WorldWideScience

Sample records for additive mutational effects

  1. Interfacial and Distal Pocket Mutations Exhibit Additive Effects on the Structure and Function of Hemoglobin†

    Science.gov (United States)

    Maillett, David H.; Simplaceanu, Virgil; Shen, Tong-Jian; Ho, Nancy T.; Olson, John S.; Ho, Chien

    2009-01-01

    Protein engineering strategies seek to develop a hemoglobin-based oxygen carrier with optimized functional properties, including (i) an appropriate O2 affinity, (ii) high cooperativity, (iii) limited NO reactivity, and (iv) a diminished rate of autooxidation. The mutations αL29F, αL29W, αV96W and βN108K individually impart some of these traits and in combinations produce hemoglobin molecules with interesting ligand-binding and allosteric properties. Studies of the ligand-binding properties and solution structures of single and multiple mutants have been performed. The aromatic side-chains placed in the distal-heme pocket environment affect the intrinsic ligand-binding properties of the mutated subunit itself, beyond what can be explained by allostery, and these changes are accompanied by local structural perturbations. In contrast, hemoglobins with mutations in the α1β1 and α1β2 interfaces display functional properties of both “R”- and “T”-state tetramers because the equilibrium between them is altered. These mutations are accompanied by global structural perturbations, suggesting an indirect, allostery-driven cause for their effects. Combinations of the distalheme pocket and interfacial mutations exhibit additive effects in both structural and functional properties, contribute to our understanding of allostery, and advance protein-engineering methods for manipulating the O2 binding properties of the hemoglobin molecule. PMID:18788751

  2. Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia.

    Science.gov (United States)

    Pisciotta, Livia; Priore Oliva, Claudio; Cefalù, Angelo Baldassare; Noto, Davide; Bellocchio, Antonella; Fresa, Raffaele; Cantafora, Alfredo; Patel, Dilip; Averna, Maurizio; Tarugi, Patrizia; Calandra, Sebastiano; Bertolini, Stefano

    2006-06-01

    Patients homozygous or compound heterozygous for LDLR mutations or double heterozygous for LDLR and apo B R3500Q mutation have higher LDL-C levels, more extensive xanthomatosis and more severe premature coronary disease (pCAD) than simple heterozygotes for mutations in either these genes or for missense mutations in PCSK9 gene. It is not known whether combined mutations in LDLR and PKCS9 are associated with such a severe phenotype. We sequenced Apo B and PCSK9 genes in two patients with the clinical diagnosis of homozygous FH who were heterozygous for LDLR gene mutations. Proband Z.P. (LDL-C 13.39 mmol/L and pCAD) was heterozygous for an LDLR mutation (p.E228K) inherited from her father (LDL-C 8.07 mmol/L) and a PCSK9 mutation (p.R496W) from her mother (LDL-C 5.58 mmol/L). Proband L.R. and her sister (LDL-C 11.51 and 10.47 mmol/L, xanthomatosis and carotid atherosclerosis) were heterozygous for an LDLR mutation (p.Y419X) inherited from their mother (LDL-C 6.54 mmol/L) and a PCSK9 mutation (p.N425S) probably from their deceased father. The LDL-C levels in double heterozygotes of these two families were 56 and 44% higher than those found in simple heterozygotes for the two LDLR mutations, respectively. The two PCSK9 mutations are novel and were not found in 110 controls and 80 patients with co-dominant hypercholesterolemia. These observations indicate that rare missense mutations of PCSK9 may worsen the clinical phenotype of patients carrying LDLR mutations.

  3. Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants.

    Science.gov (United States)

    Kroos, Marian; Hoogeveen-Westerveld, Marianne; Michelakakis, Helen; Pomponio, Robert; Van der Ploeg, Ans; Halley, Dicky; Reuser, Arnold

    2012-08-01

    Pompe disease is an autosomal recessive lysosomal glycogen storage disorder, characterized by progressive muscle weakness. Deficiency of acid α-glucosidase (EC; 3.2.1.20/3) can be caused by numerous pathogenic variants in the GAA gene. The Pompe Disease Mutation Database at http://www.pompecenter.nl aims to list all variants and their effect. This update reports on 94 variants. We examined 35 novel and 34 known mutations by site-directed mutagenesis and transient expression in COS-7 cells or HEK293T cells. Each of these mutations was given a severity rating using a previously published system, based on the level of acid α-glucosidase activity in medium and transfected cells and on the quantity and quality of the different molecular mass species in the posttranslational modification and transport of acid α-glucosidase. This approach enabled to classify 55 missense mutations as pathogenic and 13 as likely nonpathogenic. Based on their nature and the use of in silico analysis (Alamut® software), 12 of the additional 25 novel mutations were predicted to be pathogenic including 4 splicing mutations, 6 mutations leading to frameshift, and 2 point mutations causing stop codons. Seven of the additional mutations were considered nonpathogenic (4 silent and 3 occurring in intron regions), and 6 are still under investigation. © 2012 Wiley Periodicals, Inc.

  4. Analysis of the fitness effect of compensatory mutations

    OpenAIRE

    Zhang, Liqing; Watson, Layne T.

    2008-01-01

    This paper extends previous work on the Darwinian evolutionary fitness effect of the fixation of deleterious mutations by incorporating compensatory mutations, which are mutations (deleterious by themselves) that ameliorate other deleterious mutations, thus reducing the genetic load of populations. Since having compensatory mutations essentially changes the distributional shapes of deleterious mutations, the effect of compensatory mutations is studied by comparing distributions of deleterious...

  5. The additive effect of p53 Arg72Pro and RNASEL Arg462Gln genotypes on age of disease onset in Lynch syndrome patients with pathogenic germline mutations in MSH2 or MLH1.

    Science.gov (United States)

    Krüger, Stefan; Engel, Christoph; Bier, Andrea; Silber, Ann-Sophie; Görgens, Heike; Mangold, Elisabeth; Pagenstecher, Constanze; Holinski-Feder, Elke; von Knebel Doeberitz, Magnus; Royer-Pokora, Brigitte; Dechant, Stefan; Pox, Christian; Rahner, Nils; Müller, Annegret; Schackert, Hans K

    2007-07-08

    p53 and the prostate-cancer-susceptibility gene RNASEL are tumour suppressor genes involved in apoptosis. We have previously reported that the common, functionally different variants Arg72Pro in p53 and Arg462Gln in RNASEL are associated with the age of disease onset of colorectal cancer in Lynch syndrome patients. To assess the combined effect of both variants, we screened 246 unrelated Lynch syndrome patients with a pathogenic germline mutation either in MSH2 (n=138) or in MLH1 (n=108) and colorectal cancer as first tumour, and 245 healthy controls. The global log rank test revealed significant differences in the age of disease onset for the genotypes of each variant (p=0.0176 for p53 and p=0.0358 for RNASEL) and for the combined genotypes of both variants (p=0.0174). The highest difference in median age of disease onset was seen between homozygotes for the wild-types in both genes (42years [range 22-75]) and homozygotes for the variant alleles in both genes (30years [range 26-47]). A multivariate Cox regression model indicated that only the p53 and RNASEL genotypes had a significant influence on age of disease onset (p=0.016 for p53 and p=0.014 for RNASEL) in an additive mode of inheritance, and that the effects of both variants are purely additive, which supports the notion that the p53 and RNaseL pathways do not interact. These findings may be relevant for preventive strategies in Lynch syndrome.

  6. Additive effect of the mutations in the beta3-adrenoceptor gene and UCP3 gene promoter on body fat distribution and glycemic control after weight reduction in overweight subjects with CAD or metabolic syndrome.

    Science.gov (United States)

    Kim, O Y; Cho, E Y; Park, H Y; Jang, Y; Lee, J H

    2004-03-01

    To analyze the effects of the mutations in the beta3-adrenoceptor (beta3-AR) gene and/or uncoupling protein3 (UCP3) gene promoter on body fat distribution and glycemic control after mild weight reduction in overweight-obese subjects with coronary artery disease (CAD) or metabolic syndrome. Clinical intervention study of the -300 kcal/day mild weight reduction program for 12 weeks. A total of 224 overweight-obese subjects with CAD or metabolic disorder, subdivided into the following four categories: (1) wild type (TT-CC, n=73); (2) only UCP3 promoter variant (TT-CT/TT, n=90); (3) only beta3-AR variant (TA/AA-CC, n=29); (4) both variants (TA/AA-CT/TT, n=32). Body mass index (BMI), blood pressure, calorie intakes, body fat distribution, serum glucose, insulin, free fatty acids, C-peptide and lipids before and after weight reduction. After 12 weeks, all subjects lost approximately 5% of their initial body weight. Despite similar weight reduction, the highest decreases in abdominal adipose tissue at both L1 and L4 levels were observed in the 'wild-type' group (Pfat area at the L4 level. All subjects except both variant-carriers showed significant reductions in the fasting levels of glucose and FFA. The response areas of glucose (Pfat distribution and glycemic control were greatest in the 'wild-type' group and smallest in 'both variants' group. In addition, these effects were less beneficial in carriers with beta3-AR gene variant than with UCP3 gene promoter variant.

  7. The effect of the additional cytogenetic abnormalities on major molecular response and BCR-ABL kinase domain mutations in long-term follow-up chronic myeloid leukemia patients, a cross sectional study.

    Science.gov (United States)

    Savasoglu, Kaan; Payzin, Kadriye Bahriye; Ozdemirkiran, Fusun; Subasioglu, Asli; Yilmaz, Asu Fergun

    2017-08-01

    The aim of the study was to examine the relation between additional chromosomal aberrations (ACAs) with major molecular response (MMR) and BCR-ABL kinase domain (KD) mutations in the long-term follow-up of the chronic myeloid leukemia (CML) disease. The study design was cross-sectional observational and used the CML patients' data of Izmir Ataturk Education and Research Hospital from 2011 to 2015. Conventional cytogenetic, fluorescence in situ hybridization (FISH), quantitative real-time polymerase chain reaction (RQ-PCR) test results from 89 CML patients' and pyrosequencing analysis results from 17 patients' were set up for comparison analysis. The chi-square test was used in statistical analysis of the experimental data. There were no statistically significant correlations between ACAs and MMR (p = .361, p > .05) groups or BCR-ABL KD mutations (p = .576, p > .05) groups observed in the study. This study has revealed that MMR and BCR-ABL KD mutations did not correlate with ACAs.

  8. effects of sulphur addition on addition on and mechanical properties

    African Journals Online (AJOL)

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    234-8034714355. 8034714355. 1. EFFECTS OF SULPHUR ADDITION ON. ADDITION ON. 2. AND MECHANICAL PROPERTIES O. 3. 4. C. W. Onyia. 5. 1DEPT. OF METALLURGICAL AND MATERIALS. 6. 2, 4DEPT. OF METALLURGICAL ...

  9. The Mozart Effect: Additional Data.

    Science.gov (United States)

    Hughes, John R.

    2002-04-01

    After the review of the Mozart effect was published in this journal (Hughes JR. Epilepsy Behav 2001;2:369-417), additional data from the music of Haydn and Liszt have been analyzed that may account for the decrease in seizure activity originally reported during Mozart music. Even with these added data Mozart music continued to score significantly higher than the selections from the other six composers in one of the important characteristics of this music, namely, the repetition of the melody. However Haydn's values were second highest among Mozart, J. S. Bach, Wagner, Beethoven, Chopin, and Liszt.

  10. High frequency of additional gene mutations in acute myeloid leukemia with MLL partial tandem duplication: DNMT3A mutation is associated with poor prognosis.

    Science.gov (United States)

    Kao, Hsiao-Wen; Liang, D Cherng; Kuo, Ming-Chung; Wu, Jin-Hou; Dunn, Po; Wang, Po-Nan; Lin, Tung-Liang; Shih, Yu-Shu; Liang, Sung-Tzu; Lin, Tung-Huei; Lai, Chen-Yu; Lin, Chun-Hui; Shih, Lee-Yung

    2015-10-20

    The mutational profiles of acute myeloid leukemia (AML) with partial tandem duplication of mixed-lineage leukemia gene (MLL-PTD) have not been comprehensively studied. We studied 19 gene mutations for 98 patients with MLL-PTD AML to determine the mutation frequency and clinical correlations. MLL-PTD was screened by reverse-transcriptase PCR and confirmed by real-time quantitative PCR. The mutational analyses were performed with PCR-based assays followed by direct sequencing. Gene mutations of signaling pathways occurred in 63.3% of patients, with FLT3-ITD (44.9%) and FLT3-TKD (13.3%) being the most frequent. 66% of patients had gene mutations involving epigenetic regulation, and DNMT3A (32.7%), IDH2 (18.4%), TET2 (18.4%), and IDH1 (10.2%) mutations were most common. Genes of transcription pathways and tumor suppressors accounted for 23.5% and 10.2% of patients. RUNX1 mutation occurred in 23.5% of patients, while none had NPM1 or double CEBPA mutation. 90.8% of MLL-PTD AML patients had at least one additional gene mutation. Of 55 MLL-PTD AML patients who received standard chemotherapy, age older than 50 years and DNMT3A mutation were associated with inferior outcome. In conclusion, gene mutations involving DNA methylation and activated signaling pathway were common co-existed gene mutations. DNMT3A mutation was a poor prognostic factor in MLL-PTD AML.

  11. Phenotypic effect of mutations in evolving populations of RNA molecules

    Directory of Open Access Journals (Sweden)

    Manrubia Susanna C

    2010-02-01

    Full Text Available Abstract Background The secondary structure of folded RNA sequences is a good model to map phenotype onto genotype, as represented by the RNA sequence. Computational studies of the evolution of ensembles of RNA molecules towards target secondary structures yield valuable clues to the mechanisms behind adaptation of complex populations. The relationship between the space of sequences and structures, the organization of RNA ensembles at mutation-selection equilibrium, the time of adaptation as a function of the population parameters, the presence of collective effects in quasispecies, or the optimal mutation rates to promote adaptation all are issues that can be explored within this framework. Results We investigate the effect of microscopic mutations on the phenotype of RNA molecules during their in silico evolution and adaptation. We calculate the distribution of the effects of mutations on fitness, the relative fractions of beneficial and deleterious mutations and the corresponding selection coefficients for populations evolving under different mutation rates. Three different situations are explored: the mutation-selection equilibrium (optimized population in three different fitness landscapes, the dynamics during adaptation towards a goal structure (adapting population, and the behavior under periodic population bottlenecks (perturbed population. Conclusions The ratio between the number of beneficial and deleterious mutations experienced by a population of RNA sequences increases with the value of the mutation rate μ at which evolution proceeds. In contrast, the selective value of mutations remains almost constant, independent of μ, indicating that adaptation occurs through an increase in the amount of beneficial mutations, with little variations in the average effect they have on fitness. Statistical analyses of the distribution of fitness effects reveal that small effects, either beneficial or deleterious, are well described by a Pareto

  12. Impacts of mutation effects and population size on mutation rate in asexual populations: a simulation study

    Directory of Open Access Journals (Sweden)

    Huang Zhuoran

    2010-09-01

    Full Text Available Abstract Background In any natural population, mutation is the primary source of genetic variation required for evolutionary novelty and adaptation. Nevertheless, most mutations, especially those with phenotypic effects, are harmful and are consequently removed by natural selection. For this reason, under natural selection, an organism will evolve to a lower mutation rate. Overall, the action of natural selection on mutation rate is related to population size and mutation effects. Although theoretical work has intensively investigated the relationship between natural selection and mutation rate, most of these studies have focused on individual competition within a population, rather than on competition among populations. The aim of the present study was to use computer simulations to investigate how natural selection adjusts mutation rate among asexually reproducing subpopulations with different mutation rates. Results The competition results for the different subpopulations showed that a population could evolve to an "optimum" mutation rate during long-term evolution, and that this rate was modulated by both population size and mutation effects. A larger population could evolve to a higher optimum mutation rate than could a smaller population. The optimum mutation rate depended on both the fraction and the effects of beneficial mutations, rather than on the effects of deleterious ones. The optimum mutation rate increased with either the fraction or the effects of beneficial mutations. When strongly favored mutations appeared, the optimum mutation rate was elevated to a much higher level. The competition time among the subpopulations also substantially shortened. Conclusions Competition at the population level revealed that the evolution of the mutation rate in asexual populations was determined by both population size and mutation effects. The most striking finding was that beneficial mutations, rather than deleterious mutations, were the

  13. BRAF mutation in papillary thyroid microcarcinoma – additional marker of risk stratification

    Directory of Open Access Journals (Sweden)

    Dmitriy Yuriyevich Semyonov

    2014-11-01

    Full Text Available BackgroundPapillary thyroid microcarcinoma (PTMC is heterogeneous group of tumor less than 1 cm in the diameter. The volume of surgical treatment stay unstable because unclear biological potential of PTMC.AimThe aim of our study was to assess the utility of BRAF gene mutation as preoperative additional marker of risk stratification.Materials and methodsWe include 44 patient who were operated in general surgery department Pavlov State Medical University from 2001 to 2013. In all 44 cases BRAF gene mutation was detected and compared with clinic-morphological features (multifocality, invasive growth, lymph node metastasis, recurrence retrospectivelyResultsIn our study the frequency of BRAF gene mutation was 68.2%. On multivariate regression analysis the presence of bilateral tumoural foci, lymph node metastasis and the presence of capsular invasion were significantly related to BRAF positive gene status.ConclusionsThus, appropriate volume for the BRAF positive PTMC is thyroidectomy with central compartment lymph node dissection.

  14. Fitness is strongly influenced by rare mutations of large effect in a microbial mutation accumulation experiment.

    Science.gov (United States)

    Heilbron, Karl; Toll-Riera, Macarena; Kojadinovic, Mila; MacLean, R Craig

    2014-07-01

    Our understanding of the evolutionary consequences of mutation relies heavily on estimates of the rate and fitness effect of spontaneous mutations generated by mutation accumulation (MA) experiments. We performed a classic MA experiment in which frequent sampling of MA lines was combined with whole genome resequencing to develop a high-resolution picture of the effect of spontaneous mutations in a hypermutator (ΔmutS) strain of the bacterium Pseudomonas aeruginosa. After ∼644 generations of mutation accumulation, MA lines had accumulated an average of 118 mutations, and we found that average fitness across all lines decayed linearly over time. Detailed analyses of the dynamics of fitness change in individual lines revealed that a large fraction of the total decay in fitness (42.3%) was attributable to the fixation of rare, highly deleterious mutations (comprising only 0.5% of fixed mutations). Furthermore, we found that at least 0.64% of mutations were beneficial and probably fixed due to positive selection. The majority of mutations that fixed (82.4%) were base substitutions and we failed to find any signatures of selection on nonsynonymous or intergenic mutations. Short indels made up a much smaller fraction of the mutations that were fixed (17.4%), but we found evidence of strong selection against indels that caused frameshift mutations in coding regions. These results help to quantify the amount of natural selection present in microbial MA experiments and demonstrate that changes in fitness are strongly influenced by rare mutations of large effect. Copyright © 2014 by the Genetics Society of America.

  15. Fitness effects of fixed beneficial mutations in microbial populations

    NARCIS (Netherlands)

    Rozen, D.; Visser, de J.A.G.M.; Gerrish, P.J.

    2002-01-01

    Beneficial mutations are intuitively relevant to understanding adaptation [1-3], yet not all beneficial mutations are of consequence to the long-term evolutionary outcome of adaptation. Many beneficial mutations - mostly those of small effect - are lost due either to (1) genetic drift [4, 5] or to

  16. EGFR mutation frequency and effectiveness of erlotinib

    DEFF Research Database (Denmark)

    Weber, Britta; Hager, Henrik; Sorensen, Boe S

    2014-01-01

    OBJECTIVES: In 2008, we initiated a prospective study to explore the frequency and predictive value of epidermal growth factor receptor (EGFR) mutations in an unselected population of Danish patients with non-small cell lung cancer offered treatment with erlotinib, mainly in second-line. MATERIALS...... AND METHODS: Four hundred and eighty eight patients with advanced NSCLC were included. The mutation status was assessed using the cobas EGFR Mutation Test. Erlotinib was administrated (150 mg/d) until disease progression or unacceptable toxicities occurred. The primary endpoint was progression-free survival....... Secondary endpoints were overall survival and response. RESULTS: Biopsies were retrieved from 467 patients, and mutation results obtained for 462. We identified 57 (12%) patients with EGFR mutations: 33 exon 19 deletions, 13 exon 21 mutations, 5 exon 18 mutations, 3 exon 20 insertions, 1 exon 20 point...

  17. A DSPP Mutation Causing Dentinogenesis Imperfecta and Characterization of the Mutational Effect

    Directory of Open Access Journals (Sweden)

    Sook-Kyung Lee

    2013-01-01

    Full Text Available Mutations in the DSPP gene have been identified in nonsyndromic hereditary dentin defects, but the genotype-phenotype correlations are not fully understood. Recently, it has been demonstrated that the mutations of DSPP affecting the IPV leader sequence result in mutant DSPP retention in rough endoplasmic reticulum (ER. In this study, we identified a Korean family with dentinogenesis imperfecta type III. To identify the disease causing mutation in this family, we performed mutational analysis based on candidate gene sequencing. Exons and exon-intron boundaries of DSPP gene were sequenced, and the effects of the identified mutation on the pre-mRNA splicing and protein secretion were investigated. Candidate gene sequencing revealed a mutation (c.50C > T, p.P17L in exon 2 of the DSPP gene. The splicing assay showed that the mutation did not influence pre-mRNA splicing. However, the mutation interfered with protein secretion and resulted in the mutant protein remaining largely in the ER. These results suggest that the mutation affects ER-to-Golgi apparatus export and results in the reduction of secreted DSPP and ER overload. This may induce cell stress and damage processing and/or transport of dentin matrix proteins or other critical proteins.

  18. Additive and non-additive effects on fitness traits

    African Journals Online (AJOL)

    GScholtz

    2014-11-09

    Nov 9, 2014 ... this study was to estimate genetic components of fitness traits measured in Afrikaner (A), Brahman (B),. Charolais (C) ... group means were equated with their genetic expectations assuming recombination effects were nil and the heterosis effects were ..... The genetics of inbreeding depression. Nature Rev.

  19. Effects of additional data on Bayesian clustering.

    Science.gov (United States)

    Yamazaki, Keisuke

    2017-10-01

    Hierarchical probabilistic models, such as mixture models, are used for cluster analysis. These models have two types of variables: observable and latent. In cluster analysis, the latent variable is estimated, and it is expected that additional information will improve the accuracy of the estimation of the latent variable. Many proposed learning methods are able to use additional data; these include semi-supervised learning and transfer learning. However, from a statistical point of view, a complex probabilistic model that encompasses both the initial and additional data might be less accurate due to having a higher-dimensional parameter. The present paper presents a theoretical analysis of the accuracy of such a model and clarifies which factor has the greatest effect on its accuracy, the advantages of obtaining additional data, and the disadvantages of increasing the complexity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Sintering of magnesia: effect of additives

    Indian Academy of Sciences (India)

    Department of Ceramic Engineering, National Institute of Technology, Rourkela 769008, India ... negative. The capillary pressure is p = γ (1/γ+1/x) and is negative (γ = surface energy). Summed over powder com- pact, the capillary pressure gives a modest net ... Nelson and Culter10 studied the effect of many additives in.

  1. Sintering of magnesia: effect of additives

    Indian Academy of Sciences (India)

    Effect of different additives, namely Cr2O3, Fe2O3 and TiO2, up to 2 wt% was studied on the sintering and microstructural developments of the chemically pure magnesia using the pressureless sintering technique between ... Department of Ceramic Engineering, National Institute of Technology, Rourkela 769008, India ...

  2. Oncogenic potential is related to activating effect of cancer single and double somatic mutations in receptor tyrosine kinases

    Science.gov (United States)

    Hashimoto, Kosuke; Rogozin, Igor B.; Panchenko, Anna R.

    2012-01-01

    Aberrant activation of receptor tyrosine kinases (RTKs) is a common feature of many cancer cells. It was previously suggested that the mechanisms of kinase activation in cancer might be linked to transitions between active and inactive states. Here we estimate the effects of single and double cancer mutations on the stability of active and inactive states of the kinase domains from different RTKs. We show that singleton cancer mutations destabilize active and inactive states, however inactive states are destabilized more than the active ones leading to kinase activation. We show that there exists a relationship between the estimate of oncogenic potential of cancer mutation and kinase activation. Namely, more frequent mutations have a higher activating effect, which might allow us to predict the activating effect of the mutations from the mutation spectra. Independent evolutionary analysis of mutation spectra complements this observation and finds the same frequency threshold defining mutation hot spots. We analyze double mutations and report a positive epistasis and additional advantage of doublets with respect to cancer cell fitness. The activation mechanisms of double mutations differ from those of single mutations and double mutation spectrum is found to be dissimilar to the mutation spectrum of singletons. PMID:22753356

  3. Effective Structural Health Monitoring with Additive Manufacturing

    OpenAIRE

    De Baere, Dieter; Strantza, Maria; Hinderdael, Michaël; Devesse, Wim; Guillaume, Patrick

    2014-01-01

    International audience; The current remaining challenges for structural health monitoring (SHM) systems prevented the introduction of SHM systems on a large scale within industrial applications. An effective SHM system is required for the reduction of the direct operation costs, improvement of the life-safety and the introduction of additive manufactured components for critical structures. In this paper, a new structural health monitoring methodology will be presented for components that can ...

  4. New approaches for effective mutation induction in gamma field

    Energy Technology Data Exchange (ETDEWEB)

    Nagatomi, Shigeki [National Institute of Agrobiological Resources, Institute of Radiation Breeding, Omiya, Ibaraki (Japan)

    2001-03-01

    The purpose of the report is to clarify the effects of chronic irradiation using in vitro culture on inducing the mutation of two model plants. Culture technique combined with irradiation can overcome the problem of chimera formation and provided 10 times greater mutation efficiency than conventional method. Proper mutagenic treatment using cultured materials is indispensable to effective mutation induction. The chronic culture method showed the widest color spectrum in chrysanthemum and extended toward not only the negative but positive direction. However, the acute culture methods indicated a relatively low mutation rate and a very limited flower color spectrum. Flower color mutation of the regenerations could be induced more from petals and buds than from leaves. These facts is supposed that the gene loci fully expressed on floral organs may be unstable for mutation by mutagenesis or culture. It may be likely to control a direction of desired mutation. One possible reason why the chronic culture methods showed higher frequencies is that most of the cells composing the tissue and organs continually irradiated into a cell division which was highly sensitive and more mutable to irradiation. Under these conditions, many mutated sectors may accumulate in the cells of the growing organs. Regenerated mutant lines show remarkable decrease of chromosome numbers by irradiation. It is a proper indicator to monitor radiation damage. In this study, the six flower color mutant varieties registered were derived from chronic irradiation. The combined method of chronic irradiation with floral organ cultures proved to be of particularly great practical use in mutation breeding for not only flower species but any other species. (author)

  5. Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies.

    Science.gov (United States)

    Xu, Mingchu; Xie, Yajing Angela; Abouzeid, Hana; Gordon, Christopher T; Fiorentino, Alessia; Sun, Zixi; Lehman, Anna; Osman, Ihab S; Dharmat, Rachayata; Riveiro-Alvarez, Rosa; Bapst-Wicht, Linda; Babino, Darwin; Arno, Gavin; Busetto, Virginia; Zhao, Li; Li, Hui; Lopez-Martinez, Miguel A; Azevedo, Liliana F; Hubert, Laurence; Pontikos, Nikolas; Eblimit, Aiden; Lorda-Sanchez, Isabel; Kheir, Valeria; Plagnol, Vincent; Oufadem, Myriam; Soens, Zachry T; Yang, Lizhu; Bole-Feysot, Christine; Pfundt, Rolph; Allaman-Pillet, Nathalie; Nitschké, Patrick; Cheetham, Michael E; Lyonnet, Stanislas; Agrawal, Smriti A; Li, Huajin; Pinton, Gaëtan; Michaelides, Michel; Besmond, Claude; Li, Yumei; Yuan, Zhisheng; von Lintig, Johannes; Webster, Andrew R; Le Hir, Hervé; Stoilov, Peter; Amiel, Jeanne; Hardcastle, Alison J; Ayuso, Carmen; Sui, Ruifang; Chen, Rui; Allikmets, Rando; Schorderet, Daniel F

    2017-04-06

    Pre-mRNA splicing factors play a fundamental role in regulating transcript diversity both temporally and spatially. Genetic defects in several spliceosome components have been linked to a set of non-overlapping spliceosomopathy phenotypes in humans, among which skeletal developmental defects and non-syndromic retinitis pigmentosa (RP) are frequent findings. Here we report that defects in spliceosome-associated protein CWC27 are associated with a spectrum of disease phenotypes ranging from isolated RP to severe syndromic forms. By whole-exome sequencing, recessive protein-truncating mutations in CWC27 were found in seven unrelated families that show a range of clinical phenotypes, including retinal degeneration, brachydactyly, craniofacial abnormalities, short stature, and neurological defects. Remarkably, variable expressivity of the human phenotype can be recapitulated in Cwc27 mutant mouse models, with significant embryonic lethality and severe phenotypes in the complete knockout mice while mice with a partial loss-of-function allele mimic the isolated retinal degeneration phenotype. Our study describes a retinal dystrophy-related phenotype spectrum as well as its genetic etiology and highlights the complexity of the spliceosomal gene network. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  6. Effects of intronic mutations in the LDLR gene on pre-mRNA splicing: Comparison of wet-lab and bioinformatics analyses

    NARCIS (Netherlands)

    Holla, Øystein L.; Nakken, Sigve; Mattingsdal, Morten; Ranheim, Trine; Berge, Knut Erik; Defesche, Joep C.; Leren, Trond P.

    2009-01-01

    Screening for mutations in the low density lipoprotein receptor (LDLR) gene has identified more than 1000 mutations as the cause of familial hypercholesterolemia (FH). In addition, numerous intronic mutations with uncertain effects on pre-mRNA splicing have also been identified. In this study, we

  7. Nurse Scheduling by Cooperative GA with Effective Mutation Operator

    Science.gov (United States)

    Ohki, Makoto

    In this paper, we propose an effective mutation operators for Cooperative Genetic Algorithm (CGA) to be applied to a practical Nurse Scheduling Problem (NSP). The nurse scheduling is a very difficult task, because NSP is a complex combinatorial optimizing problem for which many requirements must be considered. In real hospitals, the schedule changes frequently. The changes of the shift schedule yields various problems, for example, a fall in the nursing level. We describe a technique of the reoptimization of the nurse schedule in response to a change. The conventional CGA is superior in ability for local search by means of its crossover operator, but often stagnates at the unfavorable situation because it is inferior to ability for global search. When the optimization stagnates for long generation cycle, a searching point, population in this case, would be caught in a wide local minimum area. To escape such local minimum area, small change in a population should be required. Based on such consideration, we propose a mutation operator activated depending on the optimization speed. When the optimization stagnates, in other words, when the optimization speed decreases, the mutation yields small changes in the population. Then the population is able to escape from a local minimum area by means of the mutation. However, this mutation operator requires two well-defined parameters. This means that user have to consider the value of these parameters carefully. To solve this problem, we propose a periodic mutation operator which has only one parameter to define itself. This simplified mutation operator is effective over a wide range of the parameter value.

  8. A rapid and effective method for screening, sequencing and reporter verification of engineered frameshift mutations in zebrafish

    Directory of Open Access Journals (Sweden)

    Sergey V. Prykhozhij

    2017-06-01

    Full Text Available Clustered regularly interspaced palindromic repeats (CRISPR/Cas-based adaptive immunity against pathogens in bacteria has been adapted for genome editing and applied in zebrafish (Danio rerio to generate frameshift mutations in protein-coding genes. Although there are methods to detect, quantify and sequence CRISPR/Cas9-induced mutations, identifying mutations in F1 heterozygous fish remains challenging. Additionally, sequencing a mutation and assuming that it causes a frameshift does not prove causality because of possible alternative translation start sites and potential effects of mutations on splicing. This problem is compounded by the relatively few antibodies available for zebrafish proteins, limiting validation at the protein level. To address these issues, we developed a detailed protocol to screen F1 mutation carriers, and clone and sequence identified mutations. In order to verify that mutations actually cause frameshifts, we created a fluorescent reporter system that can detect frameshift efficiency based on the cloning of wild-type and mutant cDNA fragments and their expression levels. As proof of principle, we applied this strategy to three CRISPR/Cas9-induced mutations in pycr1a, chd7 and hace1 genes. An insertion of seven nucleotides in pycr1a resulted in the first reported observation of exon skipping by CRISPR/Cas9-induced mutations in zebrafish. However, of these three mutant genes, the fluorescent reporter revealed effective frameshifting exclusively in the case of a two-nucleotide deletion in chd7, suggesting activity of alternative translation sites in the other two mutants even though pycr1a exon-skipping deletion is likely to be deleterious. This article provides a protocol for characterizing frameshift mutations in zebrafish, and highlights the importance of checking mutations at the mRNA level and verifying their effects on translation by fluorescent reporters when antibody detection of protein loss is not possible.

  9. A rapid and effective method for screening, sequencing and reporter verification of engineered frameshift mutations in zebrafish.

    Science.gov (United States)

    Prykhozhij, Sergey V; Steele, Shelby L; Razaghi, Babak; Berman, Jason N

    2017-06-01

    Clustered regularly interspaced palindromic repeats (CRISPR)/Cas-based adaptive immunity against pathogens in bacteria has been adapted for genome editing and applied in zebrafish (Danio rerio) to generate frameshift mutations in protein-coding genes. Although there are methods to detect, quantify and sequence CRISPR/Cas9-induced mutations, identifying mutations in F1 heterozygous fish remains challenging. Additionally, sequencing a mutation and assuming that it causes a frameshift does not prove causality because of possible alternative translation start sites and potential effects of mutations on splicing. This problem is compounded by the relatively few antibodies available for zebrafish proteins, limiting validation at the protein level. To address these issues, we developed a detailed protocol to screen F1 mutation carriers, and clone and sequence identified mutations. In order to verify that mutations actually cause frameshifts, we created a fluorescent reporter system that can detect frameshift efficiency based on the cloning of wild-type and mutant cDNA fragments and their expression levels. As proof of principle, we applied this strategy to three CRISPR/Cas9-induced mutations in pycr1a, chd7 and hace1 genes. An insertion of seven nucleotides in pycr1a resulted in the first reported observation of exon skipping by CRISPR/Cas9-induced mutations in zebrafish. However, of these three mutant genes, the fluorescent reporter revealed effective frameshifting exclusively in the case of a two-nucleotide deletion in chd7, suggesting activity of alternative translation sites in the other two mutants even though pycr1a exon-skipping deletion is likely to be deleterious. This article provides a protocol for characterizing frameshift mutations in zebrafish, and highlights the importance of checking mutations at the mRNA level and verifying their effects on translation by fluorescent reporters when antibody detection of protein loss is not possible. © 2017. Published by

  10. Dominance effects of deleterious and beneficial mutations in a single gene of the RNA virus ϕ6.

    Directory of Open Access Journals (Sweden)

    Sarah B Joseph

    Full Text Available Most of our knowledge of dominance stems from studies of deleterious mutations. From these studies we know that most deleterious mutations are recessive, and that this recessivity arises from a hyperbolic relationship between protein function (i.e., protein concentration or activity and fitness. Here we investigate whether this knowledge can be used to make predictions about the dominance of beneficial and deleterious mutations in a single gene. We employed a model system--the bacteriophage φ6--that allowed us to generate a collection of mutations in haploid conditions so that it was not biased toward either dominant beneficial or recessive deleterious mutations. Screening for the ability to infect a bacterial host that does not permit infection by the wildtype φ6, we generated a collection of mutations in P3, a gene involved in attachment to the host and in phage particle assembly. The resulting collection contained mutations with both deleterious and beneficial effects on fitness. The deleterious mutations in our collection had additive effects on fitness and the beneficial mutations were recessive. Neither of these observations were predicted from previous studies of dominance. This pattern is not consistent with the hyperbolic (diminishing returns relationship between protein function and fitness that is characteristic of enzymatic genes, but could have resulted from a curve of increasing returns.

  11. Rosiglitazone and Fenofibrate Additive Effects on Lipids

    Directory of Open Access Journals (Sweden)

    Ahmad Slim

    2011-01-01

    Full Text Available Background. To evaluate the effect of rosiglitazone, fenofibrate, or their combined use on plasma lipids in normoglycemic healthy adults. Methods and Results. Subjects were randomized in a double-blind fashion to rosiglitazone + placebo, fenofibrate + placebo, rosiglitazone + fenofibrate, or matching double placebo. The between-group difference in the change in fasting TG, high-density lipoprotein cholesterol (HDL-C, LDL-C, and plasma apolipoproteins A-I, A-II, and C-III level were compared after 12 weeks of treatment. A total of 548 subjects were screened and 41 met the inclusion criteria. After 12 weeks of therapy, the median change in the triglyceride levels showed a significant reduction ranging from 47 to 55 mg per deciliter in the fenofibrate only and rosiglitazone/fenofibrate groups compared with placebo (=0.0496. However, the rosiglitazone only group did not show significant change in triglyceride level. The change in the Apo AII showed increase in all the treatment groups compared with placebo (=0.009. There was also significant change in the Apo CIII that showed reduction of its level in the fenofibrate only and rosiglitazone/fenofibrate groups (=0.0003. Conclusion. Rosiglitazone does not appear to modulate hypertriglyceridemia in patients with elevated triglycerides independent of glucose metabolism.

  12. Epistatic and combinatorial effects of pigmentary gene mutations in the domestic pigeon.

    Science.gov (United States)

    Domyan, Eric T; Guernsey, Michael W; Kronenberg, Zev; Krishnan, Shreyas; Boissy, Raymond E; Vickrey, Anna I; Rodgers, Clifford; Cassidy, Pamela; Leachman, Sancy A; Fondon, John W; Yandell, Mark; Shapiro, Michael D

    2014-02-17

    Understanding the molecular basis of phenotypic diversity is a critical challenge in biology, yet we know little about the mechanistic effects of different mutations and epistatic relationships among loci that contribute to complex traits. Pigmentation genetics offers a powerful model for identifying mutations underlying diversity and for determining how additional complexity emerges from interactions among loci. Centuries of artificial selection in domestic rock pigeons (Columba livia) have cultivated tremendous variation in plumage pigmentation through the combined effects of dozens of loci. The dominance and epistatic hierarchies of key loci governing this diversity are known through classical genetic studies, but their molecular identities and the mechanisms of their genetic interactions remain unknown. Here we identify protein-coding and cis-regulatory mutations in Tyrp1, Sox10, and Slc45a2 that underlie classical color phenotypes of pigeons and present a mechanistic explanation of their dominance and epistatic relationships. We also find unanticipated allelic heterogeneity at Tyrp1 and Sox10, indicating that color variants evolved repeatedly though mutations in the same genes. These results demonstrate how a spectrum of coding and regulatory mutations in a small number of genes can interact to generate substantial phenotypic diversity in a classic Darwinian model of evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. The Periplasmic Protein MppA Requires an Additional Mutated Locus To Repress marA Expression in Escherichia coli

    OpenAIRE

    Bina, Xiaowen; Perreten, Vincent; Levy, Stuart B.

    2003-01-01

    Escherichia coli strain TP985, which has an insertional mutation in the gene for the periplasmic murein tripeptide binding protein MppA, was previously reported to overproduce MarA and exhibit a multiple-antibiotic resistance (Mar) phenotype (H. Li and J. T. Park, J. Bacteriol. 181:4842-4847, 1999). We found that TP985 contained a previously unrecognized marR mutation which was responsible for the Mar phenotype. Transduction of the mppA mutation from TP985 to another wild-type strain did not ...

  14. Integrated genetic and epigenetic analysis of bladder cancer reveals an additive diagnostic value of FGFR3 mutations and hypermethylation events

    DEFF Research Database (Denmark)

    Serizawa, Reza R; Ralfkiaer, Ulrik; Steven, Kenneth

    2011-01-01

    .0001). FGFR3 mutation in combination with three methylation markers (APC, RASSF1A and SFRP2) provided a sensitivity of 90% in tumors and 62% in urine with 100% specificity. These results suggest an inverse correlation between FGFR3 mutations and hypermethylation events, which may be used to improve......The bladder cancer genome harbors numerous oncogenic mutations and aberrantly methylated gene promoters. The aim of our study was to generate a profile of these alterations and investigate their use as biomarkers in urine sediments for noninvasive detection of bladder cancer. We systematically...... screened FGFR3, PIK3CA, TP53, HRAS, NRAS and KRAS for mutations and quantitatively assessed the methylation status of APC, ARF, DBC1, INK4A, RARB, RASSF1A, SFRP1, SFRP2, SFRP4, SFRP5 and WIF1 in a prospective series of tumor biopsies (N = 105) and urine samples (N = 113) from 118 bladder tumor patients. We...

  15. Integrated genetic and epigenetic analysis of bladder cancer reveals an additive diagnostic value of FGFR3 mutations and hypermethylation events.

    Science.gov (United States)

    Serizawa, Reza R; Ralfkiaer, Ulrik; Steven, Kenneth; Lam, Gitte W; Schmiedel, Sven; Schüz, Joachim; Hansen, Alastair B; Horn, Thomas; Guldberg, Per

    2011-07-01

    The bladder cancer genome harbors numerous oncogenic mutations and aberrantly methylated gene promoters. The aim of our study was to generate a profile of these alterations and investigate their use as biomarkers in urine sediments for noninvasive detection of bladder cancer. We systematically screened FGFR3, PIK3CA, TP53, HRAS, NRAS and KRAS for mutations and quantitatively assessed the methylation status of APC, ARF, DBC1, INK4A, RARB, RASSF1A, SFRP1, SFRP2, SFRP4, SFRP5 and WIF1 in a prospective series of tumor biopsies (N = 105) and urine samples (N = 113) from 118 bladder tumor patients. We also analyzed urine samples from 33 patients with noncancerous urinary lesions. A total of 95 oncogenic mutations and 189 hypermethylation events were detected in the 105 tumor biopsies. The total panel of markers provided a sensitivity of 93%, whereas mutation and methylation markers alone provided sensitivities of 72% and 70%, respectively. In urine samples, the sensitivity was 70% for all markers, 50% for mutation markers and 52% for methylation markers. FGFR3 mutations occurred more frequently in tumors with no methylation events than in tumors with one or more methylation events (78% vs. 33%; p FGFR3 mutation in combination with three methylation markers (APC, RASSF1A and SFRP2) provided a sensitivity of 90% in tumors and 62% in urine with 100% specificity. These results suggest an inverse correlation between FGFR3 mutations and hypermethylation events, which may be used to improve noninvasive, DNA-based detection of bladder cancer. Copyright © 2010 UICC.

  16. Deep Mutational Scanning: A Highly Parallel Method to Measure the Effects of Mutation on Protein Function.

    Science.gov (United States)

    Starita, Lea M; Fields, Stanley

    2015-08-03

    Deep mutational scanning is a method that makes use of next-generation sequencing technology to measure in a single experiment the activity of 10(5) or more unique variants of a protein. Because of this depth of mutational coverage, this strategy provides data that can be analyzed to reveal many protein properties. Deep mutational scanning approaches are particularly amenable to being performed in Saccharomyces cerevisiae, given the extensive toolkit of reagents and technologies available for this organism. © 2015 Cold Spring Harbor Laboratory Press.

  17. Hot-foot murine mutation: behavioral effects and neuroanatomical alterations.

    Science.gov (United States)

    Guastavino, J M; Sotelo, C; Damez-Kinselle, I

    1990-07-23

    We have studied the behavior of a new neurological mouse mutant, the hot-foot mutant. The most obvious phenotypic characteristic of the mutation is an abnormality of posture (body flattened on the ground, back limbs spread wide) and of locomotion (backing up and jerky movements of the hind limbs). Neuroanatomical analysis of the cerebellum showed abnormalities mainly related to the Purkinje cells, which have ectopic spines devoid of presynaptic innervations. The correspondence between the cerebellar alterations and the abnormalities of locomotion is thus clearly illustrated. However, the mild degree of the anatomical alterations does not seem sufficient to account for the degree of effect on locomotion and posture.

  18. Drag reduction by natural polymeric additives in PMDS microchannel: Effect of types of additives

    Directory of Open Access Journals (Sweden)

    Ling Fiona W.M.

    2017-01-01

    Full Text Available Drag reduction technology was used in medical applications to enhance the blood flow in semiclogged blood streams which can be an alternative treatment for atherosclerosis. In this present study, natural polymeric drag reducing additives (DRA was introduced to replace synthetic polymer which has the possibility of bringing side effects to human health. Three different sources, namely okra, aloe vera and hibiscus were utilized to extract the natural polymeric additives which were then tested in custom made microchannel simulating human heart blood vessels. The performance of different types of additives was evaluated using pressure measurements. The maximum drag reduction up to 63.48% is achieved using 300 ppm of hibiscus mucilage at operating pressure of 50 mbar. In this present work, hibiscus showed the best drag reduction performance, giving the highest %FI in most of the cases. This experimental results proved that these natural polymeric additives could be utilized as DRA in enhancing the blood flow in semiclogged blood streams.

  19. Familial hypertrophic cardiomyopathy: Functional effects of myosin mutation R723G in cardiomyocytes

    NARCIS (Netherlands)

    Kraft, T.; Witjas-Paalberends, E.R.; Boontje, N.; Tripathi, S.; Brandis, A.; Montag, J.; Hodgkinson, J.L.; Francino, A.; Navarro-Lopez, F.; Brenner, B.; Stienen, G.J.M.; van der Velden, J.

    2013-01-01

    Familial Hypertrophic Cardiomyopathy (FHC) is frequently caused by mutations in the β-cardiac myosin heavy chain (β-MyHC). To identify changes in sarcomeric function triggered by such mutations, distinguishing mutation effects from other functional alterations of the myocardium is essential. We

  20. Increased prevalence of lung, breast and pancreatic cancers in addition to melanoma risk in families bearing the CDKN2A mutation: Implications for genetic counseling

    Science.gov (United States)

    Potrony, Miriam; Puig-Butillé, Joan Anton; Aguilera, Paula; Badenas, Celia; Carrera, Cristina; Malvehy, Josep; Puig, Susana

    2014-01-01

    BACKGROUND CDKN2A is the major high-risk susceptibility gene for melanoma. OBJECTIVE To evaluate the effect of CDKN2A mutations in high-risk Spanish melanoma patients and the association with clinical and family history features. METHODS A cross-sectional study design was used to analyze the CDKN2A impact in 702 Spanish patients with a high-risk of developing melanoma. RESULTS The CDKN2A mutation prevalence was 8.5% in sporadic multiple primary melanoma patients and 14.1% in familial melanoma. Number of cases in the family, number of primary melanomas and age of onset were associated with the presence of CDKN2A mutation. Having a CDKN2A mutation in the family increased the prevalence of other cancers (PR=2.99, p=0.012), pancreatic (PR=2.97, p=0.006), lung (PR=3.04, pMelanoma-prone families with mutations in CDKN2A have an increased prevalence of a broad spectrum of cancers including lung, pancreatic and breast cancer. This information should be included in genetic counseling and cancer prevention programs for CDKN2A mutation carriers. PMID:25064638

  1. Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first-line chronic lymphocytic leukemia.

    Science.gov (United States)

    Le Bris, Yannick; Struski, Stéphanie; Guièze, Romain; Rouvellat, Caroline; Prade, Naïs; Troussard, Xavier; Tournilhac, Olivier; Béné, Marie C; Delabesse, Eric; Ysebaert, Loïc

    2017-12-01

    Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder of remarkable heterogeneity as demonstrated by cytogenetics and molecular analyses. Complex karyotype (CK), TP53 deletions and/or mutations (TP53 disruption), IGVH mutational status, and, more recently, recurrent somatic mutations have been identified as prognostic markers in CLL. On a cohort of 110 patients with CLL treated with first-line fludarabin, cyclophosphamide, and rituximab treatment compared with 33 untreated (watch and wait) patients with CLL, we report more frequent complex karyotypes (34 vs 15%; P = .05), unmutated IGHV (70 vs 21%; P karyotyping therefore appears to be of value, CK being an additional factor, undetectable in classical FISH, in patients with CLL at the stage when therapy becomes required. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Ticagrelor and Rosuvastatin Have Additive Cardioprotective Effects via Adenosine.

    Science.gov (United States)

    Birnbaum, Yochai; Birnbaum, Gilad D; Birnbaum, Itamar; Nylander, Sven; Ye, Yumei

    2016-12-01

    Ticagrelor inhibits the equilibrative-nucleoside-transporter-1 and thereby, adenosine cell re-uptake. Ticagrelor limits infarct size (IS) in non-diabetic rats and the effect is adenosine-dependent. Statins, via ecto-5'-nucleotidase activation, also increase adenosine levels and limit IS. Ticagrelor and rosuvastatin have additive effects on myocardial adenosine levels, and therefore, on IS and post-reperfusion activation of the NLRP3-inflammasome. Diabetic ZDF rats received via oral gavage; water (control), ticagrelor (150 mg/kg/d), prasugrel (7.5 mg/kg/d), rosuvastatin (5 mg/kg/d), ticagrelor + rosuvastatin and prasugrel + rosuvastatin for 3d. On day 4, rats underwent 30 min coronary artery occlusion and 24 h of reperfusion. Two additional groups received, ticagrelor + rosuvastatin or water in combination with CGS15943 (CGS, an adenosine receptor antagonist, 10 mg/kg i.p. 1 h before ischemia). Both ticagrelor and rosuvastatin increased myocardial adenosine levels with an additive effect of the combination whereas prasugrel had no effect. Similarly, both ticagrelor and rosuvastatin significantly reduced IS with an additive effect of the combination whereas prasugrel had no effect. The effect on IS was adenosine dependent as CGS15943 reversed the effect of ticagrelor + rosuvastatin. The ischemia-reperfusion injury increased myocardial mRNA levels of NLRP3, ASC, IL-1β and IL-6. Ticagrelor and rosuvastatin, but not prasugrel, significantly decreased these pro-inflammatory mediators with a trend to an additive effect of the combination. The combination also increased the levels of anti-inflammatory 15-epilipoxin A4. Ticagrelor and rosuvastatin when given in combination have an additive effect on local myocardial adenosine levels in the setting of ischemia reperfusion. This translates into an additive cardioprotective effect mediated by adenosine-induced effects including downregulation of pro- but upregulation of anti-inflammatory mediators.

  3. Mutational founder effect in recessive dystrophic epidermolysis bullosa families from Southern Tunisia.

    Science.gov (United States)

    Ben Brick, Ahlem Sabrine; Laroussi, Nadia; Mesrati, Hela; Kefi, Rym; Bchetnia, Mbarka; Lasram, Khaled; Ben Halim, Nizar; Romdhane, Lilia; Ouragini, Houyem; Marrakchi, Salaheddine; Boubaker, Mohamed Samir; Meddeb Cherif, Mounira; Castiglia, Daniele; Hovnanian, Alain; Abdelhak, Sonia; Turki, Hamida

    2014-05-01

    Dystrophic epidermolysis bullosa (DEB) is a group of heritable bullous skin disorders caused by mutations in the COL7A1 gene. One of the most severe forms of DEB is the severe generalized [recessive dystrophic epidermolysis bullosa (RDEB-SG)] subtype, which is inherited in an autosomal recessive manner. This subtype is most often due to COL7A1 mutations resulting in a premature termination codon on both alleles. We report here, the molecular investigation of 15 patients belonging to 14 nuclear families from the city of Sfax in Southern Tunisia, with clinical features of RDEB-SG complicated by squamous cell carcinoma in 3 patients. We identified two novel mutations, p.Val769LeufsX1 and p.Ala2297SerfsX91, in addition to one previously reported mutation (p.Arg2063Trp). The p.Val769LeufsX1 mutation was shared by 11 families and haplotype analysis indicated that it is a founder mutation. The p.Ala2297SerfsX91 mutation was a private mutation found in only one family. Together with the previously described recurrent mutations in Tunisia, screening for the founder p.Val769LeufsX1 mutation should provide a rapid molecular diagnosis tool for mutation screening in RDEB patients from Southern Tunisia and possibly from other Mediterranean populations sharing the same genetic background.

  4. Effect of bauxite addition on densification and mullitization ...

    Indian Academy of Sciences (India)

    Administrator

    Abstract. The effect of bauxite addition on the densification and mullitization of reaction sintered bauxite– clay mixture had been studied in the temperature range 1400–1500°C. The maximum bulk density (2⋅89 g/cc) and minimum apparent porosity (0⋅58%) was achieved by addition of 50 wt% bauxite. The impurities ...

  5. A novel missense mutation in the signal peptide of the human POMC gene: a possible additional link between early-onset type 2 diabetes and obesity.

    Science.gov (United States)

    Mencarelli, Monica; Zulian, Alessandra; Cancello, Raffaella; Alberti, Luisella; Gilardini, Luisa; Di Blasio, Anna Maria; Invitti, Cecilia

    2012-12-01

    Rare mutations in several genes have a critical role in the control of homeostatic mechanisms such as food-intake, energy balance and glucose metabolism. In this study, we performed a mutational screening in a 58-year-old woman presenting early-onset type 2 diabetes and central obesity. The entire coding regions of MC4R, MC3R, HNF1A, GCK and POMC (pro-opiomelanocortin) genes were analyzed by direct sequencing. A new missense mutation was identified within the POMC gene signal peptide sequence, resulting in a heterozygous substitution of an arginine for a glycine at codon 15 (p.A15G) that was excluded in 300 healthy normal weight controls. The mutation segregated in the family and was associated with overweight, type 2 diabetes, hypertension and coronary heart disease in the carriers. Functional studies demonstrated that POMC protein was not detectable in β-TC3 cells transfected with A15G-POMC vector as well as in their culture media, despite POMC mRNA levels were comparable for amount and stability to those of wild-type-transfected cells. In silico RNA folding prediction indicated that the mutation gives rise to a different RNA secondary structure, suggesting that it might affect translation and protein synthesis. To the best of our knowledge, this is the first report addressing the functional consequences of a mutation in the signal peptide of POMC. These findings further support the hypothesis that POMC-derived peptides might have a role in the control of peripheral glucose metabolism and suggest that disruption of central POMC secretion might represent an additional link between type 2 diabetes and obesity.

  6. Functional Characterization of Three Concomitant MtDNA LHON Mutations Shows No Synergistic Effect on Mitochondrial Activity.

    Science.gov (United States)

    Cruz-Bermúdez, Alberto; Vicente-Blanco, Ramiro J; Hernández-Sierra, Rosana; Montero, Mayte; Alvarez, Javier; González Manrique, Mar; Blázquez, Alberto; Martín, Miguel Angel; Ayuso, Carmen; Garesse, Rafael; Fernández-Moreno, Miguel A

    2016-01-01

    The presence of more than one non-severe pathogenic mutation in the same mitochondrial DNA (mtDNA) molecule is very rare. Moreover, it is unclear whether their co-occurrence results in an additive impact on mitochondrial function relative to single mutation effects. Here we describe the first example of a mtDNA molecule harboring three Leber's hereditary optic neuropathy (LHON)-associated mutations (m.11778G>A, m.14484T>C, m.11253T>C) and the analysis of its genetic, biochemical and molecular characterization in transmitochondrial cells (cybrids). Extensive characterization of cybrid cell lines harboring either the 3 mutations or the single classic m.11778G>A and m.14484T>C mutations revealed no differences in mitochondrial function, demonstrating the absence of a synergistic effect in this model system. These molecular results are in agreement with the ophthalmological characteristics found in the triple mutant patient, which were similar to those carrying single mtDNA LHON mutations.

  7. Functional Characterization of Three Concomitant MtDNA LHON Mutations Shows No Synergistic Effect on Mitochondrial Activity.

    Directory of Open Access Journals (Sweden)

    Alberto Cruz-Bermúdez

    Full Text Available The presence of more than one non-severe pathogenic mutation in the same mitochondrial DNA (mtDNA molecule is very rare. Moreover, it is unclear whether their co-occurrence results in an additive impact on mitochondrial function relative to single mutation effects. Here we describe the first example of a mtDNA molecule harboring three Leber's hereditary optic neuropathy (LHON-associated mutations (m.11778G>A, m.14484T>C, m.11253T>C and the analysis of its genetic, biochemical and molecular characterization in transmitochondrial cells (cybrids. Extensive characterization of cybrid cell lines harboring either the 3 mutations or the single classic m.11778G>A and m.14484T>C mutations revealed no differences in mitochondrial function, demonstrating the absence of a synergistic effect in this model system. These molecular results are in agreement with the ophthalmological characteristics found in the triple mutant patient, which were similar to those carrying single mtDNA LHON mutations.

  8. SNPDelScore: combining multiple methods to score deleterious effects of noncoding mutations in the human genome.

    Science.gov (United States)

    Vera Alvarez, Roberto; Li, Shan; Landsman, David; Ovcharenko, Ivan

    2017-09-14

    Addressing deleterious effects of noncoding mutations is an essential step towards the identification of disease-causal mutations of gene regulatory elements. Several methods for quantifying the deleteriousness of noncoding mutations using artificial intelligence, deep learning, and other approaches have been recently proposed. Although the majority of the proposed methods have demonstrated excellent accuracy on different test sets, there is rarely a consensus. In addition, advanced statistical and artificial learning approaches used by these methods make it difficult porting these methods outside of the labs that have developed them. To address these challenges and to transform the methodological advances in predicting deleterious noncoding mutations into a practical resource available for the broader functional genomics and population genetics communities, we developed SNPDelScore, which uses a panel of proposed methods for quantifying deleterious effects of noncoding mutations to precompute and compare the deleteriousness scores of all common SNPs in the human genome in 44 cell lines. The panel of deleteriousness scores of a SNP computed using different methods is supplemented by functional information from the GWAS Catalog, libraries of transcription factor binding sites, and genic characteristics of mutations. SNPDelScore comes with a genome browser capable of displaying and comparing large sets of SNPs in a genomic locus and rapidly identifying consensus SNPs with the highest deleteriousness scores making those prime candidates for phenotype-causal polymorphisms. https://www.ncbi.nlm.nih.gov/research/snpdelscore/. Supplementary data are available at Bioinformatics online.

  9. Interactive effects of nutrient additions and predation on infaunal communities

    Science.gov (United States)

    Posey, M.H.; Alphin, T.D.; Cahoon, L.; Lindquist, D.; Becker, M.E.

    1999-01-01

    Nutrient additions represent an important anthropogenic stress on coastal ecosystems. At moderate levels, increased nutrients may lead to increased primary production and, possibly, to increased biomass of consumers although complex trophic interactions may modify or mask these effects. We examined the influence of nutrient additions and interactive effects of trophic interactions (predation) on benthic infaunal composition and abundances through small-scale field experiments in 2 estuaries that differed in ambient nutrient conditions. A blocked experimental design was used that allowed an assessment of direct nutrient effects in the presence and absence of predation by epibenthic predators as well as an assessment of the independent effects of predation. Benthic microalgal production increased with experimental nutrient additions and was greater when infaunal abundances were lower, but there were no significant interactions between these factors. Increased abundances of one infaunal taxa, Laeonereis culveri, as well as the grazer feeding guild were observed with nutrient additions and a number of taxa exhibited higher abundances with predator exclusion. In contrast to results from freshwater systems there were no significant interactive effects between nutrient additions and predator exclusion as was predicted. The infaunal responses observed here emphasize the importance of both bottom-up (nutrient addition and primary producer driven) and top-down (predation) controls in structuring benthic communities. These processes may work at different spatial and temporal scales, and affect different taxa, making observation of potential interactive effects difficult.

  10. Effects of Grain Refining Additions to Aluminum Alloys

    Science.gov (United States)

    Gennone, R. J.; Coyle, F. T.; Farrior, G. M.

    An efficient method of controlling the grain-size of commercial aluminum alloys is by continuous additions of grain-refining agents in the form of master-alloy rod which is fed automatically into the launder during casting. The simultaneous addition of titanium and boron in a single rod is more efficient and more economical than separate additions. Response of various alloys to grain refining may be determined using the laboratory test described. Effects of these additions on 6063 alloy are presented; preliminary results on other commercial alloys are included.

  11. Effects of some polymeric additives on the cocrystallization of caffeine

    Science.gov (United States)

    Chung, Jihae; Kim, Il Won

    2011-11-01

    Effects of polymeric additives on the model cocrystallization were examined. The model cocrystal was made from caffeine and oxalic acid, and poly(ethylene glycol) (PEG), poly( L-lactide) (PLLA), poly(ɛ-caprolactone) (PCL), and poly(acrylic acid) (PAA) were the additives. The cocrystals were formed as millimeter-sized crystals without additives, and they became microcrystals with PLLA and PCL, and nanocrystals with PAA. XRD and IR revealed that the cocrystal structure was unchanged despite the strong effects of the additives on the crystal morphology, although some decrease in crystallinity was observed with PAA as confirmed by DSC. The DSC study also showed that the cocrystal melted and recrystallized to form α-caffeine upon heating. The present study verified that the polymeric additives can be utilized to modulate the size and morphology of the cocrystals without interfering the intermolecular interactions essential to the integrity of the cocrystal structures.

  12. POEM: Identifying Joint Additive Effects on Regulatory Circuits.

    Science.gov (United States)

    Botzman, Maya; Nachshon, Aharon; Brodt, Avital; Gat-Viks, Irit

    2016-01-01

    Expression Quantitative Trait Locus (eQTL) mapping tackles the problem of identifying variation in DNA sequence that have an effect on the transcriptional regulatory network. Major computational efforts are aimed at characterizing the joint effects of several eQTLs acting in concert to govern the expression of the same genes. Yet, progress toward a comprehensive prediction of such joint effects is limited. For example, existing eQTL methods commonly discover interacting loci affecting the expression levels of a module of co-regulated genes. Such "modularization" approaches, however, are focused on epistatic relations and thus have limited utility for the case of additive (non-epistatic) effects. Here we present POEM (Pairwise effect On Expression Modules), a methodology for identifying pairwise eQTL effects on gene modules. POEM is specifically designed to achieve high performance in the case of additive joint effects. We applied POEM to transcription profiles measured in bone marrow-derived dendritic cells across a population of genotyped mice. Our study reveals widespread additive, trans-acting pairwise effects on gene modules, characterizes their organizational principles, and highlights high-order interconnections between modules within the immune signaling network. These analyses elucidate the central role of additive pairwise effect in regulatory circuits, and provide computational tools for future investigations into the interplay between eQTLs. The software described in this article is available at csgi.tau.ac.il/POEM/.

