 and greater than 95% at pH 6.5. Under one set of experimental conditions, in vitro binding to bacteria of 99m Tc-UBI was 35% and identical to that of 99m Tc-HYNIC-UBI/tricine and 99m Tc-HYNIC-UBI/tricine/EDDA at 32% and 31% respectively. The biodistribution of 99m Tc-UBI in mice showed a rapid renal clearance. To help identify the site(s) of 99m Tc binding following direct labeling, molecular mechanics and quantum-mechanical calculations were performed which showed that the amine groups of Arg 7 and Lys are the most probable site. The calculations show that these groups can form a square pyramid with two water molecules for the Tc cation (dxysp 3 ). It will be necessary to isolate and characterize the 99 Tc(V)(O)-UBI . (H 2 O) n complex to confirm these results

Altın Fiyatlarının Yapay Sinir Ağları ile Tahmini ve Bir Uygulama

Directory of Open Access Journals (Sweden)

Rıdvan YÜKSEL

2016-03-01

Full Text Available Bu çalışmada altın fiyatlarını yapay sinir ağları ile öngörmek amacıyla, altın fiyatlarını etkileyebileceği düşünülen değişkenler olan Gümüş fiyatları, Brent Petrol fiyatları, ABD doları/ EUR paritesi, EuroNext100 endeksi, Amerika Dow Jones Endeksi, 13 Hafta vadeli ABD bonosu faiz oranı ve ABD TÜFE endeksi kullanılarak modeller kurulmuştur. Yapay sinir ağları ile kurulan modellerden elde edilen tahmin sonuçları, gerçek değerler ile R2, RMSE, MAE ve MAPE (% gibi performans kriterleri hesaplanarak karşılaştırılmıştır. Elde edilen bulgular yapay sinir ağlarının altın fiyatlarının tahmininde başarı ile kullanılabileceğini göstermektedir. Yapılan duyarlılık analizinin sonuçları değerlendirildiğinde altın fiyatlarını etkileyen faktörlerin başında gümüş ve petrol fiyatlarının geldiği tespit edilmiştir.

Antioxidant potentials of local fruits and foreign wines sold in Ile-Ife ...

African Journals Online (AJOL)

Some locally consumed fruits, sugarcane and wines sold in Ile-Ife, Nigeria, were investigated for their phenol content and antioxidant potential of the methanolic extracts with a view of exploring the healthpromoting effect of the fruits and wines. The total phenolic content in each fruit and wines was determined ...

Three new species of the genus Arge (Hymenoptera: Symphyta: Argidae from South Korea with key to species of the subfamily Arginae

Directory of Open Access Journals (Sweden)

Jin-Kyung Choi

2016-06-01

Full Text Available Three new species, Arge koreana Wei & Lee sp. nov. from South Korea, Arge pseudorejecta Wei & Lee sp. nov., and Arge shengi Wei & Lee sp. nov. from South Korea and China are described. Keys to known genera of Argidae and known species of Arginae from South Korea are provided.

Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity.

Science.gov (United States)

Gialeraki, Argyri; Markatos, Christos; Grouzi, Elisabeth; Merkouri, Efrosyni; Travlou, Anthi; Politou, Marianna

2010-04-01

Acenocoumarol is mainly catabolized by CYP2C9 isoform of cytochrome P450 (CYP) liver complex and exerts its anticoagulant effect through the inhibition of Vitamin K Epoxide Reductase (VKOR). The most important genetic polymorphisms which lead to an impaired enzymatic activity and therefore predispose to acenocoumarol sensitivity, are considered to be CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A, respectively. In this study we compared the results of the PGXThrombo StripAssay kit (ViennaLab Diagnostics,Vienna, Austria) with direct DNA sequencing and in house Restriction Fragment Length Polymorphisms (RFLP) for the detection of the aforementioned Single Nucleotide Polymorphisms (SNPs). The reverse hybridization StripAssay was found to be equally effective with RFLP and direct DNA sequencing for the detection of CYP2C9*2 and CYP2C9*3 polymorphisms, respectively. The comparison of the RFLP reference method with the reverse hybridization StripAssay for the detection of VKORC1-1639 G>A polymorphism showed that the reverse hybridization StripAsssay might misclassify some A/A homozygotes as heterozygotes. Optimization of the hybridization procedures may eliminate the extra low signal band observed in some samples at the reverse hybridization StripAssay and improve its diagnostic value.

ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums[S

Science.gov (United States)

Chan, Jeannie; Mahaney, Michael C.; Kushwaha, Rampratap S.; VandeBerg, Jane F.; VandeBerg, John L.

2010-01-01

High-responding opossums are susceptible to developing hypercholesterolemia on a high-cholesterol diet, but low-responding opossums are resistant. The observation of low biliary cholesterol and low biliary phospholipids in high responders suggested that the ABCB4 gene affects response to dietary cholesterol. Two missense mutations (Arg29Gly and Ile235Leu) were found in the ABCB4 gene of high responders. High responders (ATHH strain) were bred with low responders (ATHE or ATHL strain) to produce F1 and F2 progeny in two different genetic crosses (KUSH6 and JCX) to determine the effect of ABCB4 allelic variants on plasma cholesterol concentrations after a dietary challenge. Pedigree-based genetic association analyses consistently implicated a variant in ABCB4 or a closely linked locus as a major, but not the sole, genetic contributor to variation in the plasma cholesterol response to dietary cholesterol. High responders, but not low responders, developed liver injury as indicated by elevated plasma biomarkers of liver function, probably reflecting damage to the canalicular membrane by bile salts because of impaired phospholipid secretion. Our results implicate ABCB4 as a major determinant of diet-induced hypercholesterolemia in high-responding opossums and suggest that other genes interact with ABCB4 to regulate lipemic response to dietary cholesterol. PMID:20488799

ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums.

Science.gov (United States)

Chan, Jeannie; Mahaney, Michael C; Kushwaha, Rampratap S; VandeBerg, Jane F; VandeBerg, John L

2010-10-01

High-responding opossums are susceptible to developing hypercholesterolemia on a high-cholesterol diet, but low-responding opossums are resistant. The observation of low biliary cholesterol and low biliary phospholipids in high responders suggested that the ABCB4 gene affects response to dietary cholesterol. Two missense mutations (Arg29Gly and Ile235Leu) were found in the ABCB4 gene of high responders. High responders (ATHH strain) were bred with low responders (ATHE or ATHL strain) to produce F1 and F2 progeny in two different genetic crosses (KUSH6 and JCX) to determine the effect of ABCB4 allelic variants on plasma cholesterol concentrations after a dietary challenge. Pedigree-based genetic association analyses consistently implicated a variant in ABCB4 or a closely linked locus as a major, but not the sole, genetic contributor to variation in the plasma cholesterol response to dietary cholesterol. High responders, but not low responders, developed liver injury as indicated by elevated plasma biomarkers of liver function, probably reflecting damage to the canalicular membrane by bile salts because of impaired phospholipid secretion. Our results implicate ABCB4 as a major determinant of diet-induced hypercholesterolemia in high-responding opossums and suggest that other genes interact with ABCB4 to regulate lipemic response to dietary cholesterol.

Development of Chemically Defined Media to Express Trp-Analog-Labeled Proteins in a Lactococcus lactis Trp Auxotroph.

Science.gov (United States)

Shao, Jinfeng; Marcondes, Marcelo F M; Oliveira, Vitor; Broos, Jaap

2016-01-01

Chemically defined media for growth of Lactococcus lactis strains contain about 50 components, making them laborious and expensive growth media. However, they are crucial for metabolism studies as well as for expression of heterologous proteins labeled with unnatural amino acids. In particular, the L. lactis Trp auxotroph PA1002, overexpressing the tryptophanyl tRNA synthetase enzyme of L. lactis, is very suitable for the biosynthetic incorporation of Trp analogs in proteins because of its most relaxed substrate specificity reported towards Trp analogs. Here we present two much simpler defined media for L. lactis, which consist of only 24 or 31 components, respectively, and with which the L. lactis Trp auxotroph shows similar growth characteristics as with a 50-component chemically defined medium. Importantly, the expression levels of two recombinant proteins used for evaluation were up to 2-3 times higher in these new media than in the 50-component medium, without affecting the Trp analog incorporation efficiency. Taken together, the simplest chemically defined media reported so far for L. lactis are presented. Since L. lactis also shows auxotrophy for Arg, His, Ile, Leu Val, and Met, our simplified media may also be useful for the biosynthetic incorporation of analogs of these five amino acids. © 2016 The Author(s) Published by S. Karger AG, Basel.

Production of leu high density fuels at Babcock and Wilcox

International Nuclear Information System (INIS)

Freim, J.B.

1983-01-01

A large number of fuel elements of all types are produced for both international and domestic customers by Nuclear Fuel Division of Babcock and Wilcox. A brief history of the division, included previous and present research reactor fuel element fabrication experience is discussed. The manufacturing facilities are briefly described. The fabrication of LEU fuels and economic analysis of the production are included. (A.J.)

Ranalexin. A novel antimicrobial peptide from bullfrog (Rana catesbeiana) skin, structurally related to the bacterial antibiotic, polymyxin.

Science.gov (United States)

Clark, D P; Durell, S; Maloy, W L; Zasloff, M

1994-04-08

Antimicrobial peptides comprise a diverse class of molecules used in host defense by plants, insects, and animals. In this study we have isolated a novel antimicrobial peptide from the skin of the bullfrog, Rana catesbeiana. This 20 amino acid peptide, which we have termed Ranalexin, has the amino acid sequence: NH2-Phe-Leu-Gly-Gly-Leu-Ile-Lys-Ile-Val-Pro-Ala-Met-Ile-Cys-Ala-Val-Thr- Lys-Lys - Cys-COOH, and it contains a single intramolecular disulfide bond which forms a heptapeptide ring within the molecule. Structurally, Ranalexin resembles the bacterial antibiotic, polymyxin, which contains a similar heptapeptide ring. We have also cloned the cDNA for Ranalexin from a metamorphic R. catesbeiana tadpole cDNA library. Based on the cDNA sequence, it appears that Ranalexin is initially synthesized as a propeptide with a putative signal sequence and an acidic amino acid-rich region at its amino-terminal end. Interestingly, the putative signal sequence of the Ranalexin cDNA is strikingly similar to the signal sequence of opioid peptide precursors isolated from the skin of the South American frogs Phyllomedusa sauvagei and Phyllomedusa bicolor. Northern blot analysis and in situ hybridization experiments demonstrated that Ranalexin mRNA is first expressed in R. catesbeiana skin at metamorphosis and continues to be expressed into adulthood.

Replacement of two amino acids of 9R-dioxygenase-allene oxide synthase of Aspergillus niger inverts the chirality of the hydroperoxide and the allene oxide.

Science.gov (United States)

Sooman, Linda; Wennman, Anneli; Hamberg, Mats; Hoffmann, Inga; Oliw, Ernst H

2016-02-01

The genome of Aspergillus niger codes for a fusion protein (EHA25900), which can be aligned with ~50% sequence identity to 9S-dioxygenase (DOX)-allene oxide synthase (AOS) of Fusarium oxysporum, homologues of the Fusarium and Colletotrichum complexes and with over 62% sequence identity to homologues of Aspergilli, including (DOX)-9R-AOS of Aspergillus terreus. The aims were to characterize the enzymatic activities of EHA25900 and to identify crucial amino acids for the stereospecificity. Recombinant EHA25900 oxidized 18:2n-6 sequentially to 9R-hydroperoxy-10(E),12(Z)-octadecadienoic acid (9R-HPODE) and to a 9R(10)-allene oxide. 9S- and 9R-DOX-AOS catalyze abstraction of the pro-R hydrogen at C-11, but the direction of oxygen insertion differs. A comparison between twelve 9-DOX domains of 9S- and 9R-DOX-AOS revealed conserved amino acid differences, which could contribute to the chirality of products. The Gly616Ile replacement of 9R-DOX-AOS (A. niger) increased the biosynthesis of 9S-HPODE and the 9S(10)-allene oxide, whereas the Phe627Leu replacement led to biosynthesis of 9S-HPODE and the 9S(10)-allene oxide as main products. The double mutant (Gly616Ile, Phe627Leu) formed over 90% of the 9S stereoisomer of HPODE. 9S-HPODE was formed by antarafacial hydrogen abstraction and oxygen insertion, i.e., the original H-abstraction was retained but the product chirality was altered. We conclude that 9R-DOX-AOS can be altered to 9S-DOX-AOS by replacement of two amino acids (Gly616Ile, Phe627Leu) in the DOX domain. Copyright © 2015 Elsevier B.V. All rights reserved.

[Construction of Corynebacterium crenatum AS 1.542 δ argR and analysis of transcriptional levels of the related genes of arginine biosynthetic pathway].

Science.gov (United States)

Chen, Xuelan; Tang, Li; Jiao, Haitao; Xu, Feng; Xiong, Yonghua

2013-01-04

ArgR, coded by the argR gene from Corynebacterium crenatum AS 1.542, acts as a negative regulator in arginine biosynthetic pathway. However, the effect of argR on transcriptional levels of the related biosynthetic genes has not been reported. Here, we constructed a deletion mutant of argR gene: C. crenatum AS 1.542 Delta argR using marker-less knockout technology, and compared the changes of transcriptional levels of the arginine biosynthetic genes between the mutant strain and the wild-type strain. We used marker-less knockout technology to construct C. crenatum AS 1.542 Delta argR and analyzed the changes of the relate genes at the transcriptional level using real-time fluorescence quantitative PCR. C. crenatum AS 1.542 Delta argR was successfully obtained and the transcriptional level of arginine biosynthetic genes in this mutant increased significantly with an average of about 162.1 folds. The arginine biosynthetic genes in C. crenatum are clearly controlled by the negative regulator ArgR. However, the deletion of this regulator does not result in a clear change in arginine production in the bacteria.

Bazı Bisküvi Çeşitlerinin Kimyasal Özellikleri ile Mineral ve Vitamin İçerikleri Üzerinde Araştırmalar

Directory of Open Access Journals (Sweden)

Hazım Özkaya

2015-02-01

Full Text Available Araştırmada üç firmaya ait 30 bisküvi örneğinin kimyasal bileşimleri ile mineral ve vitamin içerikleri araştırılmıştır. Bisküvi çeşitlerinin rutubet miktarları %2.1 ile %7.7 arasında değişmiş ve ortalama rutubet miktarı %4.3 olarak saptanmıştır. Kül miktarı %0.40 ile %1.54 arasında değişmiş, ortalama kül miktarı %0.74 olarak bulunmuştur. Protein miktarı çeşitler arasında %5.3 ile %10.4 arasında değişmiş ortalama protein miktarı %6.9 bulunmuştur. Örneklerin ham selüloz miktarları %0.14 ile %1.92 arasında olup ortalama ham selüloz miktarı %0.93’dür. Tuz miktarı bisküvi çeşitlerinde %0.18 ile %2.75 arasında değişmiş ortalama tuz miktarı %1.10 olarak bulunmuştur. Yağ miktarı %4.4 ile %30.5 arasında, ortalama %16.1 çıkmıştır. Örneklerin tiamin ve riboflavin miktarları sırası ile 0.35 mik. g/g ile 2.05 mik. g/g ve 0.35 mik. g/g ile 2.75 mik. g/g arasında değişmiş; ortalama tiamin ve riboflavin miktarları 0.92 mik. g/g ve 0.77 mik. g/g çıkmıştır. Ürünlerin makro ve mikro element miktarı, özellikle Fe ve Mn içerikleri normal bisküvilik una kıyasla daha yüksek bulunmuştur. Çeşitlerde saptanan mineral element miktarları birbiriyle korelasyon halinde çıkmamıştır.

Ses veya Arayüz Yardımı ile Kontrol Edilebilen Mobil Robot Kol Tasarımı

Directory of Open Access Journals (Sweden)

Köksal GÜNDOĞDU

2014-06-01

Full Text Available Robot teknolojisinin hızlı gelişimine paralel olarak mobil araç, robot kol ve ses işleme teknolojisi de hızlı bir gelişim göstermiştir. Bu teknolojik gelişmede robotlardan beklenen en önemli parametrelerin başında güvenlik, çözüm üretme ve hız gelmektedir. Bu çalışmada, mobil araç üzerine bir robot kol yerleştirilmesi ve bu sitemlerin tasarlanan arayüz ve ses sistemi ile kontrol edilerek daha verimli ve hızlı çalışması amaçlanmıştır. Amaçlar doğrultusunda önce üzerinde bir robot kol bulunan bir mobil araç tasarımı gerçekleştirilmiş, sonrada bu mobil aracın ve robot kolun hem arayüz hem de ses komutları ile kontrol edilmesi sağlanmıştır. Yapılan test sonuçları incelendiğinde ses komutları ile kontrol sisteminin, arayüz ile kontrol sistemine göre daha verimli olduğu gözlenmiştir

Intercomparison of rod-worth measurement techniques in a LEU-HTR assembly

International Nuclear Information System (INIS)

Williams, T.; Chawla, R.

1994-01-01

The measurement of absorber-rod worths in the radial reflector of a LEU-HTR pebble bed system is described. Particular emphasis is placed on the choice of complementary measurement techniques to ensure that sensitivities to systematic errors in the calculated parameters used in the analysis are minimised. (author) 3 figs., 3 tabs., 8 refs

Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women

OpenAIRE

Saliba,Louise F.; Reis,Rodrigo S.; Brownson,Ross C.; Hino,Adriano A.; Tureck,Luciane V.; Valko,Cheryl; Souza,Ricardo L.R. de; Furtado-Alle,Lupe

2014-01-01

The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (...

Comparative MD Simulations Indicate a Dual Role for Arg1323.50 in Dopamine-Dependent D2R Activation.

Directory of Open Access Journals (Sweden)

Ralf C Kling

Full Text Available Residue Arg3.50 belongs to the highly conserved DRY-motif of class A GPCRs, which is located at the bottom of TM3. On the one hand, Arg3.50 has been reported to help stabilize the inactive state of GPCRs, but on the other hand has also been shown to be crucial for stabilizing active receptor conformations and mediating receptor-G protein coupling. The combined results of these studies suggest that the exact function of Arg3.50 is likely to be receptor-dependent and must be characterized independently for every GPCR. Consequently, we now present comparative molecular-dynamics simulations that use our recently described inactive-state and Gα-bound active-state homology models of the dopamine D2 receptor (D2R, which are either bound to dopamine or ligand-free, performed to identify the function of Arg1323.50 in D2R. Our results are consistent with a dynamic model of D2R activation in which Arg1323.50 adopts a dual role, both by stabilizing the inactive-state receptor conformation and enhancing dopamine-dependent D2R-G protein coupling.

Branched-chain Amino Acid Biosensing Using Fluorescent Modified Engineered Leucine/Isoleucine/Valine Binding Protein

Directory of Open Access Journals (Sweden)

Koji Sode

2007-06-01

Full Text Available A novel fluorescence sensing system for branched-chain amino acids (BCAAswas developed based on engineered leucine/isoleucine/valine-binding proteins (LIVBPsconjugated with environmentally sensitive fluorescence probes. LIVBP was cloned fromEscherichia coli and Gln149Cys, Gly227Cys, and Gln254Cys mutants were generated bygenetic engineering. The mutant LIVBPs were then modified with environmentallysensitive fluorophores. Based on the fluorescence intensity change observed upon thebinding of the ligands, the MIANS-conjugated Gln149Cys mutant (Gln149Cys-M showedthe highest and most sensitive response. The BCAAs Leu, Ile, and Val can each bemonitored at the sub-micromolar level using Gln149Cys-M. Measurements were alsocarried out on a mixture of BCAFAs and revealed that Gln149Cys-M-based measurementis not significantly affected by the change in the molar ratio of Leu, Ile and Val in thesample. Its high sensitivity and group-specific molecular recognition ability make the newsensing system ideally suited for the measurement of BCAAs and the determination of theFischer ratio, an indicator of hepatic disease involving metabolic dysfunction.