  13. Single Molecule Effects of Osteogenesis Imperfecta Mutations in Tropocollagen Protein Domains

    Science.gov (United States)

    2008-12-02

    Single molecule effects of osteogenesis imperfecta mutations in tropocollagen protein domains Alfonso Gautieri,1,2 Simone Vesentini,2 Alberto...DATES COVERED 00-00-2008 to 00-00-2008 4. TITLE AND SUBTITLE Single molecule effects of osteogenesis imperfecta mutations in tropocollagen...already at the single molecule level. This is in contrast to recent studies of mutations related to muscle dys- trophies21 that have shown that the

  14. Ecotoxicological effects of activated carbon addition to sediments.

    Science.gov (United States)

    Jonker, Michiel T O; Suijkerbuijk, Martin P W; Schmitt, Heike; Sinnige, Theo L

    2009-08-01

    Activated carbon (AC) addition is a recently developed technique for the remediation of sediments and soils contaminated with hydrophobic organic chemicals. Laboratory and field experiments have demonstrated that the addition of 3-4% of AC can reduce aqueous concentrations and the bioaccumulation potential of contaminants. However, one aspect of the technique that has hardly received any attention is the possible occurrence of secondary, eco(toxico)logical effects, i.e., effects of AC addition on the health, behavior, and habitat quality of local organisms. In the present study, several ecotoxicological effects were investigated in AC-water and AC-enriched (0-25%) sediment systems. It was demonstrated that (i) powdered activated carbons can be toxic to aquatic invertebrates (Lumbriculus variegatus, Daphnia magna, and Corophium volutator) based on different mechanisms and preferably should be washed prior to application; (ii) Asellus aquaticus and Corophium volutator may physically avoid AC-enriched sediments; (iii) exposure of Lumbriculus variegatus to AC-enriched sediments lead to a time and dose-dependent reduction in the worms' lipid content, which was most probably caused by the observation that (iv) worm egestion rates decreased drastically upon AC addition, indicating that the presence of AC disturbed feeding behavior; and (v) there were no obvious effects on the microbiological community structure. All in all, these results suggest potential ecotoxicological effects of powdered AC addition and stress the need for a detailed further investigation of secondary effects of the technique, prior to any large-scale field application.

  15. Expected Effect of Deleterious Mutations on Within-Host Adaptation of Pathogens

    Science.gov (United States)

    2015-01-01

    ABSTRACT Adaptation is a common theme in both pathogen emergence, for example, in zoonotic cross-species transmission, and pathogen control, where adaptation might limit the effect of the immune response and antiviral treatment. When such evolution requires deleterious intermediate mutations, fitness ridges and valleys arise in the pathogen's fitness landscape. The effect of deleterious intermediate mutations on within-host pathogen adaptation is examined with deterministic calculations, appropriate for pathogens replicating in large populations with high error rates. The effect of deleterious intermediate mutations on pathogen adaptation is smaller than their name might suggest: when two mutations are required and each individual single mutation is fully deleterious, the pathogen can jump across the fitness valley by obtaining two mutations at once, leading to a proportion of adapted mutants that is 20-fold lower than that in the situation where the fitness of all mutants is neutral. The negative effects of deleterious intermediates are typically substantially smaller and outweighed by the fitness advantages of the adapted mutant. Moreover, requiring a specific mutation order has a substantially smaller effect on pathogen adaptation than the effect of all intermediates being deleterious. These results can be rationalized when the number of routes of mutation available to the pathogen is calculated, providing a simple approach to estimate the effect of deleterious mutations. The calculations discussed here are applicable when the effect of deleterious mutations on the within-host adaptation of pathogens is assessed, for example, in the context of zoonotic emergence, antigenic escape, and drug resistance. IMPORTANCE Adaptation is critical for pathogens after zoonotic transmission into a new host species or to achieve antigenic immune escape and drug resistance. Using a deterministic approach, the effects of deleterious intermediate mutations on pathogen adaptation

  16. Direct and Maternal Additive Effects on Rabbit Growth and Linear ...

    African Journals Online (AJOL)

    Growth and linear body measurements of rabbits which consisted of 17 ew Zealand White (ZW), 19 Chinchilla (CH), 29 ZW x CH and 33 CH x ZW kittens were compared. The aim of the experiment was to evaluate the crossbreeding effects (i.e direct and maternal additive effect) for growth (individual body weight, IBW) and ...

  17. IDH1 and IDH2 mutations confer an adverse effect in patients with acute myeloid leukemia lacking the NPM1 mutation.

    Science.gov (United States)

    Yamaguchi, Shunichiro; Iwanaga, Eisaku; Tokunaga, Kenji; Nanri, Tomoko; Shimomura, Taizo; Suzushima, Hitoshi; Mitsuya, Hiroaki; Asou, Norio

    2014-06-01

    We examined the incidence and prognostic effect of IDH1 and IDH2 mutations in 233 Japanese adults with acute myeloid leukemia (AML). IDH1 R132 mutations were detected in 20 (8.6%) patients with AML. IDH2 mutations were found in 19 (8.2%, 17 R140 and two R172) patients. IDH1 and IDH2 mutations were mutually exclusive and were associated with normal karyotype AML, cytogenetic intermediate-risk group, and NPM1 mutations. Five-year overall survival (OS) rates were significantly lower (15.6%) in patients harboring the IDH mutations than in patients lacking the IDH mutation (32.0%) in the entire cohort of AML (P = 0.005). Among patients aged 59 yr or younger with IDH mutations, 5-yr OS in patients who underwent allogeneic stem cell transplantation (SCT) was significantly higher than that in those not receiving allogeneic SCT (50% vs. 10.6%, P = 0.020). Of 51 patients with NPM1 mutations, there was no significant difference in 5-yr OS rates between patients with and those without the IDH mutations. In contrast, among 175 patients lacking the NPM1 mutations, 5-yr OS rate in patients with IDH mutations was significantly lower than that in those without IDH mutations (0% vs. 34.7%, P = mutations have an unfavorable effect in AML, especially AML with the NPM1 wild type and younger AML patients with IDH mutations may benefit from allogeneic SCT. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. The effect of chemical additives on the synthesis of ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, S.S.C.

    1990-11-01

    The objective of this research is to elucidate the role of additives on the ethanol synthesis over Rh- and Ni-based catalysts. Chemical additives used for this study will include S, P, Ag, Cu, Mn, and Na which have different electronegativities. The effect of additives on the surface state of the catalysts, heat of adsorption of reactant molecules, reaction intermediates, reaction pathways, reaction kinetics, and product distributions is/will be investigated by a series of experimental studies of NO adsorption, reaction probing, study state rate measurement, and transient kinetic study. A better understanding of the role of additive on the synthesis reaction may allow them to use chemical additives to manipulate the catalytic properties of Rh- and Ni-based catalysts for producing high yields of ethanol from syngas. 49 refs., 6 figs., 3 tabs.

  19. The effect of chemical additives on the synthesis of ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, S.S.C.

    1990-04-09

    The objective of this research is to elucidate the role of various chemical additives on ethanol synthesis over Rh- and Ni-based catalysts. Chemical additives used for this study will include S, P, Ag, Cu, Mn, and Na which have different electronegativities. The effect of additives on the surface state of the catalysts, heat of adsorption of reactant molecules, reaction intermediates, reaction pathways, reaction kinetics, and product distributions is/will be investigated by a series of experimental studies of NO adsorption, reaction probing, study state rate measurement, and transient kinetic study. A better understanding of the role of additive on the synthesis reaction may allow us to use chemical additives to manipulate the catalytic properties of Rh- and Ni-based catalysts for producing high yields of ethanol from syngas.

  20. Effect of Additives on Some Physical Parameters of Palm Oil

    Directory of Open Access Journals (Sweden)

    N. O. Eddy

    2007-01-01

    Full Text Available Effect of additives (carrot, lime, paw paw and red dye on the density, viscosity, moisture content and melting point of palm oil (PO was investigated by dissolving 1g of each additive to 10 mL of pre-analysed oil in a beaker. The mixture was heated and their their moisture content, melting point, viscosity and density were determined. The result of the analysis shows that all the additives significantly increased the density, moisture content and viscosity (except lime of the oil. Addition of paw paw and red dye also increased the melting point of the oil while the addition of carrot and lime juice decreased the melting point of the oil.

  1. Point Mutations Effects on Charge Transport Properties of the Tumor-Suppressor Gene p53

    Science.gov (United States)

    Roemer, Rudolf A.; Shih, Chi-Tin; Roche, Stephan

    2008-03-01

    We report on a theoretical study of point mutations effects on charge transfer properties in the DNA sequence of the tumor-suppressor p53 gene. On the basis of effective tight-binding models which simulate hole propagation along the DNA, a statistical analysis of mutation-induced charge transfer modifications is performed. In contrast to non-cancerous mutations, mutation hotspots tend to result in significantly weaker changes of transmission properties. This suggests that charge transport could play a significant role for DNA-repairing deficiency yielding carcinogenesis.

  2. Variation in Mutational Robustness between Different Proteins and the Predictability of Fitness Effects.

    Science.gov (United States)

    Lind, Peter A; Arvidsson, Lars; Berg, Otto G; Andersson, Dan I

    2017-02-01

    Random mutations in genes from disparate protein classes may have different distributions of fitness effects (DFEs) depending on different structural, functional, and evolutionary constraints. We measured the fitness effects of 156 single mutations in the genes encoding AraC (transcription factor), AraD (enzyme), and AraE (transporter) used for bacterial growth on l-arabinose. Despite their different molecular functions these genes all had bimodal DFEs with most mutations either being neutral or strongly deleterious, providing a general expectation for the DFE. This contrasts with the unimodal DFEs previously obtained for ribosomal protein genes where most mutations were slightly deleterious. Based on theoretical considerations, we suggest that the 33-fold higher average mutational robustness of ribosomal proteins is due to stronger selection for reduced costs of translational and transcriptional errors. Whereas the large majority of synonymous mutations were deleterious for ribosomal proteins genes, no fitness effects could be detected for the AraCDE genes. Four mutations in AraC and AraE increased fitness, suggesting that slightly advantageous mutations make up a significant fraction of the DFE, but that they often escape detection due to the limited sensitivity of commonly used fitness assays. We show that the fitness effects of amino acid substitutions can be predicted based on evolutionary conservation, but those weakly deleterious mutations are less reliably detected. This suggests that large-effect mutations and the fraction of highly deleterious mutations can be computationally predicted, but that experiments are required to characterize the DFE close to neutrality, where many mutations ultimately fixed in a population will occur. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  3. Systematic analysis of disease-related regulatory mutation classes reveals distinct effects on transcription factor binding.

    Science.gov (United States)

    Laurila, Kirsti; Lähdesmäki, Harri

    2009-01-01

    Detailed knowledge of the mechanisms of transcriptional regulation is essential in understanding the gene expression in its entirety. Transcription is regulated, among other things, by transcription factors that bind to DNA and can enhance or repress the transcription process. If a transcription factor fails to bind to DNA or binds to a wrong DNA region that can cause severe effects to the gene expression, to the cell and even to the individual. The problems in transcription factor binding can be caused by alterations in DNA structure which often occurs when parts of the DNA strands are mutated. An increasing number of the identified disease-related mutations occur in gene regulatory sequences. These regulatory mutations can disrupt transcription factor binding sites or create new ones. We have studied effects of mutations on transcription factor binding affinity computationally. We have compared our results with experimentally verified cases where a mutation in a gene regulatory region either creates a new transcription factor binding site or deletes a previously existing one. We have investigated the statistical properties of the changes on transcription factor binding affinity according to the mutation type. Our analysis shows that the probability of a loss of a transcription factor binding site and a creation of a new one varies remarkably by the mutation type. Our results demonstrate that computational analysis provides valuable information about the effect of mutations on transcription factor binding sites. The analysis results also give a useful test set for in vitro studies of regulatory mutation effects.

  4. Promotional effects of new types of additives on fat crystallization.

    Science.gov (United States)

    Yoshikawa, Shinichi; Kida, Haruyasu; Sato, Kiyotaka

    2014-01-01

    We examined the promotional effects of additives on fat crystallization, such as inorganic (talc, carbon nanotube (CNT), and graphite) and organic (theobromine, ellagic acid dihydrate (EAD), and terephthalic acid) materials. The triacylglycerols (TAGs) of trilauroylglycerol (LLL), trimyristoylglycerol (MMM), and tripalmitoylglycerol (PPP) were employed as the fats. The additives (1 wt%) were added to the molten TAGs, and then the mixtures were cooled at a rate of 1°C/min followed by heating at a rate of 5°C/min. The crystallization and melting properties were observed using differential scanning calorimetry, X-ray diffraction, and polarized optical microscope (POM). Consequently, we found that the above six additives remarkably increased the initial temperatures of crystallization (Ti) on cooling without changing the melting temperatures. For example, in the case of LLL, the increases in Ti were 2.6°C (talc), 3.9°C (CNT), 8.1°C (graphite), 1.1°C (theobromine), 2.0°C (EAD), and 6.8°C (terephthalic acid). Very similar effects were observed for the crystallization of MMM and PPP with the six additives. Furthermore, the polymorphs of the first occurring crystals were changed from metastable to more stable forms by many of these additives. The POM observation revealed that the crystallization was initiated at the surfaces of additive particles. This study has shown for the first time that the heterogeneous nucleation of fat crystals can be greatly promoted by new types of additives. Such additives have great potential to promote fat crystallization by not only hydrophobic but also hydrophilic molecular interactions between the fats and additives.

  5. Mutational effects of space flight on Zea mays seeds

    Science.gov (United States)

    Mei, M.; Qiu, Y.; He, Y.; Bucker, H.; Yang, C. H.

    1994-01-01

    The growth and development of more than 500 Zea mays seeds flown on Long Duration Exposure Facility (LDEF) were studied. Somatic mutations, including white-yellow stripes on leaves, dwarfing, change of leaf sheath color or seedling color were observed in plants developed from these seeds. When the frequency of white-yellow formation was used as the endpoint and compared with data from ground based studies, the dose to which maize seeds might be exposed during the flight was estimated to be equivalent to 635 cGy of gamma rays. Seeds from one particular holder gave a high mutation frequency and a wide mutation spectrum. White-yellow stripes on leaves were also found in some of the inbred progenies from plants displayed somatic mutation. Electron microscopy studies showed that the damage of chloroplast development in the white-yellow stripe on leaves was similar between seeds flown on LDEF and that irradiated by accelerated heavy ions on ground.

  6. Effect of fluoride additives on production and characterization of ...

    Indian Academy of Sciences (India)

    The effects of ZnF2 additive and milling on the phase transformation as well as micrograph of the prepared -Al2O3 particles were investigated. The samples were characterized by different techniques such as X-ray diffraction, thermogravimetry analysis, differential scanning calorimetry, Fourier transform infrared spectra, ...

  7. Effect Of Formulating Additives On The Properties Of Ibuprofen Tablets

    African Journals Online (AJOL)

    A study of the comparative effects of different formulating additives and film coating on the properties of ibuprofen tablets was made. The tested properties were hardeness (H), friability (F), the disintegration time (D) and dissolution characteristics of ibuprofen tablets. The hardeness, friability, the hardeness friability ratio ...

  8. Effects of sulphur addition on modification and mechanical ...

    African Journals Online (AJOL)

    The effects of sulphur addition on the microstructure and mechanical properties of sand cast Al-12wt%Si alloy have been investigated in this study. For this purpose, different amounts of sulphur were added to Al-12wt%Si alloy in an induction furnace to produce sand castings for micro-structural and mechanical properties ...

  9. Additive effects of dietary glycotoxins and androgen excess on the ...

    African Journals Online (AJOL)

    Sotiria Palimeri

    2015-08-08

    Aug 8, 2015 ... PCOS. Abstract Background: Dietary glycotoxins and androgen excess have been independently associ- ated with a negative influence on the kidney. There are no data concerning the additive effects of these two factors on the kidney function and structure, in females. The present study aims to inves-.

  10. Effects of non-antibiotic feed additives on performance, immunity ...

    African Journals Online (AJOL)

    p2492989

    Beneficial effects of dietary additives such as probiotics, prebiotics and organic acids, on the energy ... prebiotics and organic acids on performance, immunity and the intestinal morphology of broilers fed. Copyright .... architecture and increases in villi height have been reported to be due to the supplementation of prebiotics.

  11. Additive Effects of Rhizophora Racemose (Red Mangrove) On Blood ...

    African Journals Online (AJOL)

    An experiment was carried out at the Teaching and Research Farm of Rivers State University of Science and Technology, Port Harcourt to determine the additive effect of pulverized Rhizophora racemosa (Red Mangrove) leaves on the hematology and bursa of Fabricus of broilers. Sixty (60) day-old, Anak broiler chicks ...

  12. Effects of enzyme Additive on Nutrient intake, Digestibility and ...

    African Journals Online (AJOL)

    Effects of enzyme Additive on Nutrient intake, Digestibility and Rumen metabolites of yearling Cattle fed Grass-hay based diet. ... Nigerian Journal of Animal Science ... There were no significant differences among other levels of inclusion for total dry matter intake, Crude protein intake and Acid Detergent Fibre intake.

  13. Experimental analysis on the effect of addition of Rhizoma ...

    African Journals Online (AJOL)

    The effect of addition of Rhizoma gastrodiae on mycelia and exopolysaccharide production by submerged culture of Grifola frondosa was investigated. About 7% (v/v) of R. gastrodiae extract was added to the basal medium used for its biomass and exopolysaccharide productions. The biomass and exopolysaccharide ...

  14. Effects of water and sawdust additives on thermal effusivity, thermal ...

    African Journals Online (AJOL)

    The effects of water and sawdust additives on the thermal effusivity (e), thermal conductivity (λ), and durability of cement-stabilized laterites were investigated. The thermal effusivity (e) and conductivity(λ) have direct influ-ence on heat transfer and thermal insulation in buildings, and the parameters were determined by hot ...

  15. Effects of Adansonia digitata (Baobab) bark meal additive on growth ...

    African Journals Online (AJOL)

    Effects of Adansonia digitata (Baobab) bark meal additive on growth performance and nutrient utlization of Clarias gariepinus fingerlings. M.S. Bayon, N.B. Ikenweiwe, D.O. Odulate, O.O. Adewumi, W.O. Alegbeleye, O.E. Babalola, A.A. Alimi ...

  16. Effects of various additives to enhance growth performance, blood ...

    African Journals Online (AJOL)

    Effects of various additives to enhance growth performance, blood profiles, and reduce malodour emissions in growing pigs. W.G. Kwak, I.H. Park, W Yun, J.H. Lee, C.H. Lee, S.Y. Oh, H.J. Oh, Shudong Liu, Y.H. Kim, J.C. Park, G.S. Kim, J.H. Cho ...

  17. The Inhibitory Effects of Aqueous Extract from Guava Twigs, Psidium guajava L., on Mutation and Oxidative Damage

    OpenAIRE

    Zhi-Chyang Kang; Ming-Tsung Yen; Chih-Kwang Chiu; Horng-Cherng Wu; Shu-Ling Huang; Shan-Pao Tai; Bor-Sen Wang

    2013-01-01

    This study examines the inhibitory effects of the aqueous extract from guava twigs (GTE), Psidium guajava L., on mutation and oxidative damage. The results show that GTE inhibits the mutagenicity of 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen, and 2-aminoanthracene (2-AA), an indirect mutagen, toward Salmonella typhimurium TA 98 and TA 100. In addition, GTE shows radical scavenging, reducing activities, tyrosinase inhibition, and liposome protection effects. Meanwhile, GTE in the range...

  18. The Fitness Effects of Spontaneous Mutations Nearly Unseen by Selection in a Bacterium with Multiple Chromosomes.

    Science.gov (United States)

    Dillon, Marcus M; Cooper, Vaughn S

    2016-11-01

    Mutation accumulation (MA) experiments employ the strategy of minimizing the population size of evolving lineages to greatly reduce effects of selection on newly arising mutations. Thus, most mutations fix within MA lines independently of their fitness effects. This approach, more recently combined with genome sequencing, has detailed the rates, spectra, and biases of different mutational processes. However, a quantitative understanding of the fitness effects of mutations virtually unseen by selection has remained an untapped opportunity. Here, we analyzed the fitness of 43 sequenced MA lines of the multi-chromosome bacterium Burkholderia cenocepacia that had each undergone 5554 generations of MA and accumulated an average of 6.73 spontaneous mutations. Most lineages exhibited either neutral or deleterious fitness in three different environments in comparison with their common ancestor. The only mutational class that was significantly overrepresented in lineages with reduced fitness was the loss of the plasmid, though nonsense mutations, missense mutations, and coding insertion-deletions were also overrepresented in MA lineages whose fitness had significantly declined. Although the overall distribution of fitness effects was similar between the three environments, the magnitude and even the sign of the fitness of a number of lineages changed with the environment, demonstrating that the fitness of some genotypes was environmentally dependent. These results present an unprecedented picture of the fitness effects of spontaneous mutations in a bacterium with multiple chromosomes and provide greater quantitative support for the theory that the vast majority of spontaneous mutations are neutral or deleterious. Copyright © 2016 by the Genetics Society of America.

  19. Multitrophic effects of nutrient addition in upland grassland.

    Science.gov (United States)

    Fountain, M T; Brown, V K; Gange, A C; Symondson, W O C; Murray, P J

    2008-06-01

    Although the effects of nutrient enhancement on aquatic systems are well documented, the consequences of nutritional supplements on soil food webs are poorly understood, and results of past research examining bottom-up effects are often conflicting. In addition, many studies have failed to separate the effects of nutrient enrichment and the physical effects of adding organic matter. In this field study, we hypothesised that the addition of nitrogen to soil would result in a trophic cascade, through detritivores (Collembola) to predators (spiders), increasing invertebrate numbers and diversity. Nitrogen and lime were added to plots in an upland grassland in a randomised block design. Populations of Collembola and spiders were sampled by means of pitfall traps and identified to species. Seventeen species of Collembola were identified from the nitrogen plus lime (N+L) and control plots. Species assemblage, diversity, richness, evenness and total number were not affected by nutrient additions. However, there was an increase in the number of Isotomidae juveniles and Parisotoma anglicana trapped in the N+L plots. Of the 44 spider species identified, over 80% were Linyphiidae. An effect on species assemblage from the addition of N+L to the plots was observed on two of the four sampling dates (July 2002 and June 2003). The linyphiid, Oedothorax retusus, was the only species significantly affected by the treatments and was more likely to be trapped in the control plots.The increased number of juvenile Collembola, and change in community composition of spiders, were consequences of the bottom-up effect caused by nutrient inputs. However, despite efforts to eliminate the indirect effects of nutrient inputs, a reduction in soil moisture in the N+L plots cannot be eliminated as a cause of the invertebrate population changes observed. Even so, this experiment was not confounded by the physical effects of habitat structure reported in most previous studies. It provides evidence

  20. Effect of Zr addition on precipitates in K4169 superalloy

    Directory of Open Access Journals (Sweden)

    Liu Jie

    2012-02-01

    Full Text Available In order to investigate the effect of Zr addition on the precipitations of K4169 superalloy, a manual electric arc furnace was used to prepare the superalloy with different Zr addition from 0.03wt.% to 0.07wt%. After standard heat treatment and long-time aging, the microstructures of the alloys were observed using XRD, SEM and TEM. The results show that Zr not only inhibits the precipitation of Laves phase at the grain boundary, but also significantly promotes the precipitation of earlobe-like γ′and γ″ phases. After long time aging at 680 ℃ for 500 h, the γ″phase grows up obviously and forms a γ′/γ′′clad microstructure when the Zr addition is 0.03 wt.%. A large number of fine orbed γ′particles precipitate in the grains and some γ″phase transforms to disk-like δ phase when the Zr addition increases to 0.05wt.%. The nano-polycrystalline γ′phase precipitates in the grains and there is a little δ phase when the Zr addition is 0.07wt.%. As the Zr addition increases, the amount of Laves phase at the grain boundary decreases at first, and then increases and forms flaky morphology.

  1. DNMT3A (R882) mutation features and prognostic effect in acute myeloid leukemia in Coexistent with NPM1 and FLT3 mutations.

    Science.gov (United States)

    Kumar, Dushyant; Mehta, Anurag; Panigrahi, Manoj Kumar; Nath, Sukanta; Saikia, Kandarpa Kumar

    2017-10-18

    In the absence of high-risk cytogenetic, DNMT3A (DNA Methyltransferase 3a) mutation status has an impact on outcome in the presence of FLT3 (FMS-like Tyrosine Kinase3) and/or NPM1 (Nucleophosmin). In this study, we focus on the features and effect of DNMT3A (R882) mutation in acute myeloid leukemia (AML) in the presence or absence of NPM1 and FLT3 mutations. A total of 174 cytogenetically normal (CN)-AML cases were analyzed for NPM1, FLT3, and DNMT3A mutations. For NPM1 mutation detection, we used the pyrosequencing technique; for FLT3 mutations, polymerase chain reaction and RFLP with ECO-RV techniques were used, and for DNMT3A mutation analysis, we used Sanger sequencing and RFLP (Restriction Fragment Length Polymorphism) techniques. NPM1 mutation was found in 40.80%, DNMT3A in 12.06%, and FLT3 mutation was found in 16.66% of 174 CN-AML patients. We also found seven cases which were (NPM1+, FLT3+), 10 cases which were (NPM1+, DNMT3A+), and two cases were found positive for (DNMT3A+, FLT3+) mutations. Adult patients had significantly higher frequency of NPM1 mutation than children (72.22% vs. 16.66%; p = .020), whereas FLT3/ITD and DNMT3A mutation was associated with higher white blood count (p = .081). Immunophenotypically, NPM1 and DNMT3A mutations were significantly associated with the lack of CD34, whereas FLT3/ITD mutation was positively associated with the expression of CD7. We also assessed the overall survival and progression-free survival of DNMT3A mutation status among patients with CN-AML. Indeed, DNMT3A mutations within the CN-AML subset were associated with significantly shorter overall survival and progression-free survival compared to NPM1 and FLT3 mutated patients (p = .067 and p = .065, respectively). DNMT3A R882 mutation plays an important role in CN-AML patients' prognosis and clinical outcomes in the presence and absence of NPM1 and FLT3 mutations. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by

  2. Effects of additional nanosilica of compressive strength on mortar

    Science.gov (United States)

    Retno Setiati, N.

    2017-07-01

    The use of nanosilica as one of the innovations in concrete technology has developed very rapidly. Some research mentioned that nanosilica obtained from the synthesis process silica sand is a type of material that is as pozolan when added to the concrete mix, so as to accelerate the hydration process in concrete. With the addition of nanosilica into the concrete mix, the compressive strength of the concrete can be increased and it has a high durability. This study aims to determine the effect from the addition of nanosilica on mechanical properties of concrete. Laboratory testing is conducted by making the mortar test specimen size of 50 mm x 50 mm x 50 mm. The material used is composed of silica sand, nanosilica, gravel, superplasticizer, cement, and water. Nanosilica percentage amount is added as much as 5, 10, and 15% by weight of cement. Testing of mechanical properties such as compressive strength mortar done at age 3, 7, 14, and 28 days. Based on the analysis and discussion obtained that at 28 days, mortar with the addition of 5% and 15% nanosilica has the compressive strength of 23 MPa. Addition nanosilika into the mortar to improve the mechanical properties by increasing the compressive strength of mortar. The compressive strength of mortar with the addition of 10% nanosilica is 19 MPa. The increase in compressive strength of mortar with the addition of 5% and 15% nano silica is 21% larger than the mortar with the addition of 10% nanosilica and without nanosilica. Nanosilica addition of more than 10% can cause agglomeration when mixed into the mortar so that the impact on the compressive strength of mortar.

  3. Study of the effect of HFE gene mutations on iron overload in ...

    African Journals Online (AJOL)

    Background: HFE gene mutations have been shown to be responsible for hereditary hemochromatosis. Their effect on iron load in β-thalassemia patients and carriers remains controversial. Objectives: We aimed to determine the prevalence of HFE gene mutations (C282Y and H63D) in β-thalassemia patients and carriers ...

  4. Study of the effect of HFE gene mutations on iron overload in ...

    African Journals Online (AJOL)

    Manal Michel Wilson

    2015-03-04

    Mar 4, 2015 ... Abstract Background: HFE gene mutations have been shown to be responsible for hereditary hemochromatosis. Their effect on iron load in b-thalassemia patients and carriers remains contro- versial. Objectives: We aimed to determine the prevalence of HFE gene mutations (C282Y and H63D) in.

  5. Effects of gyrA and parC Mutations in Quinolones Resistant Clinical ...

    African Journals Online (AJOL)

    The most important of fluoroquinolones resistance mechanisms is the accumulation of mutations in the bacterial enzymes targeted by fluoroquinolones; DNA gyrase and DNA topoisomerase IV. The effect of gyrase and Topoisomerase IV enzymes mutations on quinolones resistance in clinical Gram negative bacteria in ...

  6. Effects and interactions of myostatin and callipyge mutations. I. Growth and carcass traits

    Science.gov (United States)

    Objectives were to document effects of the Texel myostatin mutation (MSTN) on growth, carcass, and meat quality traits and also test whether or not interactions with the callipyge mutation (CLPG) could be detected. Twelve rams heterozygous at both loci on the two different chromosomes were mated to ...

  7. Pleiotropic effects of coat colour-associated mutations in humans, mice and other mammals.

    Science.gov (United States)

    Reissmann, Monika; Ludwig, Arne

    2013-01-01

    The characterisation of the pleiotropic effects of coat colour-associated mutations in mammals illustrates that sensory organs and nerves are particularly affected by disorders because of the shared origin of melanocytes and neurocytes in the neural crest; e.g. the eye-colour is a valuable indicator of disorders in pigment production and eye dysfunctions. Disorders related to coat colour-associated alleles also occur in the skin (melanoma), reproductive tract and immune system. Additionally, the coat colour phenotype of an individual influences its general behaviour and fitness. Mutations in the same genes often produce similar coat colours and pleiotropic effects in different species (e.g., KIT [reproductive disorders, lethality], EDNRB [megacolon] and LYST [CHS]). Whereas similar disorders and similar-looking coat colour phenotypes sometimes have a different genetic background (e.g., deafness [EDN3/EDNRB, MITF, PAX and SNAI2] and visual diseases [OCA2, RAB38, SLC24A5, SLC45A2, TRPM1 and TYR]). The human predilection for fancy phenotypes that ignore disorders and genetic defects is a major driving force for the increase of pleiotropic effects in domestic species and laboratory subjects since domestication has commenced approximately 18,000 years ago. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Segregation of S292F TPO gene mutation in three large Tunisian families with thyroid dyshormonogenesis: evidence of a founder effect.

    Science.gov (United States)

    Bougacha-Elleuch, Noura; Charfi, Nadia; Miled, Nabil; Bouhajja, Houda; Belguith, Neila; Mnif, Mouna; Jaurge, Paula; Chikhrouhou, Nessrine; Ayadi, Hammadi; Hachicha, Mongia; Abid, Mohamed

    2015-11-01

    We aimed to identify causal mutation(s) in 13 patients with thyroid dyshormonogenesis (TD) from three consanguineous Tunisian families. A 12-year clinical follow-up showed phenotypic variability ranging from the presence to the absence of goiter, sensorineural deafness, and mental retardation. Genetic analysis using microsatellite markers within two candidate genes (TPO and PDS) gave evidence of linkage with the TPO gene. Sequencing of its 17 exons and their flanking intron-exon junctions revealed the previously described c.875C>T (p.S292F) mutation in homozygous state. No additional mutations were found in either a 900 bp of the TPO gene promoter or PDS gene. In silico analysis showed that p.S292F mutation might reduce the catalytic cavity of the TPO which would restrict access of a potential substrate to the catalytic pocket. Using 4SNPs and one microsatellite marker in the TPO gene, an associated haplotype: G-C-G-G-214 was found, giving evidence of a founder mutation. This is the first description of a TD causing mutation in Tunisia and thus may help to develop a genetic screening protocol for congenital hypothyroidism in the studied region. Although structural modeling suggested a pathogenic effect of this mutation, functional studies are needed. Additional causing and/or modifier genes, together with late diagnosis could explain the clinical variability observed in our patients.

  9. The effect of chemical additives on the synthesis of ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, S.S.C.

    1989-02-04

    The objective of this research is to elucidate the role of various chemical additives on ethanol synthesis over Rh- and Ni-based catalysts. Chemical additives used will include S, P, Ag, Cu, Mn, and Na. The effect of additives on the surface state of the catalysts, heat of adsorption of reactant molecules, reaction intermediates, reaction pathways, reaction kinetics, and product distributions is/will be investigated by a series of studies including temperature programmed desorption, infrared study of NO adsorption, reactive probing, steady state rate measurement, and transient kinetic study. A better understanding of the role of additive may allow us to use chemical additives to manipulate the catalytic properties of Rh- and Ni-based catalysts for producing high yields of ethanol from syngas. CO insertion is known to be a key step to the formation of acetaldehyde and ethanol from CO hydrogenation over Rh catalysts. Ethylene hydroformylation has often served as a probe to determine CO insertion capabilities of Rh catalysts. The mechanism of CO insertion in ethylene hydroformylation over Rh/SiO{sub 2} was investigated.

  10. Survival of free and microencapsulated Bifidobacterium: effect of honey addition.

    Science.gov (United States)

    Favarin, Luciana; Laureano-Melo, Roberto; Luchese, Rosa Helena

    2015-01-01

    This study evaluated the effect of honey addition on the viability of free and emulsion encapsulated cells of two strains of Bifidobacterium that underwent simulation of human upper gastrointestinal transit. In the control condition, without honey, free cells were drastically reduced after exposure to gastrointestinal conditions. The reduction was more pronounced with Bifidobacterium J7 of human origin. On the other hand, when cells were encapsulated, the viability reduction was higher for strain Bifidobacterium Bb12. The microencapsulation improved the viability maintenance of both Bifidobacterium strains, in recommended amounts for probiotic activity, after exposure to simulated gastrointestinal conditions. Moreover, suspending free cells of both Bifidobacterium strains in honey solutions resulted in a protective effect, equivalent to the plain microencapsulation with sodium alginate 3%. It is concluded that microencapsulation and the addition of honey improved the ability of Bifidobacterium to tolerate gastrointestinal conditions in vitro.

  11. Effect of additives on densification and deformation of tetragonal zirconia

    NARCIS (Netherlands)

    Boutz, M.M.R.; Boutz, M.M.R.; Winnubst, Aloysius J.A.; Hartgers, F.; Burggraaf, A.J.; Burggraaf, Anthonie

    1994-01-01

    The effect of additives (Bi2O3, Fe2O3) on densification and creep rates of tetragonal ZrO2-Y2O3 has been investigated. In Bi2O3-doped Y-TZP, a reactive liquid forms at temperatures above 800–900DaggerC, which leads to a strong enhancement of densification for concentrations of 1–2 mol % Bi2O3.

  12. Transformation of brushite to hydroxyapatite and effects of alginate additives

    Science.gov (United States)

    Ucar, Seniz; Bjørnøy, Sindre H.; Bassett, David C.; Strand, Berit L.; Sikorski, Pawel; Andreassen, Jens-Petter

    2017-06-01

    Phase transformations are important processes during mineral formation in both in vivo and in vitro model systems and macromolecules are influential in regulating the mineralization processes. Calcium phosphate mineralized alginate hydrogels are potential candidates for hard tissue engineering applications and transformation of the resorbable calcium phosphate phases to apatitic bone mineral in vivo enhances the success of these composite materials. Here, the transformation of brushite to hydroxyapatite (HA) and the effects of alginate additives on this process are studied by the investigation of supersaturation profiles with HA-seeded and unseeded experiments. This experimental design allows for detailed kinetic interpretation of the transformation reactions and deduction of information on the nucleation stage of HA by evaluating the results of seeded and unseeded experiments together. In the experimental conditions of this work, transformation was controlled by HA growth until the point of near complete brushite dissolution where the growth and dissolution rates were balanced. The presence of alginate additives at low concentration were not highly influential on transformation rates during the growth dominated region but their retardant effect became more pronounced as the dissolution and growth rates reached an equilibrium where both reactions were effective on transformation kinetics. Decoupling of seeded and unseeded transformation experiments suggested that alginate additives retard HA nucleation and this was most evident in the presence of G-block oligomers.

  13. Effect of Urea Addition on Soda Pulping of Oak Wood

    OpenAIRE

    Cho, Nam-Seok; Matsumoto, Yuji; Shin, Soo-Jeong; Oga, Shoji

    2008-01-01

    Many studies have been conducted to find a sulfur-free additive for alkaline pulping liquors that would have an effect similar to that of sulfide in kraft pulping. Some reagents that partially fulfill this role have been found, but they are too expensive to be used in the quantities required to make them effective. As an alternative method to solve air pollution problem and difficulty of pulp bleaching of kraft pulping process, NaOH-Urea pulping was applied. The properties of NaOH-Urea pul...

  14. KLF6: mutational analysis and effect on cancer cell proliferation.

    Science.gov (United States)

    Yin, Dong; Komatsu, Naoki; Miller, Carl W; Chumakov, Alexey M; Marschesky, Alberto; McKenna, Robert; Black, Keith L; Koeffler, H Phillip

    2007-01-01

    Kruppel-like factor 6 (KLF6/Zf9/CPBP), a member of the Kruppel-like family of zinc finger transcription factors, has recently been suggested to be a mutated tumor suppressor in selected human cancers. Initially, we investigated whether the KLF6 gene was altered in 36 paired non-small cell lung cancers (NSCLC), 89 brain tumors, 7 normal brains, 46 cancer cell lines from a large variety of tissues, and 144 peripheral blood cells from healthy individuals using single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. Changes in the coding region of KLF6 were found in brain tumors (missense changes, 8%; silent polymorphisms, 2%), lung cancers (missense changes, 3%; silent polymorphisms, 6%) and cancer cell lines (missense changes, 2%; silent polymorphisms, 2%). All of the nucleotide changes in the lung tumor samples were present in their matched normal samples, suggesting that these changes were germline polymorphism. Many of the altered KLF6 genes found in the brain tumors were cloned into an expression vector and placed into a GBM cell line, and cell growth was monitored. Wild-type, deleted exon 3, or E30G missense KLF6 significantly reduced cell growth; in contrast, forced expression of KLF6 having either the S92R, P183L or A276G missense substitution did not alter the growth of transfected GBM cells (p > 0.05). Expression levels of KLF6 were higher in normal brain samples than in glioma samples as measured by real-time RT-PCR (p surprise, nucleotide changes were found at -4, -5, and -6 upstream of the start of translation in 45% of brain tumors, and 10% of normal blood samples. Focusing on the most frequent alteration (-4 C > A), the nucleotide change did not affect translation of KLF6. Taking together, KLF6 coding sequences are altered in 10% brain tumors, 8% NSLC, and 4% of cancer cell lines. All of those observed in lung cancer are germline polymorphisms. Several additional ones identified in GBM, have lost their ability to slow the growth of glioma

  15. Relative effectiveness of mating success and sperm competition at eliminating deleterious mutations in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Sean C A Clark

    Full Text Available Condition-dependence theory predicts that sexual selection will facilitate adaptation by selecting against deleterious mutations that affect the expression of sexually selected traits indirectly via condition. Recent empirical studies have provided support for this prediction; however, their results do not elucidate the relative effects of pre- and postcopulatory sexual selection on deleterious mutations. We used the Drosophila melanogaster model system to discern the relative contributions of pre- and postcopulatory processes to selection against deleterious mutations. To assess second-male ejaculate competition success (P2; measured as the proportion of offspring attributable to the experimental male and mating success, mutant and wild-type male D. melanogaster were given the opportunity to mate with females that were previously mated to a standard competitor male. This process was repeated for males subjected to a diet quality manipulation to test for effects of environmentally-manipulated condition on P2 and mating success. While none of the tested mutations affected P2, there was a clear effect of condition. Conversely, several of the mutations affected mating success, while condition showed no effect. Our results suggest that precopulatory selection may be more effective than postcopulatory selection at removing deleterious mutations. The opposite result obtained for our diet manipulation points to an interesting discrepancy between environmental and genetic manipulations of condition, which may be explained by the multidimensionality of condition. Establishing whether the various stages of sexual selection affect deleterious mutations differently, and to what extent, remains an important issue to resolve.

  16. Effect of surfactant addition on removal of microbubbles using ultrasound.

    Science.gov (United States)

    Kobayashi, Daisuke; Hayashida, Yoshiyuki; Sano, Kazuki; Terasaka, Koichi

    2014-08-01

    It is difficult to control the bubble in a liquid by the external operation, because the behavior of the bubble is controlled in buoyancy and flow of liquid. On the other hand, microbubbles, whose diameter is several decades μm, stably disperse in static liquid because of their small buoyancy and electrical repulsion. When an ultrasound, whose frequency was 2.4 MHz, was irradiated, the milky white microbubbles suspended solution became rapidly clear. In this study, the effects of surfactant addition on the removal of microbubbles from a liquid in an ultrasonic field were investigated. The efficiency of removal of microbubbles decreased with surfactant addition. Surfactant type influenced the size of agglomerated microbubbles, and the efficiency of removal of microbubbles changed. The surface of microbubble was modified by surfactant adsorption, and the steric inhibition influenced the removal of microbubbles. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. The effect of acetone addition on the properties of epoxy

    Directory of Open Access Journals (Sweden)

    Marcio R. Loos

    2008-03-01

    Full Text Available In this work, a varied amount of acetone was employed to dissolve an epoxy resin and then a route was followed to remove the acetone, simulating a frequently used method to disperse nanofillers in thermoset matrices. Analyses were then carried out to address the influence of residual acetone on the curing process and on the epoxy properties. The results showed a detrimental effect on the mechanical properties of the cured epoxy due to the presence of residual acetone and also a less brittle-like fracture of the specimen. Fourier transform infrared spectroscopy and thermogravimetric analyses were additionally used to characterize the cured resins and have also indicated the presence of a small amount of acetone. Nevertheless, rheological measurements indicated that 10.0 wt.% acetone addition on the resin causes a significant decrease in viscosity (around 50% which may promote a better dispersion of nanofillers.

  18. Versatility of cooperative transcriptional activation: a thermodynamical modeling analysis for greater-than-additive and less-than-additive effects.

    Directory of Open Access Journals (Sweden)

    Till D Frank

    Full Text Available We derive a statistical model of transcriptional activation using equilibrium thermodynamics of chemical reactions. We examine to what extent this statistical model predicts synergy effects of cooperative activation of gene expression. We determine parameter domains in which greater-than-additive and less-than-additive effects are predicted for cooperative regulation by two activators. We show that the statistical approach can be used to identify different causes of synergistic greater-than-additive effects: nonlinearities of the thermostatistical transcriptional machinery and three-body interactions between RNA polymerase and two activators. In particular, our model-based analysis suggests that at low transcription factor concentrations cooperative activation cannot yield synergistic greater-than-additive effects, i.e., DNA transcription can only exhibit less-than-additive effects. Accordingly, transcriptional activity turns from synergistic greater-than-additive responses at relatively high transcription factor concentrations into less-than-additive responses at relatively low concentrations. In addition, two types of re-entrant phenomena are predicted. First, our analysis predicts that under particular circumstances transcriptional activity will feature a sequence of less-than-additive, greater-than-additive, and eventually less-than-additive effects when for fixed activator concentrations the regulatory impact of activators on the binding of RNA polymerase to the promoter increases from weak, to moderate, to strong. Second, for appropriate promoter conditions when activator concentrations are increased then the aforementioned re-entrant sequence of less-than-additive, greater-than-additive, and less-than-additive effects is predicted as well. Finally, our model-based analysis suggests that even for weak activators that individually induce only negligible increases in promoter activity, promoter activity can exhibit greater-than-additive

  19. Distributions of Mutational Effects and the Estimation of Directional Selection in Divergent Lineages of Arabidopsis thaliana.

    Science.gov (United States)

    Park, Briton; Rutter, Matthew T; Fenster, Charles B; Symonds, V Vaughan; Ungerer, Mark C; Townsend, Jeffrey P

    2017-08-01

    Mutations are crucial to evolution, providing the ultimate source of variation on which natural selection acts. Due to their key role, the distribution of mutational effects on quantitative traits is a key component to any inference regarding historical selection on phenotypic traits. In this paper, we expand on a previously developed test for selection that could be conducted assuming a Gaussian mutation effect distribution by developing approaches to also incorporate any of a family of heavy-tailed Laplace distributions of mutational effects. We apply the test to detect directional natural selection on five traits along the divergence of Columbia and Landsberg lineages of Arabidopsis thaliana, constituting the first test for natural selection in any organism using quantitative trait locus and mutation accumulation data to quantify the intensity of directional selection on a phenotypic trait. We demonstrate that the results of the test for selection can depend on the mutation effect distribution specified. Using the distributions exhibiting the best fit to mutation accumulation data, we infer that natural directional selection caused divergence in the rosette diameter and trichome density traits of the Columbia and Landsberg lineages. Copyright © 2017 by the Genetics Society of America.

  20. Limited importance of the dominant-negative effect of TP53 missense mutations

    Directory of Open Access Journals (Sweden)

    Kordek Radzislaw

    2011-06-01

    Full Text Available Abstract Background Heterozygosity of TP53 missense mutations is related to the phenomenon of the dominant-negative effect (DNE. To estimate the importance of the DNE of TP53 mutations, we analysed the percentage of cancer cases showing a single heterozygous mutation of TP53 and searched for a cell line with a single heterozygous mutation of this gene. This approach was based on the knowledge that genes with evident DNE, such as EGFR and IDH1, represent nearly 100% of single heterozygous mutations in tumour specimens and cell lines. Methods Genetic analyses (LOH and sequencing performed for early and late passages of several cell lines originally described as showing single heterozygous TP53 mutations (H-318, G-16, PF-382, MOLT-13, ST-486 and LS-123. Statistical analysis of IARC TP53 and SANGER databases. Genetic analyses of N-RAS, FBXW7, PTEN and STR markers to test cross-contamination and cell line identity. Cell cloning, fluorescence-activated cell sorting and SSCP performed for the PF-382 cell line. Results A database study revealed TP53 single heterozygous mutations in 35% of in vivo (surgical and biopsy samples and only 10% of cultured cells (in vitro, although those numbers appeared to be overestimated. We deem that published in vivo TP53 mutation analyses are not as rigorous as studies in vitro, and we did not find any cell line showing a stable, single heterozygous mutation. G16, PF-382 and MOLT-13 cells harboured single heterozygous mutations temporarily. ST-486, H-318 and LS-123 cell lines were misclassified. Specific mutations, such as R175H, R273H, R273L or R273P, which are reported in the literature to exert a DNE, showed the lowest percentage of single heterozygous mutations in vitro (about 5%. Conclusion We suggest that the currently reported percentage of TP53 single heterozygous mutations in tumour samples and cancer cell lines is overestimated. Thus, the magnitude of the DNE of TP53 mutations is questionable. This scepticism

  1. Priming effects in Haplic Luvisol after different substrate additions

    Science.gov (United States)

    Bogomolova, I.; Blagodatskaya, E.; Blagodatsky, S.; Kuzyakov, Y.

    2009-04-01

    Although soils contain considerable amounts of soil organic carbon (SOC), most of it is not easily available for microorganisms. Addition of various substrates to soil (for example, plant residues, root exudates) may affect SOC mineralization. The addition of mineral nutrients, especially N, may also affect C turnover and so change the mineralization rate of SOC. Such short-term changes in mineralization of organic substance of soil were termed as "priming-effects" (Bingemann et al., 1953). Priming effect leads to additional mineralization of SOC (van Elsas and van Overbeek, 1993). It has been shown that not only plant residues induce priming effects (Sauerbeck, 1966; Stemmer et al., 1999; Bell et al., 2003), but also easily available substrates such as sugars or amino acids, which are present in soil solutions and root exudates (Vasconcellos, 1994; Shen and Bartha, 1997; Hamer and Marschner, 2002). Since easily available substrates may not only accelerate SOC mineralization, but also may retard it, Kuzyakov et al. (2000) differentiated between positive and negative priming effects. It is not clear until now, how long priming effects persists in soil after substrate addition, and if they are induced every time when a substrate becomes available in soil. So, the aim of this study was to evaluate effects of glucose and plant residues on SOM decomposition, and influence of glucose on plant residues decomposition in soil. The experimental layout was designed as two factor experiment: 1) plant residues and 2) available substrate amendment. Maize shoot residues (50 mg added to 5 g soil) were 14C labeled (9•104 DPM per 5 g soil). Soil without of any plant residues served as a control for this treatment. Two levels of D (+) glucose as easily available substrates were added after three months of pre-incubation of soil samples with maize residues: 0.009 mg glucose C g-1 soil and 0.225 mg glucose C g-1 soil. The glucose was uniformly labelled with 14C (2.37•104 DPM per 5

  2. Effect of osteogenesis imperfecta mutations in tropocollagen molecule on strength of biomimetic tropocollagen-hydroxyapatite nanocomposites

    Science.gov (United States)

    Dubey, Devendra K.; Tomar, Vikas

    2010-01-01

    Osteogenesis Imperfecta (OI) is a genetic disorder that affects cellular synthesis of Type-I collagen fibrils and causes extreme bone fragility. This study reports the effects of OI mutations in Tropocollagen (TC) molecules on strength of model Tropocollagen-Hydroxyapatite biomaterials with two different mineral [hydroxyapatite (HAP)] distributions using three dimensional atomistic simulations. Results show that the effect of TC mutations on the strength of TC-HAP biomaterials is insignificant. Instead, change in mineral distribution showed significant impact on the overall strength of TC-HAP biomaterials. Study suggests that TC mutations manifest themselves by changing the mineral distribution during hydroxyapatite growth and nucleation period.

  3. The effects of extremely low frequency magnetic fields on mutation induction in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, James W. [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom); Haines, Jackie; Sienkiewicz, Zenon [Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ (United Kingdom); Dubrova, Yuri E., E-mail: yed2@le.ac.uk [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom)

    2015-03-15

    Highlights: • The effects of 50 Hz magnetic fields on mutation induction in mice were analyzed. • The frequency of ESTR mutation was established in sperm and blood. • Exposure to 10–300 μT for 2 and 15 h did not result in mutation induction. • Mutagenic effects of 50 Hz magnetic fields are likely to be negligible. - Abstract: The growing human exposure to extremely low frequency (ELF) magnetic fields has raised a considerable concern regarding their genotoxic effects. The aim of this study was to evaluate the in vivo effects of ELF magnetic fields irradiation on mutation induction in the germline and somatic tissues of male mice. Seven week old BALB/c × CBA/Ca F{sub 1} hybrid males were exposed to 10, 100 or 300 μT of 50 Hz magnetic fields for 2 or 15 h. Using single-molecule PCR, the frequency of mutation at the mouse Expanded Simple Tandem Repeat (ESTR) locus Ms6-hm was established in sperm and blood samples of exposed and matched sham-treated males. ESTR mutation frequency was also established in sperm and blood samples taken from male mice exposed to 1 Gy of acute X-rays. The frequency of ESTR mutation in DNA samples extracted from blood of mice exposed to magnetic fields did not significantly differ from that in sham-treated controls. However, there was a marginally significant increase in mutation frequency in sperm but this was not dose-dependent. In contrast, acute exposure X-rays led to significant increases in mutation frequency in sperm and blood of exposed males. The results of our study suggest that, within the range of doses analyzed here, the in vivo mutagenic effects of ELF magnetic fields are likely to be minor if not negligible.

  4. Effect of the G375C and G346E achondroplasia mutations on FGFR3 activation.

    Directory of Open Access Journals (Sweden)

    Lijuan He

    Full Text Available Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia mutants in these experiments, a finding which supports a direct link between the severity of dwarfism phenotypes and the level and mechanism of FGFR3 over-activation. The mutations do not increase the cross-linking propensity of FGFR3, contrary to previous expectations that the achondroplasia mutations stabilize the FGFR3 dimers. Instead, the phosphorylation efficiency within un-liganded FGFR3 dimers is increased, and this increase is likely the underlying cause for pathogenesis in achondroplasia. We further investigate the G346E mutation, which has been reported to cause achondroplasia in one case. We find that this mutation does not increase FGFR3 phosphorylation and decreases FGFR3 cross-linking propensity, a finding which raises questions whether this mutation is indeed a genetic cause for human dwarfism.

  5. Effect of the G375C and G346E achondroplasia mutations on FGFR3 activation.

    Science.gov (United States)

    He, Lijuan; Serrano, Christopher; Niphadkar, Nitish; Shobnam, Nadia; Hristova, Kalina

    2012-01-01

    Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia mutants in these experiments, a finding which supports a direct link between the severity of dwarfism phenotypes and the level and mechanism of FGFR3 over-activation. The mutations do not increase the cross-linking propensity of FGFR3, contrary to previous expectations that the achondroplasia mutations stabilize the FGFR3 dimers. Instead, the phosphorylation efficiency within un-liganded FGFR3 dimers is increased, and this increase is likely the underlying cause for pathogenesis in achondroplasia. We further investigate the G346E mutation, which has been reported to cause achondroplasia in one case. We find that this mutation does not increase FGFR3 phosphorylation and decreases FGFR3 cross-linking propensity, a finding which raises questions whether this mutation is indeed a genetic cause for human dwarfism.

  6. Predator identity and additive effects in a treehole community.

    Science.gov (United States)

    Griswold, Marcus W; Lounibos, L Philip

    2006-04-01

    Multiple predator species can interact as well as strongly affect lower trophic levels, resulting in complex, nonadditive effects on prey populations and community structure. Studies of aquatic systems have shown that interactive effects of predators on prey are not necessarily predictable from the direct effects of each species alone. To test for complex interactions, the individual and combined effects of a top and intermediate predator on larvae of native and invasive mosquito prey were examined in artificial analogues of water-filled treeholes. The combined effects of the two predators were accurately predicted from single predator treatments by a multiplicative risk model, indicating additivity. Overall survivorship of both prey species decreased greatly in the presence of the top predator Toxorhynchites rutilus. By itself, the intermediate predator Corethrella appendiculata increased survivorship of the native prey species Ochlerotatus triseriatus and decreased survivorship of the invasive prey species Aedes albopictus relative to treatments without predators. Intraguild predation did not occur until alternative prey numbers had been reduced by approximately one-half. Owing to changes in size structure accompanying its growth, T. rutilus consumed more prey as time progressed, whereas C. appendiculata consumed less. The intermediate predator, C. appendiculata, changed species composition by preferentially consuming A. albopictus, while the top predator, T. rutilus, reduced prey density, regardless of species. Although species interactions were in most cases predicted from pairwise interactions, risk reduction from predator interference occurred when C. appendiculata densities were increased and when the predators were similarly sized.

  7. PREDATOR IDENTITY AND ADDITIVE EFFECTS IN A TREEHOLE COMMUNITY

    Science.gov (United States)

    Griswold, Marcus W.; Lounibos, L. Philip

    2007-01-01

    Multiple predator species can interact as well as strongly affect lower trophic levels, resulting in complex, nonadditive effects on prey populations and community structure. Studies of aquatic systems have shown that interactive effects of predators on prey are not necessarily predictable from the direct effects of each species alone. To test for complex interactions, the individual and combined effects of a top and intermediate predator on larvae of native and invasive mosquito prey were examined in artificial analogues of water-filled treeholes. The combined effects of the two predators were accurately predicted from single predator treatments by a multiplicative risk model, indicating additivity. Overall survivorship of both prey species decreased greatly in the presence of the top predator Toxorhynchites rutilus. By itself, the intermediate predator Corethrella appendiculata increased survivorship of the native prey species Ochlerotatus triseriatus and decreased survivorship of the invasive prey species Aedes albopictus relative to treatments without predators. Intraguild predation did not occur until alternative prey numbers had been reduced by approximately one-half. Owing to changes in size structure accompanying its growth, T. rutilus consumed more prey as time progressed, whereas C. appendiculata consumed less. The intermediate predator, C. appendiculata, changed species composition by preferentially consuming A. albopictus, while the top predator, T. rutilus, reduced prey density, regardless of species. Although species interactions were in most cases predicted from pairwise interactions, risk reduction from predator interference occurred when C. appendiculata densities were increased and when the predators were similarly sized. PMID:16676542

  8. Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity.

    Science.gov (United States)

    Anstett, Kaitlin; Fusco, Robert; Cutillas, Vincent; Mesplède, Thibault; Wainberg, Mark A

    2015-10-01

    We have previously shown that the addition of the raltegravir/elvitegavir (RAL/EVG) primary resistance mutation N155H to the R263K dolutegravir (DTG) resistance mutation partially compensated for the fitness cost imposed by R263K while also slightly increasing DTG resistance in vitro (K. Anstett, T. Mesplede, M. Oliveira, V. Cutillas, and M. A. Wainberg, J Virol 89:4681-4684, 2015, doi:10.1128/JVI.03485-14). Since many patients failing RAL/EVG are given DTG as part of rescue therapy, and given that the N155H substitution often is found in combination with other compensatory resistance mutations in such individuals, we investigated the effects of multiple such substitutions within integrase (IN) on each of integrase function, HIV-1 infectivity, and levels of drug resistance. To this end, each of the L74M, E92Q, T97A, E157Q, and G163R substitutions were introduced into NL4.3 subtype B HIV-1 vectors harboring N155H and R263K in tandem [termed NL4.3IN(N155H/R263K)]. Relevant recombinant integrase enzymes also were expressed, and purified and biochemical assays of strand transfer efficiency as well as viral infectivity and drug resistance studies were performed. We found that the addition of T97A, E157Q, or G163R somewhat improved the affinity of INN155H/R263K for its target DNA substrate, while the presence of L74M or E92Q had a negative effect on this process. However, viral infectivity was significantly decreased from that of NL4.3IN(N155H/R263K) after the addition of each tertiary mutation, and no increases in levels of DTG resistance were observed. This work shows that the compensatory mutations that evolve after N155H under continued DTG or RAL/EVG pressure in patients are unable to improve either enzyme efficiency or viral infectivity in an N155H/R263K background. In contrast to other drugs, dolutegravir has not selected for resistance in HIV-positive individuals when used in first-line therapy. We had previously shown that HIV containing the primary raltegravir

  9. The influence of oil additives on the effectiveness of herbicides

    Directory of Open Access Journals (Sweden)

    Andrzej Chwedoruk

    2013-12-01

    Full Text Available The possibility to decrease herbicide doses without reducing their weed controlling effectiveness was investigated in two microplots and one field experiment. The following herbicides were used: atrazine, mixture of atrazine with terbutrine, MCPA + MCPP, MCPA + dikamba, desmedipham and phenmedipham (Betanal 31, 32 or 37. They were combined with one or several of the following adjuvants: parafinic oil, refuse product of rape oil rafination, oil mixture from the Institute of Organic Chemistry Industry (IPO-Warsaw, surfactant Rokafenol N-1O, mineral oil Nr 8 (Aviol. It was shown that the doses of herbicides could be lowered by 30-50% without loosing their phytotoxic effect on weeds due to addition of adjuvants. The mineral oil 8 was very active in a mixture with Betanal 37 and was completly non toxic toward sugar beets. The oil mixture from IPO and Rokafenol N-10 were very active in mixtures with atrazine or atraizine with terbutrine.

  10. Eddy damping effect of additional conductors in superconducting levitation systems

    Science.gov (United States)

    Jiang, Zhao-Fei; Gou, Xiao-Fan

    2015-12-01

    Passive superconducting levitation systems consisting of a high temperature superconductor (HTSC) and a permanent magnet (PM) have demonstrated several fascinating applications such as the maglev system, flywheel energy storage. Generally, for the HTSC-PM levitation system, the HTSC with higher critical current density Jc can obtain larger magnetic force to make the PM levitate over the HTSC (or suspended below the HTSC), however, the process of the vibration of the levitated PM, provides very limited inherent damping (essentially hysteresis). To improve the dynamic stability of the levitated PM, eddy damping of additional conductors can be considered as the most simple and effective approach. In this article, for the HTSC-PM levitation system with an additional copper damper attached to the HTSC, we numerically and comprehensively investigated the damping coefficient c, damping ratio, Joule heating of the copper damper, and the vibration frequency of the PM as well. Furthermore, we comparatively studied four different arrangements of the copper damper, on the comprehensive analyzed the damping effect, efficiency (defined by c/VCu, in which VCu is the volume of the damper) and Joule heating, and finally presented the most advisable arrangement.

  11. Effects of Salinity and Nutrient Addition on Mangrove Excoecaria agallocha

    Science.gov (United States)

    Chen, Yaping; Ye, Yong

    2014-01-01

    Effects of salinity on seed germination and growth of young (1 month old) and old (2-year old) seedlings of Excoecaria agallocha were investigated. Combined effects of salinity and nutrient level were also examined on old seedlings. Seed germination was best at 0 and 5 psu salinity. 15 psu salinity significantly delayed root initiation and decreased final establishment rate. All seeds failed to establish at 25 psu salinity. Young seedlings performed best at 0 and 5 psu, but growth was stunned at 15 psu, and all seedlings died within 90 days at 25 psu. Old seedlings grew best at salinities below 5 psu and they survived the whole cultivation at 25 psu. This indicated that E. agallocha increased salt tolerance over time. Gas exchange was significantly compromised by salinities above 15 psu but evidently promoted by high nutrient. Proline accumulated considerably at high nutrient, and its contents increased from 0 to 15 psu but decreased at 25 psu salinity. Lipid peroxidation was aggravated by increasing salinity beyond 15 psu but markedly alleviated by nutrient addition. These responses indicated that E. agallocha was intolerant to high salinity but it can be greatly enhanced by nutrient addition. PMID:24691495

  12. Differential effects of CSF-1R D802V and KIT D816V homologous mutations on receptor tertiary structure and allosteric communication.