Oral health status and treatment needs of elderly people in Ile-ife ...

African Journals Online (AJOL)

Background: Oral health is an important and often neglected component of an older person's general health and well- being. Objectives: To determine the oral health status of elderly persons in Ile-Ife, Nigeria. Methods: The oral health status of 95 elderly patients who presented at the General outpatient clinic of the Obafemi ...

Preliminary Thermohydraulic Analysis of a New Moderated Reactor Utilizing an LEU-Fuel for Space Nuclear Thermal Propulsion

International Nuclear Information System (INIS)

Nam, Seung Hyun; Choi, Jae Young; Venneria, Paolo F.; Jeong, Yong Hoon; Chang, Soon Heung

2015-01-01

The Korea Advanced NUclear Thermal Engine Rocket utilizing an LEU fuel (KANUTER-LEU) is a non-proliferative and comparably efficient NTR engine with relatively low thrust levels of 40 - 50 kN for in-space transportation. The small modular engine can expand mission versatility, when flexibly used in a clustered engine arrangement, so that it can perform various scale missions from low-thrust robotic science missions to high-thrust manned missions. In addition, the clustered engine system can enhance engine redundancy and ensuing crew safety as well as the thrust. The propulsion system is an energy conversion system to transform the thermal energy of the reactor into the kinetic energy of the propellant to produce the powers for thrust, propellant feeding and electricity. It is mainly made up of a propellant Feeding System (PFS) comprising a Turbo-Pump Assembly (TPA), a Regenerative Nozzle Assembly (RNA), etc. For this core design study, an expander cycle is assumed to be the propulsion system. The EGS converts the thermal energy of the EHTGR in the idle operation (only 350 kW th power) to electric power during the electric power mode. This paper presents a preliminary thermohydraulic design analysis to explore the design space for the new reactor and to estimate the referential engine performance. The new non-proliferative NTR engine concept, KANUTER-LEU, is under designing to surmount the nuclear proliferation obstacles on allR and Dactivities and eventual commercialization for future generations. To efficiently implement a heavy LEU fuel for the NTR engine, its reactor design innovatively possesses the key characteristics of the high U density fuel with high heating and H 2 corrosion resistances, the thermal neutron spectrum core and also minimizing non-fission neutron loss, and the compact reactor design with protectively cooling capability. To investigate feasible design space for the moderated EHTGR-LEU and resultant engine performance, the preliminary design

ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis.

Science.gov (United States)

Chen, Hao; Yang, Peng; Guo, Jing; Kwoh, Chee Keong; Przytycka, Teresa M; Zheng, Jie

2015-01-01

Meiotic recombination hotspots play important roles in various aspects of genomics, but the underlying mechanisms for regulating the locations and strengths of recombination hotspots are not yet fully revealed. Most existing algorithms for estimating recombination rates from sequence polymorphism data can only output average recombination rates of a population, although there is evidence for the heterogeneity in recombination rates among individuals. For genome-wide association studies (GWAS) of recombination hotspots, an efficient algorithm that estimates the individualized strengths of recombination hotspots is highly desirable. In this work, we propose a novel graph mining algorithm named ARG-walker, based on random walks on ancestral recombination graphs (ARG), to estimate individual-specific recombination hotspot strengths. Extensive simulations demonstrate that ARG-walker is able to distinguish the hot allele of a recombination hotspot from the cold allele. Integrated with output of ARG-walker, we performed GWAS on the phased haplotype data of the 22 autosome chromosomes of the HapMap Asian population samples of Chinese and Japanese (JPT+CHB). Significant cis-regulatory signals have been detected, which is corroborated by the enrichment of the well-known 13-mer motif CCNCCNTNNCCNC of PRDM9 protein. Moreover, two new DNA motifs have been identified in the flanking regions of the significantly associated SNPs (single nucleotide polymorphisms), which are likely to be new cis-regulatory elements of meiotic recombination hotspots of the human genome. Our results on both simulated and real data suggest that ARG-walker is a promising new method for estimating the individual recombination variations. In the future, it could be used to uncover the mechanisms of recombination regulation and human diseases related with recombination hotspots.

Isolation: analysis and properties of three bradykinin-potentiating peptides (BPP-II, BPP-III, and BPP-V) from Bothrops neuwiedi venom.

Science.gov (United States)

Ferreira, L A; Galle, A; Raida, M; Schrader, M; Lebrun, I; Habermehl, G

1998-04-01

In the course of systematic investigations on low-molecular-weight compounds from the venom of Crotalidae and Viperidae, we have isolated and characterized at least three bradykinin-potentiating peptides (BPP-II, BPP-III, and BPP-V) from Bothrops neuwiedi venom by gel filtration on Sephadex G-25 M, Sephadex G-10 followed by HPLC. The peptides showed bradykinin-potentiating action on isolated guinea-pig ileum, for which the BPP-V was more active than of BPP-II, and BPP-III, rat arterial blood pressure, and a relevant angiotensin-converting enzyme (ACE) competitive inhibiting activity. The kinetic studies showed a Ki of the order of 9.7 x 10(-3) microM to BPP-II, 7 x 10(-3) microM to BPP-III, and 3.3 x 10(-3) microM to BPP-V. The amino acid sequence of the BPP-III has been determined to be pGlu-Gly-Gly-Trp-Pro-Arg-Pro-Gly-Pro-Glu-Ile-Pro-Pro, and the amino acid compositions of the BPP-II and BPP-V by amino acid analysis were 2Glu-2Gly-1Arg-4Pro-1Ile and 2Glu-2Gly-1Ser-3Pro-2Val-1Ile, with molecular weight of 1372, 1046, and 1078, respectively.

Characterization of an endoprotease from rat small intestinal mucosal secretory granules which generates somatostatin-28 from prosomatostatin by cleavage after a single arginine residue

NARCIS (Netherlands)

Beinfeld, M. C.; Bourdais, J.; Kuks, P.; Morel, A.; Cohen, P.

1989-01-01

We have extracted, characterized, and partially purified an enzyme from secretory granules from rat small intestinal mucosa which cleaves a synthetic prosomatostatin substrate on the carboxyl side of a single arginine residue. This substrate Leu-Gln-Arg-Ser-Ala-Asn-Ser-NH2 contains the monobasic

Coevolution of the Ile1,016 and Cys1,534 Mutations in the Voltage Gated Sodium Channel Gene of Aedes aegypti in Mexico.

Directory of Open Access Journals (Sweden)

Farah Z Vera-Maloof

2015-12-01

Full Text Available Worldwide the mosquito Aedes aegypti (L. is the principal urban vector of dengue viruses. Currently 2.5 billion people are at risk for infection and reduction of Ae. aegypti populations is the most effective means to reduce the risk of transmission. Pyrethroids are used extensively for adult mosquito control, especially during dengue outbreaks. Pyrethroids promote activation and prolong the activation of the voltage gated sodium channel protein (VGSC by interacting with two distinct pyrethroid receptor sites [1], formed by the interfaces of the transmembrane helix subunit 6 (S6 of domains II and III. Mutations of S6 in domains II and III synergize so that double mutants have higher pyrethroid resistance than mutants in either domain alone. Computer models predict an allosteric interaction between mutations in the two domains. In Ae. aegypti, a Ile1,016 mutation in the S6 of domain II was discovered in 2006 and found to be associated with pyrethroid resistance in field populations in Mexico. In 2010 a second mutation, Cys1,534 in the S6 of domain III was discovered and also found to be associated with pyrethroid resistance and correlated with the frequency of Ile1,016.A linkage disequilibrium analysis was performed on Ile1,016 and Cys1,534 in Ae. aegypti collected in Mexico from 2000-2012 to test for statistical associations between S6 in domains II and III in natural populations. We estimated the frequency of the four dilocus haplotypes in 1,016 and 1,534: Val1,016/Phe1,534 (susceptible, Val1,016/Cys1,534, Ile1,016/Phe1,534, and Ile1,016/Cys1,534 (resistant. The susceptible Val1,016/Phe1,534 haplotype went from near fixation to extinction and the resistant Ile1,016/Cys1,534 haplotype increased in all collections from a frequency close to zero to frequencies ranging from 0.5-0.9. The Val1,016/Cys1,534 haplotype increased in all collections until 2008 after which it began to decline as Ile1,016/Cys1,534 increased. However, the Ile1,016/Phe1

Stereochemical studies of the monocyclic agouti-related protein (103-122) Arg-Phe-Phe residues: conversion of a melanocortin-4 receptor antagonist into an agonist and results in the discovery of a potent and selective melanocortin-1 agonist.

Science.gov (United States)

Joseph, Christine G; Wang, Xiang S; Scott, Joseph W; Bauzo, Rayna M; Xiang, Zhimin; Richards, Nigel G; Haskell-Luevano, Carrie

2004-12-30

The agouti-related protein (AGRP) is an endogenous antagonist of the centrally expressed melanocortin receptors. The melanocortin-4 receptor (MC4R) is involved in energy homeostasis, food intake, sexual function, and obesity. The endogenous hAGRP protein is 132 amino acids in length, possesses five disulfide bridges at the C-terminus of the molecule, and is expressed in the hypothalamus of the brain. We have previously reported that a monocyclic hAGRP(103-122) peptide is an antagonist at the melanocortin receptors expressed in the brain. Stereochemical inversion from the endogenous l- to d-isomers of single or multiple amino acid modifications in this monocyclic truncated hAGRP sequence resulted in molecules that are converted from melanocortin receptor antagonists into melanocortin receptor agonists. The Asp-Pro-Ala-Ala-Thr-Ala-Tyr-cyclo[Cys-Arg-DPhe-DPhe-Asn-Ala-Phe-Cys]-Tyr-Ala-Arg-Lys-Leu peptide resulted in a 60 nM melanocortin-1 receptor agonist that is 100-fold selective versus the mMC4R, 1000-fold selective versus the mMC3R, and ca. 180-fold selective versus the mMC5R. In attempts to identify putative ligand-receptor interactions that may be participating in the agonist induced stimulation of the MC4R, selected ligands were docked into a homology molecular model of the mMC4R. These modeling studies have putatively identified hAGRP ligand DArg111-mMC4RAsn115 (TM3) and the hAGRP DPhe113-mMC4RPhe176 (TM4) interactions as important for agonist activity.