    Directory of Open Access Journals (Sweden)

    Priscila Da Silva Figueiredo Celestino Gomes

    Full Text Available The colony stimulating factor-1 receptor (CSF-1R and the stem cell factor receptor KIT, type III receptor tyrosine kinases (RTKs, are important mediators of signal transduction. The normal functions of these receptors can be compromised by gain-of-function mutations associated with different physiopatological impacts. Whereas KIT D816V/H mutation is a well-characterized oncogenic event and principal cause of systemic mastocytosis, the homologous CSF-1R D802V has not been identified in human cancers. The KIT D816V oncogenic mutation triggers resistance to the RTK inhibitor Imatinib used as first line treatment against chronic myeloid leukemia and gastrointestinal tumors. CSF-1R is also sensitive to Imatinib and this sensitivity is altered by mutation D802V. Previous in silico characterization of the D816V mutation in KIT evidenced that the mutation caused a structure reorganization of the juxtamembrane region (JMR and facilitated its departure from the kinase domain (KD. In this study, we showed that the equivalent CSF-1R D802V mutation does not promote such structural effects on the JMR despite of a reduction on some key H-bonds interactions controlling the JMR binding to the KD. In addition, this mutation disrupts the allosteric communication between two essential regulatory fragments of the receptors, the JMR and the A-loop. Nevertheless, the mutation-induced shift towards an active conformation observed in KIT D816V is not observed in CSF-1R D802V. The distinct impact of equivalent mutation in two homologous RTKs could be associated with the sequence difference between both receptors in the native form, particularly in the JMR region. A local mutation-induced perturbation on the A-loop structure observed in both receptors indicates the stabilization of an inactive non-inhibited form, which Imatinib cannot bind.

  13. Differential effects of CSF-1R D802V and KIT D816V homologous mutations on receptor tertiary structure and allosteric communication.

    Science.gov (United States)

    Da Silva Figueiredo Celestino Gomes, Priscila; Panel, Nicolas; Laine, Elodie; Pascutti, Pedro Geraldo; Solary, Eric; Tchertanov, Luba

    2014-01-01

    The colony stimulating factor-1 receptor (CSF-1R) and the stem cell factor receptor KIT, type III receptor tyrosine kinases (RTKs), are important mediators of signal transduction. The normal functions of these receptors can be compromised by gain-of-function mutations associated with different physiopatological impacts. Whereas KIT D816V/H mutation is a well-characterized oncogenic event and principal cause of systemic mastocytosis, the homologous CSF-1R D802V has not been identified in human cancers. The KIT D816V oncogenic mutation triggers resistance to the RTK inhibitor Imatinib used as first line treatment against chronic myeloid leukemia and gastrointestinal tumors. CSF-1R is also sensitive to Imatinib and this sensitivity is altered by mutation D802V. Previous in silico characterization of the D816V mutation in KIT evidenced that the mutation caused a structure reorganization of the juxtamembrane region (JMR) and facilitated its departure from the kinase domain (KD). In this study, we showed that the equivalent CSF-1R D802V mutation does not promote such structural effects on the JMR despite of a reduction on some key H-bonds interactions controlling the JMR binding to the KD. In addition, this mutation disrupts the allosteric communication between two essential regulatory fragments of the receptors, the JMR and the A-loop. Nevertheless, the mutation-induced shift towards an active conformation observed in KIT D816V is not observed in CSF-1R D802V. The distinct impact of equivalent mutation in two homologous RTKs could be associated with the sequence difference between both receptors in the native form, particularly in the JMR region. A local mutation-induced perturbation on the A-loop structure observed in both receptors indicates the stabilization of an inactive non-inhibited form, which Imatinib cannot bind.

  14. Effects of growth and mutation on pattern formation in tissues.

    Directory of Open Access Journals (Sweden)

    Benedicte Mengel Pers

    Full Text Available In many developing tissues, neighboring cells enter different developmental pathways, resulting in a fine-grained pattern of different cell states. The most common mechanism that generates such patterns is lateral inhibition, for example through Delta-Notch coupling. In this work, we simulate growth of tissues consisting of a hexagonal arrangement of cells laterally inhibiting their neighbors. We find that tissue growth by cell division and cell migration tends to produce ordered patterns, whereas lateral growth leads to disordered, patchy patterns. Ordered patterns are very robust to mutations (gene silencing or activation in single cells. In contrast, mutation in a cell of a disordered tissue can produce a larger and more widespread perturbation of the pattern. In tissues where ordered and disordered patches coexist, the perturbations spread mostly at boundaries between patches. If cell division occurs on time scales faster than the degradation time, disordered patches will appear. Our work suggests that careful experimental characterization of the disorder in tissues could pinpoint where and how the tissue is susceptible to large-scale damage even from single cell mutations.

  15. Thermal processing of EVA encapsulants and effects of formulation additives

    Energy Technology Data Exchange (ETDEWEB)

    Pern, F.J.; Glick, S.H. [National Renewable Energy Lab., Golden, CO (United States)

    1996-05-01

    The authors investigated the in-situ processing temperatures and effects of various formulation additives on the formation of ultraviolet (UV) excitable chromophores, in the thermal lamination and curing of ethylene-vinyl acetate (EVA) encapsulants. A programmable, microprocessor-controlled, double-bag vacuum laminator was used to study two commercial as formulated EVA films, A9918P and 15295P, and solution-cast films of Elvaxrm (EVX) impregnated with various curing agents and antioxidants. The results show that the actual measured temperatures of EVA lagged significantly behind the programmed profiles for the heating elements and were affected by the total thermal mass loaded inside the laminator chamber. The antioxidant Naugard P{trademark}, used in the two commercial EVA formulations, greatly enhances the formation of UV-excitable, short chromophores upon curing, whereas other tested antioxidants show little effect. A new curing agent chosen specifically for the EVA formulation modification produces little or no effect on chromophore formation, no bubbling problems in the glass/EVX/glass laminates, and a gel content of {approximately}80% when cured at programmed 155{degrees}C for 4 min. Also demonstrated is the greater discoloring effect with higher concentrations of curing-generated chromophores.

  16. The 3' addition of CCA to mitochondrial tRNASer(AGY) is specifically impaired in patients with mutations in the tRNA nucleotidyl transferase TRNT1.

    Science.gov (United States)

    Sasarman, Florin; Thiffault, Isabelle; Weraarpachai, Woranontee; Salomon, Steven; Maftei, Catalina; Gauthier, Julie; Ellazam, Benjamin; Webb, Neil; Antonicka, Hana; Janer, Alexandre; Brunel-Guitton, Catherine; Elpeleg, Orly; Mitchell, Grant; Shoubridge, Eric A

    2015-05-15

    Addition of the trinucleotide cytosine/cytosine/adenine (CCA) to the 3' end of transfer RNAs (tRNAs) is essential for translation and is catalyzed by the enzyme TRNT1 (tRNA nucleotidyl transferase), which functions in both the cytoplasm and mitochondria. Exome sequencing revealed TRNT1 mutations in two unrelated subjects with different clinical features. The first presented with acute lactic acidosis at 3 weeks of age and developed severe developmental delay, hypotonia, microcephaly, seizures, progressive cortical atrophy, neurosensorial deafness, sideroblastic anemia and renal Fanconi syndrome, dying at 21 months. The second presented at 3.5 years with gait ataxia, dysarthria, gross motor regression, hypotonia, ptosis and ophthalmoplegia and had abnormal signals in brainstem and dentate nucleus. In subject 1, muscle biopsy showed combined oxidative phosphorylation (OXPHOS) defects, but there was no OXPHOS deficiency in fibroblasts from either subject, despite a 10-fold-reduction in TRNT1 protein levels in fibroblasts of the first subject. Furthermore, in normal controls, TRNT1 protein levels are 10-fold lower in muscle than in fibroblasts. High resolution northern blots of subject fibroblast RNA suggested incomplete CCA addition to the non-canonical mitochondrial tRNA(Ser(AGY)), but no obvious qualitative differences in other mitochondrial or cytoplasmic tRNAs. Complete knockdown of TRNT1 in patient fibroblasts rendered mitochondrial tRNA(Ser(AGY)) undetectable, and markedly reduced mitochondrial translation, except polypeptides lacking Ser(AGY) codons. These data suggest that the clinical phenotypes associated with TRNT1 mutations are largely due to impaired mitochondrial translation, resulting from defective CCA addition to mitochondrial tRNA(Ser(AGY)), and that the severity of this biochemical phenotype determines the severity and tissue distribution of clinical features. © The Author 2015. Published by Oxford University Press. All rights reserved. For

  17. Eddy damping effect of additional conductors in superconducting levitation systems

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Zhao-Fei; Gou, Xiao-Fan, E-mail: xfgou@hhu.edu.cn

    2015-12-15

    Highlights: • In this article, for the eddy current damper attached to the HTSC, we • quantitatively investigated the damping coefficient c, damping ratio, Joule heating of the copper damper, and the vibration frequency of the PM as well. • presented four different arrangements of the copper damper, and comparatively studied their damping effects and Joule heating, and finally proposed the most advisable arrangement. - Abstract: Passive superconducting levitation systems consisting of a high temperature superconductor (HTSC) and a permanent magnet (PM) have demonstrated several fascinating applications such as the maglev system, flywheel energy storage. Generally, for the HTSC–PM levitation system, the HTSC with higher critical current density J{sub c} can obtain larger magnetic force to make the PM levitate over the HTSC (or suspended below the HTSC), however, the process of the vibration of the levitated PM, provides very limited inherent damping (essentially hysteresis). To improve the dynamic stability of the levitated PM, eddy damping of additional conductors can be considered as the most simple and effective approach. In this article, for the HTSC–PM levitation system with an additional copper damper attached to the HTSC, we numerically and comprehensively investigated the damping coefficient c, damping ratio, Joule heating of the copper damper, and the vibration frequency of the PM as well. Furthermore, we comparatively studied four different arrangements of the copper damper, on the comprehensive analyzed the damping effect, efficiency (defined by c/V{sub Cu}, in which V{sub Cu} is the volume of the damper) and Joule heating, and finally presented the most advisable arrangement.

  18. Previously Unreported Biallelic Mutation in DNAJC19: Are Sensorineural Hearing Loss and Basal Ganglia Lesions Additional Features of Dilated Cardiomyopathy and Ataxia (DCMA) Syndrome?

    Science.gov (United States)

    Ucar, Sema Kalkan; Mayr, Johannes A; Feichtinger, René G; Canda, Ebru; Çoker, Mahmut; Wortmann, Saskia B

    2017-01-01

    Dilated cardiomyopathy (DCM), non-progressive cerebellar ataxia (A), testicular dysgenesis, growth failure, and 3-methylglutaconic aciduria are the hallmarks of DNAJC19 defect (or DCMA syndrome) due to biallelic mutations in DNAJC19. To date DCMA syndrome has been reported in 19 patients from Canada and in two Finnish siblings. The underlying pathomechanism is unknown; however, DNAJC19 is presumed to be involved in mitochondrial membrane related processes (e.g., protein import and cardiolipin remodeling). Here, we report an additional patient with progressive cerebellar atrophy and white matter changes. A Turkish boy presented at age 2 months with dilated cardiomyopathy (initially worsening then stabilizing in the second year of life), growth failure, bilateral cryptorchidism, and facial dysmorphism. Mental and motor developmental were, respectively, moderately and severely delayed. Profound intentional tremor and dyskinesia, spasticity (particularly at the lower extremities), and dystonia were observed. Sensorineural hearing loss was also diagnosed. MRI showed bilateral basal ganglia signal alterations. Plasma lactate levels were increased, as was urinary excretion of 3-methylglutaconic acid. He deceased aged 3 years. Sanger Sequencing of DNAJC19 confirmed the clinical diagnosis of DNAJC19 defect by revealing the previously unreported homozygous stop mutation c.63delC (p.Tyr21*). Investigation of enzymes of mitochondrial energy metabolism revealed decreased activity of cytochrome c oxidase in muscle tissue. Sensorineural hearing loss and bilateral basal ganglia lesions are common symptoms of mitochondrial disorders. This is the first report of an association with DNAJC19 defect.

  19. The effect of chemical additives on the synthesis of ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, S.S.C.; Pien, S.I.

    1991-06-01

    The objective of this research is to elucidate the role of various chemical additives on ethanol synthesis over Rh- and Ni-based catalysts. Chemical additives used for this study will include S, P, Ag, Cu, Mn, and Na which have different electronegativeities. The effect of additives on the surface state of the catalysts, heat of adsorption of reactant molecules, reaction intermediates, reaction pathways, reaction kinetics, and product distributions is/will be investigated by a series of experimental studies of NO adsorption, reactive probing, steady state rate measurement, and transient kinetic study. CO insertion is known to be a key step to the formation of acetaldehyde and ethanol from CO hydrogenation. Reaction of ethylene with syngas is used as a probe to determine CO insertion capabilities of metal catalysts. During the sixth quarter of the project, the mechanism of CO insertion on Ni/SiO{sub 2} was investigated by in-situ infrared spectroscopy. Ni/SiO{sub 2}, a methanation catalyst, has been shown to exhibit CO insertion activity. In situ infrared studies of CO/H{sub 2} and C{sub 2}H{sub 4}/CO/H{sub 2} reactions show that the carbonylation of Ni/SiO{sub 2} to Ni(CO){sub 4} leads to an inhibition of methanation in CO hydrogenation but an enhancement of formation of propionaldehyde in C{sub 2}H{sub 4}/CO/H{sub 2} reaction. The results suggest that the sites for propionaldehyde formation is different from those for methanation.

  20. Mortar cohesión. The effect of additives

    Directory of Open Access Journals (Sweden)

    Castro, J. H.

    1975-12-01

    Full Text Available This study was concerned with the hydration of clinker compounds in the presence of different additives; it appeared that accelerating additives, such as calcium chloride and silicic acid, produce longer fibers of tobermorite, whereas inhibitors, such as sugar, produce shorter fibers of tobermorite. This same effect was observed in the hydration of anhydrite, in which large crystals of gypsum were produced in the presence of sodium sulphate. So the cohesion in mortars of cement and anhydrite is explained in terms of the role of fibers.Se estudia la hidratación del clínker en presencia de diferentes aditivos encontrándose que los aceleradores, como el cloruro cálcico y el ácido salicílico, producen tobermorita de fibra larga y los inhibidores, como el azúcar, tobermorita de fibra corta. Este mismo efecto se encuentra en la anhidrita, produciéndose cristales de yeso largo, en presencia del sulfato de sodio, y cristales cortos en ausencia del catalizador. La cohesión de un mortero depende luego del largo de sus fibras. Así la cohesión de los morteros de cemento y anhidrita se explican en función del rol de la fibra.

  1. Effect of Various Additives on Photocatalytic Degradation of 4-Nitrophenol

    Directory of Open Access Journals (Sweden)

    Kashif Naeem

    2009-01-01

    Full Text Available The photocatalytic degradation of 4-nitrophenol (4-NP assisted by titanium dioxide (TiO2 was investigated in aqueous suspension under irradiation by UV light. The effect of different supporting materials mixed physically with TiO2on the photocatalytic degradation of 4-NP has been studied. TiO2 with all supports exhibits good degradation efficiency of 4-NP and was better than TiO2 alone. The addition of SiO2 and ZSM-5 only caused a little change in 4-NP degradation. However, degradation of 4-NP was improved from 34.89% to 60.53% within 120 min photocatalysis in the presence of optimal amount of AC. The degradation was also fairly enhanced in the presence of cheaper rice husk and the activity was closed to AC.

  2. Study the effect of F17S mutation on the chimeric Bacillus thermocatenulatus lipase

    Directory of Open Access Journals (Sweden)

    Seyed Hossein Khaleghinejad

    2016-06-01

    Full Text Available Lipases (triacylglycerol acylhydrolase, EC 3.1.1.3 are one of the highest value commercial enzymes as they have potential applications in biotechnology for detergents, food, pharmaceuticals, leather, textiles, cosmetics, and paper industries; and are currently receiving considerable attention because of their potential applications in biotechnology. Bacillus thermocatenulatus Lipase 2 (BTL2 is one of the most important research targets, because of its potential industrial applications. In this study, the effect of substitution Phe17 with Ser in mutated BTL2 lipase, which conserved pentapeptide (112Ala-His-Ser-Gln-Gly116 was replaced with similar sequences (207Gly-Glu-Ser-Ala-Gly211 of Candida rugosa lipase (CLR at the nucleophilic elbow region. Docking results confirmed the mutated lipase to be better than the chimeric lipase. So, cloning was conducted, and the mutated and chimeric btl2 genes were expressed in Escherichia coli, and then the enzymes were purified by anion exchange chromatography. The mutation increased lipase lipolytic activity against most of the applied substrates, with the exception of tributyrin when compared with chimeric lipase. Further, the mutated lipase exhibited higher activity than the chimeric lipase at all temperatures. Optimum pH of the mutated lipase was obtained at pH 9.5, which was more than the chimeric one. Enzyme activity of the mutated lipase in the presence of organic solvents, detergents, and metal ions was also improved than the chimeric lipase.

  3. Constant-Pressure Combustion Charts Including Effects of Diluent Addition

    Science.gov (United States)

    Turner, L Richard; Bogart, Donald

    1949-01-01

    Charts are presented for the calculation of (a) the final temperatures and the temperature changes involved in constant-pressure combustion processes of air and in products of combustion of air and hydrocarbon fuels, and (b) the quantity of hydrocarbon fuels required in order to attain a specified combustion temperature when water, alcohol, water-alcohol mixtures, liquid ammonia, liquid carbon dioxide, liquid nitrogen, liquid oxygen, or their mixtures are added to air as diluents or refrigerants. The ideal combustion process and combustion with incomplete heat release from the primary fuel and from combustible diluents are considered. The effect of preheating the mixture of air and diluents and the effect of an initial water-vapor content in the combustion air on the required fuel quantity are also included. The charts are applicable only to processes in which the final mixture is leaner than stoichiometric and at temperatures where dissociation is unimportant. A chart is also included to permit the calculation of the stoichiometric ratio of hydrocarbon fuel to air with diluent addition. The use of the charts is illustrated by numerical examples.

  4. Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63.

    NARCIS (Netherlands)

    Waanders, E.; Venselaar, H.; Morsche, R.H.M. te; Koning, D.B. de; Kamath, P.S.; Torres, V.E.; Somlo, S.; Drenth, J.P.H.

    2010-01-01

    Polycystic liver disease (PCLD) is characterized by intralobular bile duct cysts in the liver. It is caused by mutations in PRKCSH, encoding hepatocystin, and SEC63, encoding Sec63p. The main goals of this study were to screen for novel mutations and to analyze mutations for effects on protein

  5. Effects of radio-opacifier addition in dental impression material

    Directory of Open Access Journals (Sweden)

    Mota Eduardo

    2010-01-01

    Full Text Available Objective: The aim of this in vitro study was to determine the effects of barium sulfate addition in two dental impression materials previously proved as radiolucent. Materials and Methods: An irreversible hydrocolloid (IH and polyether (PE were tested for optical density, linear dimension stability and detail reproduction. Statistical Analysis Used: The optical density data were submitted to Kolmogorov-Smirnov normality test and compared with two-way ANOVA and Tukey (alpha=0.05. Results: The results of optical density (pixel were: IH control 45.24 f (±7.6, PE control 54.93 e (±4.45, PE 5Wt% 60.43 d (±6.27, IH 1Wt% 61.54 cd (±5.3, PE 1Wt% 66.9 bc (±5.05, IH 5Wt% 67.17 b (±6.01, PE 10Wt% 84.55 a (±5.14, IH 10Wt% 85.33 a (±5.53. On detail reproduction, polyether control was able to copy the 6 μm line. Adding 1 or 5Wt% of barium sulfate have not change this characteristic. For the irreversible hydrocolloid, the control group was able to copy a line with 14 μm, however, adding 1Wt% barium sulfate, the capability decreased to 22 μm. Adding barium sulfate in the polyether promoted an increase in between the copied lines, for the control, the average distance was 931.6 μm, 936 μm to 1Wt% and 954.5 μm to 5 Wt%. For the IH, the control presented 975 μm in comparison to 987.25 μm for 1 Wt% samples. Conclusion: The addition of barium sulfate was capable of increasing significantly the optical density of tested material, have changed the linear dimension stability, however, have not interfered in detail reproduction only for PE.

  6. Sensitivity of quantitative traits to mutational effects and number of loci.

    Science.gov (United States)

    Schraiber, Joshua G; Landis, Michael J

    2015-06-01

    When models of quantitative genetic variation are built from population genetic first principles, several assumptions are often made. One of the most important assumptions is that traits are controlled by many genes of small effect. This leads to a prediction of a Gaussian trait distribution in the population, via the Central Limit Theorem. Since these biological assumptions are often unknown or untrue, we characterized how finite numbers of loci or large mutational effects can impact the sampling distribution of a quantitative trait. To do so, we developed a neutral coalescent-based framework, allowing us to gain a detailed understanding of how number of loci and the underlying mutational model impacts the distribution of a quantitative trait. Through both analytical theory and simulation we found the normality assumption was highly sensitive to the details of the mutational process, with the greatest discrepancies arising when the number of loci was small or the mutational kernel was heavy-tailed. In particular, skewed mutational effects will produce skewed trait distributions and fat-tailed mutational kernels result in multimodal sampling distributions, even for traits controlled by a large number of loci. Since selection models and robust neutral models may produce qualitatively similar sampling distributions, we advise extra caution should be taken when interpreting model-based results for poorly understood systems of quantitative traits. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Concentration Addition, Independent Action and Generalized Concentration Addition Models for Mixture Effect Prediction of Sex Hormone Synthesis In Vitro

    OpenAIRE

    Niels Hadrup; Camilla Taxvig; Mikael Pedersen; Christine Nellemann; Ulla Hass; Anne Marie Vinggaard

    2013-01-01

    Humans are concomitantly exposed to numerous chemicals. An infinite number of combinations and doses thereof can be imagined. For toxicological risk assessment the mathematical prediction of mixture effects, using knowledge on single chemicals, is therefore desirable. We investigated pros and cons of the concentration addition (CA), independent action (IA) and generalized concentration addition (GCA) models. First we measured effects of single chemicals and mixtures thereof on steroid synthes...

  8. No additive effect of cannabis on cognition in schizophrenia.

    Science.gov (United States)

    Power, Brian D; Dragovic, Milan; Badcock, Johanna C; Morgan, Vera A; Castle, David; Jablensky, Assen; Stefanis, Nikos C

    2015-10-01

    We aimed to examine the association between lifetime cannabis use and estimates of both premorbid and current cognitive function in psychotic disorders in an Australian cohort. In an Australian multicenter cohort, 1237 participants with an established ICD-10 diagnosis of psychotic disorder were categorised according to history of lifetime cannabis use (non-users, n=354; cannabis users, n=221; cannabis dependency, n=662). Groups were analyzed according to available indices of cognitive ability: the National Adult Reading Test - Revised (NART-R) for ability prior to illness onset; and the Digit Symbol Coding Test (DSCT) for current ability. Two-way analysis of variance was conducted without any covariate, followed by a two-way analysis of covariance (using age, age at onset of psychiatric illness, premorbid IQ and the Socio-Economic Index for Areas (SEIFA) rankings). Whilst there appeared to be a significant association between cannabis use and mean DSCT (higher DSCT scores in cannabis using groups) F(2,1080)=9.478, pcannabis use and cognitive function in psychotic disorders. Taken together, it would appear that cannabis use or dependence has no additive effect on cognitive dysfunction in these disorders. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  9. Effect of domestic dolomite additives used in the refractory production

    Energy Technology Data Exchange (ETDEWEB)

    Yeprem, H.A. [Yildiz Technical Univ., Istanbul (Turkey). Dept. of Metallurgy and Materials Engineering

    2008-07-01

    In this study, the effect of alumina addition on dolomite refractory (extracted from Konya/Turkey) which has been planned to use in refractory industry was investigated. The aim of the study is to increase the brownmillerite phase which aids the sintering process of dolomite. For that purpose, 0.5 wt-% alumina powder (including 99,5% Al{sub 2}O{sub 3}) was added to 3 to 6 mm fraction dolomite, and a sintering operation was carried out at a temperature of 1600, 1650 and 1700 C for 3 different soaking times (2, 4 and 6 h). The resultant phases occured at DOL grannies (sintered dolomite) were investigated and evaluated by X-Ray diffraction pattern (XRD) and analized by scanning electron microscopy (SEM). It turned out that periclase, lime also portlandite, alite, forsterite, tricalcium aluminate, brownmillerite, merwinite were created. The densities of DOL grannies were measured. Temperature and increase in time were investigated but convenience in density could not be established. (orig.)

  10. Effect of BET Missense Mutations on Bromodomain Function, Inhibitor Binding and Stability.

    Directory of Open Access Journals (Sweden)

    Laura Lori

    Full Text Available Lysine acetylation is an important epigenetic mark regulating gene transcription and chromatin structure. Acetylated lysine residues are specifically recognized by bromodomains, small protein interaction modules that read these modification in a sequence and acetylation dependent way regulating the recruitment of transcriptional regulators and chromatin remodelling enzymes to acetylated sites in chromatin. Recent studies revealed that bromodomains are highly druggable protein interaction domains resulting in the development of a large number of bromodomain inhibitors. BET bromodomain inhibitors received a lot of attention in the oncology field resulting in the rapid translation of early BET bromodomain inhibitors into clinical studies. Here we investigated the effects of mutations present as polymorphism or found in cancer on BET bromodomain function and stability and the influence of these mutants on inhibitor binding. We found that most BET missense mutations localize to peripheral residues in the two terminal helices. Crystal structures showed that the three dimensional structure is not compromised by these mutations but mutations located in close proximity to the acetyl-lysine binding site modulate acetyl-lysine and inhibitor binding. Most mutations affect significantly protein stability and tertiary structure in solution, suggesting new interactions and an alternative network of protein-protein interconnection as a consequence of single amino acid substitution. To our knowledge this is the first report studying the effect of mutations on bromodomain function and inhibitor binding.

  11. Computing Stability Effects of Mutations in Human Superoxide Dismutase 1

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2014-01-01

    Protein stability is affected in several diseases and is of substantial interest in efforts to correlate genotypes to phenotypes. Superoxide dismutase 1 (SOD1) is a suitable test case for such correlations due to its abundance, stability, available crystal structures and thermochemical data......, and physiological importance. In this work, stability changes of SOD1 mutations were computed with five methods, CUPSAT, I-Mutant2.0, I-Mutant3.0, PoPMuSiC, and SDM, with emphasis on structural sensitivity as a potential issue in structure-based protein calculation. The large correlation between experimental...... displayed less structural sensitivity, with the standard deviation from different high-resolution structures down to ∼0.2 kcal/mol. Structures of variable resolution and number of protein copies locally affected specific sites, emphasizing the use of state-relevant crystal structures when such sites...

  12. Relative effectiveness of additive pain interventions during vaccination in infants

    Science.gov (United States)

    Taddio, Anna; Riddell, Rebecca Pillai; Ipp, Moshe; Moss, Steven; Baker, Stephen; Tolkin, Jonathan; Malini, Dave; Feerasta, Sharmeen; Govan, Preeya; Fletcher, Emma; Wong, Horace; McNair, Caitlin; Mithal, Priyanjali; Stephens, Derek

    2017-01-01

    BACKGROUND: Vaccine injections can cause acute pain and distress in infants, which can contribute to dissatisfaction with the vaccination experience and vaccine hesitancy. We sought to compare the effectiveness of additive pain interventions administered consistently during vaccine injections in the first year of life. METHODS: We conducted a multicentre, longitudinal, double-blind, add-on, randomized controlled trial. Healthy infants were randomly assigned to 1 of 4 levels of pain management for all vaccine injections at 2, 4, 6 and 12 months: (i) placebo control; (ii) parent-directed video education about infant soothing; (iii) the video plus sucrose administered orally or (iv) the video plus sucrose plus liposomal lidocaine applied topically. All infants benefit from injection techniques that minimize pain. We used a double-dummy design; hence all parents watched a video (active psychological intervention or placebo) and all infants received oral solution (sucrose or placebo) and topical cream (lidocaine or placebo). We assessed infant distress during 3 phases — preinjection (baseline), vaccine injection (needle), and 1 minute postinjection (recovery) — using the Modified Behavioural Pain Scale (range 0–10). We compared scores between groups and across infant ages using a mixed-model repeated-measures analysis. RESULTS: A total of 352 infants participated in the study, from Jan. 17, 2012, to Feb. 2, 2016. Demographics did not differ among intervention groups (p > 0.05). Baseline pain scores did not differ among intervention groups (p = 0.4), but did differ across ages (p < 0.001). Needle pain scores differed among groups (p = 0.003) and across ages (p < 0.001). The mean (± standard deviation) needle score was 6.3 (± 0.8) in the video–sucrose–lidocaine group compared with 6.7 (± 0.8) in each of the other groups. There were no other between-group differences. Recovery scores did not differ among groups (p = 0.98), but did differ across ages (p < 0

  13. Mutation accumulation and fitness effects in hybridogenetic populations: a comparison to sexual and asexual systems

    Directory of Open Access Journals (Sweden)

    Bagheri Homayoun C

    2007-05-01

    Full Text Available Abstract Background Female only unisexual vertebrates that reproduce by hybridogenesis show an unusual genetic composition. They are of hybrid origin but show no recombination between the genomes of their parental species. Instead, the paternal genome is discarded from the germline prior to meiosis, and gametes (eggs only contain solely unrecombined maternal genomes. Hence hybridogens only transmit maternally inherited mutations. Hybridity is restored each generation by backcrossing with males of the sexual parental species whose genome was eliminated. In contrast, recombining sexual species propagate an intermixed pool of mutations derived from the maternal and paternal parts of the genome. If mutation rates are lower in female gametes than males, it raises the possibility for lower mutation accumulation in a hybridogenetic population, and consequently, higher population fitness than its sexual counterpart. Results We show through Monte-Carlo simulations that at higher male to female mutation ratios, and sufficiently large population sizes, hybridogenetic populations can carry a lower mutation load than sexual species. This effect is more pronounced with synergistic forms of epistasis. Mutations accumulate faster on the sexual part of the genome, and with the purifying effects of epistasis, it makes it more difficult for mutations to be transmitted on the clonal part of the genome. In smaller populations, the same mechanism reduces the speed of Muller's Ratchet and the number of fixed mutations compared to similar asexual species. Conclusion Since mutation accumulation can be less pronounced in hybridogenetic populations, the question arises why hybridogenetic organisms are so scarce compared to sexual species. In considering this, it is likely that comparison of population fitnesses is not sufficient. Despite competition with the sexual parental species, hybrid populations are dependent on the maintenance of – and contact with – their

  14. Effect of micronized zeolite addition to lamb concentrate feeds on ...

    African Journals Online (AJOL)

    OEM

    2016-09-21

    %, 1%, 2% or 3% additional. MZ. At the end of the study, bodyweight gain and feed consumption were not affected by the treatments. Similarly, the addition of up to 2% MZ to the diet did not affect slaughter weight, hot carcass ...

  15. Ecotoxicological effects of activated carbon addition to sediments.

    NARCIS (Netherlands)

    Jonker, M.T.O.|info:eu-repo/dai/nl/175518793; Suijkerbuijk, M.P.; Schmitt, H.|info:eu-repo/dai/nl/304831042; Sinnige, T.L.

    2009-01-01

    Activated carbon (AC) addition is a recently developed technique for the remediation of sediments and soils contaminated with hydrophobic organic chemicals. Laboratory and field experiments have demonstrated that the addition of 3-4% of AC can reduce aqueous concentrations and the bioaccumulation

  16. Energy-effective Grinding of Inorganic Solids Using Organic Additives.

    Science.gov (United States)

    Mishra, Ratan K; Weibel, Martin; Müller, Thomas; Heinz, Hendrik; Flatt, Robert J

    2017-08-09

    We present our research findings related to new formulations of the organic additives (grinding aids) needed for the efficient grinding of inorganic solids. Even though the size reduction phenomena of the inorganic solid particles in a ball mill is purely a physical process, the addition of grinding aids in milling media introduces a complex physicochemical process. In addition to further gain in productivity, the organic additive helps to reduce the energy needed for grinding, which in the case of cement clinker has major environmental implications worldwide. This is primarily due to the tremendous amounts of cement produced and almost 30% of the associated electrical energy is consumed for grinding. In this paper, we examine the question of how to optimize these grinding aids linking molecular insight into their working mechanisms, and also how to design chemical additives of improved performance for industrial comminution.

  17. The Escherichia coli modE gene: effect of modE mutations on molybdate dependent modA expression.

    Science.gov (United States)

    McNicholas, P M; Chiang, R C; Gunsalus, R P

    1996-11-15

    The Escherichia coli modABCD operon, which encodes a high-affinity molybdate uptake system, is transcriptionally regulated in response to molybdate availability by ModE. Here we describe a highly effective enrichment protocol, applicable to any gene with a repressor role, and establish its application in the isolation of transposon mutations in modE. In addition we show that disruption of the ModE C-terminus abolishes derepression in the absence of molybdate, implying this region of ModE controls the repressor activity. Finally, a mutational analysis of a proposed molybdate binding motif indicates that this motif does not function in regulating the repressor activity of ModE.

  18. The effects of in utero irradiation on mutation induction and transgenerational instability in mice

    Energy Technology Data Exchange (ETDEWEB)

    Barber, Ruth C.; Hardwick, Robert J.; Shanks, Morag E.; Glen, Colin D.; Mughal, Safeer K.; Voutounou, Mariel [Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH (United Kingdom); Dubrova, Yuri E., E-mail: yed2@le.ac.uk [Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH (United Kingdom)

    2009-05-12

    Epidemiological evidence suggests that the deleterious effects of prenatal irradiation can manifest during childhood, resulting in an increased risk of leukaemia and solid cancers after birth. However, the mechanisms underlying the long-term effects of foetal irradiation remain poorly understood. This study was designed to analyse the impact of in utero irradiation on mutation rates at expanded simple tandem repeat (ESTR) DNA loci in directly exposed mice and their first-generation (F{sub 1}) offspring. ESTR mutation frequencies in the germline and somatic tissues of male and female mice irradiated at 12 days of gestation remained highly elevated during adulthood, which was mainly attributed to a significant increase in the frequency of singleton mutations. The prevalence of singleton mutations in directly exposed mice suggests that foetal irradiation results in genomic instability manifested both in utero and during adulthood. The frequency of ESTR mutation in the F{sub 1} offspring of prenatally irradiated male mice was equally elevated across all tissues, which suggests that foetal exposure results in transgenerational genomic instability. In contrast, maternal in utero exposure did not affect the F{sub 1} stability. Our data imply that the passive erasure of epigenetic marks in the maternal genome can diminish the transgenerational effects of foetal irradiation and therefore provide important clues to the still unknown mechanisms of radiation-induced genomic instability. The results of this study offer a plausible explanation for the effects of in utero irradiation on the risk of leukaemia and solid cancers after birth.

  19. In silico investigation of molecular effects caused by missense mutations in creatine transporter protein

    Science.gov (United States)

    Zhang, Zhe; Schwatz, Charles; Alexov, Emil

    2011-03-01

    Creatine transporter (CT) protein, which is encoded by SLC6A8 gene, is essential for taking up the creatine in the cell, which in turn plays a key role in the spatial and temporal maintenance of energy in skeletal and cardiac muscle cells. It was shown that some missense mutations in CT cause mental retardation, while others are harmless non-synonymous single nucleoside polymorphism (nsSNP). Currently fifteen missense mutations in CT are known, among which twelve are disease-causing. Sequence analysis reveals that there is no clear trend distinguishing disease-causing from harmless missense mutations. Because of that, we built 3D model of the CT using highly homologous template and use the model to investigate the effects of mutations of CT stability and hydrogen bond network. It is demonstrated that disease-causing mutations affect the folding free energy and ionization states of titratable group in much greater extend as compared with harmless mutations. Supported by grants from NLM, NIH, grant numbers 1R03LM009748 and 1R03LM009748-S1.

  20. Effect of Additional Structure on Effective Stack Height of Gas Dispersion in Atmosphere

    Directory of Open Access Journals (Sweden)

    Takenobu Michioka

    2016-03-01

    Full Text Available Wind-tunnel experiments were conducted to evaluate the effect of additional structure (building, sea wall and banking on the effective stack height, which is usually used in safety analyses of nuclear power facilities in Japan. The effective stack heights were estimated with and without the additional structure in addition to the reactor building while varying several conditions such as the source height, the height of additional structure and the distance between the source position and the additional structure. When the source height is equivalent to the reactor building height, the additional structure enhances both the vertical and horizontal gas dispersion widths and decreases the ground gas concentration, and it means that the additional structure does not decrease the effective stack height. When the source height is larger than the reactor height, the additional structures might affect the effective stack height. As the distance between the source and the additional structure decreases, or as the height of the additional structure increases, the structure has a larger effect on the effective stack height.

  1. Effect of a novel mutation in a Δ9-stearoyl-ACP-desaturase on soybean seed oil composition.

    Science.gov (United States)

    Ruddle, Paul; Whetten, Rebecca; Cardinal, Andrea; Upchurch, Robert G; Miranda, Lilian

    2013-01-01

    Soybean [Glycine max (L.) Merr.] oil typically contains 2-4% stearic acid. Seed oil with 20% stearic acid would be useful for solid fat applications, both for its cooking properties and health benefits. Breeding lines with high stearic acid have been developed, but many suffer from agronomic problems. This study identifies a new source of high stearic acid, determines its relationship with another high stearic locus and presents molecular markers for it is use in breeding. TCJWB03-806-7-19, a 'Holladay' mutant with high stearic acid, was crossed to two FAM94-41-derived lines that contained a point mutation in a seed-specific isoform of a Δ9-stearoyl-acyl carrier protein-desaturase (SACPD-C). Fatty acid analysis was performed over two growing seasons with F(2)-derived lines and transgressive segregation for stearic acid content was observed. Sequencing of SACPD isoforms in TCJWB03-806-7-19 revealed the deletion of an 'A' nucleotide in exon 3 of SACPD-B, which results in a protein whose final 28 amino acids are predicted to differ from Williams 82 SACPD-B. Sorting intolerant from tolerant (SIFT) analysis revealed that this frameshift mutation may affect SACPD-B protein function. Allele-specific genotyping for the SACPD-C point mutation and SACPD-B nucleotide deletion was performed in both populations. Additive effects and R(2) for stearic acid were +3.3 and 0.55 for SACPD-C and +1.9 and 0.19 for SACPD-B. Average stearic acid in lines homozygous for both mutations was 14.6%. This SACPD-B mutation represents a novel high stearic allele.

  2. Effect of micronized zeolite addition to lamb concentrate feeds on ...

    African Journals Online (AJOL)

    OEM

    2016-09-21

    %, 1%, 2% or 3% additional. MZ. ... yield of the animals, but affects serum total protein, calcium and phosphorus concentrations. ... that carry no risk of leaving harmful residues in the course of vegetable and animal production.

  3. Correlated mutations in protein sequences: Phylogenetic and structural effects

    Energy Technology Data Exchange (ETDEWEB)

    Lapedes, A.S. [Los Alamos National Lab., NM (United States). Theoretical Div.]|[Santa Fe Inst., NM (United States); Giraud, B.G. [C.E.N. Saclay, Gif/Yvette (France). Service Physique Theorique; Liu, L.C. [Los Alamos National Lab., NM (United States). Theoretical Div.; Stormo, G.D. [Univ. of Colorado, Boulder, CO (United States). Dept. of Molecular, Cellular and Developmental Biology

    1998-12-01

    Covariation analysis of sets of aligned sequences for RNA molecules is relatively successful in elucidating RNA secondary structure, as well as some aspects of tertiary structure. Covariation analysis of sets of aligned sequences for protein molecules is successful in certain instances in elucidating certain structural and functional links, but in general, pairs of sites displaying highly covarying mutations in protein sequences do not necessarily correspond to sites that are spatially close in the protein structure. In this paper the authors identify two reasons why naive use of covariation analysis for protein sequences fails to reliably indicate sequence positions that are spatially proximate. The first reason involves the bias introduced in calculation of covariation measures due to the fact that biological sequences are generally related by a non-trivial phylogenetic tree. The authors present a null-model approach to solve this problem. The second reason involves linked chains of covariation which can result in pairs of sites displaying significant covariation even though they are not spatially proximate. They present a maximum entropy solution to this classic problem of causation versus correlation. The methodologies are validated in simulation.

  4. The effect of point mutations on structure and mechanical properties of collagen-like fibril: A molecular dynamics study

    Energy Technology Data Exchange (ETDEWEB)

    Marlowe, Ashley E.; Singh, Abhishek; Yingling, Yaroslava G., E-mail: yara_yingling@ncsu.edu

    2012-12-01

    Understanding sequence dependent mechanical and structural properties of collagen fibrils is important for the development of artificial biomaterials for medical and nanotechnological applications. Moreover, point mutations are behind many collagen associated diseases, including Osteogenesis Imperfecta (OI). We conducted a combination of classical and steered atomistic molecular dynamics simulations to examine the effect of point mutations on structure and mechanical properties of short collagen fibrils which include mutations of glycine to alanine, aspartic acid, cysteine, and serine or mutations of hydroxyproline to arginine, asparagine, glutamine, and lysine. We found that all mutations disrupt structure and reduce strength of the collagen fibrils, which may affect the hierarchical packing of the fibrils. The glycine mutations were more detrimental to mechanical strength of the fibrils (WT > Ala > Ser > Cys > Asp) than that of hydroxyproline (WT > Arg > Gln > Asn > Lys). The clinical outcome for glycine mutations agrees well with the trend in reduction of fibril's tensile strength predicted by our simulations. Overall, our results suggest that the reduction in mechanical properties of collagen fibrils may be used to predict the clinical outcome of mutations. Highlights: Black-Right-Pointing-Pointer All mutations disrupt structure and bonding pattern and reduce strength of the collagen fibrils. Black-Right-Pointing-Pointer Gly based mutations are worst to mechanical integrity of fibrils than that of Hyp. Black-Right-Pointing-Pointer Lys and Arg mutations most dramatically destabilize collagen fibril properties. Black-Right-Pointing-Pointer Clinical outcome of mutations may be related to the reduced mechanical properties of fibrils.

  5. Concentration addition, independent action and generalized concentration addition models for mixture effect prediction of sex hormone synthesis in vitro.

    Science.gov (United States)

    Hadrup, Niels; Taxvig, Camilla; Pedersen, Mikael; Nellemann, Christine; Hass, Ulla; Vinggaard, Anne Marie

    2013-01-01

    Humans are concomitantly exposed to numerous chemicals. An infinite number of combinations and doses thereof can be imagined. For toxicological risk assessment the mathematical prediction of mixture effects, using knowledge on single chemicals, is therefore desirable. We investigated pros and cons of the concentration addition (CA), independent action (IA) and generalized concentration addition (GCA) models. First we measured effects of single chemicals and mixtures thereof on steroid synthesis in H295R cells. Then single chemical data were applied to the models; predictions of mixture effects were calculated and compared to the experimental mixture data. Mixture 1 contained environmental chemicals adjusted in ratio according to human exposure levels. Mixture 2 was a potency adjusted mixture containing five pesticides. Prediction of testosterone effects coincided with the experimental Mixture 1 data. In contrast, antagonism was observed for effects of Mixture 2 on this hormone. The mixtures contained chemicals exerting only limited maximal effects. This hampered prediction by the CA and IA models, whereas the GCA model could be used to predict a full dose response curve. Regarding effects on progesterone and estradiol, some chemicals were having stimulatory effects whereas others had inhibitory effects. The three models were not applicable in this situation and no predictions could be performed. Finally, the expected contributions of single chemicals to the mixture effects were calculated. Prochloraz was the predominant but not sole driver of the mixtures, suggesting that one chemical alone was not responsible for the mixture effects. In conclusion, the GCA model seemed to be superior to the CA and IA models for the prediction of testosterone effects. A situation with chemicals exerting opposing effects, for which the models could not be applied, was identified. In addition, the data indicate that in non-potency adjusted mixtures the effects cannot always be

  6. Concentration addition, independent action and generalized concentration addition models for mixture effect prediction of sex hormone synthesis in vitro.

    Directory of Open Access Journals (Sweden)

    Niels Hadrup

    Full Text Available Humans are concomitantly exposed to numerous chemicals. An infinite number of combinations and doses thereof can be imagined. For toxicological risk assessment the mathematical prediction of mixture effects, using knowledge on single chemicals, is therefore desirable. We investigated pros and cons of the concentration addition (CA, independent action (IA and generalized concentration addition (GCA models. First we measured effects of single chemicals and mixtures thereof on steroid synthesis in H295R cells. Then single chemical data were applied to the models; predictions of mixture effects were calculated and compared to the experimental mixture data. Mixture 1 contained environmental chemicals adjusted in ratio according to human exposure levels. Mixture 2 was a potency adjusted mixture containing five pesticides. Prediction of testosterone effects coincided with the experimental Mixture 1 data. In contrast, antagonism was observed for effects of Mixture 2 on this hormone. The mixtures contained chemicals exerting only limited maximal effects. This hampered prediction by the CA and IA models, whereas the GCA model could be used to predict a full dose response curve. Regarding effects on progesterone and estradiol, some chemicals were having stimulatory effects whereas others had inhibitory effects. The three models were not applicable in this situation and no predictions could be performed. Finally, the expected contributions of single chemicals to the mixture effects were calculated. Prochloraz was the predominant but not sole driver of the mixtures, suggesting that one chemical alone was not responsible for the mixture effects. In conclusion, the GCA model seemed to be superior to the CA and IA models for the prediction of testosterone effects. A situation with chemicals exerting opposing effects, for which the models could not be applied, was identified. In addition, the data indicate that in non-potency adjusted mixtures the effects cannot

  7. Effect of Ferrous Additives on Magnesia Stone Hydration

    Science.gov (United States)

    Zimich, V.

    2017-11-01

    The article deals with the modification of the magnesia binder with additives containing two- and three-valent iron cations which could be embedded in the chloromagnesium stone structure and also increase the strength from 60 MPa in a non-additive stone to 80MPa, water resistance from 0.58 for clear stone to 0.8 and reduce the hygroscopicity from 8% in the non-additive stone to 2% in the modified chloromagnesium stone. It is proposed to use the iron hydroxide sol as an additive in the quantities of up to 1% of the weight of the binder. The studies were carried out using the modern analysis methods: the differentialthermal and X-ray phase analysis. The structure was studied with an electron microscope with an X-ray microanalyzer. A two-factor plan-experiment was designed which allowed constructing mathematical models characterizing the influence of variable factors, such as the density of the zatcher and the amount of sol in the binder, on the basic properties of the magnesian stone. The result of the research was the magnesia stone with the claimed properties and formed from minerals characteristic for magnesian materials as well as additionally formed from amachenite and goethite. It has been established that a highly active iron hydroxide sol the ion sizes of which are commensurate with magnesium ions is actively incorporated into the structure of pentahydroxychloride and magnesium hydroxide changing the habit of crystals compacting the structure of the stone and changing its hygroscopicity.

  8. Effect of Hereditary Hemochromatosis Gene H63D and C282Y Mutations on Iron Overload in Sickle Cell Disease Patients

    Directory of Open Access Journals (Sweden)

    Yunus Kasım Terzi

    2016-12-01

    Full Text Available Objective: Hemochromatosis is an autosomal recessive disease that is one of the most important reasons for iron overload. Sickle cell disease is a hemoglobinopathy that occurs as a result of a homozygous mutation in the hemoglobin gene. Erythrocyte transfusion is frequently used in the treatment of this disease. Iron overload as a result of transfusion is important in the mortality and morbidity of sickle cell anemia patients as well as in other hemoglobinopathies. In this study, the effect of hemochromatosis gene (HFE p.H63D and p.C282Y mutations on transfusion-related cardiac and liver iron overload in sickle cell disease patients who carry homozygous hemoglobin S mutation has been investigated. Materials and Methods: This is a prospective single-center crosssectional study in patients with homozygous hemoglobin S mutation between the years 2008 and 2013. The patients were divided into two groups. The first group (group A, n=31 was receiving chelation therapy and the second group (group B, n=13 was not. Direct and indirect iron loads were analyzed by magnetic resonance imaging and biochemically, respectively. HFE gene mutations were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analyses were performed by independent samples t-test. Results: p.H63D mutation was detected in 10 (32.3% patients in group A and in only 1 patient (7.7% in group B. When the 2 groups were compared for iron overload, iron deposition in the liver was significantly higher in group B (p=0.046. In addition, in group A, iron deposition was significantly higher in HFE mutation carriers compared to patients without the mutation (p=0.05. Conclusion: Results of this study showed that HFE gene mutations are important in iron deposition in the liver in patients with sickle cell disease.

  9. How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects.

    Directory of Open Access Journals (Sweden)

    Christopher H Chandler

    2017-11-01

    Full Text Available For a given gene, different mutations influence organismal phenotypes to varying degrees. However, the expressivity of these variants not only depends on the DNA lesion associated with the mutation, but also on factors including the genetic background and rearing environment. The degree to which these factors influence related alleles, genes, or pathways similarly, and whether similar developmental mechanisms underlie variation in the expressivity of a single allele across conditions and among alleles is poorly understood. Besides their fundamental biological significance, these questions have important implications for the interpretation of functional genetic analyses, for example, if these factors alter the ordering of allelic series or patterns of complementation. We examined the impact of genetic background and rearing environment for a series of mutations spanning the range of phenotypic effects for both the scalloped and vestigial genes, which influence wing development in Drosophila melanogaster. Genetic background and rearing environment influenced the phenotypic outcome of mutations, including intra-genic interactions, particularly for mutations of moderate expressivity. We examined whether cellular correlates (such as cell proliferation during development of these phenotypic effects matched the observed phenotypic outcome. While cell proliferation decreased with mutations of increasingly severe effects, surprisingly it did not co-vary strongly with the degree of background dependence. We discuss these findings and propose a phenomenological model to aid in understanding the biology of genes, and how this influences our interpretation of allelic effects in genetic analysis.

  10. How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects.

    Science.gov (United States)

    Chandler, Christopher H; Chari, Sudarshan; Kowalski, Alycia; Choi, Lin; Tack, David; DeNieu, Michael; Pitchers, William; Sonnenschein, Anne; Marvin, Leslie; Hummel, Kristen; Marier, Christian; Victory, Andrew; Porter, Cody; Mammel, Anna; Holms, Julie; Sivaratnam, Gayatri; Dworkin, Ian

    2017-11-01

    For a given gene, different mutations influence organismal phenotypes to varying degrees. However, the expressivity of these variants not only depends on the DNA lesion associated with the mutation, but also on factors including the genetic background and rearing environment. The degree to which these factors influence related alleles, genes, or pathways similarly, and whether similar developmental mechanisms underlie variation in the expressivity of a single allele across conditions and among alleles is poorly understood. Besides their fundamental biological significance, these questions have important implications for the interpretation of functional genetic analyses, for example, if these factors alter the ordering of allelic series or patterns of complementation. We examined the impact of genetic background and rearing environment for a series of mutations spanning the range of phenotypic effects for both the scalloped and vestigial genes, which influence wing development in Drosophila melanogaster. Genetic background and rearing environment influenced the phenotypic outcome of mutations, including intra-genic interactions, particularly for mutations of moderate expressivity. We examined whether cellular correlates (such as cell proliferation during development) of these phenotypic effects matched the observed phenotypic outcome. While cell proliferation decreased with mutations of increasingly severe effects, surprisingly it did not co-vary strongly with the degree of background dependence. We discuss these findings and propose a phenomenological model to aid in understanding the biology of genes, and how this influences our interpretation of allelic effects in genetic analysis.

  11. Effect of additives on formation of natural gas hydrate

    Energy Technology Data Exchange (ETDEWEB)

    C.S. Zhang; S.S. Fan; D.Q. Liang; K.H. Guo [Chinese Academy of Sciences, Guangzhou (China). Guangzhou Center for Gas Hydrate Research, Guangzhou Institute of Energy Conversion

    2004-11-01

    The formation of natural gas hydrate (NGH) is studied in this work. Kinetics data of hydrate formation with no agitation were collected at various concentrations of the aqueous solutions with different additives such as alkylpolyglucside, sodium dodecyl benzene sulfonate and potassium oxalate monohydrate. Various kinds of additive increased the formation rates of NGH and its storage capacity and reduced the induction time of NGH formation. Moreover, the storage capacity, the induction time and the hydrate formation rate were influenced by the concentration of the aqueous solution. 24 refs., 7 figs., 4 tabs.

  12. PREDATOR IDENTITY AND ADDITIVE EFFECTS IN A TREEHOLE COMMUNITY

    OpenAIRE

    GRISWOLD, MARCUS W.; Lounibos,L Philip

    2006-01-01

    Multiple predator species can interact as well as strongly affect lower trophic levels, resulting in complex, nonadditive effects on prey populations and community structure. Studies of aquatic systems have shown that interactive effects of predators on prey are not necessarily predictable from the direct effects of each species alone. To test for complex interactions, the individual and combined effects of a top and intermediate predator on larvae of native and invasive mosquito prey were ex...

  13. Effects of organic additives on microstructure and mechanical ...

    Indian Academy of Sciences (India)

    Administrator

    Abstract. Green bodies of porous Si3N4 ceramics were shaped by extrusion technique using different organic additives as binder during extrusion molding. Different porosity, microstructures and mechanical properties after the extrusion, drying, debinding and sintering stages were investigated. The solid slurry content of 70 ...

  14. Effect of carbon nanofibre addition on the mechanical properties of ...

    Indian Academy of Sciences (India)

    Carbon-epoxy (C-epoxy) laminated composites having different fibre volume fractions (40, 50, 60 and 70) were fabricated with and without the addition of aminofunctionalized carbon nanofibres (A-CNF). Flexural strength, interlaminar shear strength (ILSS) and tensile strength of the composite laminates were determined.

  15. Effects of Video Games as Reinforcers for Computerized Addition Performance.

    Science.gov (United States)

    Axelrod, Saul; And Others

    1987-01-01

    Four 2nd-grade students completed addition problems on a computer, using video games as reinforcers. Two variable ratio schedules of reinforcement failed to increase student accuracy or the rate of correct responses. In a no-games reinforcement condition, students had more opportunities to respond and had a greater number of correct answers.…

  16. Effect of Additives on the Physicochemical and Drug Release ...

    African Journals Online (AJOL)

    Erah

    increased from 22.6 to 29.3 MPa) and reduced elastic recovery of compacts (from 8.1 to 5.5 %) compared ... from melt precipitation and growth in the presence of additives [2]. Fine crystals are preferred to large crystals of poorly soluble pharmaceuticals as they provide greater .... Agglomerates were coated with a thin gold-.

  17. Effect of Additives on the Physicochemical and Drug Release ...

    African Journals Online (AJOL)

    Method: Spherical agglomerates of pioglitazone hydrochloride were prepared by emulsion solvent diffusion method with and without additives (polyethylene glycol 6000, polyvinyl pyrrolidone, β cyclodextrin, Eudragit RS100, low acyl gellan gum and xanthan gum) using methanol, chloroform and water as good solvent, ...

  18. Effect of fluxing additive on sintering temperature, microstructure and ...

    Indian Academy of Sciences (India)

    doping have been described and discussed. Additionally, in situ Raman spectroscopy has been used for the first time to investigate and compare the phase transition temperatures of pure and Li2CO3-added BaTiO3. 2. Experimental. Batches (50g) of GPR grade TiO2 and BaCO3 (Aldrich. Chemicals Company Inc.) powder ...

  19. EFFECTS OF PROPERTIES POLYMERIC ADDITIVES IN RHEOLOGIC AND DRILLING FLUIDS

    Directory of Open Access Journals (Sweden)

    Danielly Vieira de Lucena

    2014-03-01

    Full Text Available The influence of carboxymethylcellulose, CMC (filtrate reducer and xanthan gum (viscosifier in plastic and apparent viscosity at yield strength and the volume of filtrate in the composition of drilling fluids based on water was investigated based on statistical design. Five formulations consist of a range of concentrations used commercially were utilized in the design of the experiment. The formulations were prepared in accordance with company standards Petrobras. Regression models were calculated and correlated with the properties of the compositions. The relevance and validation of the models were confirmed by statistical analysis. The design can be applied to statistically optimize the mud properties considering the addition of CMC and xanthan gum, and to provide a better understanding of the influence of additives on the properties of polymer-based fluid system water. From the study it was observed that the values of the rheological properties vary with the concentration of additives, increasing with increasing concentration of the same, and that the concentration of the additives caused a decline of parameter values filtration.

  20. Effect of Additives on the Selectivity and Reactivity of Enzymes.

    Science.gov (United States)

    Liang, Yi-Ru; Wu, Qi; Lin, Xian-Fu

    2017-01-01

    Enzymes have been widely used as efficient, eco-friendly, and biodegradable catalysts in organic chemistry due to their mild reaction conditions and high selectivity and efficiency. In recent years, the catalytic promiscuity of many enzymes in unnatural reactions has been revealed and studied by chemists and biochemists, which has expanded the application potential of enzymes. To enhance the selectivity and activity of enzymes in their natural or promiscuous reactions, many methods have been recommended, such as protein engineering, process engineering, and media engineering. Among them, the additive approach is very attractive because of its simplicity to use and high efficiency. In this paper, we will review the recent developments about the applications of additives to improve the catalytic performances of enzymes in their natural and promiscuous reactions. These additives include water, organic bases, water mimics, cosolvents, crown ethers, salts, surfactants, and some particular molecular additives. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Supplemental effects of feed additives on the utilization of cassava ...

    African Journals Online (AJOL)

    One hundred and fifty 7-day old (hybro strain) broiler chicks were randomly distributed into five dietary treatments in a completely randomized design. Diet 1 which served as the control had 25% CPM, while diets 2, 3, 4 and 5 had the same composition as diet 1 but with the inclusion of feed additives, bakers' yeast, enzyme ...

  2. Softening effect of Ikpiru and Yanyanku, two traditional additives ...

    African Journals Online (AJOL)

    Ikpiru and Yanyanku are two additives used for the traditional alkaline fermentation of African locust bean (Parkia biglobosa. Benth) to produce food condiments in Benin. In this study, African locust beans (Parkia biglobosa. Benth) were fermented with or without Ikpiru and Yanyanku to assess the factors explaining the ...

  3. Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations

    Science.gov (United States)

    Sardanyés, Josep; Simó, Carles; Martínez, Regina; Solé, Ricard V.; Elena, Santiago F.

    2014-04-01

    The distribution of mutational fitness effects (DMFE) is crucial to the evolutionary fate of quasispecies. In this article we analyze the effect of the DMFE on the dynamics of a large quasispecies by means of a phenotypic version of the classic Eigen's model that incorporates beneficial, neutral, deleterious, and lethal mutations. By parameterizing the model with available experimental data on the DMFE of Vesicular stomatitis virus (VSV) and Tobacco etch virus (TEV), we found that increasing mutation does not totally push the entire viral quasispecies towards deleterious or lethal regions of the phenotypic sequence space. The probability of finding regions in the parameter space of the general model that results in a quasispecies only composed by lethal phenotypes is extremely small at equilibrium and in transient times. The implications of our findings can be extended to other scenarios, such as lethal mutagenesis or genomically unstable cancer, where increased mutagenesis has been suggested as a potential therapy.

  4. Peer support and additional information in group medical consultations (GMCs) for BRCA1/2 mutation carriers: A randomized controlled trial.

    Science.gov (United States)

    Visser, Annemiek; van Laarhoven, Hanneke W M; Woldringh, Gwendolyn H; Hoogerbrugge, Nicoline; Prins, Judith B

    2016-01-01

    Group medical consultations (GMCs) provide individual medical visits in the presence of ≤ 7 peer- patients. This study evaluated the efficacy of GMCs in the yearly breast cancer surveillance of BRCA mutation carriers. This randomized controlled trial compared GMCs (intervention group, n = 63) with individual medical visits (control group, n = 59). Between-group differences on the primary outcomes distress and empowerment, were analyzed one week and three months after the visit. Feasibility is evaluated in terms of demand, acceptability and practicability. No between-group differences were found on primary outcomes. More themes were discussed in GMCs. Seventy-five percent of GMC-participants experienced peer support. Carriers reported significantly higher satisfaction with individual visits. GMCs were less time-efficient. This is the first GMC study which reports results in favor of individual visits. The hereditary nature of the condition differentiates our study population from earlier studied GMC groups. Even though most participants experienced peer support and received more information, the lower patient satisfaction may be explained by the lack of individual time with the clinician and disruption of normal surveillance routines. As the need for peer support and additional information is present in a substantial part of carriers, future research should study the process of peer support.

  5. K137R mutation on adeno-associated viral capsids had minimal effect on enhancing gene delivery in vivo.

    Science.gov (United States)

    Qiao, Chunping; Li, Chengwen; Zhao, Chunxia; Li, Jianbin; Bian, Tao; Grieger, Joshua; Li, Juan; Samulski, R Jude; Xiao, Xiao

    2014-02-01

    The adeno-associated viral (AAV) vector has emerged as an attractive vector for gene therapy applications. Development of AAV vectors with enhanced gene transduction efficiency is important to ease the burden of AAV production and minimize potential immune responses. Rational mutations on AAV capsids have gained attention as a simple method of enhancing AAV transduction efficiency. A single-amino acid mutation, K137R, on AAV1 and AAV8 was recently reported to increase liver transgene expression by 5-10-fold. To determine whether the same mutation on other AAV serotypes would result in similar gene enhancement effects, K137R mutants were generated on AAV7, AAV8, and AAV9, and their effects were evaluated in vivo. Two reporter genes were utilized: the nuclear LacZ gene driven by the cytomegalovirus promoter and the luciferase gene driven by the CB promoter. Surprisingly, we found no difference in luciferase gene expression in the liver or other tissues using either the wild-type AAV8 capsid or AAV8-K137R. LacZ gene expression in the liver by AAV8-K137R was about onefold higher than that of wild-type AAV8. However, no difference was found in other tissues, such as skeletal muscle and cardiac muscle. In addition, no difference was found in transgene expression with either AAV7-K137R or AAV9-K137R mutants. Our results indicated that the K137R mutation on AAV7, AAV8, and AAV9 had minimal to no effect on transduction efficiency in vivo.

  6. The effect of parental gender on the GAA dynamic mutation in the FRDA gene

    Energy Technology Data Exchange (ETDEWEB)

    Pianese, L.; Cavalcanti, F.; Calabrese, O. [Federico II Univ., Naples (Italy)]|[Neuromed, Pozzili (Italy)] [and others

    1997-02-01

    Within a cooperative study, we recently isolated the defective gene (X25) causing Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disorder. X25 encodes a 210-amino acid protein, frataxin, whose function is unknown. Frataxin mRNA levels are reduced in FRDA patients. The most frequent mutation is the expansion of a (GAA){sub n} trinucleotide repeat in the first X25 intron. Normal chromosomes contain 8-22 copies of the triplet, whereas FRDA chromosomes contain >200 copies. In addition, we described few patients with point mutations. The expansion of trinucleotide repeats has been previously demonstrated to be the mutational mechanism associated with eight human diseases. Trinucleotide repeats occur both in coding and noncoding regions of the gene. Although trinucleotide repeats in the normal size range are relatively stable, expanded repeats are highly variable when transmitted from one generation to the next. For the eight previously described diseases, meiotic instability is generally associated with a mutational bias toward an increase in repeat number. Here, we analyze intergenerational variability in FRDA chromosomes in parent-carrier child pairs. In addition, we studied the stability of FRDA expanded alleles in male gametogenesis, directly analyzing male germ cells. 9 refs., 3 figs., 1 tab.

  7. Selective mutation accumulation: a computational model of the paternal age effect.

    Science.gov (United States)

    Whelan, Eoin C; Nwala, Alexander C; Osgood, Christopher; Olariu, Stephan

    2016-12-15

    As the mean age of parenthood grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father, but have a deleterious effect in offspring. In this paper we present a computational technique to model the SSC niche in order to examine the phenomenon and draw conclusions across different genes and disorders. We used a Markov chain to model the probabilities of mutation and positive selection with cell divisions. The model was fitted to available data on disease incidence and also mutation assays of sperm donors. Strength of selective advantage is presented for a range of disorders including Apert's syndrome and achondroplasia. Incidence of the diseases was predicted closely for most disorders and was heavily influenced by the site-specific mutation rate and the number of mutable alleles. The model also successfully predicted a stronger selective advantage for more strongly activating gain-of-function mutations within the same gene. Both positive selection and the rate of copy-error mutations are important in adequately explaining the paternal age effect. C ++/R source codes and documentation including compilation instructions are available under GNU license at https://github.com/anwala/NicheSimulation CONTACT: ewhel001@odu.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Effect of Calcium Additive on the Crystallization of Struvite

    Directory of Open Access Journals (Sweden)

    Perwitasari Dyah Suci

    2016-01-01

    Full Text Available Crystallization of struvite [MgNH4PO4.6H2O] may lead to the deposition of scale which may create significant problems in the process pipes, pumps and other industrial equipment. However, struvite precipitation can be benefited for phosphate recovery for use of fertilizer. The aim at the present work was to investigate calcium additive on struvite precipitation. The experiment was carried out in a batch mode using a 1-liter Pyrex glass vessel mechanically agitated for 200 rpm. The scale-forming solution was prepared for mixing solutions to MgCl2 and NH4H2PO4 with Mg+2 , NH4+ and PO4-3 in a molar ratio of 1: 1:1. The crystallization temperature of 30 and 40 °C was selected. Ca was added into the crystallizing solution to chloride dihydrate 0.4M (CaCl2•2H2O. Then each solution was pH adjusted to 9 by addition of KOH. The crystals obtained were characterized using SEM for morphology, EDS for elemental analysis as well as XRPD Rietveld analysis for crystaline phases. The induction periods varied from 10 to 90 min, which means that the struvite crystals began forming 10 to 90 min after mixing of the solution. It was observed that the Ca additive may inhibit the struvite crystallization. SEM analysis revealed that the struvite crystals obtained were predominantly of irregular prismatic morphology. Furthermore, the EDS pattern revealed that the elemental composition of the crystals consisted of Ca, Cl, S Mg, N, and P, providing that many crystalline phase found in the crystals such as Gypsum, CaCl2, struvite, struvite-(K and sylvite. It was observed that the Ca additive appeared to inhibit the struvite crystallization.

  9. THE EFFECT OF ADDITION OF Nd3 + ON DIELECTRIC ...

    African Journals Online (AJOL)

    31 déc. 2011 ... permittivity, the resistivity, increase with the addition of Nd+3 1%. ... examinée en utilisant un pont de mesure de type RLC en fonction de la température, la ... Température (°C). 1 kHZ. 10 kHZ. 100 kHZ. 200 kHZ. Fig.1. La variation de la constante diélecrique en fonctions du pourcentage de dopants à: (a)- ...

  10. Effects of additives on thermal stability of Li ion cells

    Science.gov (United States)

    Doughty, Daniel H.; Roth, E. Peter; Crafts, Chris C.; Nagasubramanian, G.; Henriksen, Gary; Amine, Khalil

    Li ion cells are being developed for high-power applications in hybrid electric vehicles, because these cells offer superior combination of power and energy density over current cell chemistries. Cells using this chemistry are proposed for battery systems in both internal combustion engine and fuel cell-powered hybrid electric vehicles. However, the safety of these cells needs to be understood and improved for eventual widespread commercial applications. The thermal-abuse response of Li ion cells has been improved by the incorporation of more stable anode carbons and electrolyte additives. Electrolyte solutions containing vinyl ethylene carbonate (VEC), triphenyl phosphate (TPP), tris(trifluoroethyl)phosphate (TFP) as well as some proprietary flame-retardant additives were evaluated. Test cells in the 18,650 configuration were built at Sandia National Laboratories using new stable electrode materials and electrolyte additives. A special test fixture was designed to allow determination of self-generated cell heating during a thermal ramp profile. The flammability of vented gas and expelled electrolyte was studied using a novel arrangement of a spark generator placed near the cell to ignite vent gas if a flammable gas mixture was present. Flammability of vent gas was somewhat reduced by the presence of certain additives. Accelerating rate calorimetry (ARC) was also used to characterize 18,650-size test cell heat and gas generation. Gas composition was analyzed by gas chromatography (GC) and was found to consist of CO 2, H 2, CO, methane, ethane, ethylene and small amounts of C1-C4 organic molecules.

  11. Effect of shaddock albedo addition on the properties of frankfurters.

    Science.gov (United States)

    Shan, Bing; Li, Xingmin; Pan, Teng; Zheng, Limin; Zhang, Hao; Guo, Huiyuan; Jiang, Lu; Zhen, Shaobo; Ren, Fazheng

    2015-07-01

    To explore the potential as a natural auxiliary emulsifier, shaddock albedo was added into frankfurters at six different levels: 0.0, 2.5, 5.0, 7.5, 10 and 12.5 %. The emulsion capacity (EC) of meat batters and cooking properties of frankfurters were evaluated. EC of meat batters was improved with the addition of shaddock albedo and the maximum value was reached at the 5 % albedo concentration. The addition of shaddock albedo resulted in lower cooking losses of frankfurters, with the lowest value obtained at the 7.5 % level. The presence of shaddock albedo decreased the total expressible fluid (TEF) and the proportion of fat in total expressible fluid (PF) which indicated the emulsion stability of frankfurters and the lowest values both occurred at the concentration of 7.5 %. Shaddock albedo inclusion increased the lightness and yellowness of frankfurters and decreased redness. Texture profile analysis showed increased hardness and decreased chewiness of frankfurters with the addition of shaddock albedo. Consequently, shaddock albedo could be a potential source of auxiliary emulsifier filler for emulsion-type meat products.

  12. Splicing aberrations caused by constitutional RB1 gene mutations in ...

    Indian Academy of Sciences (India)

    Analysis of RB1 mRNA from blood leukocytes of patients with retinoblastoma identified the effects of mutations involving consensus splice site, exonic substitution and whole-exon deletions identified in genomic DNA of these patients. In addition, this study identified mutations in cases in which no mutations were detectable ...

  13. Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations

    Directory of Open Access Journals (Sweden)

    Colombo Elisa A

    2012-01-01

    Full Text Available Abstract Background Poikiloderma with Neutropenia (PN is a rare autosomal recessive genodermatosis caused by C16orf57 mutations. To date 17 mutations have been identified in 31 PN patients. Results We characterize six PN patients expanding the clinical phenotype of the syndrome and the mutational repertoire of the gene. We detect the two novel C16orf57 mutations, c.232C>T and c.265+2T>G, as well as the already reported c.179delC, c.531delA and c.693+1G>T mutations. cDNA analysis evidences the presence of aberrant transcripts, and bioinformatic prediction of C16orf57 protein structure gauges the mutations effects on the folded protein chain. Computational analysis of the C16orf57 protein shows two conserved H-X-S/T-X tetrapeptide motifs marking the active site of a two-fold pseudosymmetric structure recalling the 2H phosphoesterase superfamily. Based on this model C16orf57 is likely a 2H-active site enzyme functioning in RNA processing, as a presumptive RNA ligase. According to bioinformatic prediction, all known C16orf57 mutations, including the novel mutations herein described, impair the protein structure by either removing one or both tetrapeptide motifs or by destroying the symmetry of the native folding. Finally, we analyse the geographical distribution of the recurrent mutations that depicts clusters featuring a founder effect. Conclusions In cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of C16orf57 gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance. The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the

  14. Novel muscle chloride channel mutations and their effects on heterozygous carriers

    Energy Technology Data Exchange (ETDEWEB)

    Mailaender, V.; Heine, R.; Deymeer, F. [Univ. of Ulm (Germany)] [and others

    1996-02-01

    Mutations within CLCN1, the gene encoding the major skeletal muscle chloride channel, cause either dominant Thomsen disease or recessive Becker-type myotonia, which are sometimes difficult to discriminate, because of reduced penetrance or lower clinical expressivity in females. We screened DNA of six unrelated Becker patients and found four novel CLCN1 mutations (Gln-74-Stop, Tyr-150-Cys, Tyr-261-Cys, and Ala-415-Val) and a previously reported 14-bp deletion. Five patients were homozygous for the changes (Gln-74-Stop, Ala-41 5-Val, and 14-bp deletion), four of them due to parental consanguinity. The sixth patient revealed compound heterozygosity for Tyr-150-Cys and Tyr-261-Cys. Heterozygous carriers of the Becker mutations did not display any clinical symptoms of myotonia. However, all heterozygous males, but none of the heterozygous females, exhibited myotonic discharges in the electromyogram suggesting (1) a gene dosage effect of the mutations on the chloride conductance and (2) male predominance of subclinical myotonia. Furthermore, we report a novel Gly-200-Arg mutation resulting in a dominant phenotype in a male and a partially dominant phenotype in his mother. We discuss potential causes of the gender preference and the molecular mechanisms that may determine the mode of inheritance. 31 refs., 4 figs., 1 tab.

  15. Founder effect of a prevalent phenylketonuria mutation in the Oriental population

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tao (Baylor College of Medicine, Houston, TX (United States) Chinese Academy of Medical Sciences, Beijing (China)); Okano, Yoshiyuki; Eisensmith, R.C.; Harvey, M.L.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States)); Lo, W.H.Y.; Yuan, Lifang (Chinese Academy of Medical Sciences, Beijing (China)); Huang, Shuzhen; Zeng, Yitao (Shanghai Children' s Hospital (China)); Furuyama, Junichi (Hyogo College of Medicine, Nishinomiya (Japan)); Oura, Toshiaki (Osaka Municipal Rehabilitation Center for the Disabled, Osaka (Japan)); Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

    1991-03-15

    A missense mutation has been identified in the human phenylalanine hydroxylase Chinese patient with classic phenylketonuria (PKU). A G-to-C transition at the second base of codon 413 in exon 12 of the gene results in the substitution of Pro{sup 413} for Arg{sup 413} in the mutant protein. This mutation (R413P) results in negligible enzymatic activity when expressed in heterologous mammalian cells and is compatible with a classic PKU phenotype in the patient. Population genetic studies reveal that this mutation is tightly linked to restriction fragment length polymorphism haplotype 4, which is the predominant haplotype of the PAH locus in the Oriental population. It accounts for 13.8% of northern Chinese and 27% of Japanese PKU alleles, but it is rare in southern Chinese (2.2%) and is absent in the Caucasian population. The data demonstrate unambiguously that the mutation occurred after racial divergence of Orientals and Caucasians and suggest that the allele has spread throughout the Orient by a founder effect. Previous protein polymorphism studies in eastern Asia have led to the hypothesis that northern Mongoloids represented a founding population in Asia. The results are compatible with this hypothesis in that the PKU mutation might have occurred in northern Mongoloids and subsequently spread to the Chinese and Japanese populations.

  16. Clinicopathologic Effect of DNMT3A Mutation in Adult T-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Aref, Salah; El Menshawy, Nadia; El-Ghonemy, Mohamed Sabry; Zeid, Tarek Abou; El-Baiomy, Mohamed Ali

    2016-01-01

    The present study aimed to determine the frequencies and clinicopathologic effect of a DNMT3A [DNA (cytosine-5)-methyltransferase 3A] mutation in patients with adult T-cell acute lymphoblastic leukemia (T-ALL). A total of 64 patients with T-ALL who had been admitted to Mansoura University Oncology Center were included in the present study. For all patients, DNA extraction and amplification with sequencing analysis using the 310 ABI genetic analyzer for detection of a mutation (R882H). The DNMT3A mutation (R882H) was found in 12 of the 64 patients (18.8%). The DNMT3A mutation was frequently detected in the older age group and was associated with high leukocytic counts, a high bone marrow blast cell percentage, and the frequent presence of extramedullary disease. However, it was not associated with the hemoglobin level, red blood cell count, or platelet count. The patients with mutant T-ALL had a low tendency to achieve remission after induction. These patients had significantly shorter overall survival and shorter disease-free survival compared with those with wild-type T-ALL (P = .037 and P = .006, respectively). DNMT3A is frequently mutated in T-ALL and is associated with distinct clinicopathologic entities and a poor prognosis. These findings could help in risk stratification and treatment decisions for patients with T-ALL. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Effects of Mutations on Structure–Function Relationships of Matrix Metalloproteinase-1

    Directory of Open Access Journals (Sweden)

    Warispreet Singh

    2016-10-01

    Full Text Available Matrix metalloproteinase-1 (MMP-1 is one of the most widely studied enzymes involved in collagen degradation. Mutations of specific residues in the MMP-1 hemopexin-like (HPX domain have been shown to modulate activity of the MMP-1 catalytic (CAT domain. In order to reveal the structural and conformational effects of such mutations, a molecular dynamics (MD study was performed of in silico mutated residues in the X-ray crystallographic structure of MMP-1 complexed with a collagen-model triple-helical peptide (THP. The results indicate an important role of the mutated residues in MMP-1 interactions with the THP and communication between the CAT and the HPX domains. Each mutation has a distinct impact on the correlated motions in the MMP-1•THP. An increased collagenase activity corresponded to the appearance of a unique anti-correlated motion and decreased correlated motions, while decreased collagenase activity corresponded both to increased and decreased anti-correlated motions.

  18. SDM: a server for predicting effects of mutations on protein stability.

    Science.gov (United States)

    Pandurangan, Arun Prasad; Ochoa-Montaño, Bernardo; Ascher, David B; Blundell, Tom L

    2017-05-19

    Here, we report a webserver for the improved SDM, used for predicting the effects of mutations on protein stability. As a pioneering knowledge-based approach, SDM has been highlighted as the most appropriate method to use in combination with many other approaches. We have updated the environment-specific amino-acid substitution tables based on the current expanded PDB (a 5-fold increase in information), and introduced new residue-conformation and interaction parameters, including packing density and residue depth. The updated server has been extensively tested using a benchmark containing 2690 point mutations from 132 different protein structures. The revised method correlates well against the hypothetical reverse mutations, better than comparable methods built using machine-learning approaches, highlighting the strength of our knowledge-based approach for identifying stabilising mutations. Given a PDB file (a Protein Data Bank file format containing the 3D coordinates of the protein atoms), and a point mutation, the server calculates the stability difference score between the wildtype and mutant protein. The server is available at http://structure.bioc.cam.ac.uk/sdm2. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Effects Of Radiation On Electronics-Additional References

    Science.gov (United States)

    Bouquet, Frank L.

    1988-01-01

    Bibliography abstracts summarizing literature on effects of radiation on new electronic devices. This and second volume cover years 1984 and 1985. Third volume, covers 1982 and 1983 (previously published).

  20. Effect of hydrogen addition on autoignited methane lifted flames

    KAUST Repository

    Choin, Byung Chul

    2012-01-01

    Autoignited lifted flames in laminar jets with hydrogen-enriched methane fuels have been investigated experimentally in heated coflow air. The results showed that the autoignited lifted flame of the methane/hydrogen mixture, which had an initial temperature over 920 K, the threshold temperature for autoignition in methane jets, exhibited features typical of either a tribrachial edge or mild combustion depending on fuel mole fraction and the liftoff height increased with jet velocity. The liftoff height in the hydrogen-assisted autoignition regime was dependent on the square of the adiabatic ignition delay time for the addition of small amounts of hydrogen, as was the case for pure methane jets. When the initial temperature was below 920 K, where the methane fuel did not show autoignition behavior, the flame was autoignited by the addition of hydrogen, which is an ignition improver. The liftoff height demonstrated a unique feature in that it decreased nonlinearly as the jet velocity increased. The differential diffusion of hydrogen is expected to play a crucial role in the decrease in the liftoff height with increasing jet velocity.

  1. Cumulative effects of mutations in newly synthesised mitochondrial aspartate aminotransferase on uptake into mitochondria.

    Science.gov (United States)

    Marra, E; Azzariti, A; Giannattasio, S; Doonan, S; Quagliariello, E

    1995-09-14

    Mutant genes were constructed which coded for the precursor form of mitochondrial aspartate aminotransferase in which residue cysteine 166 was mutated to either serine or alanine and for forms of the protein lacking both the presequence and residues 1-9 of the mature protein but carrying the same cysteine mutations. The protein products of all of these mutant genes were imported into mitochondria that had been added to the expression system but with varying degrees of efficiency. The results showed that the effects of mutation of cysteine 166 and of deletion of residues 1-9 of the mature protein on sequestration into mitochondria were essentially cumulative, suggesting that these parts of the protein are involved in distinct steps on the recognition/uptake pathway.

  2. The effects of maternal irradiation during adulthood on mutation induction and transgenerational instability in mice

    Energy Technology Data Exchange (ETDEWEB)

    Abouzeid Ali, Hamdy E. [Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Radiobiological Applications Department, Nuclear Research Centre, Atomic Energy Authority, Cairo (Egypt); Barber, Ruth C. [Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Dubrova, Yuri E., E-mail: yed2@le.ac.uk [Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom)

    2012-04-01

    The long-term genetic effects of maternal irradiation remain poorly understood. To establish the effects of radiation exposure on mutation induction in the germline of directly exposed females and the possibility of transgenerational effects in their non-exposed offspring, adult female BALB/c and CBA/Ca mice were given 1 Gy of acute X-rays and mated with control males. The frequency of mutation at expanded simple tandem repeat (ESTR) loci in the germline of directly exposed females did not differ from that of controls. Using a single-molecule PCR approach, ESTR mutation frequency was also established for both germline and somatic tissues in the first-generation offspring of irradiated parents. While the frequency of ESTR mutation in the offspring of irradiated males was significantly elevated, maternal irradiation did not affect stability in their F{sub 1} offspring. Considering these data and the results of our previous study, we propose that, in sharp contrast to paternal exposure to ionising radiation, the transgenerational effects of maternal high-dose acute irradiation are likely to be negligible.

  3. ABCA4 mutational spectrum in Mexican patients with Stargardt disease: Identification of 12 novel mutations and evidence of a founder effect for the common p.A1773V mutation.

    Science.gov (United States)

    Chacón-Camacho, Oscar F; Granillo-Alvarez, Mariella; Ayala-Ramírez, Raul; Zenteno, Juan C

    2013-04-01

    The aim of this study was to assess the mutational spectrum of the ABCA4 gene in a cohort of patients with Stargardt disease from Mexico, a previously uncharacterized population. Clinical diagnosis in each patient was supported by a complete ophthalmological assessment that included visual acuity measurement, a slit lamp examination, a fundus examination and photography, electroretinography, fluorescein angiography, and computerized visual fields testing. Molecular analysis was performed by PCR amplification and direct nucleotide sequence of the 50 exons of the ABCA4 gene in genomic DNA. A total of 31 unrelated subjects with the disease were enrolled in the study. Molecular analysis in the total group of 62 alleles allowed the identification of 46 mutant ABCA4 alleles carrying 29 different pathogenic disease-associated mutations. Two ABCA4 mutant alleles were detected in 20 of the 31 patients (64.5%), a single disease allele was identified in six (19.4%), and no mutant alleles were detected in five of the cases (16.1%). Most patients with two ABCA4 mutations (11/20, 55%) were compound heterozygotes. Twelve variants were novel ABCA4 mutations. Nucleotide substitutions were the most frequent type of variation, occurring in 26 out of 29 (89.7%) different mutations. The two most common mutations in our study were the missense changes p.A1773V and p.G818E, which were identified in eight (17%) and seven (15%) of the total 46 disease-associated alleles, respectively. Haplotype analyses of intragenic SNPs in four subjects carrying the p.A1773V mutation supported a common origin for this mutation. In conclusion, this is the first report of ABCA4 molecular screening in Latin American Stargardt disease patients. Our results expand the mutational spectrum of the disease by adding 12 novel ABCA4 pathogenic variants and support the occurrence of a founder effect for the p.A1773V mutation in the Mexican population. The identification of recurrent mutations in our cohort will

  4. Effects of various additives on antioxidant and antimicrobial ...

    African Journals Online (AJOL)

    We investigated the effects of rosemary extract (RE), α-tocopherol (AT) and chitosan (CH) added individually or in combination as compared with butylated hydroxyanisole (BHA) on microbiological parameters [total viable count (TVC), lactic acid bacteria (LAB), enterobacteria (ENB), pseudomonas bacteria (PSY)], pH and ...

  5. Additive main effects and multiplicative interaction analysis for ...

    African Journals Online (AJOL)

    Genotype by environment interaction (G x E) is a major problem in the study of quantitative traits as it complicates the interpretation of genotypes evaluation experiments and makes predications of performance difficult. In order to disentangle the genetic and GxE effects and get meaningful interpretation of the results, ...

  6. Direct and maternal additive and heterotic effects in crossbreeding ...

    African Journals Online (AJOL)

    ALENDA, R., MARTIN, T.G., LASLEY, J.F. & ELLERSIECK, M.R.,. 1980. Estimation of genetic and maternal effects in crossbred cattle of Angus, Charolais and Hereford parentage. I. Birth and weaning weights. J. Anim. Sci. 50, 226. CAR1WRIGHT, T.C., 1970. Selection criteria for beef cattle for the future. J. Anim. Sci. 30, 706.

  7. Effect of dabrafenib on melanoma cell lines harbouring the BRAFV600D/R mutations

    Directory of Open Access Journals (Sweden)

    Gentilcore Giusy

    2013-01-01

    Full Text Available Abstract Background Conventional therapeutic agents are largely unsatisfactory into the treatment of malignant melanoma. Recently, an innovative approach based on inhibitors of the mutated BRAF gene (which represents the most prevalent alteration in melanoma patients appears very promising from the clinical point of view. On this regard, a new compound, dabrafenib (GSK2118436, has been demonstrated to be effective in patients carrying the BRAFV600E/K mutations. We here tested dabrafenib for its capability to inhibit cell growth on primary melanoma cell lines, established from patients' tumour tissues and carrying the BRAFV600D/R mutations. Methods Three melanoma cell lines were tested: M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D. The MTT assays were performed using standardized approaches. To evaluate the inhibition of MAPK pathway and the consequent inhibition of cellular proliferation, the phosphorylation of ERK was examined by Western Blot analysis performed on total protein extracts from cell lines after treatment with dabrafenib. Results Our experiments demonstrated an effective action of Dabrafenib (GSK2118436 and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations. Conclusion These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment.

  8. The added value of using mutational profiling in addition to cytology in diagnosing aggressive pancreaticobiliary disease: review of clinical cases at a single center

    Science.gov (United States)

    2014-01-01

    Background This study aimed to better understand the supporting role that mutational profiling (MP) of DNA from microdissected cytology slides and supernatant specimens may play in the diagnosis of malignancy in fine-needle aspirates (FNA) and biliary brushing specimens from patients with pancreaticobiliary masses. Methods Cytology results were examined in a total of 30 patients with associated surgical (10) or clinical (20) outcomes. MP of DNA from microdissected cytology slides and from discarded supernatant fluid was analyzed in 26 patients with atypical, negative or indeterminate cytology. Results Cytology correctly diagnosed aggressive disease in 4 patients. Cytological diagnoses for the remaining 26 were as follows: 16 negative (9 false negative), 9 atypical, 1 indeterminate. MP correctly determined aggressive disease in 1 false negative cytology case and confirmed a negative cytology diagnosis in 7 of 7 cases of non-aggressive disease. Of the 9 atypical cytology cases, MP correctly diagnosed 7 as positive and 1 as negative for aggressive disease. One specimen that was indeterminate by cytology was correctly diagnosed as non-aggressive by MP. When first line malignant (positive) cytology results were combined with positive second line MP results, 12/21 cases of aggressive disease were identified, compared to 4/21 cases identified by positive cytology alone. Conclusions When first line cytology results were uncertain (atypical), questionable (negative), or not possible (non-diagnostic/indeterminate), MP provided additional information regarding the presence of aggressive disease. When used in conjunction with first line cytology, MP increased detection of aggressive disease without compromising specificity in patients that were difficult to diagnose by cytology alone. PMID:25084836

  9. Nutrient additions in pristine Patagonian Sphagnum bog vegetation: can phosphorus addition alleviate (the effects of) increased nitrogen loads.

    Science.gov (United States)

    Fritz, C; van Dijk, G; Smolders, A J P; Pancotto, V A; Elzenga, T J T M; Roelofs, J G M; Grootjans, A P

    2012-05-01

    Sphagnum-bog ecosystems have a limited capability to retain carbon and nutrients when subjected to increased nitrogen (N) deposition. Although it has been proposed that phosphorus (P) can dilute negative effects of nitrogen by increasing biomass production of Sphagnum mosses, it is still unclear whether P-addition can alleviate physiological N-stress in Sphagnum plants. A 3-year fertilisation experiment was conducted in lawns of a pristine Sphagnum magellanicum bog in Patagonia, where competing vascular plants were practically absent. Background wet deposition of nitrogen was low (≈ 0.1-0.2 g · N · m(-2) · year(-1)). Nitrogen (4 g · N · m(-2) · year(-1)) and phosphorus (1 g · P · m(-2) · year(-1)) were applied, separately and in combination, six times during the growing season. P-addition substantially increased biomass production of Sphagnum. Nitrogen and phosphorus changed the morphology of Sphagnum mosses by enhancing height increment, but lowering moss stem density. In contrast to expectations, phosphorus failed to alleviate physiological stress imposed by excess nitrogen (e.g. amino acid accumulation, N-saturation and decline in photosynthetic rates). We conclude that despite improving growth conditions by P-addition, Sphagnum-bog ecosystems remain highly susceptible to nitrogen additions. Increased susceptibility to desiccation by nutrients may even worsen the negative effects of excess nitrogen especially in windy climates like in Patagonia. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

  10. Cost of Adaptation and Fitness Effects of Beneficial Mutations in Pseudomonas fluorescens

    Science.gov (United States)

    Bataillon, Thomas; Zhang, Tianyi; Kassen, Rees

    2011-01-01

    Adaptations are constructed through the sequential substitution of beneficial mutations by natural selection. However, the rarity of beneficial mutations has precluded efforts to describe even their most basic properties. Do beneficial mutations typically confer small or large fitness gains? Are their fitness effects environment specific, or are they broadly beneficial across a range of environments? To answer these questions, we used two subsets (n = 18 and n = 63) of a large library of mutants carrying antibiotic resistance mutations in the bacterium Pseudomonas fluorescens whose fitness, along with the antibiotic sensitive ancestor, was assayed across 95 novel environments differing in the carbon source available for growth. We explore patterns of genotype-by-environment (G×E) interactions and ecological specialization among the 18 mutants initially found superior to the sensitive ancestor in one environment. We find that G×E is remarkably similar between the two sets of mutants and that beneficial mutants are not typically associated with large costs of adaptation. Fitness effects among beneficial mutants depart from a strict exponential distribution: they assume a variety of shapes that are often roughly L shaped but always right truncated. Distributions of (beneficial) fitness effects predicted by a landscape model assuming multiple traits underlying fitness and a single optimum often provide a good description of the empirical distributions in our data. Simulations of data sets containing a mixture of single and double mutants under this landscape show that inferences about the distribution of fitness effects of beneficial mutants is quite robust to contamination by second-site mutations. PMID:21868607

  11. Proceedings of the 8th workshop on plant mutation breeding. Effective use of physical/chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Kume, Tamikazu; Watanabe, Kazuo; Tano, Shigemitsu (eds.) [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2001-03-01

    The Workshop on Plant Mutation Breeding of FNCA (Forum for Nuclear Cooperation in Asia), was held on 9-13 October 2000 in Hanoi, Vietnam. The Workshop was co-sponsored by the Science and Technology Agency (STA), the Ministry of Science, Technology and Environment (MOSTE of Vietnam) and the Ministry of Agriculture and Rural Development (MARD of Vietnam) in cooperation with the Ministry of Agriculture, Forestry and Fisheries (MAFF), National Institute of Agrobiological Resources (NIAR of Vietnam), the Japan Atomic Industrial Forum (JAIF) and Japan Atomic Energy Research Institute (JAERI). Two Scientists, a Project Leader and an expert on methodology for plant/crop mutation breeding, participated from each of the member countries, i.e. China, Indonesia, Malaysia, the Philippines, Thailand, Vietnam and Japan. Also attending the Workshop were, one participant from Korea, seven participants from both Japan and Vietnam. The number of the participants in the Workshop totalled about sixty people including guests and observers. Sixteen papers including eight invited papers on the current status of methodology for plant/crop mutation breeding in the participating countries were presented. Discussions were focused on the subject concerning 'Effective Use of Physical/Chemical Mutagens', as well as a detailed report on the current status of research in each participating country. In addition, the topics of developing a mutant breeding database, an information exchange for plant/crop mutation breeding, and more tightly bound international co-operative research in the near future were also high on the agenda. This proceeding compiles the invited and contributed papers that were submitted from the speakers. (author)

  12. Human Prolactin Point Mutations and Their Projected Effect on Vasoinhibin Generation and Vasoinhibin-Related Diseases

    Directory of Open Access Journals (Sweden)

    Jakob Triebel

    2017-11-01

    Full Text Available BackgroundA dysregulation of the generation of vasoinhibin hormones by proteolytic cleavage of prolactin (PRL has been brought into context with diabetic retinopathy, retinopathy of prematurity, preeclampsia, pregnancy-induced hypertension, and peripartum cardiomyopathy. Factors governing vasoinhibin generation are incompletely characterized, and the composition of vasoinhibin isoforms in human tissues or compartments, such as the circulation, is unknown. The aim of this study was to determine the possible contribution of PRL point mutations to the generation of vasoinhibins as well as to project their role in vasoinhibin-related diseases.MethodsProlactin sequences, point mutations, and substrate specificity information about the PRL cleaving enzymes cathepsin D, matrix metalloproteinases 8 and 13, and bone-morphogenetic protein 1 were retrieved from public databases. The consequences of point mutations in regard to their possible effect on vasoinhibin levels were projected on the basis of a score indicating the suitability of a particular sequence for enzymatic cleavage that result in vasoinhibin generation. The relative abundance and type of vasoinhibin isoforms were estimated by comparing the relative cleavage efficiency of vasoinhibin-generating enzymes.ResultsSix point mutations leading to amino acid substitutions in vasoinhibin-generating cleavage sites were found and projected to either facilitate or inhibit vasoinhibin generation. Four mutations affecting vasoinhibin generation in cancer tissues were found. The most likely composition of the relative abundance of vasoinhibin isoforms is projected to be 15 > 17.2 > 16.8 > 17.7 > 18 kDa vasoinhibin.ConclusionProlactin point mutations are likely to influence vasoinhibin levels by affecting the proteolysis efficiency of vasoinhibin-generating enzymes and should be monitored in patients with vasoinhibin-related diseases. Attempts to characterize vasoinhibin-related diseases

  13. The additive effects of alcohol and benzodiazepines on driving.

    Science.gov (United States)

    Maxwell, Hillary G; Dubois, Sacha; Weaver, Bruce; Bédard, Michel

    2010-01-01

    To examine the relationship between the combination of alcohol and benzodiazepines and the risk of committing an unsafe driver action. We used data from the Fatality Analysis Reporting System (1993-2006) on drivers aged 20 or older who were tested for both alcohol and drugs. Using a case-control design, we compared drivers who had at least one unsafe driver action (UDA; e.g., weaving) recorded in relation to the crash (cases) to drivers who did not (controls). Drivers who tested positive for intermediate- and long-acting benzodiazepines in combination with alcohol had significantly greater odds of a UDA compared to those under the influence of alcohol alone, up to blood alcohol concentrations (BACs) of 0.08 and 0.05 g/100 ml, respectively. The odds of a UDA with short-acting benzodiazepines combined with alcohol were no different than for alcohol alone. This study demonstrates that the combination of alcohol and benzodiazepines can have detrimental effects on driving beyond those of alcohol alone. By describing these combined effects in terms of BAC equivalencies, this study also allows for the extrapolation of simple, concrete concepts that communicate risk to the average benzodiazepine user.

  14. Effects of Charcoal Addition on the Properties of Carbon Anodes

    Directory of Open Access Journals (Sweden)

    Asem Hussein

    2017-03-01

    Full Text Available Wood charcoal is an attractive alternative to petroleum coke in production of carbon anodes for the aluminum smelting process. Calcined petroleum coke is the major component in the anode recipe and its consumption results in a direct greenhouse gas (GHG footprint for the industry. Charcoal, on the other hand, is considered as a green and abundant source of sulfur-free carbon. However, its amorphous carbon structure and high contents of alkali and alkaline earth metals (e.g., Na and Ca make charcoal highly reactive to air and CO2. Acid washing and heat treatment were employed in order to reduce the reactivity of charcoal. The pre-treated charcoal was used to substitute up to 10% of coke in the anode recipe in an attempt to investigate the effect of this substitution on final anode properties. The results showed deterioration in the anode properties by increasing the charcoal content. However, by adjusting the anode recipe, this negative effect can be considerably mitigated. Increasing the pitch content was found to be helpful to improve the physical properties of the anodes containing charcoal.

  15. The effect of yeast culture addition on utility of calves

    Directory of Open Access Journals (Sweden)

    Petr Doležal

    2004-01-01

    Full Text Available In the present study, examined was the effect of a yeast culture (Saccharomyces cerevisiae, Strain 47 on performance (especially on daily gains, feed conversion and condition in an experiment with a group of Holstein calves within the period of plant nutrition. Animals received a diet consisting of 3 kg of good maize silage, 5.5 kg of grass haylage, 1 kg of meadow hay and 1.6 kg of supplementary starter feed mixture ČOT B. The yeast culture was added to the starter in the dose of 1 g.kg–1. This means that each experimental calf received 1.6 g of yeast culture per day. The supplement of yeast culture showed a positive effect on daily gains and on the final body weight of calves; however, the differences were statistically not significant (P>0.05. In control and experimental groups, the mean conversion rates of concentrate were 2.19 kg and 2.13 kg, respectively. There was no difference in feed intake and feed conversion efficiency. The difference in final live body weights of calves in the control and experimental groups was also not significant. However, the condition of calves in the experimental group was much better and the scours were in general less frequent.

  16. Effect of Iron Additives on the Microstructure of Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    G. A. Gamal

    2013-12-01

    Full Text Available In this article, some Fe (III doped hydroxyapatite samples (FeHAp were prepared using the wet chemical method. The prepared samples were characterized via the use of X-ray diffraction (XRD and scanning electron microscopy (SEM. Detailed structural analysis were done by Scherrer and Williamson–Hall plot methods to detect the effect of iron on the structure of hydroxyapatite (HAp. XRD patterns showed that all samples were single phased HAp. Relations between the Fe content and the deformation of the lattice parameters, dislocation density, grain size, microstrain, crystallinity were investigated. The presence of iron in the HAp lattice is found to decrease both the crystal size and the dislocation density. Further results are presented and discussed.

  17. IMMUNOMODULATORY EFFECT OF PHYTO-ADDITIVES IN BROILER CHICKENS

    Directory of Open Access Journals (Sweden)

    LAVINIA ŞTEF

    2007-05-01

    Full Text Available The experiment was been performed in the sector of Nutrition and Animal Feeding discipline from Timisoara Didactic Station, on a 6 week period, beginning with hatching and finishing with 42 days of age, on 120 broilers divided into four experimental variants, each of them with 30 individuals. In LEU group was incorporated essential oils of Satureja hortensis, Mentha piperita and Hyperici herba 250 mg in 1 kg combined fodder, in LEP group was included in combined fodder structure a plants premix in 2%, in LEUP group was incorporated plants premix 2% +250 mg essential oil of Satureja hortensis, Mentha piperita, Hyperici herba in 1 kg combined fodder. After seric lizozime quntification was observed an increase with 303.46% in LEPU group, followed by LEU with 200.14%, results who demonstrated the presence of an immunological stimulation in broiler chickens. Increased values of seric properdine were observed in LEPU group, with 210.45% more increased in comparison with LM group, followed by LEU group, demonstrating that the changing of unspecific immune effectors values took place like a result of a exogenous substance with immunomodulator effect. Was also observed an easy increase of limfocytes in LPU group, but not so important like in first two determinations, if the experiment will continue, these values maybe will be significant increased, taking into consideration that these increases become more evident after a period of time after stimulation.

  18. Additional effective dose by patients undergoing NAI-131 capsules therapy

    Energy Technology Data Exchange (ETDEWEB)

    Orlic, M.; Jovanovic, M.; Spasic Jokic, V.; Cuknic, O.; Ilic, Z.; Vranjes Djuric, S. [VINCA - Institute of Nuclear Sciences, Belgrade, Serbia and Montenegro (Yugoslavia)

    2006-07-01

    Capsules or solutions containing Na{sup 131}I are indicated for the therapy of some thyroid carcinomas such as functioning metastatic papillary or follicular carcinoma of the thyroid; and for the treatment of hyperthyroidism (diffuse toxic goiter and single or multiple toxic nodular goiter). The recommended dosage ranges of Na{sup 131}I capsules or solution for the therapy of the average patient (70 kg) are: (3.7-5.55) GBq for ablation of normal thyroid tissue; (3.7-7.4) GBq for subsequent treatments; a (148-370) MBq for hyperthyroidism. The purpose of this paper is to calculate effective dose as a result of iodine-131 capsules remaining in stomach before absorption starts. This result can determine the disadvantage of capsule versus solution containing sodium iodine-131 (Na{sup 131}I) in radionuclide therapy application from radiation protection point of view. The Monte Carlo code MCNP4b was used to model transport of gamma and beta particles emitted by radionuclide {sup 131}I treated as a point source at the bottom of stomach. Absorbed energy per unit transformation in stomach and surrounding organs has been calculated. (authors)

  19. Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations.

    Science.gov (United States)

    Brough, Helen A; Simpson, Angela; Makinson, Kerry; Hankinson, Jenny; Brown, Sara; Douiri, Abdel; Belgrave, Danielle C M; Penagos, Martin; Stephens, Alick C; McLean, W H Irwin; Turcanu, Victor; Nicolaou, Nicolaos; Custovic, Adnan; Lack, Gideon

    2014-10-01

    Filaggrin (FLG) loss-of-function mutations lead to an impaired skin barrier associated with peanut allergy. Household peanut consumption is associated with peanut allergy, and peanut allergen in household dust correlates with household peanut consumption. We sought to determine whether environmental peanut exposure increases the odds of peanut allergy and whether FLG mutations modulate these odds. Exposure to peanut antigen in dust within the first year of life was measured in a population-based birth cohort. Peanut sensitization and peanut allergy (defined by using oral food challenges or component-resolved diagnostics [CRD]) were assessed at 8 and 11 years. Genotyping was performed for 6 FLG mutations. After adjustment for infantile atopic dermatitis and preceding egg skin prick test (SPT) sensitization, we found a strong and significant interaction between natural log (ln [loge]) peanut dust levels and FLG mutations on peanut sensitization and peanut allergy. Among children with FLG mutations, for each ln unit increase in the house dust peanut protein level, there was a more than 6-fold increased odds of peanut SPT sensitization, CRD sensitization, or both in children at ages 8 years, 11 years, or both and a greater than 3-fold increased odds of peanut allergy compared with odds seen in children with wild-type FLG. There was no significant effect of exposure in children without FLG mutations. In children carrying an FLG mutation, the threshold level for peanut SPT sensitization was 0.92 μg of peanut protein per gram (95% CI, 0.70-1.22 μg/g), that for CRD sensitization was 1.03 μg/g (95% CI, 0.90-1.82 μg/g), and that for peanut allergy was 1.17 μg/g (95% CI, 0.01-163.83 μg/g). Early-life environmental peanut exposure is associated with an increased risk of peanut sensitization and allergy in children who carry an FLG mutation. These data support the hypothesis that peanut allergy develops through transcutaneous sensitization in children with an impaired

  20. Effect of lipopolysaccharide mutations on recipient ability of Salmonella typhimurium for incompatibility group H plasmids.

    Science.gov (United States)

    Sherburne, C; Taylor, D E

    1997-01-01

    Previous investigations of the incompatibility group F, P, and I plasmid systems revealed the important role of the outer membrane components in the conjugal transfer of these plasmids. We have observed variability in transfer frequency of three incompatibility group H plasmids (IncHI1 plasmid R27, IncHI2 plasmid R478, and a Tn7 derivative of R27, pDT2454) upon transfer into various Salmonella typhimurium lipopolysaccharide (LPS) mutants derived from a common parental strain, SL1027. Recipients with truncated outer core via the rfaF LPS mutation increased the transfer frequency of the IncH plasmids by up to a factor of 10(3). Mutations which resulted in the truncation of the residues following 3-deoxy-D-manno-octulosonic acid, such as the rfaE and rfaD mutations, decreased the transfer frequency to undetectable levels. Addition of phosphorylethanolamine, a component of wild-type LPS, to the media decreased the frequency of transfer of R27 into wild-type and rfaF LPS mutant recipients tested. Reversing the direction of transfer, by mating LPS mutant donors with wild-type recipients, did not affect the frequency of transfer compared to the standard matings of wild-type donor with LPS mutant recipient. These findings demonstrate that conjugation interactions affected by LPS mutation are not specific for the recipient cell. Our results suggest that LPS mutation does not affect conjugation via altered pilus binding but affects some later steps in the conjugative process, and alteration of transfer frequency by O-phosphorylethanolamine and LPS truncation is due to charge-related interactions between the donor and recipient cell. PMID:9006054

  1. Mutation of Gly717Phe in human topoisomerase 1B has an effect on enzymatic function, reactivity to the camptothecin anticancer drug and on the linker domain orientation

    DEFF Research Database (Denmark)

    Wang, Zhenxing; D'Annessa, Ilda; Tesauro, Cinzia

    2015-01-01

    Human topoisomerase 1B controls the topological state of supercoiled DNA allowing the progression of fundamental cellular processes. The enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by cleaving one DNA strand and forming a transient protein......–DNA covalent adduct. In this work the role of the Gly717 residue, located in a α-helix structure bridging the active site and the linker domain, has been investigated mutating it in Phe. The mutation gives rise to drug resistance in vivo as observed through a viability assay of yeast cells. In vitro activity...... interaction with the DNA substrate, likely affecting the strand rotation and religation rate. The mutation also causes a slight rearrangement of the active site and of the drug binding site, providing an additional explanation for the lowered effect of camptothecin toward the mutant....

  2. Effect of Flap Mutations on Structure of HIV-1 Protease and Inhibition by Sanquinavir and Darunavir

    Energy Technology Data Exchange (ETDEWEB)

    Liu, F.; Kovalevsky, A.; Tie, Y.; Ghosh, A.; Harrison, R.; Weber, I. (GSU); (Purdue)

    2008-08-25

    HIV-1 (human immunodeficiency virus type 1) protease (PR) and its mutants are important antiviral drug targets. The PR flap region is critical for binding substrates or inhibitors and catalytic activity. Hence, mutations of flap residues frequently contribute to reduced susceptibility to PR inhibitors in drug-resistant HIV. Structural and kinetic analyses were used to investigate the role of flap residues Gly48, Ile50, and Ile54 in the development of drug resistance. The crystal structure of flap mutants PR{sub I50V} (PR with I50V mutation), PR{sub I54V} (PR with I54V mutation), and PR{sub I54M} (PR with I54M mutation) complexed with saquinavir (SQV) as well as PR{sub G48V} (PR with G48V mutation), PR{sub I54V}, and PR{sub I54M} complexed with darunavir (DRV) were determined at resolutions of 1.05--1.40 {angstrom}. The PR mutants showed changes in flap conformation, interactions with adjacent residues, inhibitor binding, and the conformation of the 80s loop relative to the wild-type PR. The PR contacts with DRV were closer in PR{sub G48V}-DRV than in the wild-type PR-DRV, whereas they were longer in PR{sub I54M}-DRV. The relative inhibition of PR{sub I54V} and that of PR{sub I54M} were similar for SQV and DRV. PR{sub G48V} was about twofold less susceptible to SQV than to DRV, wheres the opposite was observed for PR{sub I50V}. The observed inhibition was in agreement with the association of G48V and I50V with clinical resistance to SQV and DRV, respectively. This analysis of structural and kinetic effects of the mutants will assist in the development of more effective inhibitors for drug-resistant HIV.

  3. Novel PKD1 mutations – the effect on clinical phenotype of ADPKD patients in Lower Silesia

    Directory of Open Access Journals (Sweden)

    Hanna Augustyniak-Bartosik

    2013-03-01

    Full Text Available Introduction: Autosomal dominant polycystic kidney disease (ADPKD is characterized by the development and progressive enlargement of cysts in the kidneys. The diagnosis of ADPKD is usually determined by criteria of renal ultrasound imaging of the development and number of cysts. However, in atypical cystic disease, for the recognition of ADPKD, DNA-based assays may be required.Materials and methods: In the present study PCR amplified fragments of the PKD1 gene (covering exons 15 and 43- 44 from genomic DNA of 134 Lower Silesia patients were analyzed for mutations and polymorphisms. Among them, the clinical significance of different PKD1 mutations was investigated in 81 persons.Results: Eight new, previously undescribed, and 2 recurrent mutations were discovered. The presence of 3 known polymorphisms was confirmed. Seven of the 8 new discovered mutations were heterozygous.Discussion: The results of the present study demonstrated that the frequency of genetic abnormalities in the analyzed fragments of the PKD1 gene in the Lower Silesian population is smaller than previously reported. Moreover, we could not detect deletions and insertions, which are often present is these regions of the PKD1 gene, which may be due to the limited number of screened patients. We conclude that none of the discovered changes in the PKD1 gene had any effect on clinical phenotype of the disease. 

  4. The Potential Negative Effects of Interleukin 1 B in Multiple Sclerosis Patients with MEFV Mutation

    Directory of Open Access Journals (Sweden)

    Mahmut Alpayci

    2013-10-01

    Full Text Available Multiple sclerosis patients, who are carriers of MEditerranean FeVer (MEFV gene mutation, have faster progression than the non-carriers. However, its underlying mechanism is not well understood. This article proposes the potential role of interleukin-1β (IL-1β that may be responsible for this rapid progression. Mutations in MEFV, the gene encoding for protein pyrin, cause familial Mediterranean fever, lead to gain of pyrin function, resulting in inappropriate IL-1β release. Interleukin-1β is a major mediator of systemic inflammation and fever, and also it contributes to permeability of the blood-brain barrier in active lesions of multiple sclerosis. Moreover, IL-1β promotes apoptosis of neurons and oligodendrocytes that produce the myelin sheath, which insulates axons. Thus, inflammatory damage, the blood-brain barrier disfunction, effects of fever on the central nervous system (or Uhthoff’s phenomenon, and apoptosis of neurons and oligodendrocytes, which play an important role in the pathogenesis and clinical course of multiple sclerosis, can be induced by increased activation and release of IL-1β in the presence of MEFV gene mutations. Therefore, screening for MEFV mutations in patients with multiple sclerosis and treatment planning with IL-1β targeting drugs for the carriers, may be a logical idea that will be a source of inspiration for scientific studies.

  5. The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect

    Science.gov (United States)

    Tiemann-Boege, Irene; Navidi, William; Grewal, Raji; Cohn, Dan; Eskenazi, Brenda; Wyrobek, Andrew J.; Arnheim, Norman

    2002-01-01

    The lifelong spermatogonial stem cell divisions unique to male germ cell production are thought to contribute to a higher mutation frequency in males. The fact that certain de novo human genetic conditions (e.g., achondroplasia) increase in incidence with the age of the father is consistent with this idea. Although it is assumed that the paternal age effect is the result of an increasing frequency of mutant sperm as a man grows older, no direct molecular measurement of the germ-line mutation frequency has been made to confirm this hypothesis. Using sperm DNA from donors of different ages, we determined the frequency of the nucleotide substitution in the fibroblast growth factor receptor 3 (FGFR3) gene that causes achondroplasia. Surprisingly, the magnitude of the increase in mutation frequency with age appears insufficient to explain why older fathers have a greater chance of having a child with this condition. A number of alternatives may explain this discrepancy, including selection for sperm that carry the mutation or an age-dependent increase in premutagenic lesions that remain unrepaired in sperm and are inefficiently detected by the PCR assay. PMID:12397172

  6. Computational prediction of proarrhythmogenic effect of the V241F KCNQ1 mutation in human atrium.

    Science.gov (United States)

    Imaniastuti, Riski; Lee, Hyun Seung; Kim, Nari; Youm, Jae Boum; Shim, Eun Bo; Lim, Ki Moo

    2014-09-01

    Genetic factors play an important role in the pathogenesis of atrial flutter (AF). Although mutation in KCNQ1 has been widely correlated with AF, the mechanism by which mutation promotes AF remains poorly understood. The purpose of this study was to investigate the proarrhythmic effect of V241F KCNQ1 mutation in human atrium using the electrophysiological model of human atrium. Using 2D and 3D cardiac electrophysiological models that incorporate the Courtemanche human atrial model, we simulated electrical conduction through atrial tissue and compared spiral wave dynamics under the wild-type and V241F KCNQ1 conditions. In 2D and 3D simulation, V241F KCNQ1 showed a stable and persistent wave without spiral break-up, whereas the wild-type wave was less stable, resulting in early self-termination. According to the results, we concluded that compared to the wild type, the electrical activity of the V241F KCNQ1 mutation is more likely to sustain spiral wave. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Segregation pattern and biochemical effect of the G3460A mtDNA mutation in 27 members of LHON family.

    Science.gov (United States)

    Kaplanová, Vilma; Zeman, Jirí; Hansíková, Hana; Cerná, Leona; Houst'ková, Hana; Misovicová, Nadezda; Houstek, Josef

    2004-08-30

    Inheritance and expression of mitochondrial DNA (mtDNA) mutations are crucial for the pathogenesis of Leber hereditary optic neuropathy (LHON). We have investigated the segregation and functional consequences of G3460A mtDNA mutation in 27 members of a three-generation family with LHON syndrome. Specific activity of respiratory chain complex I in platelets was reduced in average to 56%, but no direct correlation between the mutation load and its biochemical expression was found. Heteroplasmy in blood, platelets and hair follicles varied from 7% to 100%. Segregation pattern exhibited tissue specificity and influence of different nuclear backgrounds in four branches of the pedigree. Longitudinal analysis revealed a significant (p=0.02) decrease in blood mutation load. Although enzyme assay showed reduction of complex I activity, our results give additional support to the hypothesis that expression of LHON mutation depends on complex nuclear-mitochondrial interaction.

  8. Combined Effect of the Cfr Methyltransferase and Ribosomal Protein L3 Mutations on Resistance to Ribosome-Targeting Antibiotics

    DEFF Research Database (Denmark)

    Pakula, Kevin K; Hansen, Lykke H; Vester, Birte

    2017-01-01

    . The presence of Cfr has a very minor influence on the growth rate. The resistance of the transformants to linezolid, tiamulin, florfenicol, and Synercid (a combination of quinupristin and dalfopristin [Q-D]) was measured by MIC assays. The resistance from Cfr was, in all cases, stronger than the effects...... of the L3 mutations, but various effects were obtained with the combinations of Cfr and L3 mutations ranging from a synergistic to an antagonistic effect. Linezolid and tiamulin susceptibility varied greatly among the L3 mutations, while no significant effects on florfenicol and Q-D susceptibility were...

  9. Pathogenic mutation of spastin has gain-of-function effects on microtubule dynamics.

    Science.gov (United States)

    Solowska, Joanna M; D'Rozario, Mitchell; Jean, Daphney C; Davidson, Michael W; Marenda, Daniel R; Baas, Peter W

    2014-01-29

    Mutations to the SPG4 gene encoding the microtubule-severing protein spastin are the most common cause of hereditary spastic paraplegia. Haploinsufficiency, the prevalent model for the disease, cannot readily explain many of its key aspects, such as its adult onset or its specificity for the corticospinal tracts. Treatment strategies based solely on haploinsufficiency are therefore likely to fail. Toward developing effective therapies, here we investigated potential gain-of-function effects of mutant spastins. The full-length human spastin isoform called M1 or a slightly shorter isoform called M87, both carrying the same pathogenic mutation C448Y, were expressed in three model systems: primary rat cortical neurons, fibroblasts, and transgenic Drosophila. Although both isoforms had ill effects on motor function in transgenic flies and decreased neurite outgrowth from primary cortical neurons, mutant M1 was notably more toxic than mutant M87. The observed phenotypes did not result from dominant-negative effects of mutated spastins. Studies in cultured cells revealed that microtubules can be heavily decorated by mutant M1 but not mutant M87. Microtubule-bound mutant M1 decreased microtubule dynamics, whereas unbound M1 or M87 mutant spastins increased microtubule dynamics. The alterations in microtubule dynamics observed in the presence of mutated spastins are not consistent with haploinsufficiency and are better explained by a gain-of-function mechanism. Our results fortify a model wherein toxicity of mutant spastin proteins, especially mutant M1, contributes to axonal degeneration in the corticospinal tracts. Furthermore, our results provide details on the mechanism of the toxicity that may chart a course toward more effective treatment regimens.

  10. Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease.

    Science.gov (United States)

    Goriely, Anne; Wilkie, Andrew O M

    2012-02-10

    Advanced paternal age has been associated with an increased risk for spontaneous congenital disorders and common complex diseases (such as some cancers, schizophrenia, and autism), but the mechanisms that mediate this effect have been poorly understood. A small group of disorders, including Apert syndrome (caused by FGFR2 mutations), achondroplasia, and thanatophoric dysplasia (FGFR3), and Costello syndrome (HRAS), which we collectively term "paternal age effect" (PAE) disorders, provides a good model to study the biological and molecular basis of this phenomenon. Recent evidence from direct quantification of PAE mutations in sperm and testes suggests that the common factor in the paternal age effect lies in the dysregulation of spermatogonial cell behavior, an effect mediated molecularly through the growth factor receptor-RAS signal transduction pathway. The data show that PAE mutations, although arising rarely, are positively selected and expand clonally in normal testes through a process akin to oncogenesis. This clonal expansion, which is likely to take place in the testes of all men, leads to the relative enrichment of mutant sperm over time-explaining the observed paternal age effect associated with these disorders-and in rare cases to the formation of testicular tumors. As regulation of RAS and other mediators of cellular proliferation and survival is important in many different biological contexts, for example during tumorigenesis, organ homeostasis and neurogenesis, the consequences of selfish mutations that hijack this process within the testis are likely to extend far beyond congenital skeletal disorders to include complex diseases, such as neurocognitive disorders and cancer predisposition. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  11. Peer support and additional information in group medical consultations (GMCs) for BRCA1/2 mutation carriers: A randomized controlled trial

    NARCIS (Netherlands)

    Visser, Annemiek; van Laarhoven, Hanneke W. M.; Woldringh, Gwendolyn H.; Hoogerbrugge, Nicoline; Prins, Judith B.

    2016-01-01

    Group medical consultations (GMCs) provide individual medical visits in the presence of ≤ 7 peer- patients. This study evaluated the efficacy of GMCs in the yearly breast cancer surveillance of BRCA mutation carriers. This randomized controlled trial compared GMCs (intervention group, n = 63) with

  12. Effects of Interference Between Selected Loci on the Mutation Load, Inbreeding Depression, and Heterosis.

    Science.gov (United States)

    Roze, Denis

    2015-10-01

    A classical prediction from single-locus models is that inbreeding increases the efficiency of selection against partially recessive deleterious alleles (purging), thereby decreasing the mutation load and level of inbreeding depression. However, previous multilocus simulation studies found that increasing the rate of self-fertilization of individuals may not lead to purging and argued that selective interference among loci causes this effect. In this article, I derive simple analytical approximations for the mutation load and inbreeding depression, taking into account the effects of interference between pairs of loci. I consider two classical scenarios of nonrandomly mating populations: a single population undergoing partial selfing and a subdivided population with limited dispersal. In the first case, correlations in homozygosity between loci tend to reduce mean fitness and increase inbreeding depression. These effects are stronger when deleterious alleles are more recessive, but only weakly depend on the strength of selection against deleterious alleles and on recombination rates. In subdivided populations, interference increases inbreeding depression within demes, but decreases heterosis between demes. Comparisons with multilocus, individual-based simulations show that these analytical approximations are accurate as long as the effects of interference stay moderate, but fail for high deleterious mutation rates and low dominance coefficients of deleterious alleles. Copyright © 2015 by the Genetics Society of America.

  13. Additive genetic, non-additive genetic and permanent environmental effects for female reproductive performance in seasonal calving dairy females

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    Kelleher M.M.

    2016-06-01

    Full Text Available Excellent reproductive performance (i.e. 365-day calving interval is paramount to herd profit in seasonal-calving dairy systems. Reproductive targets are currently not being achieved in Irish dairy herds. Furthermore, most research on the genetics of reproductive performance in dairy cattle has focused primarily on lactating cows and relatively few studies have attempted to quantify the genetic contribution to differences in reproductive performance in nulliparae. The objective of the present study was to estimate the contribution of both the additive and non-additive genetic components, as well as the permanent environmental component, to phenotypic variation in the reproductive traits in nulliparous, primiparous and multiparous seasonal-calving dairy females. Reproductive phenotypes were available on up to 202,525 dairy females. Variance components were estimated using (repeatability where appropriate linear animal mixed models; fixed effects included in the mixed models were contemporary group, parity (where appropriate, breed proportion, inter-breed specific heterosis coefficients and inter-breed specific recombination loss coefficients. Heritability of the reproductive traits ranged from 0.004 (pregnancy rate to first service to 0.17 (age at first service in nulliparae, while repeatability estimates for the reproductive traits in cows ranged from 0.01 (calving interval to 0.11 (pregnant in the first 42 days of the breeding season. Breed-specific heterosis regression coefficients suggest that, relative to the parental mean, a first-cross Holstein–Jersey crossbred was almost 7 days younger at first calving, had a 9-day shorter calving interval, a 6 percentage unit greater pregnancy rate in the first 42 days of the breeding season and a 3 percentage unit greater survival rate to next lactation. Heifer calving rate traits were strongly genetically correlated with age at first calving (–0.97 to –0.66 and calving rate in the first 42 days

  14. Functional effects of the TMEM43 Ser358Leu mutation in the pathogenesis of arrhythmogenic right ventricular cardiomyopathy

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    Rajkumar Revathi

    2012-03-01

    Full Text Available Abstract Background The Ser358Leu mutation in TMEM43, encoding an inner nuclear membrane protein, has been implicated in arrhythmogenic right ventricular cardiomyopathy (ARVC. The pathogenetic mechanisms of this mutation are poorly understood. Methods To determine the frequency of TMEM43 mutations as a cause of ARVC, we screened 11 ARVC families for mutations in TMEM43 and five desmosomal genes previously implicated in the disease. Functional studies were performed in COS-7 cells transfected with wildtype, mutant, and 1:2 wildtype:mutant TMEM43 to determine the effect of the Ser358Leu mutation on the stability and cellular localization of TMEM43 and other nuclear envelope and desmosomal proteins, assessed by solubility assays and immunofluorescence imaging. mRNA expression was assessed of genes potentially affected by dysfunction of the nuclear lamina. Results Three novel mutations in previously documented desmosomal genes, but no mutations in TMEM43, were identified. COS-7 cells transfected with mutant TMEM43 exhibited no change in desmosomal stability. Stability and nuclear membrane localization of mutant TMEM43 and of lamin B and emerin were normal. Mutant TMEM43 did not alter the expression of genes located on chromosome 13, previously implicated in nuclear envelope protein mutations leading to skeletal muscular dystrophies. Conclusions Mutant TMEM43 exhibits normal cellular localization and does not disrupt integrity and localization of other nuclear envelope and desmosomal proteins. The pathogenetic role of TMEM43 mutations in ARVC remains uncertain.

  15. Mapping the Effect of Gly Mutations in Collagen on α2β1 Integrin Binding.

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    Yigit, Sezin; Yu, Hongtao; An, Bo; Hamaia, Samir; Farndale, Richard W; Kaplan, David L; Lin, Yu-Shan; Brodsky, Barbara

    2016-09-02

    The replacement of one Gly in the essential repeating tripeptide sequence of the type I collagen triple helix results in the dominant hereditary bone disorder osteogenesis imperfecta. The mechanism leading to pathology likely involves misfolding and autophagy, although it has been hypothesized that some mutations interfere with known collagen interactions. Here, the effect of Gly replacements within and nearby the integrin binding GFPGER sequence was investigated using a recombinant bacterial collagen system. When a six-triplet human type I collagen sequence containing GFPGER was introduced into a bacterial collagen-like protein, this chimeric protein bound to integrin. Constructs with Gly to Ser substitutions within and nearby the inserted human sequence still formed a trypsin-resistant triple helix, suggesting a small local conformational perturbation. Gly to Ser mutations within the two Gly residues in the essential GFPGER sequence prevented integrin binding and cell attachment as predicted from molecular dynamics studies of the complex. Replacement of Gly residues C-terminal to GFPGER did not affect integrin binding. In contrast, Gly replacements N-terminal to the GFPGER sequence, up to four triplets away, decreased integrin binding and cell adhesion. This pattern suggests either an involvement of the triplets N-terminal to GFPGER in initial binding or a propagation of the perturbation of the triple helix C-terminal to a mutation site. The asymmetry in biological consequences relative to the mutation site may relate to the observed pattern of osteogenesis imperfecta mutations near the integrin binding site. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Differential effects of radical scavengers on X-ray-induced mutation and cytotoxicity in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Corn, B.W.; Liber, H.L.; Little, J.B.