ABSORPSİYONLU SOGUTMA SİSTEMLERİ ile KLASiK SİSTEMLERİN KARŞILAŞTIRILMASI

Directory of Open Access Journals (Sweden)

MUSTAFA ÇELİK

2003-04-01

Full Text Available Bu çalışmada, doğalgaz ile çalışan absorpsiyonlu soğutma sistenıi ve klasik soğutma sisteminin karşıl aştırılması yapılmıştır. LiBr-H20 eriyiği kullanan bir ticari absorpsiyon makinasının sistem eleman larının termodinamik analizi yapılmıştır. Bu sistemde soğutma devresi eşa njörü ve eriyik devresi eşanjörlü sistem ile eş anjörsüz sistemlerin soğutma tesir katsayıları (STK ve ısıtma tesir katsayıları (ITK hesaplanarak, karşılaştırılması yapılmıştır. Bir vi Ila için LiBr-H20 eriyiği kulJaoan 23 KW'lık soğutma yüküne sahip absorpsiyon makinası ile klasik sisteme göre çalışa n soğutma makinasının ilk yatırım ve işletme giderlerine göre karşılaştırılmaları yapılmıştır

Neutron flux measurement in the central channel (XC-1) of TRIGA 14 MW LEU core

International Nuclear Information System (INIS)

BARBOS, D.; BUSUIOC, P.; ROTH, Cs.; PAUNOIU, C.

2008-01-01

The TRIGA 14 MW reactor, operated by Institute for Nuclear Research Pitesti, Romania, is a pool type reactor, and has a rectangular shape which holds fuel bundles and is surrounded with beryllium reflectors. Each fuel bundle is composed of 25 nuclear fuel rods. The TRIGA 14 MW reactor was commissioned 28 years ago with HEU fuel rods. The conversion was gradually achieved, starting in February 1992 and completed in March 2006. The full conversion of the 14 MW TRIGA Research Reactor was completed in May 2006 and each step of the conversion was achieved by removal of HEU fuel, replaced by LEU fuel, accompanied by a large set of theoretical evaluation and physical measurements intended to confirm the performances of gradual conversion. After the core full conversion, a program of measurements and comparisons with previous results of core physics and measurements is underway, allowing data acquisition for normal operation, demonstration of safety and economics of the converted core. Neutron flux spectrum measurements in the XC in the XC-1 water 1 water-filled channel were performed using multi multi-foil activation techniques. The neutron spectra and flux are obtained by unfolding from measured reaction rates using SAND II computer code. The integral neutron flux value for LEU core is greater of 13% than for the standard HEU core. Also thermal neutron flux value for converted LEU core is smaller by 0.38% than for the standard HEU core. These differences appear because the foil activation detectors have been irradiated using a pneumatic rabbit having a diameter of 32 mm, whereas foil irradiations in standard HEU core has been performed with a pneumatic rabbit having a diameter of 14 mm, and therefore the neutron spectra in LEU core is less thermalized and the weight of fast neutron is greater

A Conserved Leucine Occupies the Empty Substrate Site of LeuT in the Na+-free Return State

DEFF Research Database (Denmark)

Malinauskaite, Lina; Said, Saida; Sahin, Caglanur

2016-01-01

Bacterial members of the neurotransmitter:sodium symporter (NSS) family perform Na+-dependent amino-acid uptake and extrude H+ in return. Previous NSS structures represent intermediates of Na+/substrate binding or intracellular release, but not the inward-to-outward return transition. Here we...... report crystal structures of Aquifex aeolicus LeuT in an outward-oriented, Na+- and substrate-free state likely to be H+-occluded. We find a remarkable rotation of the conserved Leu25 into the empty substrate-binding pocket and rearrangements of the empty Na+ sites. Mutational studies of the equivalent...

Data of evolutionary structure change: 1BS5A-3CPMA [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1BS5A-3CPMA 1BS5 3CPM A A -----SVLQVLHIPDERLRKVAKPVEEVNAEIQRIVDDM...line> 3CPM A 3CPMA THR CA 218 GLY CA 252 ILE CA 234 3CPM... A 3CPMA IKKYSDKLVPFILE CA 320 ARG CA 317 GLN CA 243 3CPM

ADRB3 Gene Trp64Arg Polymorphism and Essential Hypertension: A Meta-Analysis Including 9,555 Subjects.

Science.gov (United States)

Li, Yan-Yan; Lu, Xin-Zheng; Wang, Hui; Zhou, Yan-Hong; Yang, Xin-Xing; Geng, Hong-Yu; Gong, Ge; Kim, Hyun Jun

2018-01-01

Background: Presence of the β 3-Adrenergic receptor (ADRB3) gene Trp64Arg (T64A) polymorphism may be associated with an increased susceptibility for essential hypertension (EH). A clear consensus, however, has yet to be reached. Objective and methods: To further elucidate the relationship between the ADRB3 gene Trp64Arg polymorphism and EH, a meta-analysis of 9,555 subjects aggregated from 16 individual studies was performed. The combined odds ratios (ORs) and their corresponding 95% confidence intervals (CI) were evaluated using either a random or fixed effect model. Results: We found a marginally significant association between ADRB3 gene Trp64Arg polymorphism and EH in the whole population under the additive genetic model (OR: 1.200, 95% CI: 1.00-1.43, P = 0.049). Association within the Chinese subgroup, however, was significant under allelic (OR: 1.150, 95% CI: 1.002-1.320, P = 0.046), dominant (OR: 1.213, 95% CI: 1.005-1.464, P = 0.044), heterozygous (OR: 1.430, 95% CI:1.040-1.970, P = 0.03), and additive genetic models (OR: 1.280, 95% CI: 1.030-1.580, P = 0.02). A significant association was also found in the Caucasian subgroup under allelic (OR: 1.850, 95% CI: 1. 260-2.720, P = 0.002), dominant (OR: 2.004, 95% CI: 1.316-3.052, P = 0.001), heterozygous (OR: 2.220, 95% CI: 1.450-3.400, P = 0.0002), and additive genetic models (OR: 2.000, 95% CI: 1. 330-3.010, P = 0.0009). Conclusions: The presence of the ADRB3 gene Trp64Arg polymorphism is positively associated with EH, especially in the Chinese and Caucasian population. The Arg allele carriers of ADRB3 gene Trp64Arg polymorphism may be at an increased risk for developing EH.

Thermal-hydraulic analysis of research reactor core with different LEU fuel types using RELAP5

Energy Technology Data Exchange (ETDEWEB)

El-Sahlamy, Neama M. [Nuclear and Radiological Regulatory Authority, Cairo (Egypt)

2017-11-15

In the current work, comparisons between the core performances when using different LEU fuels are done. The fuels tested are UA1{sub X}-A1, U{sub 3}O{sub 8}-Al, and U{sub 3}Si{sub 2}-Al fuels with 19.7 % enrichment. Calculations are done using RELAP5 code to evaluate the thermal-hydraulic performance of the IAEA benchmark 10 MW reactor. First, a reassessment of the slow reactivity insertion transient with UA1{sub X}-A1 LEU fuel to compare the results with those reported in the IAEA TECDOC [1]. Then, comparisons between the thermal-hydraulic core performances when using the three LEU fuels are done. The assessment is performed at initial power of 1.0 W. The reactor power is calculated using the RELAP5 point kinetic model. The reactivity feedback, from changes in water density and fuel temperature, is considered for all cases. From the results it is noticed that U{sub 3}Si{sub 2}-Al fuel gives the best fuel performance since it has the minimum value of peak fuel temperature and the minimum peak clad surface temperature, as operating parameters. Also, it gives the maximum value of the Critical Heat Flux Ratio and the lowest tendency to flow instability occurrence.

Neutronic analysis of the JMTR with LEU fuel and burnable poison

Energy Technology Data Exchange (ETDEWEB)

Nagaoka, Yoshiharu; Oyamada, Rokuro [Japan Atomic Energy Research Institute, Oarai-machi Ibaraki-ken (Japan); Matos, J E; Woodruff, W L [Argonne National Laboratory, Argonne, IL (United States)

1985-07-01

The results of neutronics calculations are presented for the JMTR equilibrium core with LEU silicide fuel, boron and cadmium burnable poisons in the sideplates, and a cycle length of 24 days instead of 11 days with the current HEU fuel. The data indicate that several options are feasible provided that silicide fuels with high uranium densities are successfully demonstrated and licensed (author)

Neutronic analysis of the JMTR with LEU fuel and burnable poison

International Nuclear Information System (INIS)

Nagaoka, Yoshiharu; Oyamada, Rokuro; Matos, J.E.; Woodruff, W.L.

1985-01-01

The results of neutronics calculations are presented for the JMTR equilibrium core with LEU silicide fuel, boron and cadmium burnable poisons in the sideplates, and a cycle length of 24 days instead of 11 days with the current HEU fuel. The data indicate that several options are feasible provided that silicide fuels with high uranium densities are successfully demonstrated and licensed (author)

Penetrance of NOD2/CARD15 genetic variants in the general population

DEFF Research Database (Denmark)

Yazdanyar, Shiva; Kamstrup, Pia R; Tybjaerg-Hansen, Anne

2010-01-01

In case-control studies of Europeans, heterozygosity for Arg702Trp(rs2066844), Gly908Arg(rs2066845) and Leu1007fsinsC(rs5743293) on the NOD2/CARD15 gene is associated with a 2-fold greater risk of Crohn disease, whereas homozygosity or compound heterozygosity is associated with a 17-fold greater ...... risk. However, the importance of these genetic variants if identified in particular individuals within the general population is unknown. We undertook this study to estimate the penetrance of these variants in the general population....