    1987-01-01

    The cytotoxic and mutagenic effects of X irradiation on a human lymphoblast cell line were examined in the presence of two radioprotective agents which modulate damage to DNA. The cells were treated with X rays alone or in the presence of either dimethyl sulfoxide or cysteamine. Surviving fraction and mutation to trifluorothymidine resistance (tk locus) and to 6-thioguanine resistance (hgprt locus) were measured. Survival was enhanced when the cells were irradiated in the presence of dimethyl sulfoxide; the D0 rose from 58 to 107 rad. However, at both genetic loci the induced mutant fractions were identical in the presence or absence of dimethyl sulfoxide. Survival was enhanced to a greater degree when the cells were irradiated in the presence of cysteamine; the D0 rose from 58 to 200 rad. Cysteamine also protected the cells from X-ray-induced mutation; the frequencies of X-ray-induced mutation at both the tk and hgprt loci were reduced by 50-75%. No protective effects were observed unless dimethyl sulfoxide or cysteamine was present during irradiation. These findings are discussed in terms of the hypothesis that, unlike for cell killing, radiation-induced mutagenesis in human lymphoblast cells is not mediated by the actions of aqueous free radicals, but rather by the direct effects of ionizing radiation.

  17. Effects of prd circadian clock mutations on FRQ-less rhythms in Neurospora.

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    Li, Sanshu; Lakin-Thomas, Patricia

    2010-04-01

    Rhythmic conidiation (spore formation) in Neurospora crassa provides a model system for investigating the molecular mechanisms of circadian rhythmicity. A feedback loop involving the frq, wc-1, and wc-2 gene products (FRQ/ WCC) is an important component of the mechanism; however, rhythmic conidiation can still be observed when these gene products are absent. The nature of the oscillator(s) that drives this FRQ-less rhythmicity (FLO) is an important question in Neurospora circadian biology. We have looked for interactions between FRQ/WCC and FLO by assaying the effects on FRQ-less rhythms of mutations known to affect the period in the presence of FRQ. We assayed 4 prd mutations (prd-1, prd-2, prd-3, and prd-4) under 2 conditions in frq(null) strains: long-period free-running rhythms in chol-1 strains grown without choline, and heat-entrainable rhythms in choline-sufficient conditions. We found effects of all 4 mutations on both types of FRQ-less rhythms. The greatest effects were seen with prd-1 and prd-2, which abolished free-running rhythms in the chol-1; frq(10) backgrounds and significantly affected entrained peak timing under heat-entrainment conditions in frq( 10) backgrounds. The prd-3 and prd-4 mutations had more subtle effects on period and stability of free-running rhythms in the chol-1; frq(10) backgrounds and had little effect on peak timing under heat-entrainment conditions in frq(10) backgrounds. These results, along with previously published evidence for effects of prd mutations on other FRQ-less rhythms, suggest that either there are common components shared between the FRQ/WCC oscillator and several FRQ-less oscillators or that there is a single oscillator driving all conidiation rhythms. We favor a model of the Neurospora circadian system in which a single FRQ-less oscillator drives conidiation and interacts with the FRQ/WCC feedback loop; the output or amplitude of the FRQ-less oscillator can be affected by many gene products and metabolic

  18. The effect of colistin resistance-associated mutations on the fitness of Acinetobacter baumannii

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    Xinli Mu

    2016-11-01

    Full Text Available Acinetobacter baumannii had emerged as an important nosocomial and opportunistic pathogen worldwide. To determine the evolutionary pathway of colistin resistance in A. baumannii and its influence on bacterial fitness, five independent colonies of A. baumannii ATCC 17978 were exposed to colistin in agar (4/5 and liquid media (1/5 with increasing and constant concentrations. Stable resistance isolates were sent for whole genome sequencing. All strains were colistin resistant after exposure to colistin. In addition to the previously reported lpxCAD and pmrAB mutations, we detected four novel putative colistin resistance genes: A1S_1983, hepA, A1S_3026, and rsfS. Lipopolysaccharide (LPS loss mutants exhibited higher fitness costs than the pmrB mutant in nutrient-rich medium. The colistin-resistant mutants showed higher inhibition ratio in the serum growth experiment than the wild type strain in 100% serum. The MIC results showed that the LPS-deficient but not the pmrB mutant altered the antibiotic resistance profile. The compensatory mutations partially or completely recovered the LPS-deficient’s fitness, suggesting that compensatory mutations played an important role in the emergence and spread of colistin resistant A. baumannii.

  19. Computational analysis of KRAS mutations: implications for different effects on the KRAS p.G12D and p.G13D mutations.

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    Chih-Chieh Chen

    Full Text Available BACKGROUND: The issue of whether patients diagnosed with metastatic colorectal cancer who harbor KRAS codon 13 mutations could benefit from the addition of anti-epidermal growth factor receptor therapy remains under debate. The aim of the current study was to perform computational analysis to investigate the structural implications of the underlying mutations caused by c.38G>A (p.G13D on protein conformation. METHODS: Molecular dynamics (MD simulations were performed to understand the plausible structural and dynamical implications caused by c.35G>A (p.G12D and c.38G>A (p.G13D. The potential of mean force (PMF simulations were carried out to determine the free energy profiles of the binding processes of GTP interacting with wild-type (WT KRAS and its mutants (MT. RESULTS: Using MD simulations, we observed that the root mean square deviation (RMSD increased as a function of time for the MT c.35G>A (p.G12D and MT c.38G>A (p.G13D when compared with the WT. We also observed that the GTP-binding pocket in the c.35G>A (p.G12D mutant is more open than that of the WT and the c.38G>A (p.G13D proteins. Intriguingly, the analysis of atomic fluctuations and free energy profiles revealed that the mutation of c.35G>A (p.G12D may induce additional fluctuations in the sensitive sites (P-loop, switch I and II regions. Such fluctuations may promote instability in these protein regions and hamper GTP binding. CONCLUSIONS: Taken together with the results obtained from MD and PMF simulations, the present findings implicate fluctuations at the sensitive sites (P-loop, switch I and II regions. Our findings revealed that KRAS mutations in codon 13 have similar behavior as KRAS WT. To gain a better insight into why patients with metastatic colorectal cancer (mCRC and the KRAS c.38G>A (p.G13D mutation appear to benefit from anti-EGFR therapy, the role of the KRAS c.38G>A (p.G13D mutation in mCRC needs to be further investigated.

  20. Potent antiatherosclerotic effects of alogliptin in addition to its potent antidiabetic effects

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    Kapoor S

    2012-05-01

    Full Text Available Shailendra KapoorMechanicsville, Richmond, VA, USAI read with great interest the article by Andukuri et al in a recent issue of your journal.1 The article makes compelling reading. Interestingly, research over the past few years has shown that in addition to its significant diabetic-modulating effects, alogliptin also exerts significant direct antiatherosclerotic effects.View original paper by Andukuri and colleagues

  1. Separating the effects of mutation and selection in producing DNA skew in bacterial chromosomes

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    Morton Brian R

    2007-10-01

    Full Text Available Abstract Background Many bacterial chromosomes display nucleotide asymmetry, or skew, between the leading and lagging strands of replication. Mutational differences between these strands result in an overall pattern of skew that is centered about the origin of replication. Such a pattern could also arise from selection coupled with a bias for genes coded on the leading strand. The relative contributions of selection and mutation in producing compositional skew are largely unknown. Results We describe a model to quantify the contribution of mutational differences between the leading and lagging strands in producing replication-induced skew. When the origin and terminus of replication are known, the model can be used to estimate the relative accumulation of G over C and of A over T on the leading strand due to replication effects in a chromosome with bidirectional replication arms. The model may also be implemented in a maximum likelihood framework to estimate the locations of origin and terminus. We find that our estimations for the origin and terminus agree very well with the location of genes that are thought to be associated with the replication origin. This indicates that our model provides an accurate, objective method of determining the replication arms and also provides support for the hypothesis that these genes represent an ancestral cluster of origin-associated genes. Conclusion The model has several advantages over other methods of analyzing genome skew. First, it quantifies the role of mutation in generating skew so that its effect on composition, for example codon bias, can be assessed. Second, it provides an objective method for locating origin and terminus, one that is based on chromosome-wide accumulation of leading vs lagging strand nucleotide differences. Finally, the model has the potential to be utilized in a maximum likelihood framework in order to analyze the effect of chromosome rearrangements on nucleotide composition.

  2. A highly precise and portable genome engineering method allows comparison of mutational effects across bacterial species.

    Science.gov (United States)

    Nyerges, Ákos; Csörgő, Bálint; Nagy, István; Bálint, Balázs; Bihari, Péter; Lázár, Viktória; Apjok, Gábor; Umenhoffer, Kinga; Bogos, Balázs; Pósfai, György; Pál, Csaba

    2016-03-01

    Currently available tools for multiplex bacterial genome engineering are optimized for a few laboratory model strains, demand extensive prior modification of the host strain, and lead to the accumulation of numerous off-target modifications. Building on prior development of multiplex automated genome engineering (MAGE), our work addresses these problems in a single framework. Using a dominant-negative mutant protein of the methyl-directed mismatch repair (MMR) system, we achieved a transient suppression of DNA repair in Escherichia coli, which is necessary for efficient oligonucleotide integration. By integrating all necessary components into a broad-host vector, we developed a new workflow we term pORTMAGE. It allows efficient modification of multiple loci, without any observable off-target mutagenesis and prior modification of the host genome. Because of the conserved nature of the bacterial MMR system, pORTMAGE simultaneously allows genome editing and mutant library generation in other biotechnologically and clinically relevant bacterial species. Finally, we applied pORTMAGE to study a set of antibiotic resistance-conferring mutations in Salmonella enterica and E. coli. Despite over 100 million y of divergence between the two species, mutational effects remained generally conserved. In sum, a single transformation of a pORTMAGE plasmid allows bacterial species of interest to become an efficient host for genome engineering. These advances pave the way toward biotechnological and therapeutic applications. Finally, pORTMAGE allows systematic comparison of mutational effects and epistasis across a wide range of bacterial species.

  3. Non-local effects of point mutations on the stability of a protein module

    Science.gov (United States)

    Chwastyk, Mateusz; Vera, Andrés M.; Galera-Prat, Albert; Gunnoo, Melissabye; Thompson, Damien; Carrión-Vázquez, Mariano; Cieplak, Marek

    2017-09-01

    We combine experimental and theoretical methods to assess the effect of a set of point mutations on c7A, a highly mechanostable type I cohesin module from scaffoldin CipA from Clostridium thermocellum. We propose a novel robust and computationally expedient theoretical method to determine the effects of point mutations on protein structure and stability. We use all-atom simulations to predict structural shifts with respect to the native protein and then analyze the mutants using a coarse-grained model. We examine transitions in contacts between residues and find that changes in the contact map usually involve a non-local component that can extend up to 50 Å. We have identified mutations that may lead to a substantial increase in mechanical and thermodynamic stabilities by making systematic substitutions into alanine and phenylalanine in c7A. Experimental measurements of the mechanical stability and circular dichroism data agree qualitatively with the predictions provided the thermal stability is calculated using only the contacts within the secondary structures.

  4. Effect of tumor promoters on ultraviolet light-induced mutation and mitotic recombination in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kunz, B A; Hannan, M A; Haynes, R H

    1980-07-01

    Recently, it has been suggested that mitotic recombination is involved in tumor promotion. On this basis, one might expect tumor promoters to be recombinagenic. D7 is a diploid strain of yeast in which both mutation and mitotic recombination can be measured. We have used this strain to assay the known tumor promoters, iodoacetate, anthralin, and 12-O-tetradecanoylphorbol-13-acetate, and the cocarcinogen, catechol, for mutagenicity, recombinagenicity, and the ability to enhance ultraviolet light (UV)-induced genetic events. In the absence of preirradiation with UV, iodoacetate was found to be recombinagenic whereas catechol was mutagenic; however, in both cases, the effects were small. Iodoacetate, anthralin, and catechol potentiated UV-induced mitotic crossing-over, aberrant colony formation, and mutation, while catechol also increased UV-induced gene conversion. We were unable to detect any mutagenic or recombinagenic effect of 12-O-tetradecanoyl-phorbol-13-acetate in either whole cells or spheroplasts. Our results do not indicate any consistent correlation between tumor-promoting activity and the ability of an agent to induce mitotic recombination in yeast. However, the ability to potentiate UV-induced mutation and mitotic recombination may reflect the cocarcinogenic activity of certain promoters.

  5. Cost-effectiveness of MRI for breast cancer screening in BRCA1/2 mutation carriers.

    Science.gov (United States)

    Pataky, Reka; Armstrong, Linlea; Chia, Stephen; Coldman, Andrew J; Kim-Sing, Charmaine; McGillivray, Barbara; Scott, Jenna; Wilson, Christine M; Peacock, Stuart

    2013-07-10

    Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting. We constructed a Markov model of annual MRI and mammography screening for BRCA1/2 carriers, using local data and published values. We calculated cost-effectiveness as cost per quality-adjusted life-year gained (QALY), and conducted one-way and probabilistic sensitivity analysis. The incremental cost-effectiveness ratio (ICER) of annual mammography plus MRI screening, compared to annual mammography alone, was $50,900/QALY. After incorporating parameter uncertainty, MRI screening is expected to be a cost-effective option 86% of the time at a willingness-to-pay of $100,000/QALY, and 53% of the time at a willingness-to-pay of $50,000/QALY. The model is highly sensitive to the cost of MRI; as the cost is increased from $200 to $700 per scan, the ICER ranges from $37,100/QALY to $133,000/QALY. The cost-effectiveness of using MRI and mammography in combination to screen for breast cancer in BRCA1/2 mutation carriers is finely balanced. The sensitivity of the results to the cost of the MRI screen itself warrants consideration: in jurisdictions with higher MRI costs, screening may not be a cost-effective use of resources, but improving the efficiency of MRI screening will also improve cost-effectiveness.

  6. Founder effect of the BRCA1 5382insC mutation in Brazilian patients with hereditary breast ovary cancer syndrome.

    Science.gov (United States)

    da Costa, E C B; Vargas, F R; Moreira, A S; Lourenço, J J; Caleffi, M; Ashton-Prolla, P; Martins Moreira, M A M

    2008-07-01

    The 5382insC mutation in BRCA1 is a frequently reported mutation, being very prevalent in Central and Eastern Europe. This mutation was recurrently reported in Brazil and one case was reported Portugal, but not in Spain and other South-American countries,. We analyzed the haplotypic profile of seven Brazilian carriers of 5382insC to characterize a possible founder effect. The analyses indicated that mutation carriers shared an identical haplotype. The absence of this mutation in Spain, other South American countries, and sub-Saharan populations, as well as the patients' own ancestry, point to a significant Central or Eastern European contribution to the present genetic background of Brazilian population, different from the population structuring of remaining South American countries.

  7. Effects of missense mutations in sortase A gene on enzyme activity in Streptococcus mutans.

    Science.gov (United States)

    Zhuang, P L; Yu, L X; Tao, Y; Zhou, Y; Zhi, Q H; Lin, H C

    2016-04-11

    Streptococcus mutans (S. mutans) is the major aetiological agent of dental caries, and the transpeptidase Sortase A (SrtA) plays a major role in cariogenicity. The T168G and G470A missense mutations in the srtA gene may be linked to caries susceptibility, as demonstrated in our previous studies. This study aimed to investigate the effects of these missense mutations of the srtA gene on SrtA enzyme activity in S. mutans. The point mutated recombinant S.mutans T168G and G470A sortases were expressed in expression plasmid pET32a. S. mutans UA159 sortase coding gene srtA was used as the template for point mutation. Enzymatic activity was assessed by quantifying increases in the fluorescence intensity generated when a substrate Dabcyl-QALPNTGEE-Edans was cleaved by SrtA. The kinetic constants were calculated based on the curve fit for the Michaelis-Menten equation. SrtA△N40(UA159) and the mutant enzymes, SrtA△N40(D56E) and SrtA△N40(R157H), were expressed and purified. A kinetic analysis showed that the affinity of SrtA△N40(D56E) and SrtA△N40(R157H) remained approximately equal to the affinity of SrtA△N40(UA159), as determined by the Michaelis constant (K m ). However, the catalytic rate constant (k cat ) and catalytic efficiency (k cat /K m ) of SrtA△N40(D56E) were reduced compared with those of SrtA△N40(R157H) and SrtA△N40(UA159), whereas the k cat and k cat /K m values of SrtA△N40(R157H) were slightly lower than those of SrtA△N40(UA159). The findings of this study indicate that the T168G missense mutation of the srtA gene results in a significant reduction in enzymatic activity compared with S. mutans UA159, suggesting that the T168G missense mutation of the srtA gene may be related to low cariogenicity.

  8. Microsatellite instability and B-type Raf proto-oncogene mutation in colorectal cancer: Clinicopathological characteristics and effects on survival

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    Sebnem Batur

    2016-11-01

    Full Text Available Prognostic significance of microsatellite instability (MSI status and B-type Raf proto-oncogene (BRAF mutation in colorectal cancer is controversial. The aim of this study was to examine the clinical and pathological characteristics associated with microsatellite stability and the effect of MSI and BRAF mutation on the survival of patients with colorectal cancer. The study included 145 colorectal cancer cases. All the patients were examined for DNA mismatch repair (MMR proteins with an immunohistochemical method. Molecular assessment of MSI was available in a subset of 41 patients. In addition, BRAF mutation analysis was performed in 30 cases. Immunohistochemically, MMR deficiency was present in 28 (19.3% patients. Female gender (p = 0.001, lesion size ≥5 cm (p = 0.013, Crohn-like response (p = 0.035, and right-sided localization (p < 0.001 were significantly more frequent among MMR-deficient patients. The overall survival was 44.1 ± 5.1 months (95% confidence interval [CI], 33.7-54.4. Multivariate analyses identified only high tumor grade as an independent predictor of poor overall survival: odd ratio, 6.7 (95% CI 2.1-21.7, p = 0.002. In the subset of patients with available BRAF assessment (n = 30, a negative BRAF status was associated with better survival when compared to a positive BRAF status (36.7 ± 2.1 vs. 34.1 ± 7.2 months, p = 0.048. The sensitivity and specificity of the immunohistochemical method in predicting positive MSI status, with the molecular method as a reference, were 85.7% (95% CI: 56.2%-97.5% and 88.9% (95% CI: 69.7%-97.1%, respectively. BRAF appears to be a significant predictor of a worse outcome in patients with colorectal cancer. Further studies with a large spectrum of clinical and biological variables are warranted.

  9. Non-additive and Additive Genetic Effects on Extraversion in 3314 Dutch Adolescent Twins and Their Parents.

    NARCIS (Netherlands)

    Rettew, D.C.; Rebollo Mesa, I.; Hudziak, J.; Willemsen, G.; Boomsma, D.I.

    2008-01-01

    The influence of non-additive genetic influences on personality traits has been increasingly reported in adult populations. Less is known, however, with respect to younger samples. In this study, we examine additive and non-additive genetic contributions to the personality trait of extraversion in

  10. Effects of track structure and cell inactivation on the calculation of heavy ion mutation rates in mammalian cells

    Science.gov (United States)

    Cucinotta, F. A.; Wilson, J. W.; Shavers, M. R.; Katz, R.

    1996-01-01

    It has long been suggested that inactivation severely effects the probability of mutation by heavy ions in mammalian cells. Heavy ions have observed cross sections of inactivation that approach and sometimes exceed the geometric size of the cell nucleus in mammalian cells. In the track structure model of Katz the inactivation cross section is found by summing an inactivation probability over all impact parameters from the ion to the sensitive sites within the cell nucleus. The inactivation probability is evaluated using the dose-response of the system to gamma-rays and the radial dose of the ions and may be equal to unity at small impact parameters for some ions. We show how the effects of inactivation may be taken into account in the evaluation of the mutation cross sections from heavy ions in the track structure model through correlation of sites for gene mutation and cell inactivation. The model is fit to available data for HPRT mutations in Chinese hamster cells and good agreement is found. The resulting calculations qualitatively show that mutation cross sections for heavy ions display minima at velocities where inactivation cross sections display maxima. Also, calculations show the high probability of mutation by relativistic heavy ions due to the radial extension of ions track from delta-rays in agreement with the microlesion concept. The effects of inactivation on mutations rates make it very unlikely that a single parameter such as LET or Z*2/beta(2) can be used to specify radiation quality for heavy ion bombardment.

  11. Theoretical prediction of familial amyotrophic lateral sclerosis missense mutation effects on Cu/Zn superoxide dismutase structural stability

    Energy Technology Data Exchange (ETDEWEB)

    Potier, M.; Tu, Y. [Universite de Montreal, Quebec (Canada)

    1994-09-01

    Cu/Zn superoxide dismutase (SOD) deficiency is associated with the progressive paralytic disorder familial amyotrophic lateral sclerosis (FALS). Fifteen missense mutations in the SOD gene were identified in several patients. These mutations may prevent correct promoter folding or hamper homodimer formation necessary for SOD activity. To understand the effect of the missense mutations on SOD structure and function, we used a theoretical analysis of structural effects based on two predictive methods using the modeled tertiary structure of human SOD. The first method uses the TORSO program which optimizes amino acid side-chains repacking in both wild-type and mutant SODs and calculates protein internal packing energy. The second method uses a hydrophobicity scale of the amino acid residues and considers both solvent accessibility and hydrophobic nature of residue substitutions to compute a stabilization energy change ({delta}E). These predictive methods have been tested in 187 single and multiple missense mutants of 8 proteins (T4 lysozyme, human carbonic anhydrase II, chymotrypsin inhibitor 2, f1 gene V protein, barnase, {lambda}-repressor, chicken and human lysozymes) with experimentally determined thermostability. The overall prediction accuracy with these proteins was 88%. Analysis of FALS missense mutations {delta}E predicts that 14 of 15 mutations destabilize the SOD structure. The other missense mutation is located at the homodimer interface and may hinder dimer formation. This approach is applicable to any protein with known tertiary structure to predict missense mutation effects on protein stability.

  12. Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers

    NARCIS (Netherlands)

    Vos, Janet R.; Oosterwijk, Jan C.; Aalfs, Cora M.; Rookus, Matti A.; Adank, Muriel A.; van der Hout, Annemarie H.; van Asperen, Christi J.; Gómez Garcia, Encarna B.; Mensenkamp, Arjen R.; Jager, Agnes; Ausems, Margreet G. E. M.; Mourits, Marian J.; de Bock, Geertruida H.

    2016-01-01

    Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the BRCA1/2 mutation

  13. Effects of additional oxazepam in long-term users of oxazepam.

    NARCIS (Netherlands)

    Oude Voshaar, R.C.; Verkes, R.J.; Luijtelaar, E.L.J.M. van; Edelbroek, P.M.; Zitman, F.G.

    2005-01-01

    Although additional dosages of benzodiazepines in long-term users of benzodiazepines are common, it is unknown whether these additional dosages resort any effect. The effects of an additional 20-mg dosage oxazepam were assessed in a double-blind, balanced-order, crossover randomized study comparing

  14. Effect of point mutations on Herbaspirillum seropedicae NifA activity

    Directory of Open Access Journals (Sweden)

    B. Aquino

    2015-08-01

    Full Text Available NifA is the transcriptional activator of the nif genes in Proteobacteria. It is usually regulated by nitrogen and oxygen, allowing biological nitrogen fixation to occur under appropriate conditions. NifA proteins have a typical three-domain structure, including a regulatory N-terminal GAF domain, which is involved in control by fixed nitrogen and not strictly required for activity, a catalytic AAA+ central domain, which catalyzes open complex formation, and a C-terminal domain involved in DNA-binding. In Herbaspirillum seropedicae, a β-proteobacterium capable of colonizing Graminae of agricultural importance, NifA regulation by ammonium involves its N-terminal GAF domain and the signal transduction protein GlnK. When the GAF domain is removed, the protein can still activate nif genes transcription; however, ammonium regulation is lost. In this work, we generated eight constructs resulting in point mutations in H. seropedicae NifA and analyzed their effect on nifH transcription in Escherichia coli and H. seropedicae. Mutations K22V, T160E, M161V, L172R, and A215D resulted in inactive proteins. Mutations Q216I and S220I produced partially active proteins with activity control similar to wild-type NifA. However, mutation G25E, located in the GAF domain, resulted in an active protein that did not require GlnK for activity and was partially sensitive to ammonium. This suggested that G25E may affect the negative interaction between the N-terminal GAF domain and the catalytic central domain under high ammonium concentrations, thus rendering the protein constitutively active, or that G25E could lead to a conformational change comparable with that when GlnK interacts with the GAF domain.

  15. Stereochemical criteria for prediction of the effects of proline mutations on protein stability.

    Directory of Open Access Journals (Sweden)

    Kanika Bajaj

    2007-12-01

    Full Text Available When incorporated into a polypeptide chain, proline (Pro differs from all other naturally occurring amino acid residues in two important respects. The phi dihedral angle of Pro is constrained to values close to -65 degrees and Pro lacks an amide hydrogen. Consequently, mutations which result in introduction of Pro can significantly affect protein stability. In the present work, we describe a procedure to accurately predict the effect of Pro introduction on protein thermodynamic stability. Seventy-seven of the 97 non-Pro amino acid residues in the model protein, CcdB, were individually mutated to Pro, and the in vivo activity of each mutant was characterized. A decision tree to classify the mutation as perturbing or nonperturbing was created by correlating stereochemical properties of mutants to activity data. The stereochemical properties including main chain dihedral angle phi and main chain amide H-bonds (hydrogen bonds were determined from 3D models of the mutant proteins built using MODELLER. We assessed the performance of the decision tree on a large dataset of 163 single-site Pro mutations of T4 lysozyme, 74 nsSNPs, and 52 other Pro substitutions from the literature. The overall accuracy of this algorithm was found to be 81% in the case of CcdB, 77% in the case of lysozyme, 76% in the case of nsSNPs, and 71% in the case of other Pro substitution data. The accuracy of Pro scanning mutagenesis for secondary structure assignment was also assessed and found to be at best 69%. Our prediction procedure will be useful in annotating uncharacterized nsSNPs of disease-associated proteins and for protein engineering and design.

  16. Effect of point mutations on Herbaspirillum seropedicae NifA activity

    Energy Technology Data Exchange (ETDEWEB)

    Aquino, B.; Stefanello, A.A.; Oliveira, M.A.S.; Pedrosa, F.O.; Souza, E.M.; Monteiro, R.A.; Chubatsu, L.S. [Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, PR (Brazil)

    2015-07-10

    NifA is the transcriptional activator of the nif genes in Proteobacteria. It is usually regulated by nitrogen and oxygen, allowing biological nitrogen fixation to occur under appropriate conditions. NifA proteins have a typical three-domain structure, including a regulatory N-terminal GAF domain, which is involved in control by fixed nitrogen and not strictly required for activity, a catalytic AAA+ central domain, which catalyzes open complex formation, and a C-terminal domain involved in DNA-binding. In Herbaspirillum seropedicae, a β-proteobacterium capable of colonizing Graminae of agricultural importance, NifA regulation by ammonium involves its N-terminal GAF domain and the signal transduction protein GlnK. When the GAF domain is removed, the protein can still activate nif genes transcription; however, ammonium regulation is lost. In this work, we generated eight constructs resulting in point mutations in H. seropedicae NifA and analyzed their effect on nifH transcription in Escherichia coli and H. seropedicae. Mutations K22V, T160E, M161V, L172R, and A215D resulted in inactive proteins. Mutations Q216I and S220I produced partially active proteins with activity control similar to wild-type NifA. However, mutation G25E, located in the GAF domain, resulted in an active protein that did not require GlnK for activity and was partially sensitive to ammonium. This suggested that G25E may affect the negative interaction between the N-terminal GAF domain and the catalytic central domain under high ammonium concentrations, thus rendering the protein constitutively active, or that G25E could lead to a conformational change comparable with that when GlnK interacts with the GAF domain.

  17. Cost-Effectiveness of an Individualized First-Line Treatment Strategy Offering Erlotinib Based on EGFR Mutation Testing in Advanced Lung Adenocarcinoma Patients in Germany.

    Science.gov (United States)

    Schremser, Katharina; Rogowski, Wolf H; Adler-Reichel, Sigrid; Tufman, Amanda L H; Huber, Rudolf M; Stollenwerk, Björn

    2015-11-01

    Lung cancer is among the top causes of cancer-related deaths. Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors can increase progression-free survival compared with standard chemotherapy in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). The aim of the study was to evaluate the cost-effectiveness of EGFR mutation analysis and first-line therapy with erlotinib for mutation-positive patients compared with non-individualized standard chemotherapy from the perspective of German statutory health insurance. A state transition model was developed for a time horizon of 10 years (reference year 2014). Data sources were published data from the European Tarceva versus Chemotherapy (EURTAC) randomized trial for drug efficacy and safety and German cost data. We additionally performed deterministic, probabilistic and structural sensitivity analyses. The individualized strategy incurred 0.013 additional quality-adjusted life-years (QALYs) and additional costs of € 200, yielding an incremental cost-effectiveness ratio (ICER) of € 15,577/QALY. Results were most sensitive to uncertainty in survival curves and changes in utility values. Cross-validating health utility estimates with recent German data increased the ICER to about € 58,000/QALY. The probabilistic sensitivity analysis indicated that the individualized strategy is cost-effective, with a probability exceeding 50 % for a range of possible willingness-to-pay thresholds. The uncertainty of the predicted survival curves is substantial, particularly for overall survival, which was not a primary endpoint in the EURTAC study. Also, there is limited data on quality of life in metastatic lung cancer patients. Individualized therapy based on EGFR mutation status has the potential to provide a cost-effective alternative to non-individualized care for patients with advanced adenocarcinoma. Further clinical research is needed to confirm these results.

  18. Germline and somatic mosaicism for FGFR2 mutation in the mother of a child with Crouzon syndrome: Implications for genetic testing in ?paternal age-effect? syndromes

    OpenAIRE

    Goriely, Anne; Lord, Helen; Lim, Jasmine; Johnson, David; Lester, Tracy; Firth, Helen V.; Wilkie, Andrew OM

    2010-01-01

    Crouzon syndrome is a dominantly inherited disorder characterized by craniosynostosis and facial dysostosis, caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene; it belongs to a class of disorders that mostly arise as de novo mutations and exhibit a near-exclusive paternal origin of mutation and elevated paternal age (?paternal age effect?). However, even if this is the major mode of origin of mutations in paternal age-effect disorders, germline mosaicism may also occu...

  19. Effects of partial hepatectomy on induction of mutation frequency by gamma-rays in new HITEC mice

    Energy Technology Data Exchange (ETDEWEB)

    Ootsuyam, A.; Kato, F.; Norimura, T. [Univ. of Occupational and Environmental Health, Kitakyushu, (Japan)

    2002-07-01

    Mutations induced in vivo by radiation were studied with a transgenic mouse strain, called New HITEC (Hypersensitive In vitro Test of Carcinogenecity), carrying the rpsL gene as a reporter for mutation detection. The wild-type rpsL gene and a gene inducing a kanamycin-resistant phenotype were placed on a pSSW plasmid shuttle vector, and were transfected into E. coli by electroporation after extraction from mouse genomic DNA. Transfected cells were plated on LB plates containing Kanamycine (Km) or Km plus Streptomycine (Sm). The ratio of the colony number on Km and Sm plates to that on Km plates is defined as the rpsL mutation frequency. We had previously investigated differences in mutation frequencies in the testis, spleen, liver, brain, and thymus using rpsL transgenic mice. However, there were some problems in the analysis with a high background mutation frequency. To solve this problem, a partial hepatectomy was tried to increase the mutation frequency detection. The mice were exposed to 3 Gy of gamma rays at 24, 40, 48, or 72 hours after the hepatectomy. Then, the liver was resected on day 7-10 after irradiation, and the mutation frequencies were analyzed. In the mice exposed 24 hours after hepatectomy, the mutation frequency increased approximately four times compared with that of the control mice. In the mice exposed 40, 48, or 72 hours after hepatectomy, the increase in mutation frequency was 2-3 times greater than that of the control mice. These results indicate that hepatectomy is effective in raising the mutation frequency along with the appropriate timing of irradiation.

  20. Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice.

    Science.gov (United States)

    Frýdlová, Jana; Rychtarčíková, Zuzana; Gurieva, Iuliia; Vokurka, Martin; Truksa, Jaroslav; Krijt, Jan

    2017-01-01

    Tmprss6-mutated mask mice display iron deficiency anemia and high expression of hepcidin. The aim of the study was to determine the effect of erythropoietin administration on proteins participating in the control of iron homeostasis in the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6 mice, no such increase was seen in mask mice. Erythropoietin administration decreased hepcidin expression in C57BL/6 mice, but not in mask mice. Erythropoietin treatment significantly increased the spleen size in both C57BL/6 and mask mice. Furthermore, erythropoietin administration increased splenic Fam132b, Fam132a and Tfr2 mRNA content. At the protein level, erythropoietin increased the amount of splenic erythroferrone and transferrin receptor 2 both in C57BL/6 and mask mice. Splenic ferroportin content was decreased in erythropoietin-treated mask mice in comparison with erythropoietin-treated C57BL/6 mice. In mask mice, the amount of liver hemojuvelin was decreased in comparison with C57BL/6 mice. The pattern of hemojuvelin cleavage was different between C57BL/6 and mask mice: In both groups, a main hemojuvelin band was detected at approximately 52 kDa; in C57BL/6 mice, a minor cleaved band was seen at 47 kDa. In mask mice, the 47 kDa band was absent, but additional minor bands were detected at approximately 45 kDa and 48 kDa. The results provide support for the interaction between TMPRSS6 and hemojuvelin in vivo; they also suggest that hemojuvelin could be cleaved by another as yet unknown protease in the absence of functional TMPRSS6. The lack of effect of erythropoietin on hepcidin expression in mask mice can not be explained by changes in erythroferrone synthesis, as splenic erythroferrone content increased after erythropoietin administration in both C57BL/6 and mask mice.

  1. Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice.

    Directory of Open Access Journals (Sweden)

    Jana Frýdlová

    Full Text Available Tmprss6-mutated mask mice display iron deficiency anemia and high expression of hepcidin. The aim of the study was to determine the effect of erythropoietin administration on proteins participating in the control of iron homeostasis in the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6 mice, no such increase was seen in mask mice. Erythropoietin administration decreased hepcidin expression in C57BL/6 mice, but not in mask mice. Erythropoietin treatment significantly increased the spleen size in both C57BL/6 and mask mice. Furthermore, erythropoietin administration increased splenic Fam132b, Fam132a and Tfr2 mRNA content. At the protein level, erythropoietin increased the amount of splenic erythroferrone and transferrin receptor 2 both in C57BL/6 and mask mice. Splenic ferroportin content was decreased in erythropoietin-treated mask mice in comparison with erythropoietin-treated C57BL/6 mice. In mask mice, the amount of liver hemojuvelin was decreased in comparison with C57BL/6 mice. The pattern of hemojuvelin cleavage was different between C57BL/6 and mask mice: In both groups, a main hemojuvelin band was detected at approximately 52 kDa; in C57BL/6 mice, a minor cleaved band was seen at 47 kDa. In mask mice, the 47 kDa band was absent, but additional minor bands were detected at approximately 45 kDa and 48 kDa. The results provide support for the interaction between TMPRSS6 and hemojuvelin in vivo; they also suggest that hemojuvelin could be cleaved by another as yet unknown protease in the absence of functional TMPRSS6. The lack of effect of erythropoietin on hepcidin expression in mask mice can not be explained by changes in erythroferrone synthesis, as splenic erythroferrone content increased after erythropoietin administration in both C57BL/6 and mask mice.

  2. Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice

    Science.gov (United States)

    Frýdlová, Jana; Rychtarčíková, Zuzana; Gurieva, Iuliia; Vokurka, Martin; Truksa, Jaroslav

    2017-01-01

    Tmprss6-mutated mask mice display iron deficiency anemia and high expression of hepcidin. The aim of the study was to determine the effect of erythropoietin administration on proteins participating in the control of iron homeostasis in the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6 mice, no such increase was seen in mask mice. Erythropoietin administration decreased hepcidin expression in C57BL/6 mice, but not in mask mice. Erythropoietin treatment significantly increased the spleen size in both C57BL/6 and mask mice. Furthermore, erythropoietin administration increased splenic Fam132b, Fam132a and Tfr2 mRNA content. At the protein level, erythropoietin increased the amount of splenic erythroferrone and transferrin receptor 2 both in C57BL/6 and mask mice. Splenic ferroportin content was decreased in erythropoietin-treated mask mice in comparison with erythropoietin-treated C57BL/6 mice. In mask mice, the amount of liver hemojuvelin was decreased in comparison with C57BL/6 mice. The pattern of hemojuvelin cleavage was different between C57BL/6 and mask mice: In both groups, a main hemojuvelin band was detected at approximately 52 kDa; in C57BL/6 mice, a minor cleaved band was seen at 47 kDa. In mask mice, the 47 kDa band was absent, but additional minor bands were detected at approximately 45 kDa and 48 kDa. The results provide support for the interaction between TMPRSS6 and hemojuvelin in vivo; they also suggest that hemojuvelin could be cleaved by another as yet unknown protease in the absence of functional TMPRSS6. The lack of effect of erythropoietin on hepcidin expression in mask mice can not be explained by changes in erythroferrone synthesis, as splenic erythroferrone content increased after erythropoietin administration in both C57BL/6 and mask mice. PMID:29073189

  3. Profound Effects of Aggregatibacter actinomycetemcomitans Leukotoxin Mutation on Adherence Properties Are Clarified in in vitro Experiments.

    Directory of Open Access Journals (Sweden)

    Senthil Kumar Velusamy

    Full Text Available Leukotoxin (Ltx is a prominent virulence factor produced by Aggregatibacter actinomycetemcomitans, an oral microorganism highly associated with aggressive periodontitis. Ltx compromises host responsiveness by altering the viability of neutrophils, lymphocytes, and macrophages. Previously, we developed a Rhesus (Rh monkey colonization model designed to determine the effect of virulence gene mutations on colonization of A. actinomycetemcomitans. Unexpectedly, an A. actinomycetemcomitans leukotoxin (ltxA mutant (RhAa-VS2 failed to colonize in the Rh model. No previous literature suggested that Ltx was associated with A. actinomycetemcomitans binding to tooth surfaces. These results led us to explore the broad effects of the ltxA mutation in vitro. Results indicated that LtxA activity was completely abolished in RhAa-VS2 strain, while complementation significantly (P<0.0001 restored leukotoxicity compared to RhAa-VS2 strain. RT-PCR analysis of ltx gene expression ruled out polar effects. Furthermore, binding of RhAa-VS2 to salivary-coated hydroxyapatite (SHA was significantly decreased (P<0.0001 compared to wild type RhAa3 strain. Real time RT-PCR analysis of the genes related to SHA binding in RhAa-VS2 showed that genes related to binding were downregulated [rcpA (P = 0.018, rcpB (P = 0.02, tadA (P = 0.002] as compared to wild type RhAa3. RhAa-VS2 also exhibited decreased biofilm depth (P = 0.008 and exo-polysaccharide production (P<0.0001. Buccal epithelial cell (BEC binding of RhAa-VS2 was unaffected. Complementation with ltxA restored binding to SHA (P<0.002 but had no effect on biofilm formation when compared to RhAa3. In conclusion, mutation of ltxA diminished hard tissue binding in vitro, which helps explain the previous in vivo failure of a ltxA knockout to colonize the Rh oral cavity. These results suggest that; 1 one specific gene knockout (in this case ltxA could affect other seemingly unrelated genes (such as rcpA, rcpB tadA etc, and 2

  4. The Mutational Robustness of Influenza A Virus.

    Directory of Open Access Journals (Sweden)

    Elisa Visher

    2016-08-01

    Full Text Available A virus' mutational robustness is described in terms of the strength and distribution of the mutational fitness effects, or MFE. The distribution of MFE is central to many questions in evolutionary theory and is a key parameter in models of molecular evolution. Here we define the mutational fitness effects in influenza A virus by generating 128 viruses, each with a single nucleotide mutation. In contrast to mutational scanning approaches, this strategy allowed us to unambiguously assign fitness values to individual mutations. The presence of each desired mutation and the absence of additional mutations were verified by next generation sequencing of each stock. A mutation was considered lethal only after we failed to rescue virus in three independent transfections. We measured the fitness of each viable mutant relative to the wild type by quantitative RT-PCR following direct competition on A549 cells. We found that 31.6% of the mutations in the genome-wide dataset were lethal and that the lethal fraction did not differ appreciably between the HA- and NA-encoding segments and the rest of the genome. Of the viable mutants, the fitness mean and standard deviation were 0.80 and 0.22 in the genome-wide dataset and best modeled as a beta distribution. The fitness impact of mutation was marginally lower in the segments coding for HA and NA (0.88 ± 0.16 than in the other 6 segments (0.78 ± 0.24, and their respective beta distributions had slightly different shape parameters. The results for influenza A virus are remarkably similar to our own analysis of CirSeq-derived fitness values from poliovirus and previously published data from other small, single stranded DNA and RNA viruses. These data suggest that genome size, and not nucleic acid type or mode of replication, is the main determinant of viral mutational fitness effects.

  5. Dissection of additive, dominance, and imprinting effects for production and reproduction traits in Holstein cattle

    Science.gov (United States)

    Although genome-wide association and genomic selection studies have primarily focused on additive effects, dominance and imprinting effects play an important role in mammalian biology and development. The degree to which these non-additive genetic effects contribute to phenotypic variation and wheth...

  6. Mutations to the formin homology 2 domain of INF2 protein have unexpected effects on actin polymerization and severing.

    Science.gov (United States)

    Ramabhadran, Vinay; Gurel, Pinar S; Higgs, Henry N

    2012-10-05

    INF2 (inverted formin 2) is a formin protein with unusual biochemical characteristics. As with other formins, the formin homology 2 (FH2) domain of INF2 accelerates actin filament assembly and remains at the barbed end, modulating elongation. The unique feature of INF2 is its ability to sever filaments and enhance depolymerization, which requires the C-terminal region. Physiologically, INF2 acts in the secretory pathway and is mutated in two human diseases, focal and segmental glomerulosclerosis and Charcot-Marie-Tooth disease. In this study, we investigate the effects of mutating two FH2 residues found to be key in other formins: Ile-643 and Lys-792. Surprisingly, neither mutation abolishes barbed end binding, as judged by pyrene-actin and total internal reflection (TIRF) microscopy elongation assays. The I643A mutation causes tight capping of a subset of filaments, whereas K792A causes slow elongation of all filaments. The I643A mutation has a minor inhibitory effect on polymerization activity but causes almost complete abolition of severing and depolymerization activity. The K792A mutation has relatively small effects on polymerization, severing, and depolymerization. In cells, the K792A mutant causes actin accumulation around the endoplasmic reticulum to a similar extent as wild type, whereas the I643A mutant causes no measurable polymerization. The inability of I643A to induce actin polymerization in cells is explained by its inability to promote robust actin polymerization in the presence of capping protein. These results highlight an important point: it is dangerous to assume that mutation of conserved FH2 residues will have equivalent effects in all formins. The work also suggests that both mutations have effects on the mechanism of processive elongation.

  7. Mutations to the Formin Homology 2 Domain of INF2 Protein Have Unexpected Effects on Actin Polymerization and Severing*

    Science.gov (United States)

    Ramabhadran, Vinay; Gurel, Pinar S.; Higgs, Henry N.

    2012-01-01

    INF2 (inverted formin 2) is a formin protein with unusual biochemical characteristics. As with other formins, the formin homology 2 (FH2) domain of INF2 accelerates actin filament assembly and remains at the barbed end, modulating elongation. The unique feature of INF2 is its ability to sever filaments and enhance depolymerization, which requires the C-terminal region. Physiologically, INF2 acts in the secretory pathway and is mutated in two human diseases, focal and segmental glomerulosclerosis and Charcot-Marie-Tooth disease. In this study, we investigate the effects of mutating two FH2 residues found to be key in other formins: Ile-643 and Lys-792. Surprisingly, neither mutation abolishes barbed end binding, as judged by pyrene-actin and total internal reflection (TIRF) microscopy elongation assays. The I643A mutation causes tight capping of a subset of filaments, whereas K792A causes slow elongation of all filaments. The I643A mutation has a minor inhibitory effect on polymerization activity but causes almost complete abolition of severing and depolymerization activity. The K792A mutation has relatively small effects on polymerization, severing, and depolymerization. In cells, the K792A mutant causes actin accumulation around the endoplasmic reticulum to a similar extent as wild type, whereas the I643A mutant causes no measurable polymerization. The inability of I643A to induce actin polymerization in cells is explained by its inability to promote robust actin polymerization in the presence of capping protein. These results highlight an important point: it is dangerous to assume that mutation of conserved FH2 residues will have equivalent effects in all formins. The work also suggests that both mutations have effects on the mechanism of processive elongation. PMID:22879592

  8. An effect from anticipation also in hereditary nonpolyposis colorectal cancer families without identified mutations

    DEFF Research Database (Denmark)

    Timshel, Susanne; Therkildsen, Christina; Bendahl, Pär-Ola

    2009-01-01

    the Amsterdam criteria for HNPCC and showed normal MMR function and/or lack of disease-predisposing MMR gene mutation. In total, 319 cancers from 212 parent-child pairs in 99 families were identified. A paired t-test and a bivariate statistical model were used to assess anticipation. Both methods demonstrated......Optimal prevention of hereditary cancer is central and requires initiation of surveillance programmes and/or prophylactic measures at a safe age. Anticipation, expressed as an earlier age at onset in successive generations, has been demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC...... an effect from anticipation with cancer diagnosed mean 11.4 years (t-test, p

  9. Effect of mutations on the thermostability of Aspergillus aculeatus β-1,4-galactanase

    Directory of Open Access Journals (Sweden)

    Søs Torpenholt

    2015-01-01

    Given the practical importance of kinetic stability, the kinetics of the irreversible enzyme inactivation process were also investigated for the wild-type and three variants and found to be biphasic. The half-lives of thermal inactivation were approximately doubled in G306A, unchanged for D182N and, disappointingly, a lot lower for D58N. In conclusion, this study tests a new method for estimating Tm changes for mutants, adds to the available data on the effect of substitutions on protein thermostability and identifies an interesting thermostabilizing mutation, which may be beneficial also in other galactanases.

  10. An effect from anticipation also in hereditary nonpolyposis colorectal cancer families without identified mutations

    DEFF Research Database (Denmark)

    Timshel, Susanne; Therkildsen, Christina; Bendahl, Pär-Ola

    2009-01-01

    Optimal prevention of hereditary cancer is central and requires initiation of surveillance programmes and/or prophylactic measures at a safe age. Anticipation, expressed as an earlier age at onset in successive generations, has been demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC...... the Amsterdam criteria for HNPCC and showed normal MMR function and/or lack of disease-predisposing MMR gene mutation. In total, 319 cancers from 212 parent-child pairs in 99 families were identified. A paired t-test and a bivariate statistical model were used to assess anticipation. Both methods demonstrated...... an effect from anticipation with cancer diagnosed mean 11.4 years (t-test, p

  11. SALL1 mutations in sporadic Townes-Brocks syndrome are of predominantly paternal origin without obvious paternal age effect.

    Science.gov (United States)

    Böhm, Johann; Munk-Schulenburg, Susanne; Felscher, Stephanie; Kohlhase, Jürgen

    2006-09-15

    Autosomal dominant Townes-Brocks syndrome (TBS) is characterized by imperforate anus, triphalangeal and supernumerary thumbs, dysplastic ears and sensorineural hearing loss, and may also involve other organ systems. Strong inter- and intrafamiliar variability is known. Approximately 50% of TBS cases are sporadic and due to de novo mutations in the SALL1 gene. SALL1 encodes a zinc finger protein operating as a transcriptional repressor and localizing to pericentromeric heterochromatin. We traced the parental origin of SALL1 mutations in sporadic TBS by analysis of linkage between SALL1 mutations and exonic or intronic polymorphisms in 16 families with 10 different mutations. Mutations were of paternal origin in 14 of 16 cases (87.5%). Paternal origin was independent of the mutation type. The mean paternal age at conception was 29.9 and the mean maternal age 26.5 years. We conclude that de novo mutations in SALL1 mostly occur on the paternally derived chromosome 16 without an obvious age effect.

  12. Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance.

    Directory of Open Access Journals (Sweden)

    Jonathan D Gruber

    2012-02-01

    Full Text Available Genetic variation within and between species can be shaped by population-level processes and mutation; however, the relative impact of "survival of the fittest" and "arrival of the fittest" on phenotypic evolution remains unclear. Assessing the influence of mutation on evolution requires understanding the relative rates of different types of mutations and their genetic properties, yet little is known about the functional consequences of new mutations. Here, we examine the spectrum of mutations affecting a focal gene in Saccharomyces cerevisiae by characterizing 231 novel haploid genotypes with altered activity of a fluorescent reporter gene. 7% of these genotypes had a nonsynonymous mutation in the coding sequence for the fluorescent protein and were classified as "coding" mutants; 2% had a change in the S. cerevisiae TDH3 promoter sequence controlling expression of the fluorescent protein and were classified as "cis-regulatory" mutants; 10% contained two copies of the reporter gene and were classified as "copy number" mutants; and the remaining 81% showed altered fluorescence without a change in the reporter gene itself and were classified as "trans-acting" mutants. As a group, coding mutants had the strongest effect on reporter gene activity and always decreased it. By contrast, 50%-95% of the mutants in each of the other three classes increased gene activity, with mutants affecting copy number and cis-regulatory sequences having larger median effects on gene activity than trans-acting mutants. When made heterozygous in diploid cells, coding, cis-regulatory, and copy number mutant genotypes all had significant effects on gene activity, whereas 88% of the trans-acting mutants appeared to be recessive. These differences in the frequency, effects, and dominance among functional classes of mutations might help explain why some types of mutations are found to be segregating within or fixed between species more often than others.

  13. Analysis of the Effects of a gerP Mutation on the Germination of Spores of Bacillus subtilis

    Science.gov (United States)

    2012-11-01

    REPORT Analysis of the effects of a gerP mutation on the germination of spores of Bacillus subtilis 14. ABSTRACT 16. SECURITY CLASSIFICATION OF... Bacillus subtilis spores with a gerP mutation triggered spore germination via nutrient germinant receptors (GRs) slowly, although this defect was...gerP, Bacillus subtilis , dipicolinic acid Xuan Y. Butzin, Anthony J. Troiano, William H. Coleman, Keren K. Griffiths, Christopher J. Doona, Florence E

  14. Differential effects of genistein on prostate cancer cells depend on mutational status of the androgen receptor.

    Directory of Open Access Journals (Sweden)

    Abeer M Mahmoud

    Full Text Available Blocking the androgen receptor (AR activity is the main goal of therapies for advanced prostate cancer (PCa. However, relapse with a more aggressive, hormone refractory PCa arises, which harbors restored AR activity. One mechanism of such reactivation occurs through acquisition of AR mutations that enable its activation by various steroidal and non-steroidal structures. Thus, natural and chemical compounds that contribute to inappropriate (androgen-independent activation of the AR become an area of intensive research. Here, we demonstrate that genistein, a soy phytoestrogen binds to both the wild and the Thr877Ala (T877A mutant types of AR competitively with androgen, nevertheless, it exerts a pleiotropic effect on PCa cell proliferation and AR activity depending on the mutational status of the AR. Genistein inhibited, in a dose-dependent way, cell proliferation and AR nuclear localization and expression in LAPC-4 cells that have wild AR. However, in LNCaP cells that express the T877A mutant AR, genistein induced a biphasic effect where physiological doses (0.5-5 µmol/L stimulated cell growth and increased AR expression and transcriptional activity, and higher doses induced inhibitory effects. Similar biphasic results were achieved in PC-3 cells transfected with AR mutants; T877A, W741C and H874Y. These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy.

  15. L30A Mutation of Phospholemman Mimics Effects of Cardiac Glycosides in Isolated Cardiomyocytes.

    Science.gov (United States)

    Himes, Ryan D; Smolin, Nikolai; Kukol, Andreas; Bossuyt, Julie; Bers, Donald M; Robia, Seth L

    2016-11-08

    To determine if mutations introduced into phospholemman (PLM) could increase the level of PLM-Na,K-ATPase (NKA) binding, we performed scanning mutagenesis of the transmembrane domain of PLM and measured Förster resonance energy transfer (FRET) between each mutant and NKA. We observed an increased level of binding to NKA for several PLM mutants compared to that of the wild type (WT), including L27A, L30A, and I32A. In isolated cardiomyocytes, overexpression of WT PLM increased the amplitude of the Ca(2+) transient compared to the GFP control. The Ca(2+) transient amplitude was further increased by L30A PLM overexpression. The L30A mutation also delayed Ca(2+) extrusion and increased the duration of cardiomyocyte contraction. This mimics aspects of the effect of cardiac glycosides, which are known to increase contractility through inhibition of NKA. No significant differences between WT and L30A PLM-expressing myocytes were observed after treatment with isoproterenol, suggesting that the superinhibitory effects of L30A are reversible with β-adrenergic stimulation. We also observed a decrease in the extent of PLM tetramerization with L30A compared to WT using FRET, suggesting that L30 is an important residue for mediating PLM-PLM binding. Molecular dynamics simulations revealed that the potential energy of the L30A tetramer is greater than that of the WT, and that the transmembrane α helix is distorted by the mutation. The results identify PLM residue L30 as an important determinant of PLM tetramerization and of functional inhibition of NKA by PLM.

  16. An investigation of the effect of pit latrine additives on VIP latrine ...

    African Journals Online (AJOL)

    Manufacturers of various commercial pit latrine additives claim that by addition of this product to pit content, accumulation rate and pit content volume can be reduced, thereby preventing the pit from ever reaching capacity. This paper presents a comprehensive study conducted to determine the effects of additives on pit ...

  17. Cost effectiveness of population based BRCA1 founder mutation testing in Sephardi Jewish women.

    Science.gov (United States)

    Patel, Shreeya; Legood, Rosa; Evans, D Gareth; Turnbull, Clare; Antoniou, Antonis C; Menon, Usha; Jacobs, Ian; Manchanda, Ranjit

    2017-12-26

    Population-based BRCA1/BRCA2 founder-mutation testing has been demonstrated as cost-effective compared to family-history(FH) based testing in Ashkenazi Jewish(AJ) women. However, only one of the three AJ BRCA1/BRCA2 founder-mutations (185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT)) is found in the Sephardi Jewish(SJ) population (185delAG(c.68_69delAG)) and the overall prevalence of BRCA mutations in the SJ population is accordingly lower (0.7% compared to 2.5% in the AJ population). Cost-effectiveness analyses of BRCA testing have not previously been performed at these lower BRCA prevalence levels seen in SJ. Here we present a cost-effectiveness analysis for UK and US populations comparing population-testing with Clinical-criteria/FH-based testing in SJ women. A Markov model was built comparing the lifetime costs-&-effects of population-based BRCA1-testing with testing using FH-based clinical criteria in SJ women ≥30years. BRCA1-carriers identified were offered MRI/mammograms and risk-reducing surgery. Costs are reported at 2015 prices. Outcomes include breast cancer(BC), ovarian cancer(OC) and excess deaths from heart disease. All costs-&-outcomes are discounted at 3.5%. The time horizon is life-time, and perspective is payer. The incremental-cost-effectiveness-ratio (ICER) per quality-adjusted life-year (QALY) was calculated. Parameter uncertainty was evaluated through one-way and probabilistic-sensitivity-analysis (PSA). Population-testing resulted in gain in life-expectancy of 12months (QALY=1.00). The baseline discounted ICER for UK population-based testing =£67.04/QALY and for US population=$308.42/QALY. Results were robust in the one-way sensitivity analysis. The PSA showed 100% of simulations were cost-effective at £20,000/QALY UK and the $100,000/QALY US WTP thresholds. Scenario analysis showed, population-testing remains cost-effective in UK and US populations even if pre-menopausal oophorectomy does not reduce BC-risk or if

  18. DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumors: a potential association with androgenic effects.

    Science.gov (United States)

    Kato, Noriko; Kusumi, Tomomi; Kamataki, Akihisa; Tsunoda, Rikiya; Fukase, Masayuki; Kurose, Akira

    2017-01-01

    Sertoli-Leydig cell tumors (SLCTs) are representative of androgenic ovarian tumors, and they show diverse histologic differentiation, including heterologous differentiation. Genetically, SLCTs are characterized by the presence of DICER1 mutations. In the present study, we analyzed the correlation between somatic DICER1 hotspot mutations and clinicopathological features in 10 ovarian SLCTs. Six of the 10 (60%) SLCTs harbored a DICER1 hotspot mutation. Five of the 6 DICER1-mutated SLCT patients showed androgenic manifestations, including amenorrhea and hirsutism, and 4 of the 6 were associated with the significant elevation of serum testosterone. In contrast, none of the 4 DICER1 wild-type SLCT patients showed virilization. The patient age at diagnosis was lower in those with DICER1-mutated SLCTs (average, 24.7; range, 17-43) than in those with DICER1 wild-type tumors (average, 64.8; range, 47-77). Histologically, heterologous differentiation was found in 4 SLCTs, all of which were DICER1 mutant. Heterologous components included gastrointestinal-type mucinous epithelium (n=3), carcinoid (n=1), and rhabdomyosarcoma (n=1). In the latter, the rhabdomyosarcomatous component was dominant to the SLCT component. In summary, DICER1 hotspot mutations are closely associated with androgenic effects in ovarian SLCTs. It is suggested that DICER1 mutations are involved in the dysregulation of sex hormone synthesis in SLCT patients. Somatic DICER1 hotspot mutations are more common in SLCT patients during the reproductive years than in those during the postreproductive years. DICER1 hotspot mutations may support the pathological diagnosis of SLCTs in cases wherein the heterologous component overwhelms and masks the SLCT component. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. [Food additive intake and health effects: public health challenges in Brazil].

    Science.gov (United States)

    Polônio, Maria Lúcia Teixeira; Peres, Frederico

    2009-08-01

    This study uses a systematic literature review to contextualize the risks associated with food additive intake. Studies comparing food additive intake and cancer showed that adverse health effects appeared when Acceptable Daily Intake (ADI) was exceeded. The review also detected a lack of studies on attention deficit-hyperactivity disorder. There were more studies on non-specific hypersensitivity, highlighting such clinical manifestations as rhinitis, urticaria, and angioedema, all associated with food additives, particularly artificial colorants. Children are a vulnerable group as potential consumers of food additives, particularly artificial colorants. Studies on food additive intake should provide the basis for effective food and nutritional surveillance strategies, aiming to promote healthy eating habits.

  20. Modulation of Additive and Interactive Effects in Lexical Decision by Trial History

    Science.gov (United States)

    Masson, Michael E. J.; Kliegl, Reinhold

    2013-01-01

    Additive and interactive effects of word frequency, stimulus quality, and semantic priming have been used to test theoretical claims about the cognitive architecture of word-reading processes. Additive effects among these factors have been taken as evidence for discrete-stage models of word reading. We present evidence from linear mixed-model…

  1. Additive Effects of Word Frequency and Stimulus Quality: The Influence of Trial History and Data Transformations

    Science.gov (United States)

    Balota, David A.; Aschenbrenner, Andrew J.; Yap, Melvin J.

    2013-01-01

    A counterintuitive and theoretically important pattern of results in the visual word recognition literature is that both word frequency and stimulus quality produce large but additive effects in lexical decision performance. The additive nature of these effects has recently been called into question by Masson and Kliegl (in press), who used linear…

  2. Multi-mutational model for cancer based on age-time patterns of radiation effects: 2. Biological aspects

    Energy Technology Data Exchange (ETDEWEB)

    Mendelsohn, M.L.; Pierce, P.A.

    1997-09-04

    Biological properties of relevance when modeling cancers induced in the atom bomb survivors include the wide distribution of the induced cancers across all organs, their biological indistinguishability from background cancers, their rates being proportional to background cancer rates, their rates steadily increasing over at least 50 years as the survivors age, and their radiation dose response being linear. We have successfully described this array of properties with a modified Armitage-Doll model using 5 to 6 somatic mutations, no intermediate growth, and the dose-related replacement of any one of these time-driven mutations by a radiation-induced mutation. Such a model is contrasted to prevailing models that use fewer mutations combined with intervening growth. While the rationale and effectiveness of our model is compelling for carcinogenesis in the atom bomb survivors, the lack of a promotional component may limit the generality of the model for other types of human carcinogenesis.

  3. A Substantial Fraction of Barley (Hordeum vulgare L. Low Phytic Acid Mutations Have Little or No Effect on Yield across Diverse Production Environments

    Directory of Open Access Journals (Sweden)

    Victor Raboy

    2015-04-01

    Full Text Available The potential benefits of the low phytic acid (lpa seed trait for human and animal nutrition, and for phosphorus management in non-ruminant animal production, are well documented. However, in many cases the lpa trait is associated with impaired seed or plant performance, resulting in reduced yield. This has given rise to the perception that the lpa trait is tightly correlated with reduced yield in diverse crop species. Here we report a powerful test of this correlation. We measured grain yield in lines homozygous for each of six barley (Hordeum vulgare L. lpa mutations that greatly differ in their seed phytic acid levels. Performance comparisons were between sibling wild-type and mutant lines obtained following backcrossing, and across two years in five Idaho (USA locations that greatly differ in crop yield potential. We found that one lpa mutation (Hvlpa1-1 had no detectable effect on yield and a second (Hvlpa4-1 resulted in yield losses of only 3.5%, across all locations. When comparing yields in three relatively non-stressful production environments, at least three lpa mutations (Hvlpa1-1, Hvlpa3-1, and Hvlpa4-1 typically had yields similar to or within 5% of the wild-type sibling isoline. Therefore in the case of barley, lpa mutations can be readily identified that when simply incorporated into a cultivar result in adequately performing lines, even with no additional breeding for performance within the lpa line. In conclusion, while some barley lpa mutations do impact field performance, a substantial fraction appears to have little or no effect on yield.