Association between the ghrelin Leu72Met polymorphism and type 2 diabetes risk: a meta-analysis.

Science.gov (United States)

Liao, Ning; Xie, Zi-Kang; Huang, Jian; Xie, Zheng-Fu

2013-04-01

Data on the association between the ghrelin Leu72Met polymorphism and type 2 diabetes are conflicting. A meta-analysis was performed on this topic. We searched for case-control studies using electronic databases (Medline and PubMed) and reference lists of studies. Odds ratios (OR) and 95% confidence intervals (CI) assuming dominant, recessive and homozygote comparison genetic models were calculated. Six case-control studies involving a total of 3417 cases and 3081 controls were included in this meta-analysis. No association was found between the ghrelin Leu72Met polymorphism and type 2 diabetes risk in the overall population in dominant, recessive and homozygote comparison models. However, in subgroup analyses stratified by ethnicity, we found that the risk for type 2 diabetes was decreased in subjects with Met72+ genotypes in Caucasians (OR=0.79, 95% CI: 0.64-0.98, P(z)=0.030). The ghrelin Leu72Met polymorphism was protective against type 2 diabetes in Caucasians. Future studies performed in larger sample size are needed to allow a more definitive conclusion. Copyright © 2012 Elsevier B.V. All rights reserved.

Chimeric NDP-MSH and MTII melanocortin peptides with agouti-related protein (AGRP) Arg-Phe-Phe amino acids possess agonist melanocortin receptor activity.

Science.gov (United States)

Joseph, Christine G; Wilczynski, Andrzej; Holder, Jerry R; Xiang, Zhimin; Bauzo, Rayna M; Scott, Joseph W; Haskell-Luevano, Carrie

2003-12-01

Agouti-related protein (AGRP) is one of only two known endogenous antagonists of G-protein coupled receptors (GPCRs). Specifically, AGRP antagonizes the brain melanocortin-3 and -4 receptors involved in energy homeostasis, regulation of feeding behavior, and obesity. Alpha-melanocyte stimulating hormone (alpha-MSH) is one of the known endogenous agonists for these receptors. It has been hypothesized that the Arg-Phe-Phe (111-113) human AGRP amino acids may be mimicking the melanocortin agonist Phe-Arg-Trp (7-9) residue interactions with the melanocortin receptors that are important for both receptor molecular recognition and stimulation. To test this hypothesis, we generated thirteen chimeric peptide ligands based upon the melanocortin agonist peptides NDP-MSH (Ac-Ser-Tyr-Ser-Nle4-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2) and MTII (Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2). In these chimeric ligands, the agonist DPhe-Arg-Trp amino acids were replaced by the AGRP Arg-Phe-Phe residues, and resulted in agonist activity at the mouse melanocortin receptors (mMC1R and mMC3-5Rs), supporting the hypothesis that the AGRP antagonist ligand Arg-Phe-Phe residues mimic the agonist Phe-Arg-Trp amino acids. Interestingly, the Ac-Ser-Tyr-Ser-Nle4-Glu-His-Arg-DPhe-Phe-Gly-Lys-Pro-Val-NH2 peptide possessed 7 nM mMC1R agonist potency, and is 850-fold selective for the mMC1R versus the mMC3R, 2300-fold selective for the mMC1R versus the mMC4R, and 60-fold selective for the MC1R versus the mMC5R, resulting in the discovery of a new peptide template for the design of melanocortin receptor selective ligands.

Low-temperature heat capacity and thermodynamic properties of [Re2(Ile)4(H2O)8](ClO4)6 (Re=Nd, Er, Ile=isoleucine)

International Nuclear Information System (INIS)

Lan Xiaozheng; Tan Zhicheng; Liu Beiping; Nan Zhaodong; Sun Lixian; Xu Fen

2003-01-01

The heat capacities of two kinds of rare-earth element solid complexes with isoleucine [Re 2 (Ile) 4 (H 2 O) 8 ](ClO 4 ) 6 (where Re=Nd, Er, and Ile=isoleucine) have been measured by an automatic adiabatic calorimeter in the temperature range from 80 to 370 K. Two solid-solid phase transitions were found from the C p curve of Nd formed complex in the range of 165-175 K with a peak temperature of 167.88 K and in the range of 195-210 K with a peak temperature of 202.13 K. The corresponding molar enthalpies of these phase transitions were determined to be 404.61 J mol -1 and 2.955 kJ mol -1 , respectively. One solid-solid phase transition was found for the Er formed complex in the range of 190-205 K with a peak temperature of 193.42 K. The corresponding molar enthalpy of this transition was 14.11 kJ mol -1 . Smooth heat capacities and thermodynamic functions relative to the standard state (298.15 K), H T -H 298.15 , S T -S 298.15 and -[G T -G 298.15 ], of the two compounds, were calculated on basis of experimental heat capacity data. Possible mechanisms of thermal decompositions for the pair of compounds were suggested according to the thermogravimetric (TG) analysis

Preliminary Thermohydraulic Analysis of a New Moderated Reactor Utilizing an LEU-Fuel for Space Nuclear Thermal Propulsion

Energy Technology Data Exchange (ETDEWEB)

Nam, Seung Hyun; Choi, Jae Young; Venneria, Paolo F.; Jeong, Yong Hoon; Chang, Soon Heung [KAIST, Daejeon (Korea, Republic of)

2015-10-15

The Korea Advanced NUclear Thermal Engine Rocket utilizing an LEU fuel (KANUTER-LEU) is a non-proliferative and comparably efficient NTR engine with relatively low thrust levels of 40 - 50 kN for in-space transportation. The small modular engine can expand mission versatility, when flexibly used in a clustered engine arrangement, so that it can perform various scale missions from low-thrust robotic science missions to high-thrust manned missions. In addition, the clustered engine system can enhance engine redundancy and ensuing crew safety as well as the thrust. The propulsion system is an energy conversion system to transform the thermal energy of the reactor into the kinetic energy of the propellant to produce the powers for thrust, propellant feeding and electricity. It is mainly made up of a propellant Feeding System (PFS) comprising a Turbo-Pump Assembly (TPA), a Regenerative Nozzle Assembly (RNA), etc. For this core design study, an expander cycle is assumed to be the propulsion system. The EGS converts the thermal energy of the EHTGR in the idle operation (only 350 kW{sub th} power) to electric power during the electric power mode. This paper presents a preliminary thermohydraulic design analysis to explore the design space for the new reactor and to estimate the referential engine performance. The new non-proliferative NTR engine concept, KANUTER-LEU, is under designing to surmount the nuclear proliferation obstacles on allR and Dactivities and eventual commercialization for future generations. To efficiently implement a heavy LEU fuel for the NTR engine, its reactor design innovatively possesses the key characteristics of the high U density fuel with high heating and H{sub 2} corrosion resistances, the thermal neutron spectrum core and also minimizing non-fission neutron loss, and the compact reactor design with protectively cooling capability. To investigate feasible design space for the moderated EHTGR-LEU and resultant engine performance, the

Decapeptides as effective agonists from L-amino acids biologically equivalent to the luteinizing hormone-releasing hormone

International Nuclear Information System (INIS)

Folkers, K.; Bowers, C.Y.; Tang, P.L.; Kubota, M.

1986-01-01

Apparently, no agonist has been found that is comparable in potency to the luteinizing hormone-releasing hormone (LHRH) for release of LH and follicle-stimulating hormone (FSH) without substitutions with unnatural or D forms of natural amino acids. Of 139 known agonist analogs of LHRH, two were active in the range of 65%. The four LHRHs known to occur in nature involve a total of six amino acids (Tyr, His, Leu, Trp, Arg, Gln) in positions 5, 7, and 8. There are 16 possible peptides with these six amino acids in positions 5, 7, and 8, of which 4 are the known LHRHs, and 2 more were synthesized. The authors have synthesized the 10 new peptides and assayed 11 in vivo and in vitro, and they found not only 1 but a total of 5 that have activity equivalent to or greater than that of LHRH for the release of LH and/or FSH under at least one assay condition. These five are as follows: [His 5 ,Trp 7 ,Gln 8 ]LHRH; [His 5 ,Trp 7 ,Leu 8 ]LHRH; [His 5 ,Trp 7 ]LHRH; [Trp 7 ]LHRH; [His 5 ]LHRH. These structures are a basis for the design of antagonists without Arg 8 toward avoiding histamine release. Complete inhibition of LH and FSH release in vivo may be induced by joint use of Arg 8 and Gln 8 or Leu 8 antagonists. These potent agonists, related to LHRH, may be therapeutically useful in disorders of reproduction, the central nervous system, and for the control of hormone-dependent carcinomas. Radioreceptor assays and radioimmunoassays were utilized

Familial hypofibrinogenaemia associated with heterozygous substitution of a conserved arginine residue; Bbeta255 Arg-->His (Fibrinogen Merivale).

Science.gov (United States)

Maghzal, Ghassan J; Brennan, Stephen O; Fellowes, Andrew P; Spearing, Ruth; George, Peter M

2003-02-21

Sequencing of all three fibrinogen genes from an individual with hypofibrinogenaemia led to the identification of two new point mutations in the Bbeta gene. Family studies showed the mutations Bbeta255 Arg-->His (Fibrinogen Merivale) and Bbeta148 Lys-->Asn (Fibrinogen Merivale II) were on different alleles and that only the Bbeta255 Arg-->His mutation segregated with hypofibrinogenaemia. Three simple heterozygotes for this mutation had mean fibrinogen concentrations of 1.4 mg/ml, while heterozygotes for the Bbeta148 Lys-->Asn mutation had normal fibrinogen concentrations. ESI MS analysis of endoproteinase Asp-N digests of Bbeta chains showed that the Bbeta255 Arg-->His substitution was not expressed in plasma, confirming it as the cause of the hypofibrinogenaemia. The Bbeta148 Lys-->Asn chains, on the other hand, were equally expressed with wild-type Bbeta chains in simple heterozygotes. Genotype analysis failed to detect either substitution in 182 healthy controls. Arg(255) is located in the first strand of the five-stranded sheet that forms the main feature of the betaD domain and appears to form an essential H bond with Gly(414). Both the Arg and Gly are absolutely conserved, not only in all known Bbeta chains, but also in all homologous alphaE and gamma chains and in all fibrinogen-related proteins. Protein instability from loss of this contact could easily explain the association of this mutation with hypofibrinogenaemia.

Childhood intussusception in Ile-ife: What has changed?

Directory of Open Access Journals (Sweden)

Ademola Olusegun Talabi

2013-01-01

Full Text Available Background: Intussusception is one of the most common causes of intestinal obstruction in children. While the outcome has improved in the developed nations, the same cannot be said of the developing countries, more especially in the sub-Saharan region. This study aims to review our current experience in the management of childhood intussusception and factors affecting surgical outcome at the Obafemi Awolowo University Teaching Hospitals Complex Ile-Ife. Patients and Methods: This was a retrospective study of 78 patients treated for intussusception at paediatric surgical unit of Obafemi Awolowo University Teaching Hospitals Complex Ile-Ife between January 1993 and December 2011. The case notes of the patients were retrieved and the following information was recorded: Demographic characteristics, month of occurrence, clinical presentation, investigations, and management as well as the post-operative outcome. The patients were divided into two groups in terms of outcome. Results: There were 58 males and 20 females (M:F = 2.9-1. The age of most of the patients was between 3 months and 9 months with peak incidence at 6 months. Most patients 46 (58.9% were seen during the dry season of December to April. Only six patients (7.7% presented within 24 hours of onset of illness. More than half of the patients presented after 24 hours. Passage of red currant stool, vomiting, abdominal pain, fever, and abdominal distension, passage of watery stool, anal protrusion and palpable abdominal mass in various combinations were the clinical features. All the patients had surgical operations. The most common type of intussusception was ileo-colic type in 64 patients (82.1%. Intestinal resection rate was 41%. The overall mortality rate was 15.4%. Conclusion: There was a delay in presentation of children with intussusception with high post-operative mortality.

New cyclic peptides with osteoblastic proliferative activity from Dianthus superbus.

Science.gov (United States)

Tong, Yun; Luo, Jian-Guang; Wang, Rui; Wang, Xiao-Bing; Kong, Ling-Yi

2012-03-01

Two new cyclic peptides, dianthins G-H (1 and 2), together with the known dianthin E (3), were isolated from the traditional Chinese medicinal plant Dianthus superbus. The sequences of cyclic peptides 1 and 2 were elucidated as cyclo (-Gly(1)-Pro(2)-Leu(3)-Thr(4)-Leu(5)-Phe(6)-) and cyclo (-Gly(1)-Pro(2)-Val(3)-Thr(4)-Ile(5)-Phe(6)-), on the basis of ESI tandem mass fragmentation analysis, extensive 2D NMR methods and X-ray diffraction. The isolated three compounds all increase proliferation of MC3T3-E1 cells in vitro using MTT method. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evidence of an association between the Arg72 allele of the peptide YY and increased risk of type 2 diabetes

DEFF Research Database (Denmark)

Torekov, Signe S; Larsen, Lesli H; Glümer, Charlotte

2005-01-01

We tested the hypothesis that variants in the gene encoding the prepropeptide YY (PYY) associate with type 2 diabetes and/or obesity. Mutation analyses of DNA from 84 patients with obesity and familial type 2 diabetes identified two polymorphisms, IVS3 + 68C>T and Arg72Thr, and one rare variant......, +151C>A of PYY. The common allele of the Arg72Thr variant associated with type 2 diabetes with an allele frequency of the Arg allele of 0.667 (95% CI 0.658-0.677) among 4,639 glucose-tolerant subjects and 0.692 (0.674-0.710) among 1,326 patients with type 2 diabetes (P = 0.005, odds ratio 1.19 [95% CI...... tolerance test (OGTT) (P = 0.03), an increased area under the curve for the post-OGTT plasma glucose level (P = 0.03), and a lower insulinogenic index (P = 0.01). In conclusion, the common Arg allele of the PYY Arg72Thr variant modestly associates with type 2 diabetes and with type 2 diabetes...

Fuel conversion of JRR-4 from HEU to LEU

International Nuclear Information System (INIS)

Ichikawa, Hiroki; Nakajima, Teruo

1997-01-01

Japanese JRR-4 (Japan Research Reactor No.4) is a pool type, light water moderated and cooled, ETR type fuel reactor used for Shielding experiments, isotope production, neutron activation analyses, Si doping, reactor students training. It acieved first criticality on January 28, 1965 with maximum thermal power 3.5MW. The standard core consistes of 20 Fuel elements, 7 control rods 5 Irradiation holes, neutron source, graphite reflectors. Available thermal flux is 7x1013 n/cm2/s. Within the RERTR program plans are made for core conversion from HEU to LEU

TRIGA high wt -% LEU fuel development program. Final report

International Nuclear Information System (INIS)

West, G.B.

1980-07-01

The principal purpose of this work was to investigate the characteristics of TRIGA fuel where the contained U-235 was in a relatively high weight percent (wt %) of LEU (low enriched uranium - enrichment of less than 20%) rather than a relatively low weight percent of HEU (high enriched uranium). Fuel with up to 45 wt % U was fabricated and found to be acceptable after metallurgical examinations, fission product retention tests and physical property examinations. Design and safety analysis studies also indicated acceptable prompt negative temperature coefficient and core lifetime characteristics for these fuels

Further data of silicide fuel for the LEU conversion of JMTR

International Nuclear Information System (INIS)

Saito, M.; Futamura, Y.; Nakata, H.; Ando, H.; Sakurai, F.; Ooka, N.; Sakakura, A.; Ugajin, M.; Shirai, E.

1990-01-01

Silicide fuel data for the safety assessment of the JMTR LEU fuel conversion are being measured. The data include fission product release, thermal properties, behaviour under accident conditions, and metallurgical characteristics. The methods used in the experiments are discussed. Results of fission products release at high temperature are described. The release of iodine from the silicide fuel is considerably lower than for U-Al alloy fuel

Neutronic analysis of the JMTR with LEU fuel and burnable poison

International Nuclear Information System (INIS)

Nagaoka, Yoshiharu; Oyamada, Rokuro; Matos, J.E.; Woodruff, W.L.

1984-01-01

The results of neutronics calculations are presented for the JMTR equilibrium core with LEU silicide fuel, boron and cadmium burnable poisons in the sideplates, and a cycle length of 24 days instead of 11 days with the current HEU fuel. The data indicate that several options are feasible provided that silicide fuels with high uranium densities are successfully demonstrated and licensed. 2 refs., 10 figs., 5 tabs

Paraoxonase-1 genetic polymorphisms and susceptibility to DNA damage in workers occupationally exposed to organophosphate pesticides

International Nuclear Information System (INIS)

Singh, Satyender; Kumar, Vivek; Thakur, Sachin; Banerjee, Basu Dev; Rautela, Rajender Singh; Grover, Shyam Sunder; Rawat, Devendra Singh; Pasha, Syed Tazeen; Jain, Sudhir Kumar; Ichhpujani, Rattan Lal; Rai, Arvind

2011-01-01

Human paraoxonase 1 (PON1) is a lipoprotein-associated enzyme involved in the detoxification of organophosphate pesticides (OPs) by hydrolyzing the bioactive oxons. Polymorphisms of the PON1 gene are responsible for variation in the expression and catalytic activity of PON1 enzyme. In the present study, we have determined (a) the prevalence of two common PON1 polymorphisms, (b) the activity of PON1 and acetylcholinesterase enzymes, and (c) the influence of PON1 genotypes and phenotypes variation on DNA damage in workers exposed to OPs. We examined 230 subjects including 115 workers exposed to OPs and an equal number of normal healthy controls. The results revealed that PON1 activity toward paraoxon (179.19 ± 39.36 vs. 241.52 ± 42.32 nmol/min/ml in controls) and phenylacetate (112.74 ± 17.37 vs. 134.28 ± 25.49 μmol/min/ml in controls) was significantly lower in workers than in control subjects (p 192 QR (Gln/Arg) and PON1 55 LM (Leu/Met) in workers and control subjects (p > 0.05). The PON1 activity toward paraoxonase was found to be significantly higher in the R/R (Arg/Arg) genotypes than Q/R (Gln/Arg) and lowest in Q/Q (Gln/Gln) genotypes in both workers and control subjects (p 55 LM (Leu/Met), PON1 activity toward paraoxonase was observed to be higher in individuals with L/L (Leu/Leu) genotypes and lowest in individuals with M/M (Met/Met) genotypes in both groups (p < 0.001). No influence of PON1 genotypes and phenotypes was seen on the activity of acetylcholinesterase and arylesterase. The DNA damage was observed to be significantly higher in workers than in control subjects (p < 0.05). Further, the individuals who showed least paraoxonase activity i.e., those with (Q/Q [Gln/Gln] and M/M [Met/Met]) genotypes showed significantly higher DNA damage compared to other isoforms in workers exposed to OPs (p < 0.05). The results indicate that the individuals with PON1 Q/Q and M/M genotypes are more susceptible toward genotoxicity. In conclusion, the study suggests

Arg354 in the catalytic centre of bovine liver catalase is protected from methylglyoxal-mediated glycation.