  4. Effects of FSGS-associated mutations on the stability and function of myosin-1 in fission yeast

    Directory of Open Access Journals (Sweden)

    Jing Bi

    2015-08-01

    Full Text Available Point mutations in the human MYO1E gene, encoding class I myosin Myo1e, are associated with focal segmental glomerulosclerosis (FSGS, a primary kidney disorder that leads to end-stage kidney disease. In this study, we used a simple model organism, fission yeast Schizosaccharomyces pombe, to test the effects of FSGS-associated mutations on myosin activity. Fission yeast has only one class I myosin, Myo1, which is involved in actin patch assembly at the sites of endocytosis. The amino acid residues mutated in individuals with FSGS are conserved between human Myo1e and yeast Myo1, which allowed us to introduce equivalent mutations into yeast myosin and use the resulting mutant strains for functional analysis. Yeast strains expressing mutant Myo1 exhibited defects in growth and endocytosis similar to those observed in the myo1 deletion strain. These mutations also disrupted Myo1 localization to endocytic actin patches and resulted in mis-localization of Myo1 to eisosomes, linear membrane microdomains found in yeast cells. Although both mutants examined in this study exhibited loss of function, one of these mutants was also characterized by the decreased protein stability. Thus, using the yeast model system, we were able to determine that the kidney-disease-associated mutations impair myosin functional activity and have differential effects on protein stability.

  5. The combined effect of two mutations that alter serially homologous color pattern elements on the fore and hindwings of a butterfly

    Directory of Open Access Journals (Sweden)

    Vedder Lindsey

    2007-05-01

    differentiation of the signaling centers of a subset of the serial homologous eyespots present on both the fore and the hindwing in a dose-dependent fashion. The effect of Missing on the forewing, however, is only observed when the mutation Spotty introduces additional eyespots on this wing. Spotty, on the other hand, controls the differentiation of eyespot centers only on the forewing. Spotty, unlike Missing, may be under Ubx gene regulation, since it affects a subset of eyespots on only one of the serially homologous wings.

  6. Site-directed mutation of a laccase from Thermus thermophilus: Effect on the activity profile

    Directory of Open Access Journals (Sweden)

    Liu Xin

    2012-01-01

    Full Text Available A site-directed mutant R453T of a laccase from Thermus thermophilus HB27 (Tth-laccase was constructed in order to investigate the effect on laccase catalytic properties. The mutated gene was cloned and overexpressed in Escherichia coli. Nickel-affinity purification was achieved and followed by copper ion incorporation. The mature mutated enzyme was quantitatively equal to the wild type. A photometric assay based on the oxidation of the substrate 2,2-azino-bis-(3- ethylbenzthiazoline-6-sulfonate (ABTS was employed in comparison with the wild-type Tth-laccase on catalytic properties. The R453T mutant exhibited improvement in substrate affinity and specific activity at room temperature, whereas those parameters were not significantly influenced when the temperature increased up to 65°C or higher. The mutant had better catalytic activity than that of the wild type at acidic pH. Investigated by circular dichroism spectroscopy, the mutant Tth-laccase displayed similar profiles at low and high temperatures.

  7. UV Signature Mutations

    Science.gov (United States)

    2014-01-01

    Sequencing complete tumor genomes and exomes has sparked the cancer field's interest in mutation signatures for identifying the tumor's carcinogen. This review and meta-analysis discusses signatures and their proper use. We first distinguish between a mutagen's canonical mutations – deviations from a random distribution of base changes to create a pattern typical of that mutagen – and the subset of signature mutations, which are unique to that mutagen and permit inference backward from mutations to mutagen. To verify UV signature mutations, we assembled literature datasets on cells exposed to UVC, UVB, UVA, or solar simulator light (SSL) and tested canonical UV mutation features as criteria for clustering datasets. A confirmed UV signature was: ≥60% of mutations are C→T at a dipyrimidine site, with ≥5% CC→TT. Other canonical features such as a bias for mutations on the non-transcribed strand or at the 3' pyrimidine had limited application. The most robust classifier combined these features with criteria for the rarity of non-UV canonical mutations. In addition, several signatures proposed for specific UV wavelengths were limited to specific genes or species; non-signature mutations induced by UV may cause melanoma BRAF mutations; and the mutagen for sunlight-related skin neoplasms may vary between continents. PMID:25354245

  8. The ups and downs of mutation frequencies during aging can account for the Apert syndrome paternal age effect.

    Science.gov (United States)

    Yoon, Song-Ro; Qin, Jian; Glaser, Rivka L; Jabs, Ethylin Wang; Wexler, Nancy S; Sokol, Rebecca; Arnheim, Norman; Calabrese, Peter

    2009-07-01

    Apert syndrome is almost always caused by a spontaneous mutation of paternal origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene (FGFR2). The incidence of this disease increases with the age of the father (paternal age effect), and this increase is greater than what would be expected based on the greater number of germ-line divisions in older men. We use a highly sensitive PCR assay to measure the frequencies of the two causal mutations in the sperm of over 300 normal donors with a wide range of ages. The mutation frequencies increase with the age of the sperm donors, and this increase is consistent with the increase in the incidence rate. In both the sperm data and the birth data, the increase is non-monotonic. Further, after normalizing for age, the two Apert syndrome mutation frequencies are correlated within individual sperm donors. We consider a mathematical model for germ-line mutation which reproduces many of the attributes of the data. This model, with other evidence, suggests that part of the increase in both the sperm data and the birth data is due to selection for mutated premeiotic cells. It is likely that a number of other genetic diseases have similar features.

  9. The ups and downs of mutation frequencies during aging can account for the Apert syndrome paternal age effect.

    Directory of Open Access Journals (Sweden)

    Song-Ro Yoon

    2009-07-01

    Full Text Available Apert syndrome is almost always caused by a spontaneous mutation of paternal origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene (FGFR2. The incidence of this disease increases with the age of the father (paternal age effect, and this increase is greater than what would be expected based on the greater number of germ-line divisions in older men. We use a highly sensitive PCR assay to measure the frequencies of the two causal mutations in the sperm of over 300 normal donors with a wide range of ages. The mutation frequencies increase with the age of the sperm donors, and this increase is consistent with the increase in the incidence rate. In both the sperm data and the birth data, the increase is non-monotonic. Further, after normalizing for age, the two Apert syndrome mutation frequencies are correlated within individual sperm donors. We consider a mathematical model for germ-line mutation which reproduces many of the attributes of the data. This model, with other evidence, suggests that part of the increase in both the sperm data and the birth data is due to selection for mutated premeiotic cells. It is likely that a number of other genetic diseases have similar features.

  10. Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice.

    NARCIS (Netherlands)

    Edgar, D.; Shabalina, I.; Camara, Y.; Wredenberg, A.; Calvaruso, M.A.; Nijtmans, L.G.J.; Nedergaard, J.; Cannon, B.; Larsson, N.G.; Trifunovic, A.

    2009-01-01

    The mtDNA mutator mice have high levels of point mutations and linear deletions of mtDNA causing a progressive respiratory chain dysfunction and a premature aging phenotype. We have now performed molecular analyses to determine the mechanism whereby these mtDNA mutations impair respiratory chain

  11. Non-additive genetic effects for fertility traits in Canadian Holstein cattle (Open Access publication

    Directory of Open Access Journals (Sweden)

    Miglior Filippo

    2007-02-01

    Full Text Available Abstract The effects of additive, dominance, additive by dominance, additive by additive and dominance by dominance genetic effects on age at first service, non-return rates and interval from calving to first service were estimated. Practical considerations of computing additive and dominance relationships using the genomic relationship matrix are discussed. The final strategy utilized several groups of 1000 animals (heifers or cows in which all animals had a non-zero dominance relationship with at least one other animal in the group. Direct inversion of relationship matrices was possible within the 1000 animal subsets. Estimates of variances were obtained using Bayesian methodology via Gibbs sampling. Estimated non-additive genetic variances were generally as large as or larger than the additive genetic variance in most cases, except for non-return rates and interval from calving to first service for cows. Non-additive genetic effects appear to be of sizeable magnitude for fertility traits and should be included in models intended for estimating additive genetic merit. However, computing additive and dominance relationships for all possible pairs of individuals is very time consuming in populations of more than 200 000 animals.

  12. EFFECT OF GAMMA RADIATION OF MACRO MUTATIONS, EFFECTIVENESS AND EFFICIENCY UNDER M2 GENERATION IN PEA (Pisum sativum L.

    Directory of Open Access Journals (Sweden)

    Arvind KUMAR

    2016-06-01

    Full Text Available The present investigation was undertaken to study the spectrum of macro mutants, effectiveness and efficiency of different doses of gamma rays in pea variety (Arkel. The seeds were treated with gamma rays viz., 00kR (dry control, 05kR, 10kR, 15kR, 20kR, 25kR, 30kR, 35kR, 40kR (dry seeds and presoaked seeds of the same was exposed to 00kR (wet control, 05kR, 10kR, 15kR, 20kR (kilo Roentgen biological damage was calculated in M1 and M2 generation based on lethality (L and pollen sterility. The irradiated seeds were sown in the M1 field their respective controls and harvested in bulk to raise the M2 generation in Randomized Block Design (RBD with three replications. The spectrum of macro mutants i.e., plant stature (tall, dwarf, small dwarf, maturity (early, late, pod shape (bold, long, short, seed colour (brown, light white, light green and seed shape (small, bold, wrinkled were observed in M2 generation. The usefulness of any mutagen in plant breeding depends not only on its effectiveness but also upon if efficiency. Mutagenic effectiveness is a measure of the frequency of mutations induced by unit mutagen dose, whereas mutagenic efficiency is measure of proportion of mutations in relation of undesirable changes like lethality and sterility are used for gamma rays. A result of the indicated positive relationship in M2 generation with macro mutation, effectiveness and efficiency was found to be highest at lowest doses.

  13. Mutational meltdown in laboratory yeast populations

    NARCIS (Netherlands)

    Zeyl, C.; Mizesko, M.; Visser, de J.A.G.M.

    2001-01-01

    In small or repeatedly bottlenecked populations, mutations are expected to accumulate by genetic drift, causing fitness declines. In mutational meltdown models, such fitness declines further reduce population size, thus accelerating additional mutation accumulation and leading to extinction. Because

  14. Effect of urea addition on giant reed ensilage and subsequent methane production by anaerobic digestion.

    Science.gov (United States)

    Liu, Shan; Ge, Xumeng; Liew, Lo Niee; Liu, Zhe; Li, Yebo

    2015-09-01

    The effect of urea addition on giant reed ensilage and sequential anaerobic digestion (AD) of the ensiled giant reed was evaluated. The dry matter loss during ensilage (up to 90 days) with or without urea addition was about 1%. Addition of 2% urea enhanced production of lactic acid by about 4 times, and reduced production of propionic acid by 2-8 times. Besides, urea addition reduced degradation of cellulose and hemicellulose, and increased degradation of lignin in giant reed during ensilage. Ensilage with or without urea addition had no significant effects on the enzymatic digestibility of giant reed, but ensilage with urea addition achieved a cumulative methane yield of 173 L/kg VS, which was 18% higher than that of fresh giant reed. The improved methane yield of giant reed could be attributed to the production of organic acids and ethanol during ensilage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. The Inhibitory Effects of Aqueous Extract from Guava Twigs, Psidium guajava L., on Mutation and Oxidative Damage

    Directory of Open Access Journals (Sweden)

    Zhi-Chyang Kang

    2013-01-01

    Full Text Available This study examines the inhibitory effects of the aqueous extract from guava twigs (GTE, Psidium guajava L., on mutation and oxidative damage. The results show that GTE inhibits the mutagenicity of 4-nitroquinoline-N-oxide (4-NQO, a direct mutagen, and 2-aminoanthracene (2-AA, an indirect mutagen, toward Salmonella typhimurium TA 98 and TA 100. In addition, GTE shows radical scavenging, reducing activities, tyrosinase inhibition, and liposome protection effects. Meanwhile, GTE in the range of 0.1–0.4 mg/mL protects liver cells from tert-butyl-hydroperoxide-(t-BHP- induced cytotoxicity. Furthermore, the cytotoxicity inhibition of GTE in the t-BHP-treated cells was demonstrated in a dose-dependent manner. High-performance liquid chromatography analysis suggests that the major phenolic constituents in GTE are gallic acid, ferulic acid, and myricetin. These active phenolic components may contribute to the biological protective effects of GTE in different models. The data suggest that GTE exhibiting biological activities can be applied to antimutation, antityrosinase, and antioxidative damage.

  16. Interactive Effects of Prenatal Antidepressant Exposure and Likely Gene Disrupting Mutations on the Severity of Autism Spectrum Disorder

    Science.gov (United States)

    Ackerman, Sean; Schoenbrun, Sarah; Hudac, Caitlin; Bernier, Raphael

    2017-01-01

    To examine the interactive effects of two proposed risk factors which may contribute to symptom severity of Autism Spectrum Disorder (ASD): prenatal antidepressant exposure and likely gene-disrupting (LGD) mutations. Participants included 2748 individuals with ASD from the Simons Simplex Collection. We examined the effects of prenatal…

  17. Concentration addition, independent action and generalized concentration addition models for mixture effect prediction of sex hormone synthesis in vitro

    DEFF Research Database (Denmark)

    Hadrup, Niels; Taxvig, Camilla; Pedersen, Mikael

    2013-01-01

    Humans are concomitantly exposed to numerous chemicals. An infinite number of combinations and doses thereof can be imagined. For toxicological risk assessment the mathematical prediction of mixture effects, using knowledge on single chemicals, is therefore desirable. We investigated pros and cons...... and compared to the experimental mixture data. Mixture 1 contained environmental chemicals adjusted in ratio according to human exposure levels. Mixture 2 was a potency adjusted mixture containing five pesticides. Prediction of testosterone effects coincided with the experimental Mixture 1 data. In contrast...

  18. Nutrient additions in pristine Patagonian Sphagnum bog vegetation : can phosphorus addition alleviate (the effects of) increased nitrogen loads

    NARCIS (Netherlands)

    Fritz, C.; Dijk, G. van; Smolders, A.J.P.; Pancotto, V.A.; Elzenga, J.T.M.; Roelofs, J.G.M.; Grootjans, A.P.

    Sphagnum-bog ecosystems have a limited capability to retain carbon and nutrients when subjected to increased nitrogen (N) deposition. Although it has been proposed that phosphorus (P) can dilute negative effects of nitrogen by increasing biomass production of Sphagnum mosses, it is still unclear

  19. Effect of EP additives in synthetic base oils. Goseiyu ni taisuru kyokuatsuzai no koka

    Energy Technology Data Exchange (ETDEWEB)

    Konishi, S.; Akiba, K.; Yokomori, Y. (National Defence Academy, Kanagawa (Japan))

    1994-07-01

    Accompanying the spread of applicability of synthetic base oils, the effects of various additives on them have been discussed. As a link of a study relating to additives for synthetic oils, the anti-seizure effects of sulfur-based extreme pressure additives (abbreviated S-additives), phosphates and zinc dithiophosphate (ZDP) on three kinds of synthetic base oil- poly-[alpha] olefin (PAO), dialkyl adipate (DA), trimethylol propane ester (TMP) - were investigated in this work. In addition, various additives in these oils were compared in adsorptivity to iron powder, and pyrolytic characteristic or hydrolytic characteristic on iron powder. The anti-seizure effects of extreme pressure additives on each kind of synthetic base oil were compared as shown in the following: DA>PAO, TMP, or PAO[ge]DA>TMP in S-additives; PAO>DA, TMP in phosphates; and PAO>TMP>DA in ZDP. These relations are controlled mainly by pyrolysis in S-additives, by adsorptivity in phosphates and by both of them in ZDP. 6 refs., 4 figs., 7 tabs.

  20. 75 FR 34360 - Listing of Color Additives Exempt From Certification; Bismuth Citrate; Confirmation of Effective...

    Science.gov (United States)

    2010-06-17

    ... Certification; Bismuth Citrate; Confirmation of Effective Date AGENCY: Food and Drug Administration, HHS... level of bismuth citrate as a color additive in cosmetics intended for coloring hair on the scalp. DATES... increasing the permitted use level of bismuth citrate as a color additive in cosmetics intended for coloring...

  1. Parental Anxiety and Child Symptomatology: An Examination of Additive and Interactive Effects of Parent Psychopathology

    Science.gov (United States)

    Burstein, Marcy; Ginsburg, Golda S.; Tein, Jenn-Yun

    2010-01-01

    The current study examined relations between parent anxiety and child anxiety, depression, and externalizing symptoms. In addition, the study tested the additive and interactive effects of parent anxiety with parent depression and externalizing symptoms in relation to child symptoms. Forty-eight parents with anxiety disorders and 49 parents…

  2. Effectiveness of the Touch Math Technique in Teaching Basic Addition to Children with Autism

    Science.gov (United States)

    Yikmis, Ahmet

    2016-01-01

    This study aims to reveal whether the touch math technique is effective in teaching basic addition to children with autism. The dependent variable of this study is the children's skills to solve addition problems correctly, whereas teaching with the touch math technique is the independent variable. Among the single-subject research models, a…

  3. Effect of dietary fiber (inulin) addition on phenolics and in vitro bioaccessibility of tomato sauce

    NARCIS (Netherlands)

    Tomas, Merve; Beekwilder, Jules; Hall, Robert D.; Diez Simon, Carmen; Sagdic, Osman; Capanoglu, Esra

    2018-01-01

    The effect of the addition of inulin (5 and 10%) on the phenolic content and in vitro gastrointestinal digestion of tomato sauces has been investigated. Results have shown that the addition of inulin to tomato sauce significantly decreased the total phenolic content (57–68%), total flavonoid content

  4. Effect of Vitamin C Addition on some Quality Aspects of Wheat Bread ...

    African Journals Online (AJOL)

    Objective: The effect of vitamin C addition on some quality aspects of wheat bread was evaluated. Subjects/Materials and Methods: Wheat bread was produced using the straight dough method with addition of varying quantities of vitamin C (between 0.05 to 0.40g) as an improver, with the sample without vitamin C serving ...

  5. Effect of cold atmospheric pressure He-plasma jet on DNA change and mutation

    Science.gov (United States)

    Yaopromsiri, C.; Yu, L. D.; Sarapirom, S.; Thopan, P.; Boonyawan, D.

    2015-12-01

    Cold atmospheric pressure plasma jet (CAPPJ) effect on DNA change was studied for assessment of its safety. The experiment utilized a home-developed CAPPJ using 100% helium to directly treat naked DNA plasmid pGFP (plasmid green fluorescent protein). A traversal electric field was applied to separate the plasma components and both dry and wet sample conditions were adopted to investigate various factor roles in changing DNA. Plasma species were measured by using optical emission spectroscopy. DNA topological form change was analyzed by gel electrophoresis. The plasma jet treated DNA was transferred into bacterial Escherichia coli cells for observing mutation. The results show that the He-CAPPJ could break DNA strands due to actions from charge, radicals and neutrals and potentially cause genetic modification of living cells.

  6. Combined effect of stacking and solvation on the spontaneous mutation in DNA.

    Science.gov (United States)

    Cerón-Carrasco, José P; Zúñiga, José; Requena, Alberto; Perpète, Eric A; Michaux, Catherine; Jacquemin, Denis

    2011-08-28

    In DNA, base pairs are involved in two reciprocal interactions: interbase hydrogen bonds and stacking. Furthermore, base pairs also undergo the effects of the external entities present in the biological environment, such as water molecules and cations. In this contribution, the double spontaneous mutation has been studied with hybrid theoretical tools in a DNA-embedded guanine-cytosine model accounting for the impact of the first hydration shell. According to our findings, the combination of the neighboring base pairs and surrounding water molecules plays a crucial role in the double proton transfer. Indeed, as a consequence of these interactions, the double proton transfer (DPT) mechanism is altered: on the one hand, stacking and hydration strongly affect the geometry of base pairs, and, on the other hand, vicinal water molecules may play an active role in the tautomeric equilibrium by catalyzing the proton transfer reaction.

  7. Effect of cold atmospheric pressure He-plasma jet on DNA change and mutation

    Energy Technology Data Exchange (ETDEWEB)

    Yaopromsiri, C. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Yu, L.D., E-mail: yuld@thep-center.org [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Sarapirom, S. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Faculty of Science, Maejo University, Bang Khen, Chiang Mai 50290 (Thailand); Thopan, P.; Boonyawan, D. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand)

    2015-12-15

    Cold atmospheric pressure plasma jet (CAPPJ) effect on DNA change was studied for assessment of its safety. The experiment utilized a home-developed CAPPJ using 100% helium to directly treat naked DNA plasmid pGFP (plasmid green fluorescent protein). A traversal electric field was applied to separate the plasma components and both dry and wet sample conditions were adopted to investigate various factor roles in changing DNA. Plasma species were measured by using optical emission spectroscopy. DNA topological form change was analyzed by gel electrophoresis. The plasma jet treated DNA was transferred into bacterial Escherichia coli cells for observing mutation. The results show that the He-CAPPJ could break DNA strands due to actions from charge, radicals and neutrals and potentially cause genetic modification of living cells.

  8. Effects of resistance mutations of Pro197, Asp376 and Trp574 on the characterization of acetohydroxyacid synthase (AHAS) isozymes.

    Science.gov (United States)

    Yang, Qian; Deng, Wei; Wang, Shipeng; Liu, Hongjie; Li, Xuefeng; Zheng, Mingqi

    2018-02-09

    Descurainia sophia L., a problematic weed in winter wheat fields in China, has developed high resistance to tribenuron-methyl. Amino acid substitutions at sites Pro197, Asp376 and Trp574 in the target acetohydroxyacid synthase (AHAS) were primarily responsible for D. sophia resistance to tribenuron-methyl. In this study, D. sophia plants individually homozygous for a specific resistance mutation (Pro197Leu, Pro197His, Pro197Ser, Pro197Thr, Asp376Glu or Trp574Leu) in AHAS were purified and generated, and the effects of resistance mutations on D. sophia resistance and AHAS characterization were investigated. All resistance mutations in this study not only caused D. sophia to evolve 152 to 811-fold resistance to tribenuron-methyl but also greatly reduced AHAS sensitivity to tribenuron-methyl and increased AHAS binding affinity with the substrate pyruvate, which was primarily responsible for D. sophia resistance. The molecular docking results indicated these resistance mutations altered AHAS binding affinity with tribenuron-methyl by reducing the hydrogen bonds and changing hydrophobic interactions. Compared with the wild-type AHAS, these resistance mutations exhibited no significant effects on AHAS feedback inhibition by branched-chain amino acids (BCAAs) at concentrations less than 0.08 mM. The altered AHAS sensitivity to feedback inhibition by BCAAs did not necessarily increase or decrease the free BCAAs in resistant D. sophia plants. The AHAS resistance mutations conferred D. sophia resistance to tribenuron-methyl by decreasing the binding affinity with tribenuron-methyl or (and) increasing the binding affinity with pyruvate, but the mutations did not necessarily affect the biosynthesis of BCAAs in plants. This article is protected by copyright. All rights reserved.

  9. The additive effect of turn-taking cues in human and synthetic voice

    OpenAIRE

    2010-01-01

    Abstract A previous line of research suggests that interlocutors identify appropriate places to speak by cues in the behaviour of the preceding speaker. If used in combination, these cues have an additive effect on listeners? turn-taking attempts. The present study further explores these findings by examining the effect of such turn-taking cues experimentally. The objective is to investigate the possibilities of generating turn-taking cues with a synthetic voice. Thus, in addition ...

  10. Hypogonadotropic hypogonadism in a homozygous MC4R mutation carrier and the effect of sibutramine treatment on body weight and obesity-related health risks.

    Science.gov (United States)

    Hainerová, Irena Aldhoon; Zamrazilová, Hana; Sedláčková, Dana; Hainer, Vojtěch

    2011-01-01

    The first aim of our study was to define the hypogonadism manifested by low testosterone levels and incomplete male secondary sex characteristics in a 20-year-old male homozygous MC4R mutation carrier (G181D). The second aim of our study was to evaluate the effect of the anti-obesity drug sibutramine in this patient who failed to respond to an intensive lifestyle intervention and exhibited continuous weight gain. Anthropometric, biochemical, hormonal and psycho-behavioural parameters were investigated both at baseline and after a 1-year sibutramine treatment. To characterise the hypogonadism, sex steroid profile, concentrations of luteinizing hormone and follicle-stimulating hormone were determined. Standard tests with gonadotropin-releasing hormone, thyrotropin-releasing hormone and human chorionic gonadotropin were conducted. Brain magnetic resonance imaging was performed to exclude organic hypothalamic-pituitary lesions. Clinical examination and endocrine investigations revealed hypogonadotropic hypogonadism. Sibutramine induced body weight maintenance as well as improvement in body composition and obesity-related metabolic abnormalities. We described the first case of hypogonadotropic hypogonadism in a MC4R homozygous mutation carrier. The potential association between the hormonal disturbance and the hypothalamic derangement caused by the MC4R mutation should be considered. In addition, we demonstrated that sibutramine treatment had a favourable effect on body weight maintenance and obesity-related health risks. Copyright © 2011 S. Karger AG, Basel.

  11. Effects of Roundup formulations, nutrient addition, and Western mosquitofish (Gambusia affinis) on aquatic communities.

    Science.gov (United States)

    Geyer, Rebecca L; Smith, Geoffrey R; Rettig, Jessica E

    2016-06-01

    Aquatic communities can be affected by herbicides, nutrient addition, and non-native fish species. We conducted a mesocosm experiment to examine the direct and interactive effects of three stressors: (1) Roundup formulations (Roundup Weed and Grass Killer(®) and Roundup Poison Ivy and Tough Brush Killer Plus(®)), (2) nutrient addition, and (3) the presence of the non-native Western mosquitofish (Gambusia affinis), on experimental pond communities. Roundup formulations had the most widespread effects on the zooplankton community, but effects varied between formulations and among taxa. The only significant effect of nutrient addition was a lowering of Daphnia abundance in the nutrient addition treatments. The abundances of Daphnia, mid-sized cladocerans, and total zooplankton were lowered by mosquitofish, but no other taxa showed significant mosquitofish effects. We found several two-way and three-way interactions among the stressors, but these varied among zooplankton taxa. Chlorophyll a levels were higher with nutrient addition but were not significantly affected by Roundup formulation or mosquitofish. Our results suggest toxicity of Roundup formulations varies among taxa, and Roundup formulations differ in their toxicity to zooplankton, but with no cascading effects on primary producers. In addition, interactions among stressors affected the zooplankton community.

  12. Effect of Nano Oil Additive Proportions on Friction and Wear Performance of Automotive Materials

    Directory of Open Access Journals (Sweden)

    A. Vadiraj

    2012-03-01

    Full Text Available The effect of nano boric acid and nano copper based engine and transmission oil additives in different volume ratios (1:10, 2:10, and 3:10 on friction and wear performance of cast iron and case carburized gear steel has been investigated. The results show that coefficient of friction increases with increase in volume ratio of engine oil additives and decreases with increasing in volume ratio of transmission oil additives. Cast iron substrate shows higher wear damage than case carburized gear steel. Nano copper additive with crystalline atomic structure shows more severe three body wear compared to boric acid with layered lattice structure.

  13. Dissection of additive, dominance, and imprinting effects for production and reproduction traits in Holstein cattle.

    Science.gov (United States)

    Jiang, Jicai; Shen, Botong; O'Connell, Jeffrey R; VanRaden, Paul M; Cole, John B; Ma, Li

    2017-05-30

    Although genome-wide association and genomic selection studies have primarily focused on additive effects, dominance and imprinting effects play an important role in mammalian biology and development. The degree to which these non-additive genetic effects contribute to phenotypic variation and whether QTL acting in a non-additive manner can be detected in genetic association studies remain controversial. To empirically answer these questions, we analyzed a large cattle dataset that consisted of 42,701 genotyped Holstein cows with genotyped parents and phenotypic records for eight production and reproduction traits. SNP genotypes were phased in pedigree to determine the parent-of-origin of alleles, and a three-component GREML was applied to obtain variance decomposition for additive, dominance, and imprinting effects. The results showed a significant non-zero contribution from dominance to production traits but not to reproduction traits. Imprinting effects significantly contributed to both production and reproduction traits. Interestingly, imprinting effects contributed more to reproduction traits than to production traits. Using GWAS and imputation-based fine-mapping analyses, we identified and validated a dominance association signal with milk yield near RUNX2, a candidate gene that has been associated with milk production in mice. When adding non-additive effects into the prediction models, however, we observed little or no increase in prediction accuracy for the eight traits analyzed. Collectively, our results suggested that non-additive effects contributed a non-negligible amount (more for reproduction traits) to the total genetic variance of complex traits in cattle, and detection of QTLs with non-additive effect is possible in GWAS using a large dataset.

  14. The study of the effect of splicing mutations in von Willebrand factor using RNA isolated from patients' platelets and leukocytes.

    Science.gov (United States)

    Corrales, I; Ramírez, L; Altisent, C; Parra, R; Vidal, F

    2011-04-01

    In von Willebrand factor (VWF) the effect of mutations potentially affecting mRNA processing or splicing is less predictable than that of other mutations (e.g. nonsense or missense substitutions). Bioinformatic tools can provide a valuable means to determine the consequences of potential splice site mutations (PSSM), but functional studies are mandatory to elucidate the true effect of the variation detected. After identification of PSSM in VWD patients, we began a systematic study of their in vivo effect in RNA extracted from the patients' platelets and leukocytes. Thirteen pairs of primers were designed for full amplification of VWF mRNA by RT-PCR that, after sequencing of aberrant products, enabled elucidation of the PSSM consequences for mRNA processing. This procedure was used to study seven different PSSM identified in four patients demonstrating diverse molecular mechanisms such as exon skipping (c.533-2A>G and c.8155+3G>C) and the activation of a cryptic splice site (c.7730-1G>C). No visible effect was evident for c.1533+15G>A and c.5170+10C>T and the consequence of c.[546G>A;7082-2A>G] was hidden by nonsense-mediated mRNA decay (NMD). Results were compared with in silico predictions of four splice-site analysis tools. We demonstrate selective degradation of VWF mRNA bearing PSSM by NMD for several mutations, which suggests that NMD represents a general mechanism for truncating mutations in VWF. Furthermore, because NMD efficiency varies between cell types, use of RNA from both platelets and leukocytes for in vivo study of VWF PSSM offers complementary results, particularly in cases in which NMD occurs in the allele carrying the mutation. © 2011 International Society on Thrombosis and Haemostasis.

  15. The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss

    NARCIS (Netherlands)

    Kwon, T.J.; Oh, S.K.; Park, H.J.; Sato, O.; Venselaar, H.; Choi, S.Y.; Kim, S.; Lee, K.Y.; Bok, J.; Lee, S.H.; Vriend, G.; Ikebe, M.; Kim, U.K.; Choi, J.Y.

    2014-01-01

    Mutations in five unconventional myosin genes have been associated with genetic hearing loss (HL). These genes encode the motor proteins myosin IA, IIIA, VI, VIIA and XVA. To date, most mutations in myosin genes have been found in the Caucasian population. In addition, only a few functional studies

  16. Effect of antiwear additives in synthetic base oils. Goseiyu ni taisuru mamo boshizai no koka

    Energy Technology Data Exchange (ETDEWEB)

    Konishi, S.; Nakashima, T.; Yokomori, Y.; Nishi, S. (The National Defence Academy, Kanagawa (Japan))

    1994-01-01

    The antiwear effects of organic phosphates (tricresyl phosphate (TCP), trioctyl phosphate (TOP) and dioctyl phosphate (DOP)) and a commercial zinc dialkyl dithiophosphate (ZDP) admixed in three different types of synthetic base oils, poly [alpha] olefin (PAO), diester (DA) and trimethylol propane ester (TMP), were examined using a soda four-ball tester. As a result, effects of these antiwear additives were in the following order: PAO>DA[much gt] TMP. Adsorption of these additives on iron powder from the synthetic oil solutions, and hydrolysis or thermal decomposition in the synthetic oils, were also examined. As a result, these effects of the antiwear additives in synthetic base oils were highly affected by the relative intensity of adsorption between additives and synthetic oils on the rubbing surfaces. Furthermore, it was clarified that hydrolysis of phosphates and thermal decomposition of ZDP were affected by synthetic base oils. 14 refs., 8 figs., 4 tabs.

  17. Investigating the effects of dietary folic acid on sperm count, DNA damage and mutation in Balb/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Swayne, Breanne G.; Kawata, Alice [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); Behan, Nathalie A. [Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); Williams, Andrew; Wade, Mike G. [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); MacFarlane, Amanda J. [Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); Yauk, Carole L., E-mail: carole.yauk@hc-sc.ga.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada)

    2012-09-01

    To date, fewer than 50 mutagens have been studied for their ability to cause heritable mutations. The majority of those studied are classical mutagens like radiation and anti-cancer drugs. Very little is known about the dietary variables influencing germline mutation rates. Folate is essential for DNA synthesis and methylation and can impact chromatin structure. We therefore determined the effects of folic acid-deficient (0 mg/kg), control (2 mg/kg) and supplemented (6 mg/kg) diets in early development and during lactation or post-weaning on mutation rates and chromatin quality in sperm of adult male Balb/c mice. The sperm chromatin structure assay and mutation frequencies at expanded simple tandem repeats (ESTRs) were used to evaluate germline DNA integrity. Treatment of a subset of mice fed the control diet with the mutagen ethylnitrosourea (ENU) at 8 weeks of age was included as a positive control. ENU treated mice exhibited decreased cauda sperm counts, increased DNA fragmentation and increased ESTR mutation frequencies relative to non-ENU treated mice fed the control diet. Male mice weaned to the folic acid deficient diet had decreased cauda sperm numbers, increased DNA fragmentation index, and increased ESTR mutation frequency. Folic acid deficiency in early development did not lead to changes in sperm counts or chromatin integrity in adult mice. Folic acid supplementation in early development or post-weaning did not affect germ cell measures. Therefore, adequate folic acid intake in adulthood is important for preventing chromatin damage and mutation in the male germline. Folic acid supplementation at the level achieved in this study does not improve nor is it detrimental to male germline chromatin integrity.

  18. EF-hand Ca 2+-binding bioluminescent proteins: effects of mutations and alternative divalent cations

    Science.gov (United States)

    Rowe, Laura; Ensor, Mark; Daunert, Sylvia

    2007-02-01

    Bioluminescent photoproteins, such as aequorin and obelin, are proteins that emit light upon binding calcium. Aequorin and obelin contain four EF-hand domains arranged into a globular structure. The loop region of these EF-hand domains binds calcium by coordinating it in a pentagonal bipyramidal structure with oxygen atoms. The binding of calcium to these EF-hands causes a slight conformational change in the protein, which leads to the oxidation of the internally sequestered chromophore, coelenterazine, producing coelenteramide and CO II. The excited coelenteramide then relaxes radiatively, emitting bioluminescence at 471 nm in aequorin or 491 nm in obelin. Although calcium is the traditional, and generally the most powerful, triggering ligand in this bioluminescence reaction, alternative di- and trivalent cations can also bind to the EF-hand loops and stimulate luminescence. Species capable of this cross-reactivity include: Cd 2+, Ba 2+, Mn 2+, Sr 2+, Mg 2+, and several lanthanides. Magnesium is also known to modulate the bioluminescence of wild-type aequorin, increase its stability, and decrease its aggregation tendency. Both wild-type aequorin and wild-type obelin contain several cysteine residues, aequorin has three and obelin has five. It is believed that these cysteine residues play an important, but as of yet unknown, role in the bioluminescence of these proteins, since mutating most of these residues causes significant loss in bioluminescent activity. In order to explore whether or not these cysteine residues contributed to the specificity of the EF-hand domains for cations we generated four aequorin and obelin mutants and observed their luminescent intensity and decay kinetics by stimulation with calcium, barium, and magnesium. It was found that the cysteine mutations do appear to alter the effects that alternative divalent cations have on the bioluminescence of both aequorin and obelin.

  19. Effect of Dedifferentiation on Time to Mutation Acquisition in Stem Cell-Driven Cancers

    Science.gov (United States)

    Jilkine, Alexandra; Gutenkunst, Ryan N.

    2014-01-01

    Accumulating evidence suggests that many tumors have a hierarchical organization, with the bulk of the tumor composed of relatively differentiated short-lived progenitor cells that are maintained by a small population of undifferentiated long-lived cancer stem cells. It is unclear, however, whether cancer stem cells originate from normal stem cells or from dedifferentiated progenitor cells. To address this, we mathematically modeled the effect of dedifferentiation on carcinogenesis. We considered a hybrid stochastic-deterministic model of mutation accumulation in both stem cells and progenitors, including dedifferentiation of progenitor cells to a stem cell-like state. We performed exact computer simulations of the emergence of tumor subpopulations with two mutations, and we derived semi-analytical estimates for the waiting time distribution to fixation. Our results suggest that dedifferentiation may play an important role in carcinogenesis, depending on how stem cell homeostasis is maintained. If the stem cell population size is held strictly constant (due to all divisions being asymmetric), we found that dedifferentiation acts like a positive selective force in the stem cell population and thus speeds carcinogenesis. If the stem cell population size is allowed to vary stochastically with density-dependent reproduction rates (allowing both symmetric and asymmetric divisions), we found that dedifferentiation beyond a critical threshold leads to exponential growth of the stem cell population. Thus, dedifferentiation may play a crucial role, the common modeling assumption of constant stem cell population size may not be adequate, and further progress in understanding carcinogenesis demands a more detailed mechanistic understanding of stem cell homeostasis. PMID:24603301

  20. A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families

    Directory of Open Access Journals (Sweden)

    Escámez María-José

    2010-09-01

    Full Text Available Abstract Background Recessive Dystrophic Epidermolysis Bullosa (RDEB is a genodermatosis caused by more than 500 different mutations in the COL7A1 gene and characterized by blistering of the skin following a minimal friction or mechanical trauma. The identification of a cluster of RDEB pedigrees carrying the c.6527insC mutation in a specific area raises the question of the origin of this mutation from a common ancestor or as a result of a hotspot mutation. The aim of this study was to investigate the origin of the c.6527insC mutation. Methods Haplotypes were constructed by genotyping nine single nucleotides polymorphisms (SNPs throughout the COL7A1 gene. Haplotypes were determined in RDEB patients and control samples, both of Spanish origin. Results Sixteen different haplotypes were identified in our study. A single haplotype cosegregated with the c.6527insC mutation. Conclusion Haplotype analysis showed that all alleles carrying the c.6527insC mutation shared the same haplotype cosegregating with this mutation (CCGCTCAAA_6527insC, thus suggesting the presence of a common ancestor.

  1. The effective use of physical and chemical mutagen in the induction of mutation for crop improvement in Malaysia

    Energy Technology Data Exchange (ETDEWEB)

    Abdul Rahim Harun [Malaysian Institute for Nuclear Technology Research, Bangi, Selangor (Malaysia)

    2001-03-01

    The earliest work of induced mutations breeding program in Malaysia was reported in 1967. The project was carried out by Rubber Research Institute of Malaysia using x-radiation in an attempt to improve rubber trees for dwarfism and disease resistance. Subsequently, more efforts were taken up by the universities to promote the technology for genetic changes and creation of new genetic resources, particularly in crops that are not easily achievable through conventional techniques. Gamma radiation is always been used as physical mutagen, while ethyl methane sulfonate (EMS) was a popular chemical mutagen used in induced mutation breeding in the country. Gamma rays is an effective mutagen to which more than 30 potential mutants were produced up to now through mutagenesis of several important food crops and ornamental plants. Although chemical mutagen such as EMS were reported being used, the result is not so convincing as compared to gamma radiation. Malaysian Institute for Nuclear Technology Research (MINT) has initiated and promoted nuclear technique in mutation breeding for the improvement of importance food crops such as rice, legume and other potential crops for export, like fruit trees and ornamentals. Gamma radiation is the main source of mutagen used in mutation-breeding programme at MINT. The effectiveness of these two mutagens were verified with mutants derived through induced mutation breeding in the country which some mutant has shown outstanding improvement and released as new varieties and cultivars. This paper summarises and discuss the effects as well as achievement attained through the use of ionizing radiation and chemical mutagen in plant mutation breeding in Malaysia. (author)

  2. Nitrogen Addition Altered the Effect of Belowground C Allocation on Soil Respiration in a Subtropical Forest.

    Directory of Open Access Journals (Sweden)

    Tongxin He

    Full Text Available The availabilities of carbon (C and nitrogen (N in soil play an important role in soil carbon dioxide (CO2 emission. However, the variation in the soil respiration (Rs and response of microbial community to the combined changes in belowground C and N inputs in forest ecosystems are not yet fully understood. Stem girdling and N addition were performed in this study to evaluate the effects of C supply and N availability on Rs and soil microbial community in a subtropical forest. The trees were girdled on 1 July 2012. Rs was monitored from July 2012 to November 2013, and soil microbial community composition was also examined by phospholipid fatty acids (PLFAs 1 year after girdling. Results showed that Rs decreased by 40.5% with girdling alone, but N addition only did not change Rs. Interestingly, Rs decreased by 62.7% under the girdling with N addition treatment. The reducing effect of girdling and N addition on Rs differed between dormant and growing seasons. Girdling alone reduced Rs by 33.9% in the dormant season and 54.8% in the growing season compared with the control. By contrast, girdling with N addition decreased Rs by 59.5% in the dormant season and 65.4% in the growing season. Girdling and N addition significantly decreased the total and bacterial PLFAs. Moreover, the effect of N addition was greater than girdling. Both girdling and N addition treatments separated the microbial groups on the basis of the first principal component through principal component analysis compared with control. This indicated that girdling and N addition changed the soil microbial community composition. However, the effect of girdling with N addition treatment separated the microbial groups on the basis of the second principal component compared to N addition treatment, which suggested N addition altered the effect of girdling on soil microbial community composition. These results suggest that the increase in soil N availability by N deposition alters the

  3. A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect.

    Science.gov (United States)

    McEntagart, Meriel; Williamson, Kathleen A; Rainger, Jacqueline K; Wheeler, Ann; Seawright, Anne; De Baere, Elfride; Verdin, Hannah; Bergendahl, L Therese; Quigley, Alan; Rainger, Joe; Dixit, Abhijit; Sarkar, Ajoy; López Laso, Eduardo; Sanchez-Carpintero, Rocio; Barrio, Jesus; Bitoun, Pierre; Prescott, Trine; Riise, Ruth; McKee, Shane; Cook, Jackie; McKie, Lisa; Ceulemans, Berten; Meire, Françoise; Temple, I Karen; Prieur, Fabienne; Williams, Jonathan; Clouston, Penny; Németh, Andrea H; Banka, Siddharth; Bengani, Hemant; Handley, Mark; Freyer, Elisabeth; Ross, Allyson; van Heyningen, Veronica; Marsh, Joseph A; Elmslie, Frances; FitzPatrick, David R

    2016-05-05

    Gillespie syndrome (GS) is characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, and progressive cerebellar atrophy. Trio-based exome sequencing identified de novo mutations in ITPR1 in three unrelated individuals with GS recruited to the Deciphering Developmental Disorders study. Whole-exome or targeted sequence analysis identified plausible disease-causing ITPR1 mutations in 10/10 additional GS-affected individuals. These ultra-rare protein-altering variants affected only three residues in ITPR1: Glu2094 missense (one de novo, one co-segregating), Gly2539 missense (five de novo, one inheritance uncertain), and Lys2596 in-frame deletion (four de novo). No clinical or radiological differences were evident between individuals with different mutations. ITPR1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. The homo-tetrameric structure has been solved by cryoelectron microscopy. Using estimations of the degree of structural change induced by known recessive- and dominant-negative mutations in other disease-associated multimeric channels, we developed a generalizable computational approach to indicate the likely mutational mechanism. This analysis supports a dominant-negative mechanism for GS variants in ITPR1. In GS-derived lymphoblastoid cell lines (LCLs), the proportion of ITPR1-positive cells using immunofluorescence was significantly higher in mutant than control LCLs, consistent with an abnormality of nuclear calcium signaling feedback control. Super-resolution imaging supports the existence of an ITPR1-lined nucleoplasmic reticulum. Mice with Itpr1 heterozygous null mutations showed no major iris defects. Purkinje cells of the cerebellum appear to be the most sensitive to impaired ITPR1 function in humans. Iris hypoplasia is likely to result from either complete loss of ITPR1 activity or structure-specific disruption of multimeric interactions. Copyright © 2016 The Authors. Published by Elsevier Inc. All

  4. Effect of HLB of additives on the properties and drug release from the glyceryl monooleate matrices.

    Science.gov (United States)

    Shah, Manish H; Paradkar, Anant

    2007-08-01

    Glyceryl monooleate (GMO) is an amphiphilic surfactant, which as such can solubilize hydrophilic, lipophilic and amphiphilic drug molecules in its different polarity regions. Addition of additives with different polarities in GMO leads to change in phase behavior and related properties of GMO. Effect of the additives with different hydrophilic lipophilic balance (HLB; 1.5, 3, 4, 5, 7, 10 and 11) in GMO matrices on its phase transformation, rheological properties, mechanical properties, wetting and release behavior was investigated. Polarizing light microscopy showed that the GMO matrices incorporated with lower HLB additive (1.5, 3, 4 and 5) form cubic phase at higher rate while lamellar phase was prominent for matrices with additive of HLB 7, 10 and 11. The diametrical crushing strength and viscosity was decreased with increased HLB of additive. Lower HLB additives enhanced contact angle as compared to plain matrices and high HLB additives induced change in solid-liquid interface from hydrophobic to hydrophilic leading to decline in contact angle. Percent swelling of matrices was increased linearly with increase in HLB of additives. Tensiometric method was used for determination of bioadhesive strength of hydrated matrices and it was observed that matrices with additives of HLB 10 presented highest bioadhesion due to higher rate of hydration and formation of lamellar phase. As the HLB of additives in matrix increased, release was shifted from anomalous (non-Fickian) diffusion and/or partially erosion-controlled release to Fickian diffusion. Initial lag was observed for drug released from matrices with additive of HLB 1.5, 3, 4 and 5. Thus incorporation of the additives of different HLB changed molecular packing, which significantly affected drug release pattern.

  5. Synergistic and Additive Properties of the Beta-Globin Locus Control Region (LCR) Revealed by 5′HS3 Deletion Mutations: Implication for LCR Chromatin Architecture

    OpenAIRE

    Fang, Xiangdong; Sun, Jin; Xiang, Ping; Yu, Man; Navas, Patrick A.; Peterson, Kenneth R.; Stamatoyannopoulos, George; Li, Qiliang

    2005-01-01

    Deletion of the 234-bp core element of the DNase I hypersensitive site 3 (5′HS3) of the locus control region (LCR) in the context of a human beta-globin locus yeast artificial chromosome (β-YAC) results in profound effects on globin gene expression in transgenic mice. In contrast, deletion of a 2.3-kb 5′HS3 region, which includes the 234-bp core sequence, has a much milder phenotype. Here we report the effects of these deletions on chromatin structure in the beta-globin locus of adult erythro...

  6. Effects of soil warming and nitrogen addition on soil respiration in a New Zealand tussock grassland.

    Science.gov (United States)

    Graham, Scott L; Hunt, John E; Millard, Peter; McSeveny, Tony; Tylianakis, Jason M; Whitehead, David

    2014-01-01

    Soil respiration (RS) represents a large terrestrial source of CO2 to the atmosphere. Global change drivers such as climate warming and nitrogen deposition are expected to alter the terrestrial carbon cycle with likely consequences for RS and its components, autotrophic (RA) and heterotrophic respiration (RH). Here we investigate the impacts of a 3°C soil warming treatment and a 50 kg ha(-1) y(-1) nitrogen addition treatment on RS, RH and their respective seasonal temperature responses in an experimental tussock grassland. Average respiration in untreated soils was 0.96±0.09 μmol m(-2) s(-1) over the course of the experiment. Soil warming and nitrogen addition increased RS by 41% and 12% respectively. These treatment effects were additive under combined warming and nitrogen addition. Warming increased RH by 37% while nitrogen addition had no effect. Warming and nitrogen addition affected the seasonal temperature response of RS by increasing the basal rate of respiration (R10) by 14% and 20% respectively. There was no significant interaction between treatments for R10. The treatments had no impact on activation energy (E0). The seasonal temperature response of RH was not affected by either warming or nitrogen addition. These results suggest that the additional CO2 emissions from New Zealand tussock grassland soils as a result of warming-enhanced RS constitute a potential positive feedback to rising atmospheric CO2 concentration.

  7. Effects of WMA Additive on the Rheological Properties of Asphalt Binder and High Temperature Performance Grade

    Directory of Open Access Journals (Sweden)

    Jiupeng Zhang

    2015-01-01

    Full Text Available Sasobit additives with different dosages were added into 70# and 90# virgin asphalt binders to prepare WMA binders. The rheological properties, including G∗ and δ, were measured by using DSR at the temperature ranging from 46°C to 70°C, and the effects of temperature, additive dosage and aging on G∗/sin⁡δ, critical temperature, and H-T PG were investigated. The results indicate that WMA additive improves G∗ but reduces δ, and the improvement on 70# virgin binder is more significant. G∗/sin⁡δ exponentially decreases with the increasing temperature but linearly increases with the increasing additive dosage. Aging effect weakens the interaction between binder and additive but significantly increases the binder’s viscosity; that is why G∗/sin⁡δ is higher after short-term aging. In addition, the critical temperature increases with the increasing additive dosage, and the additive dosage should be more than 3% and 5% to improve H-T PG by one grade for 70# and 90# virgin binder, respectively.

  8. Effects of Different Addition Amounts of Superphosphate on Vegetable Waste Compost

    Directory of Open Access Journals (Sweden)

    YANG Yan

    2017-01-01

    Full Text Available The effects of different addition amounts of superphosphate on vegetable waste compost were studied. Results showed that, addition of superphosphate improved the temperature during the compost. It had the highest temperature of 64.33℃, when the addition quantity of superphosphate was 10.26% of dry matter weight. At the end of the composting, adding superphosphate had no significant effect on C/N, however, it decreased pH and improved the EC of the compost. The EC values were significantly higher than CK, when the addition amount was be tween 4.10%and 10.26%of dry matter weight. When the addition below 10.26%, the GI values were significantly higher than CK(P<0.01, and the highest value was 105.61%, when the addition was 2.05%(S5. Adding superphosphate significantly reduced the nitrogen loss rate of composting(P<0.05, and the lowest was 23.94%,when the addition was 2.05%, meanwhile, the input-output ratio was 3.93, which was the highest value. Under this experimental condition, adding superphosphate promoted the compost maturity significantly, reduced the nitrogen loss rate, and the optimal addition of superphosphate was 2.05%of dry matter weight.

  9. Additional clinical and microbiological effects of amoxicillin and metronidazole after initial periodontal therapy

    NARCIS (Netherlands)

    Winkel, EG; van Winkelhoff, AJ; van der Velden, U

    1998-01-01

    The aims of this study were to evaluate the clinical and microbiological effects of initial periodontal therapy (IT) and to determine the additional effects of systemic amoxicillin (Flemoxin Solutab(R)) 375 mg TID plus metronidazole 250 mg TID therapy, in patients with adult Actinobacillus

  10. Page 1 Magnetic separation of china clays 475 4.3 Effect of addition ...

    Indian Academy of Sciences (India)

    4.3 Effect of addition of dispersant. Before separation dispersion of the particulates in the liquid is necessary. The effect of Sodium-meta silicate and disodium hydrogen orthophosphate as dispersing agents was studied and the results for rom clay are shown in figures 5 and 6. Similar results for washed clay are shown in ...

  11. A Comprehensive Review of Effect of Biodiesel Additives on Properties, Performance, and Emission

    Science.gov (United States)

    Madiwale, S.; Karthikeyan, A.; Bhojwani, V.

    2017-05-01

    Objectives:- To presents the literature review on effect of biodiesel additives on properties, performance and on emission. Method:-In the current paper reviews are taken from previous years paper which necessitates the need of addition of additives in the blends of biodiesel and studied the its effect on properties, performance and emissions. Emissions from the diesel powered vehicles mostly damaged the earth’s environment and also increased the overall earth’s temperature. This attracts the need of alternative fuels in the field of transportation sector. Past inventions and research showed that Biodiesel can be used as an alternative fuel for the diesel engine. Biodiesel have good combustion characteristics because of their long chain hydrocarbon structure. However biodiesel possesses few disadvantages such as lower heating value, higher flow ability, much high density and not able to flow at low temperature. Higher rate of fuel consumption is identified and higher level of NOx emissions when biodiesel used in an engine as an alternative fuels. Findings:-Different additives such as antioxidants, improvers for cetane number, cold flow properties improver, etc were investigated by the many researcher and scientists and added in the different feedstock of biodiesel or blends of biodiesel with diesel in different proportions. Directly or indirectly fuel additives can improve the reduction in the emissions, improve the fuel economy, and reduce the dependency of the one’s nation on other. Performances of biodiesel vehicles were drastically improved because of additioninthe blends of biodiesel with diesel fuel in specific percentages to meet the international emission standards. Addition of additives in the biodiesel or in the blends of biodiesel basically changes the high temperature and low temperature flow properties of blends of biodiesel. Current paper finds and compares properties of different additives and its effect on blends of biodiesel properties

  12. Transcriptomic Characterization of SF3B1 Mutation Reveals Its Pleiotropic Effects in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Wang, Lili; Brooks, Angela N; Fan, Jean; Wan, Youzhong; Gambe, Rutendo; Li, Shuqiang; Hergert, Sarah; Yin, Shanye; Freeman, Samuel S; Levin, Joshua Z; Fan, Lin; Seiler, Michael; Buonamici, Silvia; Smith, Peter G; Chau, Kevin F; Cibulskis, Carrie L; Zhang, Wandi; Rassenti, Laura Z; Ghia, Emanuela M; Kipps, Thomas J; Fernandes, Stacey; Bloch, Donald B; Kotliar, Dylan; Landau, Dan A; Shukla, Sachet A; Aster, Jon C; Reed, Robin; DeLuca, David S; Brown, Jennifer R; Neuberg, Donna; Getz, Gad; Livak, Kenneth J; Meyerson, Matthew M; Kharchenko, Peter V; Wu, Catherine J

    2016-11-14

    Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1. SF3B1 mutation was found to dysregulate multiple cellular functions including DNA damage response, telomere maintenance, and Notch signaling (mediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 transcript, respectively). SF3B1 mutation leads to diverse changes in CLL-related pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Compactness of viral genomes: effect of disperse and localized random mutations

    Science.gov (United States)

    Lošdorfer Božič, Anže; Micheletti, Cristian; Podgornik, Rudolf; Tubiana, Luca

    2018-02-01

    Genomes of single-stranded RNA viruses have evolved to optimize several concurrent properties. One of them is the architecture of their genomic folds, which must not only feature precise structural elements at specific positions, but also allow for overall spatial compactness. The latter was shown to be disrupted by random synonymous mutations, a disruption which can consequently negatively affect genome encapsidation. In this study, we use three mutation schemes with different degrees of locality to mutate the genomes of phage MS2 and Brome Mosaic virus in order to understand the observed sensitivity of the global compactness of their folds. We find that mutating local stretches of their genomes’ sequence or structure is less disruptive to their compactness compared to inducing randomly-distributed mutations. Our findings are indicative of a mechanism for the conservation of compactness acting on a global scale of the genomes, and have several implications for understanding the interplay between local and global architecture of viral RNA genomes.

  14. Effect of xylanase, urea, Tween and Triton additives on bioethanol production of corn stover

    Science.gov (United States)

    Xin, Xiu; Lu, Jie; Yang, Rui-Feng; Song, Wen-jing; Li, Hai-ming; Wang, Hai-song; Zhou, Jing-hui

    2017-03-01

    Corn stover is a potential source of renewable biomass for conversion to bioethanol. Fed-batch semi-simultaneous saccharifcation and fermentation (S-SSF) of corn stover pretreated by liquid hot water (LHW) was investigated. The present study aimed to confirm the influence of xylanase, urea, Tween and Triton additives on bioethanol. Results show that the positive effect of xylanase, urea, Tween was observed. High ethanol concentration requires the addition of xylanase in the stage of saccharification. The optimal amount of xylanase was 0.2 g/g biomass and addition of Triton (Triton X-100) increases the effect of xylanase. Urea has a promotion effect on the whole fermentation process.When adding 0.1% urea in the fermentation stage,the best promoting rate is 24.2%. In the longitudinal comparison of the Tween series, under the same experimental conditions, the promoting effect of Tween series: Tween 40 > Tween 80 > Tween 20 > Tween 60.

  15. Cholera toxin A1 residues single alanine substitutional mutation and effect on activity with stimulatory G protein

    Directory of Open Access Journals (Sweden)

    Somsri Wiwanitkit

    2017-06-01

    Full Text Available Cholera is a well-known gastrointestinal infection. The cholera toxin is an important pathological substance in pathogenesis of cholera diarrhea. Cholera toxin is composed of catalytic A1 subunit, an A2 linker, and a homopentameric cell-binding B subunit. In enterocyte, cholera toxin will attach to GM1 ganglioside receptors on the apical membrane and causes retrograde vesicular trafficking to endoplasmic reticulum. At endoplasmic reticulum, cholera toxin A1 is released from the rest of the toxin into cytoplasm. The cholera toxin A1 interacts will catalyze ADP ribosylation of subunits of stimulatory G protein resulting a persistent activation of adenylate cyclase and an elevation of intracellular cAMP which further result in diarrhea. The single alanine substitutional mutation can result in the reduction of the interaction activity between cholera toxin A1 and stimulatory G protein. In this study, the four well-known mutations, H55, R67, L71, S78, or D109, of cholera toxin A1 is focused. The author hereby calculates for the reaction energy for the reaction between cholera toxin A1 and stimulatory G protein in naïve case and mutated case. To calculate, the standard bonding energy calculation technique in mutation analysis was used. It can be seen that aberrant in reaction energy in each studied mutation is different and can imply the different effect on activity with stimulatory G protein.

  16. Long-range effects and functional consequences of stabilizing mutations in the ankyrin repeat domain of IκBα.

    Science.gov (United States)

    Cervantes, Carla F; Handley, Lindsey D; Sue, Shih-Che; Dyson, H Jane; Komives, Elizabeth A

    2013-03-11

    Protein domains containing three or more ankyrin repeats (ARs) are ubiquitous in all phyla. Sequence alignments previously identified certain conserved positions, which have been shown to stabilize AR domains and promote their folding. Consensus mutations [Y254L/T257A (YLTA) and C186P/A220P (CPAP)] stabilize the naturally occuring AR domain of human IκBα to denaturation; however, only the YLTA mutations stabilize the protein to proteasomal degradation. We present results from NMR experiments designed to probe the roles of these consensus mutations in IκBα. According to residual dipolar coupling analysis, the gross structures of the AR domains of both mutants appear to be similar to the wild type (WT). Comparison of chemical shifts of mutant and WT proteins reveals that the YLTA and CPAP consensus mutations cause unexpected long-range effects throughout the AR domains. Backbone dynamics experiments reveal that the YLTA mutations in the sixth AR order the C-terminal PEST sequence on the picosecond-to-nanosecond timescale, compared to either the WT or the CPAP mutant IκBαs. This property is likely the mechanism by which the half-life of YLTA IκBα is extended in vivo. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Effect of radiation-sensitive mutations and mutagens/carcinogens on bacterial recombination and mutagenesis. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Matney, T.S.

    1978-01-01

    Progress is reported on effects of temperature sensitive DNA-initiation mutation in E. coli K-12 mutants; the use of Bacillus subtilis transforming system as an in vitro mutagenesis system; characteristics of the E. coli lysogen used to test the permeability to polycyclic aromatic hydrocarbons; and the genetic toxicology of gentian violet. (PCS)

  18. Founder effect in the Horn of Africa for an insulin receptor mutation that may impair receptor recycling

    DEFF Research Database (Denmark)

    Raffan, E; Soos, M A; Rocha, N

    2011-01-01

    Genetic insulin receptoropathies are a rare cause of severe insulin resistance. We identified the Ile119Met missense mutation in the insulin receptor INSR gene, previously reported in a Yemeni kindred, in four unrelated patients with Somali ancestry. We aimed to investigate a possible genetic fou...... founder effect, and to study the mechanism of loss of function of the mutant receptor....

  19. Effects of a stay-green mutation on plant nitrogen relations in Lolium perenne during N starvation and after defoliation.

    Science.gov (United States)

    Macduff, J H; Humphreys, M O; Thomas, H

    2002-01-01

    The stay-green mutation of the nuclear gene sid results in inhibition of chlorophyll degradation during leaf senescence in grasses, reducing N remobilization from senescing leaves. Effects on growth of Lolium perenne L. were investigated during N starvation (over 18 d) and after severe defoliation, when leaf growth depends on the remobilization of internal N. Rates of dry mater production, partitioning between shoots and roots, and re-partitioning of N from shoots to roots were very similar in stay-green and normal plants under N starvation. Km and Vmax for net uptake of NH4+ were also similar for both genotypes, and Vmax increased with the duration of N deprivation. The mutation had little effect on recovery of leaf growth following severe defoliation, but stay-green plants recommenced NO3- and K+ uptake 1 d later than normal plants. Import of remobilized N into new leaves was generally similar in both lines. However, stay-green plants remobilized less N from stubble compared with normal plants. It was concluded that the sid locus stay-green mutation has no significant adverse effect on the growth of L perenne during N starvation, or recovery from severe defoliation when plants are grown under an optimal regime of NO3- supply both before and after defoliation. The absence of any effect on leaf dry matter production implies that the difference in foliar N availability attributable to this mutation has little bearing on productivity, at least in the short to medium term.

  20. Effects of different chemical additives on biodiesel fuel properties and engine performance. A comparison review

    Directory of Open Access Journals (Sweden)

    Ali Obed Majeed

    2016-01-01

    Full Text Available Biodiesel fuel can be used as an alternative to mineral diesel, its blend up to 20% used as a commercial fuel for the existing diesel engine in many countries. However, at high blending ratio, the fuel properties are worsening. The feasibility of pure biodiesel and blended fuel at high blending ratio using different chemical additives has been reviewed in this study. The results obtained by different researchers were analysed to evaluate the fuel properties trend and engine performance and emissions with different chemical additives. It found that, variety of chemical additives can be utilised with biodiesel fuel to improve the fuel properties. Furthermore, the chemical additives usage in biodiesel is inseparable both for improving the cold flow properties and for better engine performance and emission control. Therefore, research is needed to develop biodiesel specific additives that can be adopted to improve the fuel properties and achieve best engine performance at lower exhaust emission effects.

  1. Experimental Investigations on the Effects of Cerium Oxide Nanoparticle Fuel Additives on Biodiesel

    Directory of Open Access Journals (Sweden)

    V. Sajith

    2010-01-01

    Full Text Available This paper reports the results of experimental investigations on the influence of the addition of cerium oxide in the nanoparticle form on the major physicochemical properties and the performance of biodiesel. The physicochemical properties of the base fuel and the modified fuel formed by dispersing the catalyst nanoparticles by ultrasonic agitation are measured using ASTM standard test methods. The effects of the additive nanoparticles on the individual fuel properties, the engine performance, and emissions are studied, and the dosing level of the additive is optimized. Comparisons of the performance of the fuel with and without the additive are also presented. The flash point and the viscosity of biodiesel were found to increase with the inclusion of the cerium oxide nanoparticles. The emission levels of hydrocarbon and NOx are appreciably reduced with the addition of cerium oxide nanoparticles.

  2. A comparative study on low-energy ion beam and neutralized beam modifications of naked DNA and biological effect on mutation

    Science.gov (United States)

    Sarapirom, S.; Thongkumkoon, P.; Prakrajang, K.; Anuntalabhochai, S.; Yu, L. D.

    2012-02-01

    DNA conformation change or damage induced by low-energy ion irradiation has been of great interest owing to research developments in ion beam biotechnology and ion beam application in biomedicine. Mechanisms involved in the induction of DNA damage may account for effect from implanting ion charge. In order to check this effect, we used both ion beam and neutralized beam at keV energy to bombard naked DNA. Argon or nitrogen ion beam was generated and extracted from a radiofrequency (RF) ion source and neutralized by microwave-driven plasma in the beam path. Plasmid DNA pGFP samples were irradiated with the ion or neutralized beam in vacuum, followed by gel electrophoresis to observe changes in the DNA conformations. It was revealed that the ion charge played a certain role in inducing DNA conformation change. The subsequent DNA transfer into bacteria Escherichia coli ( E. coli) for mutation analysis indicated that the charged ion beam induced DNA change had high potential in mutation induction while neutralized beam did not. The intrinsic reason was attributed to additional DNA deformation and contortion caused by ion charge exchange effect so that the ion beam induced DNA damage could hardly be completely repaired, whereas the neutralized beam induced DNA change could be more easily recoverable owing to absence of the additional DNA deformation and contortion.

  3. A comparative study on low-energy ion beam and neutralized beam modifications of naked DNA and biological effect on mutation

    Energy Technology Data Exchange (ETDEWEB)

    Sarapirom, S.; Thongkumkoon, P.; Prakrajang, K. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Anuntalabhochai, S. [Molecular Biology Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Yu, L.D., E-mail: yuld@fnrf.science.cmu.ac.th [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand)

    2012-02-01

    DNA conformation change or damage induced by low-energy ion irradiation has been of great interest owing to research developments in ion beam biotechnology and ion beam application in biomedicine. Mechanisms involved in the induction of DNA damage may account for effect from implanting ion charge. In order to check this effect, we used both ion beam and neutralized beam at keV energy to bombard naked DNA. Argon or nitrogen ion beam was generated and extracted from a radiofrequency (RF) ion source and neutralized by microwave-driven plasma in the beam path. Plasmid DNA pGFP samples were irradiated with the ion or neutralized beam in vacuum, followed by gel electrophoresis to observe changes in the DNA conformations. It was revealed that the ion charge played a certain role in inducing DNA conformation change. The subsequent DNA transfer into bacteria Escherichia coli (E. coli) for mutation analysis indicated that the charged ion beam induced DNA change had high potential in mutation induction while neutralized beam did not. The intrinsic reason was attributed to additional DNA deformation and contortion caused by ion charge exchange effect so that the ion beam induced DNA damage could hardly be completely repaired, whereas the neutralized beam induced DNA change could be more easily recoverable owing to absence of the additional DNA deformation and contortion.

  4. EFFECT OF ADDITION OF PROTEIN PREPARATIONS ON THE QUALITY OF EXTRUDED MAIZE EXTRUDATES

    Directory of Open Access Journals (Sweden)

    Elżbieta Rytel

    2013-02-01

    Full Text Available The method of extrusion enables enrichment of snacking products with protein preparation simultaneously providing a high quality of end products. Maize semolina with particle size of 500-1250 μm was used as raw material and as additives soybean protein isolate, distillery yeast Safethanol 3035 and laboratory obtained potato protein preparation. Snacks were determined for contents of dry matter, protein, fat as well as for texture, volume weight, bulk density and sensory traits. The application of 3% and 6% additions of protein preparations in extruded snacks production was found to exert a beneficial effect on their chemical composition without deteriorating sensory characteristics. The higher, 6%, addition of proteins to extrudates turned out to significantly reduce content of fat (by 18% and ash (by 50%, and to increase total protein content by 26%, on average, in the products examined as compared to the samples free of additives. The addition of potato protein to extrudates, especially at the higher dose (6%, significantly improved their consistency and texture, simultaneously diminishing the expansion ratio of ready products. The higher (6% addition of yeast protein applied in the production of extrudates resulted in slight deterioration of their taste and aroma, yet had a positive effect on the structure and expansion ratio of the ready products. The extrudates produced with the addition of soybean protein were characterized by a good expansion ratio, uniform structure, irrespective of preparation dose and simultaneously demonstrated lower bulk mass as compared to the other products obtained in the experiment.

  5. Effects of Polymeric Additives on the Crystallization and Release Behavior of Amorphous Ibuprofen

    Directory of Open Access Journals (Sweden)

    Su Yang Lee

    2013-01-01

    Full Text Available Some polymeric additives were studied to understand their effects on the amorphous phase of ibuprofen (IBU, used as a poorly water soluble pharmaceutical model compound. The amorphous IBU in bulk, as well as in nanopores (diameter ~24 nm of anodic aluminum oxide, was examined with the addition of poly(acrylic acid, poly(N-vinyl pyrrolidone, or poly(4-vinylphenol. Results of bulk crystallization showed that they were effective in limiting the crystal growth, while the nucleation of the crystalline phase in contact with water was nearly instantaneous in all cases. Poly(N-vinyl pyrrolidone, the most effective additive, was in specific interaction with IBU, as revealed by IR spectroscopy. The addition of the polymers was combined with the nanoscopic confinement to further stabilize the amorphous phase. Still, the IBU with addition of polymeric additives showed sustained release behavior. The current study suggested that the inhibition of the crystal nucleation was probably the most important factor to stabilize the amorphous phase and fully harness its high solubility.

  6. Effect of exogenous phosphorus addition on soil respiration in Calamagrostis angustifolia freshwater marshes of Northeast China

    Science.gov (United States)

    Song, Changchun; Liu, Deyan; Song, Yanyu; Yang, Guisheng; Wan, Zhongmei; Li, Yingchen; Xu, Xiaofeng

    2011-03-01

    Anthropogenic activities have increased phosphorus (P) inputs to wetland ecosystems. However, little is known about the effect of P enrichment on soil respiration in these ecosystems. To understand the effect of P enrichment on soil respiration, we conducted a field experiment in Calamagrostis angustifolia-dominated freshwater marshes, the Sanjiang Plain, Northeast China. We investigated soil respiration in the first growing season after P addition at four rates (0, 1.2, 4.8 and 9.6 g P m-2 year-1). In addition, we also examined aboveground biomass, soil labile C fractions (dissolved organic C, DOC; microbial biomass C, MBC; easily oxidizable C, EOC) and enzyme activities (invertase, urease and acid phosphatase activities) following one year of P addition. P addition decreased soil respiration during the growing season. Dissolved organic C in soil pore water increased after P addition at both 5 and 15 cm depths. Moreover, increased P input generally inhibited soil MBC and enzyme activities, and had no effects on aboveground biomass and soil EOC. Our results suggest that, in the short-term, soil respiration declines under P enrichment in C. angustifolia-dominated freshwater marshes of Northeast China, and its extent varies with P addition levels.

  7. [Effects of superphosphate addition on NH3 and greenhouse gas emissions during vegetable waste composting].

    Science.gov (United States)

    Yang, Yan; Sun, Qin-ping; Li, Ni; Liu, Chun-sheng; Li, Ji-jin; Liu, Ben-sheng; Zou, Guo-yuan

    2015-01-01

    To study the effects of superphosphate (SP) on the NH, and greenhouse gas emissions, vegetable waste composting was performed for 27 days using 6 different treatments. In addition to the controls, five vegetable waste mixtures (0.77 m3 each) were treated with different amounts of the SP additive, namely, 5%, 10%, 15%, 20% and 25%. The ammonia volatilization loss and greenhouse gas emissions were measured during composting. Results indicated that the SP additive significantly decreased the ammonia volatilization and greenhouse gas emissions during vegetable waste composting. The additive reduced the total NH3 emission by 4.0% to 16.7%. The total greenhouse gas emissions (CO2-eq) of all treatments with SP additives were decreased by 10.2% to 20.8%, as compared with the controls. The NH3 emission during vegetable waste composting had the highest contribution to the greenhouse effect caused by the four different gases. The amount of NH3 (CO2-eq) from each treatment ranged from 59.90 kg . t-1 to 81.58 kg . t-1; NH3(CO2-eq) accounted for 69% to 77% of the total emissions from the four gases. Therefore, SP is a cost-effective phosphorus-based fertilizer that can be used as an additive during vegetable waste composting to reduce the NH3 and greenhouse gas emissions as well as to improve the value of compost as a fertilizer.

  8. Cost-effectiveness of cognitive behaviour therapy in addition to mebeverine for irritable bowel syndrome.

    Science.gov (United States)

    McCrone, Paul; Knapp, Martin; Kennedy, Tom; Seed, Paul; Jones, Roger; Darnley, Simon; Chalder, Trudie

    2008-04-01

    Irritable bowel syndrome is often treated in primary-care settings, and it has a relatively large economic impact. Cognitive behaviour therapy (CBT) in addition to mebeverine has been shown to be effective in the short term, compared with treatment with mebeverine alone. This study assesses the impact that CBT in addition to mebeverine has on resource use, and its cost-effectiveness. Participants were recruited from general practices: those with ongoing symptoms were randomly allocated either to remain just on mebeverine or to receive CBT in addition to mebeverine. Service use and lost employment were measured at baseline and at the 3-month, 6-month and 12-month follow-ups. The net-benefit approach was used for combining the data on therapy costs and symptoms. The mean additional cost of CBT was pound 308. No significant impact of CBT on the use of other services or on lost employment was noted. The cost per clinically important reduction in symptoms was pound 220 by the end of treatment, pound 171 at the 3-month follow-up, pound 1027 at the 6-month follow-up and pound 3080 at the 12-month follow-up, for CBT in addition to mebeverine compared with mebeverine alone. CBT in addition to mebeverine seems to have reasonable cost-effectiveness in the short-term treatment of irritable bowel syndrome, but not beyond 3 months.

  9. Joint additive effects of temperature and UVB radiation on zoeae of the crab Taliepus dentatus

    KAUST Repository

    Carreja, B

    2016-04-06

    Warming and enhanced ultraviolet B (UVB) radiation are 2 global stressors acting across the ocean. We tested their effects on the survival and performance (consumption rates and activity) on the zoea I stage of the Chilean kelp crab Taliepus dentatus. Our goal was to resolve whether these stressors, when acting concurrently, had additive or interactive effects, either synergistic or antagonistic. A multifactorial experiment of 4 temperatures and 3 UVB irradiance levels was run. The larvae showed a significant increase in mortality with increasing temperature. Exposure to UVB reduced the thermal tolerance of the larvae by a significant increase of their mortality rate. Oxygen consumption increased as temperature increased. When exposed to UVB radiation, larval oxygen consumption increased significantly for all the temperatures tested. Two statistical models of joint effects confirmed that the combined effect of both stressors was additive, with no interaction, either synergistic or antagonistic. One of them, the independent action (IA) model, also revealed that concurrent effects on mortality remained additive when doubling the UVB dose. Additivity of the stressors improved the predictability of their effects on larval mortality. Exposure to UVB radiation increased mortality rates by 1.5 times at any temperature tested, independently of the dose. © The authors 2016.

  10. Mechanisms and modeling of the effects of additives on the nitrogen oxides emission

    Science.gov (United States)

    Kundu, Krishna P.; Nguyen, H. Lee; Kang, M. Paul

    1991-01-01

    A theoretical study on the emission of the oxides of nitrogen in the combustion of hydrocarbons is presented. The current understanding of the mechanisms and the rate parameters for gas phase reactions were used to calculate the NO(x) emission. The possible effects of different chemical species on thermal NO(x), on a long time scale were discussed. The mixing of these additives at various stages of combustion were considered and NO(x) concentrations were calculated; effects of temperatures were also considered. The chemicals such as hydrocarbons, H2, CH3OH, NH3, and other nitrogen species were chosen as additives in this discussion. Results of these calculations can be used to evaluate the effects of these additives on the NO(x) emission in the industrial combustion system.

  11. Additivity of semantic and phonological effects: Evidence from speech production in Mandarin.

    Science.gov (United States)

    Zhu, Xuebing; Zhang, Qingfang; Damian, Markus F

    2016-11-01

    A number of previous studies using picture-word interference (PWI) tasks conducted with speakers of Western languages have demonstrated non-additive effects of semantic and form overlap between pictures and words, which may indicate underlying non-discrete processing stages in lexical retrieval. The present study used Mandarin speakers and presented Chinese characters as distractors. In two experiments, we crossed semantic relatedness with "pure" phonological (i.e., orthographically unrelated) relatedness and found statistically additive effects. In a third experiment, semantic relatedness was crossed with orthographic overlap (phonological overlap was avoided), and once again we found an additive pattern. The results are discussed with regard to possible cross-linguistic differences between Western and non-Western languages in terms of phonological encoding, as well as concerning the locus of relatedness effects in PWI tasks.

  12. [Effects of menthol as an additive in tobacco products and the need for regulation].

    Science.gov (United States)

    Kahnert, S; Nair, U; Mons, U; Pötschke-Langer, M

    2012-03-01

    Menthol is the most widely used and the most prominent tobacco additive in tobacco products advertised and marketed by the tobacco industry. Besides its characteristic flavor, it possesses a variety of pharmacological properties facilitating tobacco smoke inhalation and potentiating dependence. These properties of menthol not only favor tobacco initiation and consumption but can also prevent smoking cessation. This article summarizes the effect of menthol as an additive in tobacco products and its effect on tobacco consumption that causes a number of chronic diseases and premature death and, therefore, counteracts tobacco control measures. Currently, there is no legislative regulation in Germany that considers the health hazard, addiction-enhancing and attractiveness-increasing properties of additives permitted in tobacco products. Effective regulation or even a ban could contribute to a reduction of tobacco consumption and, hence, save many people from a long-lasting tobacco dependence.

  13. Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers

    NARCIS (Netherlands)

    Vos, J.R.; Oosterwijk, J.C; Aalfs, C.M.; Rookus, M.A.; Adank, M.A.; Hout, A.H. van der; Asperen, C.J. van; Gomez Garcia, E.B.; Mensenkamp, A.R.; Jager, A..; Ausems, M.G.; Mourits, M.J.; Bock, G.H. de

    2016-01-01

    BACKGROUND: Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the

  14. Bias explains most of the parent-of-origin effect on breast cancer risk in BRCA1/2 mutation carriers

    NARCIS (Netherlands)

    Vos, Janet R.; Oosterwijk, Jan C.; Aalfs, Cora M.; Rookus, Matti A.; Adank, Muriel A.; van der Hout, Annemarie H.; van Asperen, Christi J.; Garcia, Encarna B. Gomez; Mensenkamp, Arjen R.; Jager, Agnes; Ausems, Margreet G. E. M.; Mourits, Marian J.; de Bock, Geertruida H.

    Background: Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the

  15. Bias explains most of the parent-of-origin effect on breast cancer risk in BRCA1/2 mutation carriers

    NARCIS (Netherlands)

    Vos, Janet R; Oosterwijk, Jan C; Aalfs, Cora M; Rookus, Matti A; Adank, Muriel A; van der Hout, Annemarie H; van Asperen, Christi J; Gomez-Garcia, Encarna B; Mensenkamp, Arjen R; Jager, Agnes; Ausems, Margreet G E M|info:eu-repo/dai/nl/18756969X; Mourits, Marian J; de Bock, Geertruida H; van der Luijt, RB|info:eu-repo/dai/nl/153170824; van der Pol, C. C|info:eu-repo/dai/nl/41397006X

    2016-01-01

    Background: Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the

  16. The effects of mutating Tyr9 and Arg15 on the structure, stability, conformational dynamics and mechanism of GSTA3-3

    CSIR Research Space (South Africa)

    Robertson, GJ

    2017-03-01

    Full Text Available account for GSTA3-3 having a ten-fold greater affinity for the substrate GSH. Y9F and R15L mutations, singly or together, have no effect on the structure and stability of GSTA3-3 (the same effect they have on GSTA1-1) despite the R15L mutation removing...

  17. Analysis of error-prone survival data under additive hazards models: measurement error effects and adjustments.

    Science.gov (United States)

    Yan, Ying; Yi, Grace Y

    2016-07-01

    Covariate measurement error occurs commonly in survival analysis. Under the proportional hazards model, measurement error effects have been well studied, and various inference methods have been developed to correct for error effects under such a model. In contrast, error-contaminated survival data under the additive hazards model have received relatively less attention. In this paper, we investigate this problem by exploring measurement error effects on parameter estimation and the change of the hazard function. New insights of measurement error effects are revealed, as opposed to well-documented results for the Cox proportional hazards model. We propose a class of bias correction estimators that embraces certain existing estimators as special cases. In addition, we exploit the regression calibration method to reduce measurement error effects. Theoretical results for the developed methods are established, and numerical assessments are conducted to illustrate the finite sample performance of our methods.

  18. Does the model of additive effect in placebo research still hold true? A narrative review.

    Science.gov (United States)

    Boehm, Katja; Berger, Bettina; Weger, Ulrich; Heusser, Peter

    2017-03-01

    Personalised and contextualised care has been turned into a major demand by people involved in healthcare suggesting to move toward person-centred medicine. The assessment of person-centred medicine can be most effectively achieved if treatments are investigated using 'with versus without' person-centredness or integrative study designs. However, this assumes that the components of an integrative or person-centred intervention have an additive relationship to produce the total effect. Beecher's model of additivity assumes an additive relation between placebo and drug effects and is thus presenting an arithmetic summation. So far, no review has been carried out assessing the validity of the additive model, which is to be questioned and more closely investigated in this review. Initial searches for primary studies were undertaken in July 2016 using Pubmed and Google Scholar. In order to find matching publications of similar magnitude for the comparison part of this review, corresponding matches for all included reviews were sought. A total of 22 reviews and 3 clinical and experimental studies fulfilled the inclusion criteria. The results pointed to the following factors actively questioning the additive model: interactions of various effects, trial design, conditioning, context effects and factors, neurobiological factors, mechanism of action, statistical factors, intervention-specific factors (alcohol, caffeine), side-effects and type of intervention. All but one of the closely assessed publications was questioning the additive model. A closer examination of study design is necessary. An attempt in a more systematic approach geared towards solutions could be a suggestion for future research in this field.

  19. Adhesion of Escherichia coli under flow conditions reveals potential novel effects of FimH mutations

    DEFF Research Database (Denmark)

    Feenstra, T.; Schmidt Thøgersen, Mariane; Wieser, E.

    2017-01-01

    H mutations on bacterial adhesion using a novel adhesion assay, which models the physiological flow conditions bacteria are exposed to. We introduced 12 different point mutations in the mannose binding pocket of FimH in an E. coli strain expressing type 1 fimbriae only (MSC95-FimH). We compared the bacterial...... mutations abrogated adhesion. We demonstrated that FimH residues E50 and T53 are crucial for adhesion under flow conditions. The coating of endothelial cells on biochips and modelling of physiological flow conditions enabled us to identify FimH residues crucial for adhesion. These results provide novel...

  20. Effects of nitrogen and water addition on trace element stoichiometry in five grassland species.

    Science.gov (United States)

    Cai, Jiangping; Weiner, Jacob; Wang, Ruzhen; Luo, Wentao; Zhang, Yongyong; Liu, Heyong; Xu, Zhuwen; Li, Hui; Zhang, Yuge; Jiang, Yong

    2017-07-01

    A 9-year manipulative experiment with nitrogen (N) and water addition, simulating increasing N deposition and changing precipitation regime, was conducted to investigate the bioavailability of trace elements, iron (Fe), manganese (Mn), copper (Cu), and zinc (Zn) in soil, and their uptake by plants under the two environmental change factors in a semi-arid grassland of Inner Mongolia. We measured concentrations of trace elements in soil and in foliage of five common herbaceous species including 3 forbs and 2 grasses. In addition, bioaccumulation factors (BAF, the ratio of the chemical concentration in the organism and the chemical concentration in the growth substrate) and foliar Fe:Mn ratio in each plant was calculated. Our results showed that soil available Fe, Mn and Cu concentrations increased under N addition and were negatively correlated with both soil pH and cation exchange capacity. Water addition partly counteracted the positive effects of N addition on available trace element concentrations in the soil. Foliar Mn, Cu and Zn concentrations increased but Fe concentration decreased with N addition, resulting in foliar elemental imbalances among Fe and other selected trace elements. Water addition alleviated the effect of N addition. Forbs are more likely to suffer from Mn toxicity and Fe deficiency than grass species, indicating more sensitivity to changing elemental bioavailability in soil. Our results suggested that soil acidification due to N deposition may accelerate trace element cycling and lead to elemental imbalance in soil-plant systems of semi-arid grasslands and these impacts of N deposition on semi-arid grasslands were affected by water addition. These findings indicate an important role for soil trace elements in maintaining ecosystem functions associated with atmospheric N deposition and changing precipitation regimes in the future.

  1. The effects of nectar addition on pollen removal and geitonogamy in the non-rewarding orchid Anacamptis morio.

    Science.gov (United States)

    Johnson, Steven D; Peter, Craig I; Agren, Jon

    2004-04-22

    It has been suggested that the absence of floral rewards in many orchid species causes pollinators to probe fewer flowers on a plant, and thus reduces geitonogamy, i.e. self-pollination between flowers, which may result in inbreeding depression and reduced pollen export. We examined the effects of nectar addition on pollinator visitation and pollen transfer by tracking the fate of colour-labelled pollen in Anacamptis morio, a non-rewarding orchid species pollinated primarily by queen bumble-bees. Addition of nectar to spurs of A. morio significantly increased the number of flowers probed by bumble-bees, the time spent on an inflorescence, pollinarium removal and the proportion of removed pollen involved in self-pollination through geitonogamy, but did not affect pollen carryover (the fraction of a pollinarium carried over from one flower to the next). Only visits that exceeded 18 s resulted in geitonogamy, as this is the time taken for removed pollinaria to bend into a position to strike the stigma. A mutation for nectar production in A. morio would result in an initial 3.8-fold increase in pollinarium removal per visit, but also increase geitonogamous self-pollination from less than 10% of pollen depositions to ca. 40%. Greater efficiency of pollen export will favour deceptive plants when pollinators are relatively common and most pollinaria are removed from flowers or when inbreeding depression is severe. These findings provide empirical support both for Darwin's contention that pollinarium bending is an anti-selfing mechanism in orchids and for the idea that floral deception serves to maximize the efficiency of pollen export.

  2. Effects of arginine and phytogenic additive supplementation on performance and health of brown-egg layers

    Directory of Open Access Journals (Sweden)

    Vitor Barbosa Fascina

    Full Text Available ABSTRACT This study was performed to evaluate the effects of the association of different digestible arginine and phytogenic additive dietary levels on performance and health status of brown-egg layers. In this study, a total of 504 33-week-old Hisex Brown layers were distributed into a completely randomized experimental design to a 4 × 3 factorial arrangement (dietary digestible arginine levels: 880, 968, 1056, or 1144 mg/kg of feed × phytogenic additive levels: 0, 100, and 200 mg/kg of feed with six replicate cages of seven birds per cage. The phytogenic additive was composed of extracts of Baccharis dracunculifolia (40%, Astragalus membranaceus lipopolysaccharides (20%, cinnamon, and grape seed (20%. Feed intake was reduced when diets containing 1056 mg of arginine were supplemented with 100 or 200 mg phytogenic additive per kg. Feed conversion ratio was improved when diets were supplemented with 100 mg of phytogenic additive or with 1056 mg of arginine per kg of feed. Egg mass was increased when diets were supplemented with 1056 mg arginine per kg of feed. Arginine supplementation quadratically increased albumen percentage and reduced yolk percentage. Higher arginine and phytogenic additive levels reduced heterophyl:lymphocyte ratio and blood uric acid, total cholesterol, very-low density lipoprotein, and triglyceride levels. Dietary supplementation of 100 mg of phytogenic additive associated with high arginine levels increased nitric oxide production by peritoneal macrophages and 1056 mg of arginine increased antibodies titers against Newcastle disease virus. Blood and intestinal malonaldehyde levels were reduced when 200 mg of the phytogenic additive was added. Dietary supplementation of 968 mg of arginine or 100 mg of a phytogenic additive (40% Baccharis dracunculifolia, 20% Astragalus membranaceus, 20% cinnamon, and 20% grape seed extracts per kilogram of diet improves the feed conversion ratio and associated inclusion of 1144 mg of

  3. NOTE: Effects of powder additives suspended in dielectric on crater characteristics for micro electrical discharge machining

    Science.gov (United States)

    Yeo, S. H.; Tan, P. C.; Kurnia, W.

    2007-11-01

    The effects of using powder additives suspended in dielectric on crater characteristics for micro electrical discharge machining (PSD micro-EDM) are investigated through the conduct of single RC discharge experiments at low discharge energies of 2.5 µJ, 5 µJ and 25 µJ. Through the introduction of additive particles into the dielectric, results of the single discharge experiments show the formation of craters with smaller diameters and depths, and having more consistent circular shapes than those produced in dielectric without additive. These craters also possess a noticeable morphological difference compared to those generated in dielectric without additive. In addition, discharge current measurements show a smaller amount of charges flowing between the tool electrode and workpiece, and at a slower flow rate when additives are present in the dielectric. Furthermore, based on the experimental results and findings from studies done in nanofluids, a hypothesis is made on the effects of powder suspended dielectric on the crater formation mechanism. The increased viscosity and enhanced thermal conductivity of a powder suspended dielectric lower the plasma heat flux into the electrode and raise the rate of heat dissipation away from the molten cavity. As a result, a smaller-sized crater having a larger amount of resolidified material within the crater cavity is formed.

  4. Cost-effectiveness of treatment strategies for BRAF-mutated metastatic melanoma.

    Directory of Open Access Journals (Sweden)

    Patti Curl

    Full Text Available Genetically-targeted therapies are both promising and costly advances in the field of oncology. Several treatments for metastatic melanoma with a mutation in the BRAF gene have been approved. They extend life but are more expensive than the previous standard of care (dacarbazine. Vemurafenib, the first drug in this class, costs $13,000 per month ($207,000 for a patient with median survival. Patients failing vemurafenib are often given ipilimumab, an immunomodulator, at $150,000 per course. Assessment of cost-effectiveness is a valuable tool to help navigate the transition toward targeted cancer therapy.We performed a cost-utility analysis to compare three strategies for patients with BRAF+ metastatic melanoma using a deterministic expected-value decision tree model to calculate the present value of lifetime costs and quality-adjusted life years (QALYs for each strategy. We performed sensitivity analyses on all variables.In the base case, the incremental cost-effectiveness ratio (ICER for vemurafenib compared with dacarbazine was $353,993 per QALY gained (0.42 QALYs added, $156,831 added. The ICER for vemurafenib followed by ipilimumab compared with vemurafenib alone was $158,139. In sensitivity analysis, treatment cost had the largest influence on results: the ICER for vemurafenib versus dacarbazine dropped to $100,000 per QALY gained with a treatment cost of $3600 per month.The cost per QALY gained for treatment of BRAF+ metastatic melanoma with vemurafenib alone or in combination exceeds widely-cited thresholds for cost-effectiveness. These strategies may become cost-effective with lower drug prices or confirmation of a durable response without continued treatment.

  5. The effect of lactic acid bacterial starter culture and chemical additives on wilted rice straw silage.

    Science.gov (United States)

    Wang, Yan-Su; Shi, Wei; Huang, Lin-Ting; Ding, Cheng-Long; Dai, Chuan-Chao

    2016-04-01

    Lactic acid bacteria (LAB) are suitable for rice straw silage fermentation, but have been studied rarely, and rice straw as raw material for ensiling is difficult because of its disadvantages, such as low nutrition for microbial activities and low abundances of natural populations of LAB. So we investigated the effect of application of LAB and chemical additives on the fermentation quality and microbial community of wilted rice straw silage. Treatment with chemical additives increased the concentrations of crude protein (CP), water soluble carbohydrate (WSC), acetic acid and lactic acid, reduced the concentrations of acid detergent fiber (ADF) and neutral detergent fiber (NDF), but did not effectively inhibit the growth of spoilage organisms. Inoculation with LABs did not improve the nutritional value of the silage because of poor growth of LABs in wilted rice straw. Inoculation with LAB and addition of chemical materials improved the quality of silage similar to the effects of addition of chemical materials alone. Growth of aerobic and facultatively anaerobic bacteria was inhibited by this mixed treatment and the LAB gradually dominated the microbial community. In summary, the fermentation quality of wilted rice straw silage had improved by addition of LAB and chemical materials. © 2015 Japanese Society of Animal Science.

  6. Occurrence and effects of plastic additives on marine environments and organisms: A review.

    Science.gov (United States)

    Hermabessiere, Ludovic; Dehaut, Alexandre; Paul-Pont, Ika; Lacroix, Camille; Jezequel, Ronan; Soudant, Philippe; Duflos, Guillaume

    2017-09-01

    Plastics debris, especially microplastics, have been found worldwide in all marine compartments. Much research has been carried out on adsorbed pollutants on plastic pieces and hydrophobic organic compounds (HOC) associated with microplastics. However, only a few studies have focused on plastic additives. These chemicals are incorporated into plastics from which they can leach out as most of them are not chemically bound. As a consequence of plastic accumulation and fragmentation in oceans, plastic additives could represent an increasing ecotoxicological risk for marine organisms. The present work reviewed the main class of plastic additives identified in the literature, their occurrence in the marine environment, as well as their effects on and transfers to marine organisms. This work identified polybrominated diphenyl ethers (PBDE), phthalates, nonylphenols (NP), bisphenol A (BPA) and antioxidants as the most common plastic additives found in marine environments. Moreover, transfer of these plastic additives to marine organisms has been demonstrated both in laboratory and field studies. Upcoming research focusing on the toxicity of microplastics should include these plastic additives as potential hazards for marine organisms, and a greater focus on the transport and fate of plastic additives is now required considering that these chemicals may easily leach out from plastics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Additive Effect on the Electrochemical Performance of Lithium–Sulfur Battery

    Energy Technology Data Exchange (ETDEWEB)

    Azimi, Nasim; Xue, Zheng; Hu, Libo; Takoudis, Christos; Zhang, Shengshui; Zhang, Zhengcheng

    2015-02-01

    Lithium difluoro(oxalato) borate (LiDFOB) was investigated as an electrolyte additive for the Li-S battery. This additive was identified to be an efficient electrolyte additive to suppress the polysulfide shuttling effect existing in the conventional Li-S chemistry. To detect the positive impact of the new additive, oligo (ethylene glycol) functionalized silane was employed as the electrolyte solvent due to its high solvation capability with the lithium polysulfides. The electrochemical results and the SEM data of Li-S battery using the new electrolyte confirmed the role of the LiDFOB as a critical component to eliminate the shuttling of the dissolved polysulfides thus enabling a high coulombic efficiency. (C) 2014 Elsevier Ltd. All rights reserved.

  8. Effect of mineral additives on structure and properties of concrete for pavements

    Directory of Open Access Journals (Sweden)

    Sobol Khrystyna

    2017-12-01

    Full Text Available Concrete pavements is an attractive alternative to asphalt pavements because of its lower cost and higher durability. Major contribution to sustainable development can be made by partial replacement of cement in concrete pavement with supplementary cementitious materials of different nature and origin. In this paper, the effect of natural zeolite and perlite additives in complex with chemical admixtures on the structure and properties of concrete for pavement was studied. Compressive and flexural strength test was used to study the mechanical behavior of designed concrete under load. Generally, the compressive strength of both control concrete and concrete containing mineral additives levels at the later ages of hardening. The microstructure analysis of concrete with mineral additives of different nature activity showed the formation of additional amount of hydration products such as tobermorite type calcium hydrosilicate which provide self-reinforcement of hardening concrete system.

  9. Effect of mineral additives on structure and properties of concrete for pavements

    Science.gov (United States)

    Sobol, Khrystyna; Markiv, Taras; Hunyak, Oleksii

    2017-12-01

    Concrete pavements is an attractive alternative to asphalt pavements because of its lower cost and higher durability. Major contribution to sustainable development can be made by partial replacement of cement in concrete pavement with supplementary cementitious materials of different nature and origin. In this paper, the effect of natural zeolite and perlite additives in complex with chemical admixtures on the structure and properties of concrete for pavement was studied. Compressive and flexural strength test was used to study the mechanical behavior of designed concrete under load. Generally, the compressive strength of both control concrete and concrete containing mineral additives levels at the later ages of hardening. The microstructure analysis of concrete with mineral additives of different nature activity showed the formation of additional amount of hydration products such as tobermorite type calcium hydrosilicate which provide self-reinforcement of hardening concrete system.

  10. Additive Neuroprotective Effect of Borneol with Mesenchymal Stem Cells on Ischemic Stroke in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Guang Zhang

    2018-01-01

    Full Text Available Intravenous stem cell transplantation initiates neuroprotection related to the secretion of trophic factor. Borneol, a potential herbal neuroprotective agent, is a penetration enhancer. Here, we aimed to investigate whether they have additive neuroprotective effect on cerebral ischemia. Borneol was given to mice by gavage 3 days before middle cerebral artery occlusion (MCAO induction until the day when the mice were sacrificed. Mesenchymal stem cells (MSCs were intravenously injected at 24 h after MCAO induction. Neurological deficits, infarct volume, cell death, and neurogenesis were evaluated. Combined use of MSCs and borneol could more effectively reduce infarction volume and cell apoptosis, enhance neurogenesis, and improve the functional recovery than that of MSCs alone. The findings showed that combined use of borneol and stem cells provided additive neuroprotective effect on cerebral ischemia. However, the supposed effect of borneol on the improved MSC penetration still needs further direct evidence.

  11. Effects of mineral additions on durability and physico-mechanical properties of mortar

    Science.gov (United States)

    Logbi, A.; Kriker, A.; Snisna, Z.

    2017-02-01

    This paper consists of an experimental study of the effect of some mineral admixtures on the properties of mortar. Blast furnace Slag of El-Hadjar, natural pozzolan of Beni saf and limestone of Ghardaia, all from Algeria, are crushed in high fineness and incorporated in the cement with different contents (15 % 20 % and 10%) respectively, in order to perform the physico-mechanical characteristics and durability of the mortar. The replacement of cement by 15% of natural pozzolan, or 20% of the Blast furnace Slag improves the mechanical performances of mortar in early and long ages than the mortar without additions, but 10% of limestone fillers have a positive effect only at early age. For durability the three additions have developed a beneficial effect on mechanical resistance under the free aquifers water, while their effects are different on capillary absorption.

  12. The effect of SERPINF1 in-frame mutations in osteogenesis imperfecta type VI.

    Science.gov (United States)

    Al-Jallad, Hadil; Palomo, Telma; Roughley, Peter; Glorieux, Francis H; McKee, Marc D; Moffatt, Pierre; Rauch, Frank

    2015-07-01

    Osteogenesis imperfecta type VI is caused by mutations in SERPINF1, which codes for pigment-epithelium derived factor (PEDF). Most of the reported SERPINF1 mutations lead to premature termination codons, but three in-frame insertion or deletion mutations have also been reported. It is not clear how such in-frame mutations lead to OI type VI. In the present study we therefore investigated how SERPINF1 in-frame mutations affect the intracellular localization and secretion of PEDF. Skin fibroblasts affected by SERPINF1 in-frame mutations transcribed SERPINF1 at slightly reduced levels but secretion of PEDF was markedly diminished. Two deletions (p.F277del and the deletion of SERPINF1 exon 5) were associated with retention of PEDF in the endoplasmic reticulum and a stress response in osteoblastic cells. A recurrent in-frame duplication of three amino acids (p.Ala91_Ser93dup) appeared to lead to intracellular degradation but no retention in the endoplasmic reticulum or stress response. Immunofluorescence imaging in transiently transfected osteoblastic MC3T3-E1 cells suggested that PEDF affected by in-frame mutations was not transported along the secretory pathway. MC3T3-E1 osteoblasts stably overexpressing SERPINF1 with the p.Ala91_Ser93dup mutation had decreased collagen type I deposition and mineralization. Thus, the assessed homozygous in-frame deletions or insertions lead to retention or degradation within cellular compartments and thereby interfere with PEDF secretion. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Effect of the addition of mixture of plant components on the mechanical properties of wheat bread

    Science.gov (United States)

    Wójcik, Monika; Dziki, Dariusz; Biernacka, Beata; Różyło, Renata; Miś, Antoni; Hassoon, Waleed H.

    2017-10-01

    Instrumental methods of measuring the mechanical properties of bread can be used to determine changes in the properties of it during storage, as well as to determine the effect of various additives on the bread texture. The aim of this study was to investigate the effect of the mixture of plant components on the physical properties of wheat bread. In particular, the mechanical properties of the crumb and crust were studied. A sensory evaluation of the end product was also performed. The mixture of plant components included: carob fiber, milled grain red quinoa and black oat (1:2:2) - added at 0, 5, 10, 15, 20, 25 % - into wheat flour. The results showed that the increase of the addition of the proposed additive significantly increased the water absorption of flour mixtures. Moreover, the use of the mixture of plant components above 5% resulted in the increase of bread volume and decrease of crumb density. Furthermore, the addition of the mixture of plant components significantly affected the mechanical properties of bread crumb. The hardness of crumb also decreased as a result of the mixture of plant components addition. The highest cohesiveness was obtained for bread with 10% of additive and the lowest for bread with 25% of mixture of plant components. Most importantly, the enrichment of wheat flour with the mixture of plant components significantly reduced the crust failure force and crust failure work. The results of sensory evaluation showed that the addition of the mixture of plant components of up to 10% had little effect on bread quality.

  14. Parental Anxiety and Child Symptomatology: An Examinzation of Additive and Interactive Effects of Parent Psychopathology

    Science.gov (United States)

    Ginsburg, Golda S.; Tein, Jenn-Yun

    2012-01-01

    The current study examined relations between parent anxiety and child anxiety, depression, and externalizing symptoms. In addition, the study tested the additive and interactive effects of parent anxiety with parent depression and externalizing symptoms in relation to child symptoms. Forty-eight parents with anxiety disorders and 49 parents without any psychiatric disorder participated with one of their children (ages 6 to 14 years; 46.4% male; 75.8% Caucasian). Parent anxiety was related to both child anxiety and depression, but not child externalizing symptoms. Hierarchical regression analyses showed that only parent externalizing symptoms had additive effects, beyond parent anxiety symptoms, in relation to child anxiety symptoms. Further, parent anxiety symptoms moderated the relationship between parent and child externalizing symptoms, such that the strength of this relationship was reduced in the presence of high levels of parent anxiety symptoms. Results of this study illuminate the role of parent comorbidity in understanding relations between parent and child symptoms. PMID:20432062

  15. Effect of Sr Additive Amount and Holding Time on Microstructure of A390 Aluminum Alloy

    Science.gov (United States)

    Zhang, J. H.; Xing, S. M.; Han, Q. Y.; Guo, Q.; Wang, R. F.

    2017-11-01

    The microstructure of A390 alloy under different Sr additive amounts and holding times was studied by means of direct reading spectrum analysis, energy spectrum analysis, optical microscope and electron microscope. The results show that Sr has a good modification to eutectic Si, while it has a negative effect on primary silicon. The Sr addition will increase the size of primary silicon. When the addition amount of Al-10Sr alloy is 0.6%, the modification of eutectic silicon is the optimum. The Sr has a short incubation period and a fine modification at 10min, but it is more serious burning rate in small furnace smelting, and the modification effect disappears basically after 100min.

  16. Synthetic Effect of Vivid Shark Skin and Polymer Additive on Drag Reduction Reinforcement

    Directory of Open Access Journals (Sweden)

    Huawei Chen

    2014-06-01

    Full Text Available Natural shark skin has a well-demonstrated drag reduction function, which is mainly owing to its microscopic structure and mucus on the body surface. In order to improve drag reduction, it is necessary to integrate microscopic drag reduction structure and drag reduction agent. In this study, two hybrid approaches to synthetically combine vivid shark skin and polymer additive, namely, long-chain grafting and controllable polymer diffusion, were proposed and attempted to mimic such hierarchical topography of shark skin without waste of polymer additive. Grafting mechanism and optimization of diffusion port were investigated to improve the efficiency of the polymer additive. Superior drag reduction effects were validated, and the combined effect was also clarified through comparison between drag reduction experiments.

  17. Investigations of the effects of some additives on the crystallization of tetrahydrate sodium perborate

    Science.gov (United States)

    Frances, C.; Biscans, B.; Gabas, N.; Laguérie, C.

    1993-03-01

    The presence of impurities in a system can drastically affect the growth rates of crystals grown from solutions. In this study, growth experiments with tetrahydrate sodium perborate (SPB) crystals in the presence of additives have been performed in a batch fluidized bed crystallizer. First, it has been shown that sodium metaborate (SMB) affects the solubility of SPB, reducing it at low concentration and increasing it at high concentration. Related to this, it also modifies the growth rate of SPB crystals. The effect of various kinds of mineral additives, surfactants and a polymer on growth rate has also been investigated. The retarding action observed in the presence of some of these additives has been interpreted in terms of a Langmuir-type adsorption isotherm. The apparent accelerating effect on growth rate obtained with aluminium sulfate and cetyltrimethyl ammonium bromide, a cationic surfactant, was supposed to be related to an enhancement of nucleation and agglomeration processes.

  18. Estimation of direct effects for survival data by using the Aalen additive hazards model

    DEFF Research Database (Denmark)

    Martinussen, T.; Vansteelandt, S.; Gerster, M.

    2011-01-01

    We extend the definition of the controlled direct effect of a point exposure on a survival outcome, other than through some given, time-fixed intermediate variable, to the additive hazard scale. We propose two-stage estimators for this effect when the exposure is dichotomous and randomly assigned...... Aalen's additive regression for the event time, given exposure, intermediate variable and confounders. The second stage involves applying Aalen's additive model, given the exposure alone, to a modified stochastic process (i.e. a modification of the observed counting process based on the first......-stage estimates). We give the large sample properties of the estimator proposed and investigate its small sample properties by Monte Carlo simulation. A real data example is provided for illustration....

  19. Additional Interventions to Enhance the Effectiveness of Individual Placement and Support: A Rapid Evidence Assessment

    Directory of Open Access Journals (Sweden)

    Naomi Boycott

    2012-01-01

    Full Text Available Topic. Additional interventions used to enhance the effectiveness of individual placement and support (IPS. Aim. To establish whether additional interventions improve the vocational outcomes of IPS alone for people with severe mental illness. Method. A rapid evidence assessment of the literature was conducted for studies where behavioural or psychological interventions have been used to supplement standard IPS. Published and unpublished empirical studies of IPS with additional interventions were considered for inclusion. Conclusions. Six published studies were found which compared IPS alone to IPS plus a supplementary intervention. Of these, three used skills training and three used cognitive remediation. The contribution of each discrete intervention is difficult to establish. Some evidence suggests that work-related social skills and cognitive training are effective adjuncts, but this is an area where large RCTs are required to yield conclusive evidence.

  20. Rheological behavior of functional sugar-free guava preserves : effect of the addition of salts.

    OpenAIRE

    Patrícia Aparecida Pimenta PEREIRA; Souza,Vanessa Rios de; Teixeira, Taísa Rezende; Queiroz, Fabiana; Borges, Soraia Vilela; Carneiro, João de Deus Souza

    2013-01-01

    The addition of salts to carrageenan and locust bean gum gels functions to improve the characteristics of texture, thereby increasing gel strength. This effect is widely studied in gels of model systems but is studied to a lesser extent in complex systems, such as fruit preserves. The objective of this study was to evaluate the effect of adding salts on the rheological behavior of functional sugar-free guava preserves, as well as to correlate the rheological parameters. To this end, three typ...

  1. A "dose" effect of mutations in the GBA gene on Parkinson's disease phenotype.

    Science.gov (United States)

    Thaler, Avner; Gurevich, Tanya; Bar Shira, Anat; Gana Weisz, Mali; Ash, Elissa; Shiner, Tamara; Orr-Urtreger, Avi; Giladi, Nir; Mirelman, Anat

    2017-03-01

    Mutations in the GBA gene are associated with Parkinson's disease (PD). A definite description of the clinical characteristics of PD patients who are compound heterozygotes or homozygotes for mutations in the GBA gene (GD-PD) requires further elucidation. We assessed motor, cognitive, olfactory and autonomic functions as well as demographic data and medical history in a cohort of Ashkenazi Jewish PD patients who were screened for seven common mutations in the GBA gene. We then compared three groups of patients (matched for age and disease duration) who were distinguished by their GBA mutation status, idiopathic PD (iPD), GBA heterozygote PD (GBA-PD) and GD-PD. Out of a total of 1050 AJ PD patients screened, 12 were found to be either homozygotes or compound heterozygotes for mutations in the GBA gene. These patients had an earlier age of onset, more severe motor impairment, poorer cognition and lower olfactory scores. They also had a higher prevalence of REM sleep behavior disorder and higher frequencies of hallucinations compared to both GBA-PD and iPD. The severity of PD phenotype is related to the burden of GBA mutations with GD-PD patients manifesting a more severe phenotype. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. IDH mutations associated impact on related cancer epidemiology and subsequent effect toward HIF-1α.

    Science.gov (United States)

    Semukunzi, Herve; Roy, Debmalya; Li, Hongyang; Khan, Ghulam Jilany; Lyu, Xiaodan; Yuan, Shengtao; Lin, Sensen

    2017-05-01

    Particular mutations in the isocitrate dehydrogenase gene (IDH) were discovered in several gliomas citing astrocytoma, oligodendroglioma, and glioblastoma multiform, but also in leukemia; these mutations were discovered in nearly all cases of secondary glioblastomas, they evolve from lower-grade gliomas, but are limited in primary high-grade glioblastoma multiform. These mutations distinctively produce (D)-2-hydroxyglutarate (D-2-HG) from alpha-ketoglutarate (α-KG). (D)-2-hydroxyglutarate is accumulated to very high concentrations which inhibit the function of enzymes that are dependent on alpha-ketoglutarate. This modification leads to a hyper-methylated state of DNA and histones, resulting in different gene expression that can activate oncogenes and inactivate tumor-suppressor genes. In our work we review the impact of the mutations that occur in IDH genes, we focus on their impact on distribution in cancer. As IDH mutations appear in many different conditions we expose the extent of IDH mutations and derivate their impact on cancer prognosis, diagnosis, and even their oncogenicity, we will also link their impact to HIF-1α and derivate some target and finally, we present some of the therapeutics under research and out on market. Copyright © 2017. Published by Elsevier Masson SAS.

  3. Effect of HIV-1 Subtype C integrase mutations implied using molecular modeling and docking data.

    Science.gov (United States)

    Sachithanandham, Jaiprasath; Konda Reddy, Karnati; Solomon, King; David, Shoba; Kumar Singh, Sanjeev; Vadhini Ramalingam, Veena; Alexander Pulimood, Susanne; Cherian Abraham, Ooriyapadickal; Rupali, Pricilla; Sridharan, Gopalan; Kannangai, Rajesh

    2016-01-01

    The degree of sequence variation in HIV-1 integrase genes among infected patients and their impact on clinical response to Anti retroviral therapy (ART) is of interest. Therefore, we collected plasma samples from 161 HIV-1 infected individuals for subsequent integrase gene amplification (1087 bp). Thus, 102 complete integrase gene sequences identified as HIV-1 subtype-C was assembled. This sequence data was further used for sequence analysis and multiple sequence alignment (MSA) to assess position specific frequency of mutations within pol gene among infected individuals. We also used biophysical geometric optimization technique based molecular modeling and docking (Schrodinger suite) methods to infer differential function caused by position specific sequence mutations towards improved inhibitor selection. We thus identified accessory mutations (usually reduce susceptibility) leading to the resistance of some known integrase inhibitors in 14% of sequences in this data set. The Stanford HIV-1 drug resistance database provided complementary information on integrase resistance mutations to deduce molecular basis for such observation. Modeling and docking analysis show reduced binding by mutants for known compounds. The predicted binding values further reduced for models with combination of mutations among subtype C clinical strains. Thus, the molecular basis implied for the consequence of mutations in different variants of integrase genes of HIV-1 subtype C clinical strains from South India is reported. This data finds utility in the design, modification and development of a representative yet an improved inhibitor for HIV-1 integrase.

  4. Effect of HIV-1 Subtype C integrase mutations implied using molecular modeling and docking data

    Science.gov (United States)

    Sachithanandham, Jaiprasath; Konda Reddy, Karnati; Solomon, King; David, Shoba; Kumar Singh, Sanjeev; Vadhini Ramalingam, Veena; Alexander Pulimood, Susanne; Cherian Abraham, Ooriyapadickal; Rupali, Pricilla; Sridharan, Gopalan; Kannangai, Rajesh

    2016-01-01

    The degree of sequence variation in HIV-1 integrase genes among infected patients and their impact on clinical response to Anti retroviral therapy (ART) is of interest. Therefore, we collected plasma samples from 161 HIV-1 infected individuals for subsequent integrase gene amplification (1087 bp). Thus, 102 complete integrase gene sequences identified as HIV-1 subtype-C was assembled. This sequence data was further used for sequence analysis and multiple sequence alignment (MSA) to assess position specific frequency of mutations within pol gene among infected individuals. We also used biophysical geometric optimization technique based molecular modeling and docking (Schrodinger suite) methods to infer differential function caused by position specific sequence mutations towards improved inhibitor selection. We thus identified accessory mutations (usually reduce susceptibility) leading to the resistance of some known integrase inhibitors in 14% of sequences in this data set. The Stanford HIV-1 drug resistance database provided complementary information on integrase resistance mutations to deduce molecular basis for such observation. Modeling and docking analysis show reduced binding by mutants for known compounds. The predicted binding values further reduced for models with combination of mutations among subtype C clinical strains. Thus, the molecular basis implied for the consequence of mutations in different variants of integrase genes of HIV-1 subtype C clinical strains from South India is reported. This data finds utility in the design, modification and development of a representative yet an improved inhibitor for HIV-1 integrase. PMID:28149058

  5. Differential effects of FGFR2 mutations on syndactyly and cleft palate in Apert syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Slaney, S.F.; Oldridge, M.; Wilkie, A.O.M. [Univ. of Oxford (United Kingdom)] [and others

    1996-05-01

    Apert syndrome is a distinctive human malformation characterized by craniosynostosis and severe syndactyly of the hands and feet. It is caused by specific missense substitutions involving adjacent amino acids (Ser252Trp or Pro253Arg) in the linker between the second and third extracellular immunoglobulin domains of fibroblast growth factor receptor 2 (FGFR2). We have developed a simple PCR assay for these mutations in genomic DNA, based on the creation of novel SfiI and BstUI restriction sites. Analysis of DNA from 70 unrelated patients with Apert syndrome showed that 45 had the Ser252Trp mutation and 25 had the Pro253Arg mutation. Phenotypic differences between these two groups of patients were investigated. Significant differences were found for severity of syndactyly and presence of cleft palate. The syndactyly was more severe with the Pro253Arg mutation, for both the hands and the feet. In contrast, cleft palate was significantly more common in the Ser252Trp patients. No convincing differences were found in the prevalence of other malformations associated with Apert syndrome. We conclude that, although the phenotype attributable to the two mutations is very similar, there are subtle differences. The opposite trends for severity of syndactyly and cleft palate in relation to the two mutations may relate to the varying patterns of temporal and tissue-specific expression of different fibroblast growth factors, the ligands for FGFR2. 54 refs., 5 figs., 3 tabs.

  6. Effect of CuO addition on structure and electrical properties of low ...

    Indian Academy of Sciences (India)

    3Sb2/3)0·06(Ni1/2W1/2)0·02-. (Zr0·49Ti0·51)0·92]O3. Effect of the addition on sintering temperature, structure and electrical properties of ceramics was investigated. The piezoelectric ceramics was prepared by solid-state reaction. Sintering ...

  7. Effect of CuO addition on structure and electrical properties of low ...

    Indian Academy of Sciences (India)

    0.06(Ni1/2W1/2)0.02-(Zr0.49Ti0.51)0.92]O3. Effect of the addition on sintering temperature, structure and electrical properties of ceramics was investigated. The piezoelectric ceramics was prepared by solid-state reaction. Sintering experiments ...

  8. Effect of Drilling Fluid Additives on the Niger Delta Environment: -A ...

    African Journals Online (AJOL)

    The effect of drilling fluid additives on the Soku oil fields environment has been examined. Soil and reserve pits in various locations were assessed for some physico-chemical characteristics and heavy metal content using standard methods for water and wastewater analysis. Plant growth and other biomass were also ...

  9. Enhancing crude oil degradation in a sandy soil: Effects of addition ...

    African Journals Online (AJOL)

    Natural restoration of crude oil polluted soils takes a long time, hence various soil treatments have been used to hasten the process. This study investigated the effects of the addition of poultry manure alone and in combination with surfactant (Goldcrew or Corexit) and/or alternate carbon substrate (glucose or starch) on ...

  10. The Effect of Ta and Ti Additions on the Strain Sensitivity of Bulk Niobium-Tin

    NARCIS (Netherlands)

    Mentink, M.G.T.; Dhalle, Marc M.J.; Dietderich, D.R.; Godeke, A.; Goldacker, W.; Hellman, F.; ten Kate, Herman H.J.; Sumption, M.D.; Susner, M.A.

    2012-01-01

    The effect of tantalum and titanium additions on the composition, the superconducting properties, and their sensitivity to strain of bulk Nb3Sn is investigated. Using heat capacity analysis and Scanning Electron Microscopy with Energy Dispersive X-ray Spectroscopy (SEM-EDX), it is found that the

  11. Contributions of Work-Related Stress and Emotional Intelligence to Teacher Engagement: Additive and Interactive Effects

    OpenAIRE

    Sergio Mérida-López; Natalio Extremera; Lourdes Rey

    2017-01-01

    This study examined the additive and interactive effects of role stress and emotional intelligence for predicting engagement among 288 teachers. Emotional intelligence and engagement were positively associated. Role ambiguity and role conflict showed negative associations with vigor and dedication scores. The interaction of role ambiguity and emotional intelligence was significant in explaining engagement dimensions. Similar results were found considering overall teacher engagement. Emotional...

  12. Effect of Value- Addition on the Benefits of Women Participation in ...

    African Journals Online (AJOL)

    The paper focused on the effect of value- addition on the benefits of women participation in cassava products marketing in Cross River State, Nigeria. Data were collected with the aid of a structured questionnaire from 48 randomly selected respondents. Data were analyzed using both descriptive and marketing margin ...

  13. effects of zinc powder addition to villa gloss and silka lux marine ...

    African Journals Online (AJOL)

    HP

    The anti-corrosion properties of paints can be optimised when adequate proportion of the paint constituents are used. Effect of zinc powder addition to Villa Gloss and Silka Lux Marine Enamel paints on corrosion resistance of mild steel was studied. Quantitative Analysis and Potentiodynamic Polarisation Technique were ...

  14. Effect of graded levels of Saccharum officinarum as an additive to ...

    African Journals Online (AJOL)

    An experiment was conducted to evaluate the effect of graded levels of sugar cane (Saccharum officinarum) as an additive to Guinea grass (Panicum maximum) silage. A previously established guinea grass plot, totaling an area of 625m2 was cut back and fertilized with urea at the rate of 200 kgN/ha. The pasture was then ...

  15. The Effect of Nano-TiC Addition on Sintered Nd-Fe-B Permanent Magnets

    DEFF Research Database (Denmark)

    Mural, Zorjana; Kollo, Lauri; Xia, Manlong

    2017-01-01

    This paper addresses the effect of nano-TiC addition on sintered Nd-Fe-B permanent magnets. TiC nanoparticles were added to sintered Nd-Fe-B magnets with a specific aim to improve the Curie temperature and thermal stability. A standard powder metallurgy route was adopted to prepare the magnets...

  16. Effects of novel feed additives in wheat based diets on performance ...

    African Journals Online (AJOL)

    The present study was conducted to investigate the effects of the supplementation of an antibiotic growth promoter or novel feed additives with or without a xylanase-based enzyme complex to wheat-based diets on the growth performance, carcass yields and quality and intestinal characteristics (length of the total and small ...

  17. The effect of inorganic additives to calcium phosphate on in vitro behavior of osteoblasts and osteoclasts

    NARCIS (Netherlands)

    Yang, Liang; Perez-Amodio, Soledad; Barrère, F.; Everts, Vincent; van Blitterswijk, Clemens; Habibovic, Pamela

    2010-01-01

    This study describes a medium-throughput system based on deposition of calcium phosphate films in multi-well tissue culture plates that can be used to study the effect of inorganic additives on the behavior of osteoblasts and osteoclasts in a standardized manner. All tested elements, copper, zinc,

  18. The effects of inorganic additives to calcium phosphate on in vitro behavior of osteoblasts and osteoclasts

    NARCIS (Netherlands)

    Yang, L.; Perez-Amodio, S.; Barrere-de Groot, F.Y.F.; Everts, V.; van Blitterswijk, C.A.; Habibovic, P.

    2010-01-01

    This study describes a medium-throughput system based on deposition of calcium phosphate films in multi-well tissue culture plates that can be used to study the effect of inorganic additives on the behavior of osteoblasts and osteoclasts in a standardized manner. All tested elements, copper, zinc,

  19. The Effectiveness of an Additional Stretching Exercise Program in Improving Flexibility Level among Preschool Boys

    Science.gov (United States)

    Lee, Wee Akina Sia Seng; Rengasamy, Shabeshan A/L; Raju, Subramaniam A/L

    2014-01-01

    This study was conducted to examine the effectiveness of a two minutes' additional stretching exercise program in a 30 minutes games teaching lesson in improving the flexibility level of 6 year old preschool boys (M = 5.92, SD = 0.27) in a preschool in Malaysia. Fifty (50) preschool boys were selected for the study based on the intact sampling…

  20. Effects of zinc powder addition to Villa Gloss and Silka Lux marine ...

    African Journals Online (AJOL)

    Effects of zinc powder addition to Villa Gloss and Silka Lux marine enamel paints on corrosion resistance of mild steel. ... Microstructural analysis of the samples also revealed the presence of pitting corrosion at the surfaces of the samples and their geometry, v olume fraction and distribution vary with the zinc powder ...

  1. Effect of chromium and aluminum addition on anisotropic and microstructural characteristics of ball milled nanocrystalline iron

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rajiv, E-mail: rajiv06484met@gmail.com [IITB-Monash Research Academy, Indian Institute of Technology Bombay, Powai, Mumbai 400076 (India); Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076 (India); Department of Mechanical and Aerospace Engineering, Monash University, VIC 3800 Australia (Australia); Joardar, Joydip [International Advanced Research Centre for Powder Metallurgy and New Materials, Hyderabad (India); Singh Raman, R.K. [Department of Mechanical and Aerospace Engineering, Monash University, VIC 3800 Australia (Australia); Department of Chemical Engineering, Monash University, VIC 3800 Australia (Australia); Raja, V.S. [Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076 (India); Joshi, S.V. [International Advanced Research Centre for Powder Metallurgy and New Materials, Hyderabad (India); Parida, S. [Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076 (India)

    2016-06-25

    Prior studies on synthesis of nanocrystalline elements have discussed the effect of ball milling on lattice parameter, crystallite size, and micro-strain. For elemental milled powders, the anisotropic peak broadening does not change with increasing milling time. However, the effect of alloying addition on the anisotropic behavior of ball milled nanocrystalline powders remains an unexplored area. Here we report the effect of chromium and aluminum addition on the anisotropic behavior of iron in nanocrystalline Fe–20Cr–5Al (wt%) alloy powders synthesized by ball milling. The experimental results show that the anisotropic behavior of iron changes towards isotropic with milling. This change was also correlated to the theoretically calculated anisotropic factor from the change in elastic constant of iron due to milling. Addition of alloying elements exhibited a monotonic rise in the lattice parameter with crystallite size, which was attributed to the excess grain boundary interfacial energy and excess free volume at grain boundaries. Transmission electron microscopy image confirmed the crystallite size and nature of dislocation obtained using modified Williamson-Hall method. - Highlights: • Structural evolution in Fe–20Cr–5Al alloy during ball milling is reported. • Effect of alloying addition on the anisotropic behavior of iron was studied. • Agreement in anisotropic factor calculated theoretically and experimentally.

  2. The cost-effectiveness of HPV vaccination in addition to screening : a Dutch perspective

    NARCIS (Netherlands)

    Setiawan, Didik; Luttjeboer, Jos; Westra, Tjalke Arend; Wilschut, Jan C.; Suwantika, Auliya A.; Daemen, Toos; Atthobari, Jarir; Wilffert, Bob; Postma, Maarten J.