Science.gov (United States)

Scheckhuber, Christian Q

2015-12-30

In addition to controlled post-translational modifications proteins can be modified with highly reactive compounds. Usually this leads to a compromised functionality of the protein. Methylglyoxal is one of the most common agents that attack arginine residues. Methylglyoxal is also regarded as a pro-oxidant that affects cellular redox homeostasis by contributing to the formation of reactive oxygen species. Antioxidant enzymes like catalase are required to protect the cell from oxidative damage. These enzymes are also targets for methylglyoxal-mediated modification which could severely affect their catalytic activity in breaking down reactive oxygen species to less reactive or inert compounds. Here, bovine liver catalase was incubated with high levels of methylglyoxal to induce its glycation. This treatment did not lead to a pronounced reduction of enzymatic activity. Subsequently methylglyoxal-mediated arginine modifications (hydroimidazolone and dihydroxyimidazolidine) were quantitatively analysed by sensitive nano high performance liquid chromatography/electron spray ionisation/tandem mass spectrometry. Whereas several arginine residues displayed low to moderate levels of glycation (e.g., Arg93, Arg365, Arg444) Arg354 in the active centre of catalase was never found to be modified. Bovine liver catalase is able to tolerate very high levels of the modifying α-oxoaldehyde methylglyoxal so that its essential enzymatic function is not impaired.

Core instrumentation and pre-operational procedures for core conversion HEU to LEU

International Nuclear Information System (INIS)

1984-02-01

This report is intended for the reactor operator, to be used as a manual or checklist for general guidance on pre-startup activities that need to be addressed in preparation for conversion to Low Enriched Fuel (LEU). All nuclear, thermodynamic and safety calculations should have been performed prior to this stage of the core conversion process. During these calculations and certainly before ordering the new LEU fuel elements the reactor operator needs to very carefully consider additional important factors concerning the new fuel: fuel reliability, reliability of fuel fabricator, reprocessing contract or fuel element storage and disposal, economics of the new fuel cycle. At this stage, too, a preoperational experimental programme has to be developed and presented to the regulatory authorities for approval. This experimental programme could lead to additional requirements on: in-core instrumentation, out-of-core instrumentation or additional experimental devices. Detailed instructions on specific tests and measurements are not provided in this report since much information on the subject is available in the open literature

Antidepressant Specificity of Serotonin Transporter Suggested by Three LeuT-SSRI Structures

Energy Technology Data Exchange (ETDEWEB)

Zhou, Z.; Zhen, J; Karpowich, N; Law, C; Reith, M; Wang, D

2009-01-01

Sertraline and fluoxetine are selective serotonin re-uptake inhibitors (SSRIs) that are widely prescribed to treat depression. They exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter (SERT). All SSRIs possess halogen atoms at specific positions, which are key determinants for the drugs' specificity for SERT. For the SERT protein, however, the structural basis of its specificity for SSRIs is poorly understood. Here we report the crystal structures of LeuT, a bacterial SERT homolog, in complex with sertraline, R-fluoxetine or S-fluoxetine. The SSRI halogens all bind to exactly the same pocket within LeuT. Mutation at this halogen-binding pocket (HBP) in SERT markedly reduces the transporter's affinity for SSRIs but not for tricyclic antidepressants. Conversely, when the only nonconserved HBP residue in both norepinephrine and dopamine transporters is mutated into that found in SERT, their affinities for all the three SSRIs increase uniformly. Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP.

Microcystis aeruginos strain [D-Leu1] Mcyst-LR producer, from Buenos Aires province, Argentina

Directory of Open Access Journals (Sweden)

Lorena Rosso

2014-04-01

Full Text Available Objective: To show the toxicological and phylogenetic characterization of a native Microcystis aeruginosa (M. aeruginosa strain (named CAAT 2005-3 isolated from a water body of Buenos Aires province, Argentine. Methods: A M. aeruginosa strain was isolated from the drainage canal of the sewage treatment in the town of Pila, Buenos Aires province, Argentina and acclimated to laboratory conditions. The amplification of cpcBA-IGS Phcocyanin (PC, intergenic spacer and flanking regions was carried out in order to build a phylogenetic tree. An exactive/orbitrap mass spectrometer equipped with an electrospray ionization source (Thermo Fisher Scientific, Bremen, Germany was used for the LC/ESI-HRMS microcystins analysis. The number of cell/mL and [D-Leu1] Mcyst-LR production obtained as a function of time was modelled using the Gompertz equation. Results: The phylogenetic analysis showed that the sequence clustered with others M. aeruginosa sequences obtained from NCBI. The first Argentinian strain of M. aeruginosa (CAAT 2005-3 growing under culture conditions maintains the typical colonial architecture of M. aeruginosa with profuse mucilage. M. aeruginosa CAAT 2005-3 expresses a toxin variant, that was identified by LC-HRMS/Orbitrapas as [D-Leu1] microcystin-LR ([M+H]+=1 037.8 m/z. Conclusions: [D-Leu1] microcystin-LR has been also detected in M. aeruginosa samples from Canada, Brazil and Argentina. This work provides the basis for technological development and production of analytical standards of toxins present in our region.

Installation and Testing Instructions for the Sandia Automatic Report Generator (ARG).

Energy Technology Data Exchange (ETDEWEB)

Clay, Robert L.

2018-04-01

Robert L. CLAY Sandia National Laboratories P.O. Box 969 Livermore, CA 94551, U.S.A. rlclay@sandia.gov In this report, we provide detailed and reproducible installation instructions of the Automatic Report Generator (ARG), for both Linux and macOS target platforms.

Parental Socio-Economic Status as Correlate of Child Labour in Ile-Ife, Nigeria

Science.gov (United States)

Elegbeleye, O. S.; Olasupo, M. O.

2012-01-01

This study investigated the relationship between parental socio-economic status and child labour practices in Ile-Ife, Nigeria. The study employed survey method to gather data from 200 parents which constituted the study population. Pearson Product Moment Correlation and t-test statistics were used for the data analyses. The outcome of the study…

ADH1B Arg47His polymorphism is associated with esophageal cancer risk in high-incidence Asian population: evidence from a meta-analysis.

Directory of Open Access Journals (Sweden)

Guohong Zhang

Full Text Available BACKGROUND AND OBJECTIVES: Incidence of Esophageal squamous cell carcinoma (ESCC is prevalent in Asian populations, especially in the ones from the "Asian esophageal cancer belt" along the Silk Road and the ones from East Asia (including Japan. Silk Road and Eastern Asia population genetics are relevant to the ancient population migration from central China. The Arg47His (rs1229984 polymorphism of ADH1B is the highest in East Asians, and ancient migrations along the Silk Road were thought to be contributive to a frequent ADH1B*47His allele in Central Asians. This polymorphism was identified as responsible for susceptibility in the first large-scale genome-wide association study of ESCC and that's explained by its modulation of alcohol oxidization capability. To investigate the association of ADH1B Arg47His with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis. METHODS: A dataset composed of 4,220 cases and 8,946 controls from twelve studies of Asian populations was analyzed for ADH1B Arg47His association with ESCC and its interactions with alcohol drinking and ALDH2 Glu504Lys. Heterogeneity among studies and their publication bias were also tested. RESULTS: The ADH1B*47Arg allele was found to be associated to increased risk of ESCC, with the odds ratios (OR being 1.62 (95% CI: 1.49-1.76 and 3.86 (2.96-5.03 for the His/Arg and the Arg/Arg genotypes, respectively. When compared with the His/His genotype of non-drinkers, the Arg/Arg genotype can interact with alcohol drinking and greatly increase the risk of ESCC (OR = 20.69, 95%CI: 5.09-84.13. Statistical tests also showed gene-gene interaction of ADH1B Arg+ with ALDH2 Lys+ can bring more risk to ESCC (OR  = 13.46, 95% CI: 2.32-78.07. CONCLUSION: Revealed by this meta-analysis, ADH1B*47Arg as a common ancestral allele can significantly increase the risk of ESCC in Asians, especially when coupled

ADH1B Arg47His polymorphism is associated with esophageal cancer risk in high-incidence Asian population: evidence from a meta-analysis.

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Zhang, Guohong; Mai, Ruiqin; Huang, Bo

2010-10-27

Incidence of Esophageal squamous cell carcinoma (ESCC) is prevalent in Asian populations, especially in the ones from the "Asian esophageal cancer belt" along the Silk Road and the ones from East Asia (including Japan). Silk Road and Eastern Asia population genetics are relevant to the ancient population migration from central China. The Arg47His (rs1229984) polymorphism of ADH1B is the highest in East Asians, and ancient migrations along the Silk Road were thought to be contributive to a frequent ADH1B*47His allele in Central Asians. This polymorphism was identified as responsible for susceptibility in the first large-scale genome-wide association study of ESCC and that's explained by its modulation of alcohol oxidization capability. To investigate the association of ADH1B Arg47His with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis. A dataset composed of 4,220 cases and 8,946 controls from twelve studies of Asian populations was analyzed for ADH1B Arg47His association with ESCC and its interactions with alcohol drinking and ALDH2 Glu504Lys. Heterogeneity among studies and their publication bias were also tested. The ADH1B*47Arg allele was found to be associated to increased risk of ESCC, with the odds ratios (OR) being 1.62 (95% CI: 1.49-1.76) and 3.86 (2.96-5.03) for the His/Arg and the Arg/Arg genotypes, respectively. When compared with the His/His genotype of non-drinkers, the Arg/Arg genotype can interact with alcohol drinking and greatly increase the risk of ESCC (OR = 20.69, 95%CI: 5.09-84.13). Statistical tests also showed gene-gene interaction of ADH1B Arg+ with ALDH2 Lys+ can bring more risk to ESCC (OR  = 13.46, 95% CI: 2.32-78.07). Revealed by this meta-analysis, ADH1B*47Arg as a common ancestral allele can significantly increase the risk of ESCC in Asians, especially when coupled with alcohol drinking or the ALDH2*504Lys allele.

Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes.

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Kazmier, Kelli; Claxton, Derek P; Mchaourab, Hassane S

2017-08-01

Secondary active transporters couple the uphill translocation of substrates to electrochemical ion gradients. Transporter conformational motion, generically referred to as alternating access, enables a central ligand binding site to change its orientation relative to the membrane. Here we review themes of alternating access and the transduction of ion gradient energy to power this process in the LeuT-fold class of transporters where crystallographic, computational and spectroscopic approaches have converged to yield detailed models of transport cycles. Specifically, we compare findings for the Na + -coupled amino acid transporter LeuT and the Na + -coupled hydantoin transporter Mhp1. Although these studies have illuminated multiple aspects of transporter structures and dynamics, a number of questions remain unresolved that so far hinder understanding transport mechanisms in an energy landscape perspective. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sebze Püresi ile Üretilen Yoğurtların Tekstürel ve Duyusal Özelliklerinin Belirlenmesi

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Tülay Özcan

2016-07-01

Full Text Available Bu çalışmada kontrol (K; balkabağı (YBK, havuç (YHA, bezelye (YBE ve yeşil kabak püreli (YYK yoğurt olmak üzere 5 farklı set tipi yoğurt üretilmiştir. Sebzeli yoğurtlarda bulunan diyet liflerinin bakteri gelişmesini teşvik eden potansiyel etkisi sonucu Streptococcus thermophilus ile Lactobacillus delbrueckii subsp. bulgaricus sayılarının arttığı saptanmıştır. Yoğurtların sebze püreleri ile zenginleştirilmesinin pH, titrasyon asitliği, serum ayrılması, duyusal özelikler ile sertlik, iç yapışkanlık, konsistens ve viskozite indeksi gibi tekstürel özellikler üzerinde etkili olduğu gözlenmiştir. Havuç püresi ile üretilen yoğurtlarda viskozite, konsistens ve sertliğin yüksek olduğu saptanırken, yeşil kabak ilaveli olanlar daha zayıf tekstürel özellikler göstermiştir. Sonuç olarak sebze püresi ilavesinin set tipi yoğurtlarda tekstürel özelliklerinin iyileştirilmesi konusunda önemli rol oynadığı ve fonksiyonel süt ürünlerinin geliştirilmesinde kullanılabileceği belirlenmiştir.

Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

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Mager, U; Lindi, V; Lindström, J; Eriksson, J G; Valle, T T; Hämäläinen, H; Ilanne-Parikka, P; Keinänen-Kiukaanniemi, S; Tuomilehto, J; Laakso, M; Pulkkinen, L; Uusitupa, M

2006-06-01

Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.

Foreign research reactor spent nuclear fuel inventories containing HEU and LEU of US-origin

International Nuclear Information System (INIS)

Matos, J.E.

1995-01-01

This paper provides estimates of the quantities and types of foreign research reactor spent nuclear fuel containing HEU and LEU of US-origin that are anticipated during the period beginning in January 1996 and extending for 10-15 years

Proteomic analysis of the effects of aged garlic extract and its FruArg component on lipopolysaccharide-induced neuroinflammatory response in microglial cells.

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Hui Zhou

Full Text Available Aged garlic extract (AGE is widely used as a dietary supplement, and is claimed to promote human health through anti-oxidant/anti-inflammatory activities with hypolipidemic, antiplatelet and neuroprotective effects. Prior studies of AGE have mainly focused on its organosulfur compounds, with little attention paid to its carbohydrate derivatives, such as N-α-(1-deoxy-D-fructos-1-yl-L-arginine (FruArg. The goal of this study is to investigate actions of AGE and FruArg on antioxidative and neuroinflammatory responses in lipopolysaccharide (LPS-activated murine BV-2 microglial cells using a proteomic approach. Our data show that both AGE and FruArg can significantly inhibit LPS-induced nitric oxide (NO production in BV-2 cells. Quantitative proteomic analysis by combining two dimensional differential in-gel electrophoresis (2D-DIGE with mass spectrometry revealed that expressions of 26 proteins were significantly altered upon LPS exposure, while levels of 20 and 21 proteins exhibited significant changes in response to AGE and FruArg treatments, respectively, in LPS-stimulated BV-2 cells. Notably, approximate 78% of the proteins responding to AGE and FruArg treatments are in common, suggesting that FruArg is a major active component of AGE. MULTICOM-PDCN and Ingenuity Pathway Analyses indicate that the proteins differentially affected by treatment with AGE and FruArg are involved in inflammatory responses and the Nrf2-mediated oxidative stress response. Collectively, these results suggest that AGE and FruArg attenuate neuroinflammatory responses and promote resilience in LPS-activated BV-2 cells by suppressing NO production and by regulating expression of multiple protein targets associated with oxidative stress.

HEU and Leu FueL Shielding Comparative Study Applied for Spent Fuel Transport

International Nuclear Information System (INIS)

Margeanu, C.A.; Margeanu, S.; Barbos, D.

2009-01-01

INR Pitesti owns and operates a TRIGA dual-core Research Reactor for material testing, power reactor fuel and nuclear safety studies. The dual core concept involves the operation of a 14 MW TRIGA steady-state, high flux research and material testing reactor at one end of a large pool, and the independent operation of an annular-core pulsing reactor (TRIGA-ACPR) at the other end of the pool. The steady-state reactor is mostly used for long term testing of power reactor fuel components (pellets, pins, subassemblies and fuel assemblies) followed by post-irradiation examination. Following the general trend to replace the He fuel type (High Enriched Uranium) by Leu fuel type (Low Enriched Uranium), in the light of international agreements between IAEA and the states using He fuel in their nuclear reactors, Inr Past's have been accomplished the TRIGA research reactor core full conversion on May 2006. The He fuel repatriation in US in the frame of Foreign Research Reactor Spent Nuclear Fuel Return Programme effectively started in 1999, the final stage being achieved in summer of 2008. Taking into account for the possible impact on the human and environment, in all activities associated to nuclear fuel cycle, the spent fuel or radioactive waste characteristics must be well known. Shielding calculations basic tasks consist in radiation doses calculation, in order to prevent any risks both for personnel protection and impact on the environment during the spent fuel manipulation, transport and storage. The paper is a comparative study of Leu and He fuel utilization effects for the shielding analysis during spent fuel transport. A comparison against the measured data for He spent fuel, available from the last stage of the spent fuel repatriation, is presented. All the geometrical and material data related on the spent fuel shipping cask were considered according to the Nac-Lt Cask approved model. The shielding analysis estimates radiation doses to shipping cask wall surface

An update on the LEU target development and conversion program for the MAPLE reactors and new processing facility

International Nuclear Information System (INIS)

Malkoske, G.R.; Eng, B.Sc; Eng, P.

2002-01-01

Historically, the production of molybdenum-99 in the NRU research reactors at Chalk River, Canada, has been extracted from reactor targets employing highly enriched uranium (HEU). A reliable supply of HEU metal from the United States used in the manufacture of targets for the NRU research reactor has been a key factor to enable MDS Nordion to develop a secure supply of medical isotopes for the international nuclear medicine community. The molybdenum extraction process from HEU targets provides predictable, consistent yields for our high-volume molybdenum production process. Each link of the isotope supply chain, from isotope production to ultimate use by the physician, has been established using this proven and established method of HEU target irradiation and processing to extract molybdenum-99. To ensure a continued reliable and timely supply of medical isotopes, MDS Nordion is completing the construction of two MAPLE reactors and a New Processing Facility. The design of the MAPLE facilities was based on an established process developed by Atomic Energy of Canada Ltd. (AECL)-extraction of isotopes from HEU target material. However, in concert with the global trend to utilize low enriched uranium (LEU) in research reactors, MDS Nordion has launched a three phase LEU Target Development and Conversion Program for the MAPLE facilities. Phase 1, the Initial Feasibility Study, which identified the technical issues to convert the MAPLE reactor targets from HEU to LEU for large scale commercial production was reported on at the RERTR-2000 conference. The second phase of the LEU Target Development and Conversion Program was developed with extensive consultation and involvement of experts knowledgeable in target development, process system design, enriched uranium conversion chemistry and commercial scale reactor operations and molybdenum production. This paper will provide an overview of the Phase 2 Conversion Development Program, report on progress to date, and further

Indomethacin inhibits the increased airway responsiveness to histamine following inhalation of C5a des Arg in rabbits.

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Berend, N; Armour, C L; Black, J L

1986-08-01

It has been shown that inhalation of C5a des Arg increases rabbit airway responsiveness to histamine and that this is associated with an influx of neutrophils into the airway walls. This study was undertaken to see if the augmented response to histamine can be blocked by the cyclo-oxygenase inhibitor indomethacin. Spontaneously breathing, anesthetised rabbits were studied in a volume displacement plethysmograph and pulmonary resistance (R1) was measured using the electrical subtraction technique. Histamine does response curves (HDR) were generated by measuring R1 after serial nubulisation of saline and histamine (1, 3, 10, 30 and 100 mg/ml). Aerosols of either saline or C5a des Arg (1.5 ug/ml) were then inhaled by the animals over a time period of 2 min. An HDR was then repeated 4 hours later. In 9 rabbits the inhalation of C5a des Arg resulted in an upward shift of the repeat HDR: the area under the HDR was significantly greater than under the first HDR (p less than 0.05). In 6 rabbits the repeat HDR 4 hours after saline was shifted downwards (N.S.) indicating some degree of tachyphylaxis. When rabbits were pretreated with indomethacin (5 mg/kg i.v.) the repeat HDR following either C5a des Arg (n = 7) or saline (n = 6) were also shifted downwards i.e., the increased airway responsiveness noted after C5a des Arg was abolished. There was no significant difference in baseline saline R1 during the first or second HDR in any group. These results suggest that the increased airway responsiveness following nebulisation of C5a des Arg may be due to release from neutrophils of products of the cyclo-oxygenase pathway.

Analyses for inserting fresh LEU fuel assemblies instead of fresh HEU fuel assemblies in the Dalat Nuclear Research Reactor in Vietnam