    2015-01-01

    Addition of the HPV vaccine to available cytological screening has been proposed to increase HPV-related cancer prevention. A comprehensive review on this combined strategy implemented in the Netherlands is lacking. For this review, we therefore analyzed all relevant studies on cost-effectiveness of

  3. Additive Effects of Stimulus Quality and Word Frequency on Eye Movements during Chinese Reading

    Science.gov (United States)

    Liu, Pingping; Li, Xingshan; Han, Buxin

    2015-01-01

    Eye movements of Chinese readers were recorded for sentences in which high- and low-frequency target words were presented normally or with reduced stimulus quality in two experiments. We found stimulus quality and word frequency produced strong additive effects on fixation durations for target words. The results demonstrate that stimulus quality…

  4. Anthelmintic effects of phytogenic feed additives in Ascaris suum inoculated pigs

    NARCIS (Netherlands)

    Krimpen, van M.M.; Binnendijk, G.P.; Borgsteede, F.H.M.; Gaasenbeek, C.P.H.

    2010-01-01

    Two experiments were performed to determine the anthelmintic effect of some phytogenic feed additives on a mild infection of Ascaris suum in growing and finishing pigs. Usually, an infection of A. suum is controlled by using conventional synthetic drugs. Organic farmers, however, prefer a

  5. Effect of crushed mussel shell addition on bacterial growth in acid polluted soils

    DEFF Research Database (Denmark)

    Fernandez Calviño, David; Garrido-Rodríguez, B.; Arias-Estévez, M.

    2015-01-01

    We applied three different doses of crushed mussel shell (CMS) on two Cu-polluted acid soils to study the effect of these amendments on the growth of the bacterial community during 730 days. Soil pH increased in the short and medium term due to CMS addition. In a first stage, bacterial growth was...

  6. Effect of Firm Ripe Plantain Fruit Flour Addition on the Chemical ...

    African Journals Online (AJOL)

    Effect of Firm Ripe Plantain Fruit Flour Addition on the Chemical, Sensory and Microbial Quality of Fura Powder. ... Millet flour was supplemented with plantain flour at substitution levels of 0, 10, 20, 30 and 40 to obtain fura powder. ... Similar trend was observed in protein content as it decreased from 13.0% to 10.0%.

  7. Effects of pH and additives on aqueous wetting films stabilized by a triblock copolymer

    NARCIS (Netherlands)

    Eliseeva, O.V.; Besseling, N.A.M.; Koopal, L.K.; Stuart, M.A.C.

    2007-01-01

    Effects of pH and additives (NaCl, Na2SO4, NaSCN and urea) on the adsorption of an ABA triblock copolymer (F127) with polyethylene oxide as the A blocks and polypropylene oxide as the B blocks, at the interfaces of wetting films, on film drainage and on the interaction forces in these films are

  8. Effects of carbohydrate addition on production in extensive shrimp culture systems

    NARCIS (Netherlands)

    Hari, B.; Kurup, B.M.; Varghese, J.T.; Schrama, J.W.; Verdegem, M.C.J.

    2004-01-01

    One indoor and one on-farm trial were conducted to evaluate the effect of control of carbon/ nitrogen ratio (C/N ratio) by addition of carbohydrate to the water column in extensive types of shrimp culture systems. In the indoor experiment, 25% and 40% dietary protein ('P25' and 'P40') with or

  9. Study on the Effect of Mutated Bacillus Megaterium in Two-Stage Fermentation of Vitamin C

    Science.gov (United States)

    Lü, Shujuan; Wang, Jun; Yao, Jianming; Yu, Zengliang

    2003-10-01

    Bacillus megaterium as a companion strain in two-stage fermentation of vitamin C could secrete some active substances to spur growth of Gluconobacter oxydans to produce 2-KLG. In the fermenting system where Gluconobacter oxydans was combined with GB82-a mutated strain of B. megaterium by ion implantation, the amount of 2-KLG harvested was larger than that produced by the original B. megaterium BP52 [1] being substituted for GB82. In this paper, we studied the effect of the active substances secreted by GB82 to enhance the capability of Gluconobacter oxydans to produce 2-KLG. The supernate of GB82 sampled at different cultivation times all had much more activity to spur Gluconobacter oxydans to yield 2-KLG than that of the original B. megaterium, which might be due to the genetic changes in the active components caused by ion implantation. Furthermore, the active substances of GB82's supernate would lose a part of its activity in extreme environments, which is typical of some proteins.

  10. A cost-effectiveness analysis of trametinib plus dabrafenib as first-line therapy for metastatic BRAF V600-mutated melanoma in the Swiss setting.

    Science.gov (United States)

    Matter-Walstra, K; Braun, R; Kolb, C; Ademi, Z; Dummer, R; Pestalozzi, B C; Schwenkglenks, M

    2015-12-01

    The treatment of patients with metastatic melanomas that harbour BRAF V600E or V600K mutations with trametinib plus dabrafenib appears to be superior to treatment with vemurafenib alone. This treatment regimen is likely to become available in Switzerland in the near future. To determine the cost-effectiveness of trametinib plus dabrafenib. A Markov cohort simulation was conducted to model the clinical course of typical patients with metastatic melanoma. Information on response rates, clinical condition and follow-up treatments were derived and transition probabilities estimated based on the results of a clinical trial that compared treatment with trametinib plus dabrafenib vs. vemurafenib alone. Treatment with trametinib plus dabrafenib was estimated to cost an additional CHF199 647 (Swiss francs) on average and yield a gain of 0·52 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of CHF385 603 per QALY. Probabilistic sensitivity analyses showed that a willingness-to-pay threshold of CHF100 000 per QALY would not be reached at the current US price of trametinib. The introduction of trametinib in Switzerland at US market prices for the treatment of metastatic BRAF V600-mutated melanoma with trametinib plus dabrafenib is unlikely to be cost-effective compared with vemurafenib monotherapy. A reduction in the total price of the combination therapy is required to achieve an acceptable cost-effectiveness ratio for this clinically promising treatment. © 2015 British Association of Dermatologists.

  11. Effects of water addition on soil arthropods and soil characteristics in a precipitation-limited environment

    Science.gov (United States)

    Chikoski, Jennifer M.; Ferguson, Steven H.; Meyer, Lense

    2006-09-01

    We investigated the effect of water addition and season on soil arthropod abundance and soil characteristics (%C, %N, C:N, moisture, pH). The experimental design consisted of 24 groups of five boxes distributed within a small aspen stand in Saskatchewan, Canada. The boxes depressed the soil to create a habitat with suitable microclimate for soil arthropods, and by overturning boxes we counted soil arthropods during weekly surveys from April to September 1999. Soil samples were collected at two-month intervals and water was added once per week to half of the plots. Of the eleven recognizable taxonomic units identified, only mites (Acari) and springtails (Collembola) responded to water addition by increasing abundance, whereas ants decreased in abundance with water addition. During summer, springtail numbers increased with water addition, whereas pH was a stronger determinant of mite abundance. In autumn, springtails were positively correlated with water and negatively correlated with mites, whereas mite abundance was negatively correlated with increasing C:N ratio, positively correlated to water addition, and negatively correlated with springtail abundance. Although both mite and springtail numbers decreased in autumn with a decrease in soil moisture, mites became more abundant than springtails suggesting a predator-prey (mite-springtail) relationship. Water had a significant effect on both springtails and mites in summer and autumn supporting the assertion that prairie soil communities are water limited.

  12. Mutational robustness of gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Aalt D J van Dijk

    Full Text Available Mutational robustness of gene regulatory networks refers to their ability to generate constant biological output upon mutations that change network structure. Such networks contain regulatory interactions (transcription factor-target gene interactions but often also protein-protein interactions between transcription factors. Using computational modeling, we study factors that influence robustness and we infer several network properties governing it. These include the type of mutation, i.e. whether a regulatory interaction or a protein-protein interaction is mutated, and in the case of mutation of a regulatory interaction, the sign of the interaction (activating vs. repressive. In addition, we analyze the effect of combinations of mutations and we compare networks containing monomeric with those containing dimeric transcription factors. Our results are consistent with available data on biological networks, for example based on evolutionary conservation of network features. As a novel and remarkable property, we predict that networks are more robust against mutations in monomer than in dimer transcription factors, a prediction for which analysis of conservation of DNA binding residues in monomeric vs. dimeric transcription factors provides indirect evidence.

  13. Effect of the Addition of Powder on the Physico-chemical Characteristics of Sausage

    Directory of Open Access Journals (Sweden)

    S. K. Jin

    2013-12-01

    Full Text Available The individual and interactive effects of Schisandra chinensis powder (SCP and sodium nitrite additions on color, pH, water holding capacity, residual nitrite, 2-thiobarbituric acid reactive substances (TBARS, volatile basic nitrogen, texture properties, fatty acids, amino acids and sensory evaluation of cooked pork sausages were investigated after 20 d of storage at 4°C. The powders (0, 0.5 and 1.0% were added to sausages either alone or in combination with nitrite (0 and 100 ppm. SCP added-sausages showed lower L* (lightness and W (whiteness values, and higher b* (yellowness values than sausage containing no nitrite, and exhibited the highest a* values at a 0.5% addition (p<0.05. Residual nitrite and TBARS values were found to be significantly reduced as the addition levels of SCP increased (p<0.05. As the addition of SCP increased, the sausage showed gradually decreased brittleness, cohesiveness, springiness, gumminess and chewiness, while adhesiveness increased. Polyunsaturated fatty acid, n-6 and n-6/n-3 fatty acid ratio concentrations were significantly higher in sausages containing SCP (p<0.05. The addition of SCP to sausage significantly (p<0.05 increased the ammonia content (by 0.5% SCP and aromatic amino acid concentrations (by 1.0% SCP (p<0.05. Inclusion of SCP in sausage meat resulted in a significant deterioration in quality characteristics of flavor, springiness, juiciness and overall acceptability (p<0.05. As expected, the observed changes in a*, W, pH, shear force, texture property, TBARS, fatty acid, amino acid and sensory score of sausages, depended on the rate of addition of nitrite (p<0.05. These results suggest that SCP addition is not an effective way of improving the sensory evaluation of sausages, but may beneficially affect TBARS, nitrite scavenging activity, fatty acid and amino acid content in pork sausages.

  14. The distribution of QTL additive and dominance effects in porcine F2 crosses.

    Science.gov (United States)

    Bennewitz, J; Meuwissen, T H E

    2010-06-01

    The present study used published quantitative trait loci (QTL) mapping data from three F2 crosses in pigs for 34 meat quality and carcass traits to derive the distribution of additive QTL effects as well as dominance coefficients. Dominance coefficients were calculated as the observed QTL dominance deviation divided by the absolute value of the observed QTL additive effect. The error variance of this ratio was approximated using the delta method. Mixtures of normal distributions (mixtures of normals) were fitted to the dominance coefficient using a modified EM-algorithm that considered the heterogeneous error variances of the data points. The results suggested clearly to fit one component which means that the dominance coefficients are normally distributed with an estimated mean (standard deviation) of 0.193 (0.312). For the additive effects mixtures of normals and a truncated exponential distribution were fitted. Two components were fitted by the mixtures of normals. The mixtures of normals did not predict enough QTL with small effects compared to the exponential distribution and to literature reports. The estimated rate parameter of the exponential distribution was 5.81 resulting in a mean effect of 0.172.

  15. Categorical and continuous - disentangling the neural correlates of the carry effect in multi-digit addition

    Directory of Open Access Journals (Sweden)

    Dressel Katharina

    2010-11-01

    Full Text Available Abstract Background Recently it was suggested that the carry effect observed in addition involves both categorical and continuous processing characteristics. Methods In the present study, we aimed at identifying the specific neural correlates associated with processing either categorical or continuous aspects of the carry effect in an fMRI study on multi-digit addition. Results In line with our expectations, we observed two distinct parts of the fronto-parietal network subserving numerical cognition to be associated with either one of these two characteristics. On the one hand, the categorical aspect of the carry effect was associated with left-hemispheric language areas and the basal ganglia probably reflecting increased demands on procedural and problem solving processes. Complementarily, the continuous aspect of the carry effect was associated with increased intraparietal activation indicating increasing demands on magnitude processing as well as place-value integration with increasing unit sum. Conclusions In summary, the findings suggest representations and processes underlying the carry effect in multi-digit addition to be more complex and interactive than assumed previously.

  16. Effect of additives on process stability of mesophilic anaerobic monodigestion of pig slaughterhouse waste.

    Science.gov (United States)

    Bayr, Suvi; Pakarinen, Outi; Korppoo, Aki; Liuksia, Saku; Väisänen, Ari; Kaparaju, Prasad; Rintala, Jukka

    2012-09-01

    The effect of two additives on anaerobic monodigestion of pig slaughterhouse waste was studied in three laboratory scale continuously stirred tank reactors (CSTRs) operated for 242-284 days at 35°C. A higher organic loading rate (OLR), namely 2.25 kg volatile solids (VS)/m(3)d with a hydraulic retention time (HRT) of 30 d was feasible with an additive containing Fe, HCl and trace elements while an OLR of 1.5 kg VS/m(3)d (HRT 30 d) led to instabilities in CSTR with an additive consisting of Fe and HCl and in CSTR without additives. Methane yields of ca. 700 dm(3) CH(4)/kg VS(fed) were obtained in all reactors under stable conditions. Both additives decreased H(2)S concentration of the biogas below detection limit 0.5 ppm while in a control reactor H(2)S concentration was up to 1900 ppm. In conclusion, the results suggest the possibility that additives may facilitate higher OLRs in monodigestion of pig slaughterhouse waste. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Comparative Evaluation of Small Molecular Additives and Their Effects on Peptide/Protein Identification.

    Science.gov (United States)

    Gao, Jing; Zhong, Shaoyun; Zhou, Yanting; He, Han; Peng, Shuying; Zhu, Zhenyun; Liu, Xing; Zheng, Jing; Xu, Bin; Zhou, Hu

    2017-06-06

    Detergents and salts are widely used in lysis buffers to enhance protein extraction from biological samples, facilitating in-depth proteomic analysis. However, these detergents and salt additives must be efficiently removed from the digested samples prior to LC-MS/MS analysis to obtain high-quality mass spectra. Although filter-aided sample preparation (FASP), acetone precipitation (AP), followed by in-solution digestion, and strong cation exchange-based centrifugal proteomic reactors (CPRs) are commonly used for proteomic sample processing, little is known about their efficiencies at removing detergents and salt additives. In this study, we (i) developed an integrative workflow for the quantification of small molecular additives in proteomic samples, developing a multiple reaction monitoring (MRM)-based LC-MS approach for the quantification of six additives (i.e., Tris, urea, CHAPS, SDS, SDC, and Triton X-100) and (ii) systematically evaluated the relationships between the level of additive remaining in samples following sample processing and the number of peptides/proteins identified by mass spectrometry. Although FASP outperformed the other two methods, the results were complementary in terms of peptide/protein identification, as well as the GRAVY index and amino acid distributions. This is the first systematic and quantitative study of the effect of detergents and salt additives on protein identification. This MRM-based approach can be used for an unbiased evaluation of the performance of new sample preparation methods. Data are available via ProteomeXchange under identifier PXD005405.

  18. Effects of Bi Addition on the Microstructure and Mechanical Properties of Nanocrystalline Ag Coatings

    Directory of Open Access Journals (Sweden)

    Yuxin Wang

    2017-08-01

    Full Text Available In this study we investigated the effects of Bi addition on the microstructure and mechanical properties of an electrodeposited nanocrystalline Ag coating. Microstructural features were investigated with transmission electron microscopy (TEM. The results indicate that the addition of Bi introduced nanometer-scale Ag-Bi solid solution particles and more internal defects to the initial Ag microstructures. The anisotropic elastic-plastic properties of the Ag nanocrystalline coating with and without Bi addition were examined with nanoindentation experiments in conjunction with the recently-developed inverse method. The results indicate that the as-deposited nanocrystalline Ag coating contained high mechanical anisotropy. With the addition of 1 atomic percent (at% Bi, the anisotropy within Ag-Bi coating was very small, and yield strength of the nanocrystalline Ag-Bi alloy in both longitudinal and transverse directions were improved by over 100% compared to that of Ag. On the other hand, the strain-hardening exponent of Ag-Bi was reduced to 0.055 from the original 0.16 of the Ag coating. Furthermore, the addition of Bi only slightly increased the electrical resistivity of the Ag-Bi coating in comparison to Ag. Results of our study indicate that Bi addition is a promising method for improving the mechanical and physical performances of Ag coating for electrical contacts.

  19. Effect of Ingredient Loading on Surface Migration Kinetics of Additives in Vulcanized Natural Rubber Compounds

    Directory of Open Access Journals (Sweden)

    Bryan B. Pajarito

    2014-12-01

    Full Text Available Surface migration kinetics of chemical additives in vulcanized natural rubber compounds were studied as function of ingredient loading. Rubber sheets were compounded according to a 212-8 fractional factorial design of experiment, where ingredients were treated as factors varied at two levels of loading. Amount of migrated additives in surface of rubber sheets was monitored through time at ambient conditions. The maximum amount and estimated rate of additive migration were determined from weight loss kinetic curves. Attenuated total reflection–Fourier transform infrared (ATR-FTIR spectroscopy and optical microscopy were used to characterize the chemical structure and surface morphology of sheet specimens during additive migration. ANOVA results showed that increased loading of reclaimed rubber, CaCO3, and paraffin wax signif icantly decreased the maximum amount of additive migration; by contrast, increased loading of used oil, asphalt, and mercaptobenzothiazole disulphide (MBTS increased the maximum amount. Increased loading of sulfur, diphenylguanidine (DPG, and paraffin wax significantly decreased the additive migration rate; increased loading of used oil, asphalt, and stearic acid elicited an opposite effect. Comparison of ATRFTIR spectra of migrated and cleaned rubber surfaces showed signif icant variation in intensity of specif ic absorbance bands that are also present in infrared spectra of migrating chemicals. Paraffin wax, used oil, stearic acid, MBTS, asphalt, and zinc stearate were identified to bloom and bleed in the rubber sheets. Optical micrographs of migrated rubber surfaces revealed formation of white precipitates due to blooming and of semi-transparent wet patches due to bleeding.

  20. Additive Intraocular Pressure-Lowering Effects of Ripasudil with Glaucoma Therapeutic Agents in Rabbits and Monkeys

    Directory of Open Access Journals (Sweden)

    Yoshio Kaneko

    2017-01-01

    Full Text Available Ripasudil hydrochloride hydrate (K-115, a specific Rho-associated coiled-coil containing protein kinase (ROCK inhibitor, is developed for the treatment of glaucoma and ocular hypertension. Topical administration of ripasudil decreases intraocular pressure (IOP by increasing conventional outflow through the trabeculae to Schlemm’s canal, which is different from existing agents that suppress aqueous humor production or promote uveoscleral outflow. In this study, we demonstrated that ripasudil significantly lowered IOP in combined regimens with other glaucoma therapeutic agents in rabbits and monkeys. Ripasudil showed additional effects on maximum IOP lowering or prolonged the duration of IOP-lowering effects with combined administration of timolol, nipradilol, brimonidine, brinzolamide, latanoprost, latanoprost/timolol fixed combination, and dorzolamide/timolol fixed combination. These results indicate that facilitation of conventional outflow by ripasudil provides additive IOP-lowering effect with other classes of antiglaucoma agents. Ripasudil is expected to have substantial utility in combined regimens with existing agents for glaucoma treatment.

  1. Effect of Addition of Cereal Based Beta-glucan on Technological and Functional Properties of Foods

    Directory of Open Access Journals (Sweden)

    Nihal Şimşekli

    2015-01-01

    Full Text Available Nowadays usage of dietary fibers in foods has been increasing duo to revealing of health benefits. Beta-glucans found especially in oats and barley, are polysaccharide and source of water-soluble dietary fiber. Positive effects of beta-glucans like healing coronary-heart disease, lowering blood cholesterol level, balancing blood sugar level and preventing obesity, made beta-glucans widespread functional food components for producing various foods. In addition to beneficial physiological effects of beta-glucans, they texturize, gelatinize, emulsify and stabilize the foods. They increase viscosity, replace fat and enhance rheological properties in cereal, meat and dairy products. They are also used to produce packing material depending on their mechanical properties and molecular weights. In this review, effects of addition of cereal based beta-glucans on technological and functional properties of various foods are revealed based on previous studies.

  2. Effect of indium addition in U-Zr metallic fuel on lanthanide migration

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yeon Soo; Wiencek, T.; O' Hare, E.; Fortner, J.; Wright, A.; Cheon, J. S.; Lee, B. O.

    2017-02-01

    Advanced fast reactor concepts to achieve ultra-high burnup (~50%) require prevention of fuel-cladding chemical interaction (FCCI). Fission product lanthanide accumulation at high burnup is substantial and significantly contributes to FCCI upon migration to the cladding interface. Diffusion barriers are typically used to prevent interaction of the lanthanides with the cladding. A more active method has been proposed which immobilizes the lanthanides through formation of stable compounds with an additive. Theoretical analysis showed that indium, thallium, and antimony are good candidates. Indium was the strongest candidate because of its low reactivity with iron-based cladding alloys. Characterization of the as-fabricated alloys was performed to determine the effectiveness of the indium addition in forming compounds with lanthanides, represented by cerium. Tests to examine how effectively the dopant prevents lanthanide migration under a thermal gradient were also performed. The results showed that indium effectively prevented cerium migration.

  3. Effect of oxygenated liquid additives on the urea based SNCR process.

    Science.gov (United States)

    Tayyeb Javed, M; Nimmo, W; Mahmood, Asif; Irfan, Naseem

    2009-08-01

    An experimental investigation was performed to study the effect of oxygenated liquid additives, H(2)O(2), C(2)H(5)OH, C(2)H(4)(OH)(2) and C(3)H(5)(OH)(3) on NO(x) removal from flue gases by the selective non-catalytic reduction (SNCR) process using urea as a reducing agent. Experiments were performed with a 150kW pilot scale reactor in which a simulated flue gas was generated by the combustion of methane operating with 6% excess oxygen in flue gases. The desired levels of initial NO(x) (500ppm) were achieved by doping the fuel gas with ammonia. Experiments were performed throughout the temperature range of interest, i.e. from 800 to 1200 degrees C for the investigation of the effects of the process additives on the performance of aqueous urea DeNO(x). With H(2)O(2) addition a downward shift of 150 degrees C in the peak reduction temperature from 1130 to 980 degrees C was observed during the experimentation, however, the peak reduction efficiency was reduced from 81 to 63% when no additive was used. The gradual addition of C(2)H(5)OH up to a molar ratio of 2.0 further impairs the peak NO(x) reduction efficiency by reducing it to 50% but this is accompanied by a downward shift of 180 degrees C in the peak reduction temperature. Further exploration using C(2)H(4)(OH)(2) suggested that a 50% reduction could be attained for all the temperatures higher than 940 degrees C. The use of C(3)H(5)(OH)(3) as a secondary additive has a significant effect on the peak reduction efficiency that decreased to 40% the reductions were achievable at a much lower temperature of 800 degrees C showing a downward shift of 330 degrees C.

  4. Effects of water and nitrogen addition on species turnover in temperate grasslands in northern China.

    Directory of Open Access Journals (Sweden)

    Zhuwen Xu

    Full Text Available Global nitrogen (N deposition and climate change have been identified as two of the most important causes of current plant diversity loss. However, temporal patterns of species turnover underlying diversity changes in response to changing precipitation regimes and atmospheric N deposition have received inadequate attention. We carried out a manipulation experiment in a steppe and an old-field in North China from 2005 to 2009, to test the hypothesis that water addition enhances plant species richness through increase in the rate of species gain and decrease in the rate of species loss, while N addition has opposite effects on species changes. Our results showed that water addition increased the rate of species gain in both the steppe and the old field but decreased the rates of species loss and turnover in the old field. In contrast, N addition increased the rates of species loss and turnover in the steppe but decreased the rate of species gain in the old field. The rate of species change was greater in the old field than in the steppe. Water interacted with N to affect species richness and species turnover, indicating that the impacts of N on semi-arid grasslands were largely mediated by water availability. The temporal stability of communities was negatively correlated with rates of species loss and turnover, suggesting that water addition might enhance, but N addition would reduce the compositional stability of grasslands. Experimental results support our initial hypothesis and demonstrate that water and N availabilities differed in the effects on rate of species change in the temperate grasslands, and these effects also depend on grassland types and/or land-use history. Species gain and loss together contribute to the dynamic change of species richness in semi-arid grasslands under future climate change.

  5. Predicting the effects of nanoscale cerium additives in diesel fuel on regional-scale air quality.

    Science.gov (United States)

    Erdakos, Garnet B; Bhave, Prakash V; Pouliot, George A; Simon, Heather; Mathur, Rohit

    2014-11-04

    Diesel vehicles are a major source of air pollutant emissions. Fuel additives containing nanoparticulate cerium (nCe) are currently being used in some diesel vehicles to improve fuel efficiency. These fuel additives also reduce fine particulate matter (PM2.5) emissions and alter the emissions of carbon monoxide (CO), nitrogen oxides (NOx), and hydrocarbon (HC) species, including several hazardous air pollutants (HAPs). To predict their net effect on regional air quality, we review the emissions literature and develop a multipollutant inventory for a hypothetical scenario in which nCe additives are used in all on-road and nonroad diesel vehicles. We apply the Community Multiscale Air Quality (CMAQ) model to a domain covering the eastern U.S. for a summer and a winter period. Model calculations suggest modest decreases of average PM2.5 concentrations and relatively larger decreases in particulate elemental carbon. The nCe additives also have an effect on 8 h maximum ozone in summer. Variable effects on HAPs are predicted. The total U.S. emissions of fine-particulate cerium are estimated to increase 25-fold and result in elevated levels of airborne cerium (up to 22 ng/m3), which might adversely impact human health and the environment.

  6. Contribution of CYP1B1 mutations and founder effect to primary congenital glaucoma in Mexico.

    Science.gov (United States)

    Zenteno, Juan Carlos; Hernandez-Merino, Elena; Mejia-Lopez, Herlinda; Matías-Florentino, Margarita; Michel, Norma; Elizondo-Olascoaga, Celia; Korder-Ortega, Vincent; Casab-Rueda, Homero; Garcia-Ortiz, Jose Elias

    2008-01-01

    The frequency of primary congenital glaucoma (PCG)-causing CYP1B1 mutations varies importantly among distinct populations, ranging from 20% in Indonesians and Japanese to about 100% among the Saudi Arabians and Slovakian Gypsies. Thus, the molecular characterization of large groups of PCG from different ethnic backgrounds is important to establish the actual CYP1B1 contribution in specific populations. In this work, the molecular analysis of the CYP1B1 gene in a group of Mexican PCG patients is reported. Thirty unrelated Mexican patients fulfilling the clinical criteria for PCG were included. Two cases were familial and with proven consanguinity, originating from distinct regions of the country. Polymerase chain reaction amplification and direct automated sequencing of the CYP1B1 coding region was performed in each participating subject. An identical pathogenic CYP1B1 mutation was demonstrated in 2 unrelated PCG subjects. The mutation consisted of a homozygous G to A transition at nucleotide position 1505 in exon 3, which predicted a substitution of glutamic acid for lysine at residue 387 of the protein (E387K). In the remaining 28 PCG subjects, no deleterious mutations were identified. Both subjects with the E387K mutation shared a same haplotype for 5 CYP1B1 intragenic single nucleotide polymorphisms, indicating a common origin of the allele. Mexican patients with PCG are rarely (less than 10%) due to CYP1B1 mutations. Available data indicate that most of the non-Brazilian Latin American PCG patients investigated to date are not due to CYP1B1 defects. Populations with low incidence of CYP1B1 mutations are appropriate candidates for the identification of novel PCG-causing genes.

  7. Direct nanomaterial-DNA contact effects on DNA and mutation induction.

    Science.gov (United States)

    Thongkumkoon, P; Sangwijit, K; Chaiwong, C; Thongtem, S; Singjai, P; Yu, L D

    2014-04-07

    The toxicity of nanomaterials has been well known, but mechanisms involved have been little known. This study was aimed at looking at direct interaction between nanomaterials and naked DNA for some fundamental understanding. Two different types of nanomaterials, carbon nanotubes (CNTs) and tungsten trioxide (WO₃) nanoplates, were simply mixed with naked DNA plasmid, respectively, in two different contact modes, dry or wet (in solution), for varied time periods. DNA topological forms were analyzed for changes using gel electrophoresis and fluoro-spectrometry. The nanomaterial-contacted DNA was transferred into bacteria Escherichia coli (E. coli) cells for mutation observation. Certain types and degrees of DNA damage were observed, such as single strand break and double strand break, and bacterial mutation was confirmed. The DNA damage increased with the contacting time in an exponential manner and increased more rapidly in the initial stage for the wet contact. The nanomaterials-contacted DNA transferred bacteria had about less than 10% survival but almost 100% mutation for the surviving cells. The CNTs were more offensive than the metal oxide nanomaterials. The mutation spectrum from the DNA sequencing analysis showed that DNA point mutation was dominated by transversion, which was dominated by guanine changes in the wet contact condition while by cytosine changes in the dry contact condition. The point mutation occurrence in the wet contact was more than in the dry contact, confirming the wet contact more active and thus dangerous than dry contact. This experiment, although as a model study, revealed that direct simple contacts between nanomaterials and DNA could cause DNA changes and thus induce mutations which might potentially lead to cancers, diseases and genetic changes. This could be a mechanism for nanomaterial genotoxicity to the cells and also provided a caution to applications in using nanomaterials for DNA delivery. Copyright © 2014 Elsevier Ireland

  8. The effect of Y2O3 addition on thermal shock behavior of magnesium aluminate spinel

    Directory of Open Access Journals (Sweden)

    Pošarac Milica

    2009-01-01

    Full Text Available The effect of yttria additive on the thermal shock behavior of magnesium aluminate spinel has been investigated. As a starting material we used spinel (MgAl2O4 obtained by the modified glycine nitrate procedure (MGNP. Sintered products were characterized in terms of phase analysis, densities, thermal shock, monitoring the damaged surface area in the refractory specimen during thermal shock and ultrasonic determination of the Dynamic Young modulus of elasticity. It was found that a new phase between yttria and alumina is formed, which improved thermal shock properties of the spinel refractories. Also densification of samples is enhanced by yttria addition.

  9. The Effects of Various Additive Components on the Sound Absorption Performances of Polyurethane Foams

    Directory of Open Access Journals (Sweden)

    Shuming Chen

    2015-01-01

    Full Text Available Flexible polyurethane (PU foams comprising various additive components were synthesized to improve their acoustic performances. The purpose of this study was to investigate the effects of various additive components of the PU foams on the resultant sound absorption, which was characterized by the impedance tube technique to obtain the incident sound absorption coefficient and transmission loss. The maximum enhancement in the acoustic properties of the foams was obtained by adding fluorine-dichloroethane (141b and triethanolamine. The results showed that the acoustic absorption properties of the PU foams were improved by adding 141b and triethanolamine and depended on the amount of the water, 141b, and triethanolamine.

  10. Solvent additive effects on small molecule crystallization in bulk heterojunction solar cells probed during spin casting

    KAUST Repository

    Pérez, Louis A.

    2013-09-04

    Solvent additive processing can lead to drastic improvements in the power conversion efficiency (PCE) in solution processable small molecule (SPSM) bulk heterojunction solar cells. In situ grazing incidence wide-angle X-ray scattering is used to investigate the kinetics of crystallite formation during and shortly after spin casting. The additive is shown to have a complex effect on structural evolution invoking polymorphism and enhanced crystalline quality of the donor SPSM. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Effect of additional speed endurance training on performance and muscle adaptations

    DEFF Research Database (Denmark)

    Gunnarsson, Thomas; Christensen, Peter Møller; Holse, Kris

    2012-01-01

    intensity (speed endurance training; SET) a week for 5 weeks (SET-intervention). Before and after the SET-intervention the players carried out the Yo-Yo intermittent recovery level 2 (Yo- Yo IR2) test, a sprint test (10- and 30-m) and an agility test. In addition, seven of the players had a resting muscle......PURPOSE: The present study examined the effect of additional speed-endurance training during the season on muscle adaptations and performance of trained soccer players. METHODS: Eighteen sub-elite soccer players performed one session with 6-9 30-s intervals at an intensity of 90-95 % ofmaximal...

  12. Efficacy versus effectiveness of clinical genetic testing criteria for BRCA1 and BRCA2 hereditary mutations in incident breast cancer.

    Science.gov (United States)

    Nilsson, Martin P; Winter, Christof; Kristoffersson, Ulf; Rehn, Martin; Larsson, Christer; Saal, Lao H; Loman, Niklas

    2017-04-01

    Increasing evidence supports the benefit of identifying BRCA1 and BRCA2 germline mutations in early breast cancer. Selection of patients for genetic testing is based on defined criteria taking individual and family history related factors into account. It is important to make a distinction between efficacy and effectiveness of BRCA testing criteria. Efficacy can be defined as the performance under ideal circumstances, whereas effectiveness refers to its real life performance. To allow for an unbiased and detailed evaluation of efficacy and effectiveness of the Swedish BRCA testing criteria, we retrospectively analyzed a prospectively collected cohort of 273 breast cancer patients from the well-characterized, population-based, single-site All Breast Cancer in Malmö (ABiM) study. The patients were diagnosed with breast cancer during the years 2007 through 2009. Out of 20 mutation carriers identified, 13 fulfilled Swedish criteria at time of diagnosis. Thus, the efficacy of these criteria was 65%. Excluding three patients in whom a mutation was already known at time of diagnosis, only 3/17 had been identified in the clinical routine, corresponding to an effectiveness of 18%. Here we detail the reasons why mutation carriers in our cohort were not detected though routine health care. In conclusion, effectiveness of BRCA testing criteria was much lower than efficacy. Our results indicate that current testing criteria and procedures associated with BRCA1 and BRCA2 testing are insufficient. There is room for improvement of their efficacy, but even more so regarding effectiveness. Clinical BRCA testing routines need to be critically revised.

  13. Effects of two mutations detected in medium chain acyl-CoA dehydrogenase (MCAD)-deficient patients on folding, oligomer assembly, and stability of MCAD enzyme

    DEFF Research Database (Denmark)

    Bross, P; Jespersen, C; Jensen, T G

    1995-01-01

    We have used expression of human medium chain acyl-CoA dehydrogenase (MCAD) in Escherichia coli as a model system for dissecting the molecular effects of two mutations detected in patients with MCAD deficiency. We demonstrate that the R28C mutation predominantly affects polypeptide folding. The a...

  14. Absence of Maternal Methylation in Biparental Hydatidiform Moles from Women with NLRP7 Maternal-Effect Mutations Reveals Widespread Placenta-Specific Imprinting.

    Directory of Open Access Journals (Sweden)

    Marta Sanchez-Delgado

    2015-11-01

    Full Text Available Familial recurrent hydatidiform mole (RHM is a maternal-effect autosomal recessive disorder usually associated with mutations of the NLRP7 gene. It is characterized by HM with excessive trophoblastic proliferation, which mimics the appearance of androgenetic molar conceptuses despite their diploid biparental constitution. It has been proposed that the phenotypes of both types of mole are associated with aberrant genomic imprinting. However no systematic analyses for imprinting defects have been reported. Here, we present the genome-wide methylation profiles of both spontaneous androgenetic and biparental NLRP7 defective molar tissues. We observe total paternalization of all ubiquitous and placenta-specific differentially methylated regions (DMRs in four androgenetic moles; namely gain of methylation at paternally methylated loci and absence of methylation at maternally methylated regions. The methylation defects observed in five RHM biopsies from NLRP7 defective patients are restricted to lack-of-methylation at maternal DMRs. Surprisingly RHMs from two sisters with the same missense mutations, as well as consecutive RHMs from one affected female show subtle allelic methylation differences, suggesting inter-RHM variation. These epigenotypes are consistent with NLRP7 being a maternal-effect gene and involved in imprint acquisition in the oocyte. In addition, bioinformatic screening of the resulting methylation datasets identified over sixty loci with methylation profiles consistent with imprinting in the placenta, of which we confirm 22 as novel maternally methylated loci. These observations strongly suggest that the molar phenotypes are due to defective placenta-specific imprinting and over-expression of paternally expressed transcripts, highlighting that maternal-effect mutations of NLRP7 are associated with the most severe form of multi-locus imprinting defects in humans.

  15. Two TP53 germline mutations in a classical Li-Fraumeni syndrome family.

    Science.gov (United States)

    van Hest, Liselotte P; Ruijs, Mariëlle W G; Wagner, Anja; van der Meer, Conny A; Verhoef, Senno; van't Veer, Laura J; Meijers-Heijboer, Hanne

    2007-01-01

    Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited cancer predisposition syndrome characterized by a combination of tumors including sarcoma, breast cancer, brain tumors, adrenocortical carcinoma and leukemia. Germline mutations in the tumor suppressor gene TP53 are associated with LFS. We present a family with LFS in which initially a novel germline TP53 intron 5 splice site mutation was found. A second germline TP53 mutation, the exon 7 Asn235Ser (704A-->G) mutation, was detected in this family through pre-symptomatic DNA testing. This latter mutation has been reported repeatedly in the literature as a pathogenic mutation involved in LFS. We provide evidence for pathogenicity of the novel intron 5 splice site mutation, whereas this evidence is lacking for the exon 7 Asn235Ser (704A-->G) mutation. Our findings emphasize the importance of performing additional tests in case of germline sequence variants with uncertain functional effects.

  16. Effects of lipids on thermophilic anaerobic digestion and reduction of lipid inhibition upon addition of bentonite.

    Science.gov (United States)

    Angelidaki, I; Petersen, S P; Ahring, B K

    1990-07-01

    The effect of bentonite-bound oil on thermophilic anaerobic digestion of cattle manure was investigated. In digestor experiments, addition of oil was found to be inhibitory during start-up and the inhibitory effect was less pronounced when the oil was added in the form of bentonite-bound oil compared to when the oil was added alone. After adaptation of the digestors, very rapid degradation of oil was observed and more than 80% of the oil was degraded within a few hours after daily feeding. In batch experiments, glyceride trioleate was found to be inhibitory to thermophilic anaerobic digestion when the concentrations were higher than 2.0 g/l. However, addition of bentonite (a clay mineral) at concentrations of 0.15% and 0.45% was found to partly overcome this inhibition. Addition of calcium chloride in concentration of 3 mM (0.033% w/v) showed a similar positive effect on the utilization of oil, but the effect was lower than with bentonite.

  17. Aflatoxin effect on erythrocyte profile and histopathology of broilers given different additives

    Science.gov (United States)

    Karimy, M. F.; Sutrisno, B.; Agus, A.; Suryani, A. E.; Istiqomah, L.; Damayanti, E.

    2017-12-01

    The aim of this study was to evaluate erythrocyte profile and microscopic changes effect of AF induces by low level (57.18 ppb) and chronic exposure (34 days) with administration of additive (Lactobacillus plantarum G7 and methionine). Aflatoxin-contaminated corn was prepared by inoculate Aspergillus flavus FNCC 6002 on corn. Total number of 576 broiler Lohman strain (MB202) unsexed DOC were allocated completely randomized into four treatments and 12 replicates, with 12 broiler chicks each. The treatments as follows: T1 = aflatoxin-contaminated diet, T2 = aflatoxin-contaminated diet + 1% of LAB (w/w), T3 = aflatoxin-contaminated diet + 0.8% of methionine (w/w), and T4 = aflatoxin-contaminated diet + 1% of LAB + 0.8% of methionine (w/w). The effect of treatments was evaluated using ANOVA and the difference among mean treatments were analyzed using DMRT. The result showed that administration of additives had no significant effect (P>0.05) on erythrocyte profile, liver, and bursa of Fabricius. The dose of additive in each treatment (T2, T3, T4) were insufficient to reduce adverse effect of chronic aflatoxicosis. It was concluded that the LAB dose for binding AF (57.18%) should be evaluated and the dose for methionine should be reduced for chronic treatment of aflatoxicosis.

  18. Increased Walking's Additive and No Substitution Effect on Total Physical Activity.

    Science.gov (United States)

    Kang, Bumjoon; Moudon, Anne V; Hurvitz, Philip M; Saelens, Brian E

    2017-10-09

    We assessed the associations between a change in time spent walking and a change in total physical activity (PA) time within an urban living adult sample, to test for additive or substitution effects. Participants living in the greater Seattle area were assessed in 2008-2009 and again 1-2 years later (2010-2011). At each time point, they wore accelerometers and GPS units and recorded trips and locations in a travel diary for 7 consecutive days. These data streams were combined to derive a more objective estimate of walking and total PA. Participants also completed the International Physical Activity Questionnaire to provide self-reported estimates of walking and total PA. Regression analyses assessed the associations between within-participant changes in objective and self-reported walking and total PA. Data came from 437 participants. On average, a 1-minute increase in total walking was associated with an increase in total PA of 1 minute, measured by objective data and 1.2-minute, by self-reported data. A similar additive effect was consistently found with utilitarian, transportation, or job-related walking, measured by both objective and self-reported data. For recreational walking, the effect of change was mixed between objective and self-reported results. Both objective and self-reported data confirmed an additive effect of utilitarian and total walking on PA.

  19. Effects of polymer additives in the bulk of turbulent thermal convection

    CERN Document Server

    Xie, Yi-Chao; Funfschilling, Denis; Li, Xiao-Ming; Ni, Rui; Xia, Ke-Qing

    2015-01-01

    We present experimental evidence that a minute amount of polymer additives can significantly enhance heat transport in the bulk region of turbulent thermal convection. The effects of polymer additives are found to be the \\textit{suppression} of turbulent background fluctuations that give rise to incoherent heat fluxes that make no net contribution to heat transport, and at the same time to \\textit{increase} the coherency of temperature and velocity fields. The suppression of small-scale turbulent fluctuations leads to more coherent thermal plumes that result in the heat transport enhancement. The fact that polymer additives can increase the coherency of thermal plumes is supported by the measurements of a number of local quantities, such as the extracted plume amplitude and width, the velocity autocorrelation functions and the velocity-temperature cross-correlation coefficient. The results from local measurements also suggest the existence of a threshold value for the polymer concentration, only above which c...

  20. Effect of additive on Zeta potential and particle size of nickel nanoparticles

    Science.gov (United States)

    Sharma, Vikash; Tarachand, Chotia, Chandrabhan; Okram, G. S.

    2017-05-01

    Nickel nanoparticles (NPs) were prepared by thermal decomposition method using Oleylamine (OLY) as a solvent and Trioctylphosphine (TOP) as a surfactant. We have investigated the effect of pH and addition of Ethylenediamine tetraacetic acid (EDTA) on the stability and particle size of Ni NPs using zeta potential and particle size analyser. Coating of the surfactants on the surface of Ni NPs was confirmed by Fourier transform infrared (FTIR) spectroscopy. Autotitration study of zeta potential of these NPs in ethanol by dynamic light scattering (DLS) at different pH values confirmed an isoelectric point (IEP) at pH = 3.64 in ethanol and pH = 3.04 after addition of EDTA in ethanol. It was observed that addition of EDTA in nanosuspension enhances stability of Ni-NPs significantly.

  1. Effect of heater material and coolant additives on CHF for a downward facing curved surface

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae Min, E-mail: hm-park@kaist.ac.kr [Department of Nuclear and Quantum Eng., Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Jeong, Yong Hoon, E-mail: jeongyh@kaist.ac.kr [Department of Nuclear and Quantum Eng., Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Heo, Sun, E-mail: hs@khnp.co.kr [Nuclear Engineering and Technology Institute, Korea Hydro and Nuclear Power Co., 25-1, Jang-dong, Yuseong-gu, Daejeon 305-701 (Korea, Republic of)

    2014-10-15

    Highlights: • Critical heat flux experiment for a downward facing curved surface was conducted. • We investigate the effect of heater material and coolant additives. • Critical heat flux is affected by the steel oxidation. - Abstract: The critical heat flux (CHF) in the vicinity of an inclination angle of 90° for the reactor vessel lower head external wall was measured on a downward facing curved surface. Two test sections having radii of curvature 0.15 m and 0.5 m were used. The objective was to investigate the effect of heater material and the combined effect of the heater material and additives on flow boiling CHF to assess the CHF enhancement under accident conditions. The heater material SA508 (low alloy steel) and the additive solutions of boric acid and tri-sodium phosphate (TSP, Na{sub 3}PO{sub 4}·12H{sub 2}O) were used. An enhancement of CHF with the SA508 heater was confirmed in comparison with stainless steel reference heaters, which have negligible steel oxidation. As a result of the combined effect tests, the CHF with a TSP solution was reduced and the CHFs with a boric acid and a mixed solution (boric acid and TSP) were enhanced in comparison with the deionized water reference case. The CHF results are discussed in terms of steel oxidation according to the pH of the working fluid. Steel oxidation is also affected by local flow conditions as shown in the R = 0.5 m tests in which the boric acid and mixed solution had negligible effects on CHF enhancement. Under a relatively high concentration of boric acid (2.5 wt%), additive deposition as well as steel oxidation were observed and resulted in CHF enhancement.

  2. Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions.

    Science.gov (United States)

    Suzuki, Masao; Tsuruoka, Chizuru; Kanai, Tatsuaki; Kato, Takeshi; Yatagai, Fumio; Watanabe, Masami

    2006-02-22

    We investigated the linear energy transfer (LET) dependence of mutation induction on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in normal human fibroblast-like cells irradiated with accelerated neon-ion beams. The cells were irradiated with neon-ion beams at various LETs ranging from 63 to 335 keV/microm. Neon-ion beams were accelerated by the Riken Ring Cyclotron at the Institute of Physical and Chemical Research in Japan. Mutation induction at the HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation spectrum of the deletion pattern of exons of mutants was analyzed using the multiplex polymerase chain reaction (PCR). The dose-response curves increased steeply up to 0.5 Gy and leveled off or decreased between 0.5 and 1.0 Gy, compared to the response to (137)Cs gamma-rays. The mutation frequency increased up to 105 keV/microm and then there was a downward trend with increasing LET values. The deletion pattern of exons was non-specific. About 75-100% of the mutants produced using LETs ranging from 63 to 335 keV/mum showed all or partial deletions of exons, while among gamma-ray-induced mutants 30% showed no deletions, 30% partial deletions and 40% complete deletions. These results suggested that the dose-response curves of neon-ion-induced mutations were dependent upon LET values, but the deletion pattern of DNA was not.

  3. Evidence for a founder effect for the IVS4 +4 A{r_arrow}T mutation in the Fanconi anemia gene FACC in a Jewish population

    Energy Technology Data Exchange (ETDEWEB)

    Verlander, P.C.; Kaporis, A.G.; Qian, L. [Rockefeller Univ., New York, NY (United States)] [and others

    1994-09-01

    Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disorder defined by hypersensitivity of cells to DNA cross-linking agents; a gene for complementation group C(FACC) has been cloned. Two common mutations, IVS4 +4 A{r_arrow}T and 322delG, and several rare mutations have recently been reported in affected individuals. We now report the development of amplification refractory mutation system (ARMS) assays for rapid, non-radioactive detection of these known mutations in FACC. Primer pairs specific for variant sequences were designed, with the 3{prime} terminal base of one primer matching the variant base. PCR products are separated by electrophoresis on 2.5% agarose gels; mutations are indicated by the presence of a band of a specific size. These ARMS assays can be multiplexed to allow screening for all known mutations in two PCR reactions. We have used these assays for detection of FACC mutations in affected individuals in the International Fanconi Anemia Registry (IFAR), and for carrier detection FACC families. IVS4 +4 A{r_arrow}T is the only FACC mutation found in Jewish FA patients and their families, of both Ashkenazi and Sephardic ancestry. This mutation was not found in any affected individual of non-Jewish origin. In addition, DNA samples from 1596 healthy Jewish individuals primarily of Ashkenazi ancestry were supplied to us by Dor Yeshorim. These samples, ascertained for carrier screening for Tay Sachs, cystic fibrosis, and other genetic diseases with a high frequency in the religious Jewish community served by this organization, were tested for both IVS4 +4 A{r_arrow}T and 322delG mutations; seventeen IVS4 +4 A{r_arrow}T are of Sephardic Jewish ancestry. We hypothesize that IVS4 +4 A{r_arrow}T is a very old mutation, predating the divergence of the Ashkenazi and Sephardic populations. Haplotype analysis with microsatellite markers is in progress.

  4. In silico screening of mutational effects on enzyme-proteic inhibitor affinity: a docking-based approach.

    Science.gov (United States)

    Dell'Orco, Daniele; De Benedetti, Pier Giuseppe; Fanelli, Francesca

    2007-06-08

    Molecular recognition between enzymes and proteic inhibitors is crucial for normal functioning of many biological pathways. Mutations in either the enzyme or the inhibitor protein often lead to a modulation of the binding affinity with no major alterations in the 3D structure of the complex. In this study, a rigid body docking-based approach has been successfully probed in its ability to predict the effects of single and multiple point mutations on the binding energetics in three enzyme-proteic inhibitor systems. The only requirement of the approach is an accurate structural model of the complex between the wild type forms of the interacting proteins, with the assumption that the architecture of the mutated complexes is almost the same as that of the wild type and no major conformational changes occur upon binding. The method was applied to 23 variants of the ribonuclease inhibitor-angiogenin complex, to 15 variants of the barnase-barstar complex, and to 8 variants of the bovine pancreatic trypsin inhibitor-beta Trypsin system, leading to thermodynamic and kinetic estimates consistent with in vitro data. Furthermore, simulations with and without explicit water molecules at the protein-protein interface suggested that they should be included in the simulations only when their positions are well defined both in the wild type and in the mutants and they result to be relevant for the modulation of mutational effects on the association process. The correlative models built in this study allow for predictions of mutational effects on the thermodynamics and kinetics of association of three substantially different systems, and represent important extensions of our computational approach to cases in which it is not possible to estimate the absolute free energies. Moreover, this study is the first example in the literature of an extensive evaluation of the correlative weights of the single components of the ZDOCK score on the thermodynamics and kinetics of binding of protein

  5. In silico screening of mutational effects on enzyme-proteic inhibitor affinity: a docking-based approach

    Directory of Open Access Journals (Sweden)

    De Benedetti Pier

    2007-06-01

    Full Text Available Abstract Background Molecular recognition between enzymes and proteic inhibitors is crucial for normal functioning of many biological pathways. Mutations in either the enzyme or the inhibitor protein often lead to a modulation of the binding affinity with no major alterations in the 3D structure of the complex. Results In this study, a rigid body docking-based approach has been successfully probed in its ability to predict the effects of single and multiple point mutations on the binding energetics in three enzyme-proteic inhibitor systems. The only requirement of the approach is an accurate structural model of the complex between the wild type forms of the interacting proteins, with the assumption that the architecture of the mutated complexes is almost the same as that of the wild type and no major conformational changes occur upon binding. The method was applied to 23 variants of the ribonuclease inhibitor-angiogenin complex, to 15 variants of the barnase-barstar complex, and to 8 variants of the bovine pancreatic trypsin inhibitor-β Trypsin system, leading to thermodynamic and kinetic estimates consistent with in vitro data. Furthermore, simulations with and without explicit water molecules at the protein-protein interface suggested that they should be included in the simulations only when their positions are well defined both in the wild type and in the mutants and they result to be relevant for the modulation of mutational effects on the association process. Conclusion The correlative models built in this study allow for predictions of mutational effects on the thermodynamics and kinetics of association of three substantially different systems, and represent important extensions of our computational approach to cases in which it is not possible to estimate the absolute free energies. Moreover, this study is the first example in the literature of an extensive evaluation of the correlative weights of the single components of the ZDOCK score

  6. Effects of nitrogen addition and fire on plant nitrogen use in a temperate steppe.

    Directory of Open Access Journals (Sweden)

    Hai-Wei Wei

    Full Text Available Plant nitrogen (N use strategies have great implications for primary production and ecosystem nutrient cycling. Given the increasing atmospheric N deposition received by most of the terrestrial ecosystems, understanding the responses of plant N use would facilitate the projection of plant-mediated N cycling under global change scenarios. The effects of N deposition on plant N use would be affected by both natural and anthropogenic disturbances, such as prescribed fire in the grassland. We examined the effects of N addition (5.25 g N m(-2 yr(-1 and prescribed fire (annual burning on plant N concentrations and N use characters at both species and community levels in a temperate steppe of northern China. We found that N addition and fire independently affected soil N availability and plant N use traits. Nitrogen addition increased aboveground net primary productivity (ANPP, inorganic N, and N uptake, decreased N response efficiency (NRE, but did not affect biomass-weighed N concentrations at community level. Prescribed fire did not change the community level N concentrations, but largely decreased N uptake efficiency and NRE. At the species level, the effects of N addition and fire on plant N use were species-specific. The divergent responses of plant N use at community and species levels to N addition and fire highlight the importance of the hierarchical responses of plant N use at diverse biological organization levels to the alteration of soil N availability. This study will improve our understanding of the responses of plant-mediated N cycling to global change factors and ecosystem management strategies in the semiarid grasslands.

  7. The effect of chemical admixtures and mineral additives on the properties of self-compacting mortars

    Energy Technology Data Exchange (ETDEWEB)

    Mustafa Sahmaran; Heru Ari Christianto; Ismail Ozgur Yaman [Middle East Technical University, Ankara (Turkey). Department of Civil Engineering

    2006-05-15

    Mortar serves as the basis for the workability properties of self-compacting concrete (SCC) and these properties could be assessed by self-compacting mortars (SCM). In fact, assessing the properties of SCM is an integral part of SCC design. The objective of this study was to evaluate the effectiveness of various mineral additives and chemical admixtures in producing SCMs. For this purpose, four mineral additives (fly ash, brick powder, limestone powder, and kaolinite), three superplasticizers (SP), and two viscosity modifying admixtures (VMA) were used. Within the scope of the experimental program, 43 mixtures of SCM were prepared keeping the amount of mixing water and total powder content (Portland cement and mineral additives) constant. Workability of the fresh mortar was determined using mini V-funnel and mini slump flow tests. The setting time of the mortars, were also determined. The hardened properties that were determined included ultrasonic pulse velocity and strength determined at 28 and 56 days. It was concluded that among the mineral additives used, fly ash and limestone powder significantly increased the workability of SCMs. On the other hand, especially fly ash significantly increased the setting time of the mortars, which can, however, be eliminated through the use of ternary mixtures, such as mixing fly ash with limestone powder. The two polycarboxyl based SPs yield approximately the same workability and the melamine formaldehyde based SP was not as effective as the other two.

  8. Effect of Cephalaria syriaca addition on rheological properties of composite flour

    Science.gov (United States)

    Karaoðlu, M. M.

    2012-10-01

    The study was carried out to investigate the effect of whole and defatted Cephalaria syriaca flour on the rheological properties of composite flours that used in bran bread production. Cephalaria syriaca products were used to replace 0.25, 0.75, 1.25, 1.75, and 2.25% of wheat-wheat bran composite flour, and its rheological and fermentative properties were measured by farinograph, extensograph and rheofermentometre. The data showed that the rheological parameters of flours were greatly modified by addition of Cephalaria syriaca. The rheological properties of wheatwheat bran composite flour added with whole and defatted Cephalaria syriaca flour were considerably improved with regard to especially extensograph characteristics such as dough resistance, area (energy), ratio number and rheofermentometer parameters such as Hm, T1, Tx, volume loss and gas retention, as compared to control. However addition of Cephalaria syriaca products adversely affected the farinograph characteristics. Generally, these effects of both whole and defatted Cephalaria syriaca flour increased, as the addition level increased. Maximum Tx, gas retention and area (energy) of dough were obtained from wheat-wheat bran composite flour added with 1.75% whole Cephalaria syriaca flour, while the highest dough stability was at addition level of 0.25% whole Cephalaria syriaca flour.

  9. Effect of addition of commercial rosemary extracts on potent odorants in cooked beef.

    Science.gov (United States)

    Kim, Hun; Cadwallader, Keith R; Kido, Hirotsugu; Watanabe, Yuko

    2013-06-01

    Solid-phase microextraction-gas chromatography-olfactometry (SPME-GCO) and aroma extract dilution analysis (AEDA) were applied to measure the effects of the addition of two commercial rosemary extracts (RE) on the potent odorants in cooked beef extracts (BE). On the basis of the results of SPME-GCO and AEDA, the addition of RE imparted sweet and floral notes to BE as a result of the addition of esters and terpenes of RE. In addition, RE suppressed the formation of odorants derived via lipid oxidation and Maillard reactions. The most potent lipid oxidation volatiles consisted of 1-octen-3-one (mushroom-like), (E)-2,4-epoxy-(E)-2-decenal (metallic), and eight different aldehydes (fatty). The Maillard reaction volatiles, necessary for typical cooked beef flavor, included compounds with meaty [2-methyl-3-furanthiol, 2-methyl-3-(methylthio)furan, 2-methyl-3-(methyldithio)furan], roasty (2-furanmethanethiol), caramel-like [4-hydroxy-2,5-dimethyl-3(2H)-furanone], baked potato-like [3-(methylthio)propanal], and spicy [3-hydroxy-4,5-dimethyl-2(5H)-furanone] attributes. The suppressive effects of RE may be caused by the action of antioxidative substances in RE alone or in combination with the pH increase in BE induced by the matrix components of RE. Copyright © 2013. Published by Elsevier Ltd.

  10. Effect of Micronutrient Powder Addition on Sensory Properties of Foods for Older Adults.

    Science.gov (United States)

    Field, Katherine M; Duncan, Alison M; Keller, Heather H; Stark, Ken D; Duizer, Lisa M

    2017-10-01

    Micronutrient fortification can improve nutrient intake of older adults in long-term care. However, previous studies indicate that micronutrient fortification can alter food sensory attributes and, potentially, consumer liking. Others have found no effect of fortification on liking. This research investigates the effect of micronutrient powder addition on the sensory properties of selected foods commonly served in long-term care. A micronutrient powder containing 9 vitamins and 3 minerals was added to tomato soup and oatmeal at different levels. Using projective mapping, changes in sensory properties were observed with powder addition. Descriptive analysis, used to quantify these changes, showed that both the tomato soup and oatmeal had reduced flavor as the amount of added micronutrient powder increased. Oatmeal also showed changes in texture with fortification. Consumer liking scores for tomato soup showed that micronutrient addition affected liking when 100% of a daily dose was added into the soup. Addition of 50% of the daily dose did not affect liking. Oatmeal liking did not differ between fortified and unfortified samples. Results from this research can be used to decide whether a micronutrient powder of selected vitamins and minerals can be added to foods served to older adults in long-term care. Although sensory properties of the foods will be altered, fortification of both tomato soup and oatmeal with the developed powder is possible without reducing consumer liking to the point where it is disliked. © 2017 Institute of Food Technologists®.

  11. Effects of DMSO and glycerol additives on the property of polyamide reverse osmosis membrane.

    Science.gov (United States)

    Wu, Fengjing; Liu, Xiaojuan; Au, Chaktong

    2016-10-01

    The polyamide reverse osmosis (RO) membranes were prepared through interfacial polymerization of m-phenylenediamine (MPD) and trimesoyl chloride (TMC). The use of dimethyl sulfoxide (DMSO) and glycerol as additives for the formation of thin-film composite (TFC) was investigated. We studied the effect of DMSO and glycerol addition on membrane property and RO performance. Microscopic morphology was examined by atomic force microscopy and scanning electron microscopy. The surface hydrophilicity was characterized on the basis of water contact angle and surface solid-liquid interfacial free energy (-ΔGSL). Water flux and salt rejection ability of the membranes prepared with or without the additives were evaluated by cross-flow RO tests. The results reveal that the addition of DMSO and glycerol strongly influences the property of the TFC RO membrane. Compared to the MPD/TMC membrane fabricated without DMSO and glycerol, the MPD/TMC/DMSO/glycerol membrane has a rougher surface and is more hydrophilic, showing smaller water contact angle and larger -ΔGSL value. Without decrease in salt rejection ability, the MPD/TMC/DMSO/glycerol membrane shows water flux significantly larger than that of the MPD/TMC membrane. The unique property of the MPD/TMC/DMSO/glycerol membrane is attributed to the cooperative effect of DMSO and glycerol on membrane structure during the interfacial polymerization process.

  12. Dose effect of cigarette smoking on frequency and spectrum of epidermal growth factor receptor gene mutations in Korean patients with non-small cell lung cancer.

    Science.gov (United States)

    Lee, Young Joo; Shim, Hyo Sub; Kang, Young Ae; Hong, Su Jung; Kim, Hyun Ki; Kim, Hoguen; Kim, Se Kyu; Choi, Sung Ho; Kim, Joo-Hang; Cho, Byoung Chul

    2010-12-01

    This study aimed to determine the dose effect of smoking on the mutational frequency and spectrum of epidermal growth factor receptor (EGFR) gene in Korean non-small cell lung cancer (NSCLC). Detailed smoking histories were obtained from 324 consecutively enrolled Korean NSCLC patients. Mutational status of EGFR (exon 18-21) was determined using nested polymerase chain reaction amplification. A total of 108 EGFR mutations (33.3%) were identified in 107 patients. Decreased EGFR mutation rate with increased smoking dose was observed, with 48.0% (82 of 171) in never smokers, 23.1% (15 of 65) in former smokers, and 11.4% (10 of 88) in current smokers. The incidence of EGFR mutation was significantly lower in patients who smoked for more than 25 pack-years (P smoking cigarettes less than 10 years ago (P smoke years (5.0 vs. 25.0 years in exon 20, P = 0.024), fewer total pack-years (6.3 vs. 38.9 pack-years in exon 20, P = 0.079), and more smoke-free years (11.1 vs. 3.6 years in exon 20, P = 0.027), compared with those in exon 20. Mutations in exon 19 or 21 were associated with female (P Smoking dosage affects the incidence of EGFR mutations. EGFR mutations in exon 19 or 21 are associated with low exposure to cigarette smoke, whereas EGFR mutation in exon 20 is more common in smokers.

  13. The Cumulative Effects of the MYH7-V878A and CACNA1C-A1594V Mutations in a Chinese Family with Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Wang, Bo; Guo, Rui-Qi; Wang, Jing; Yang, Fan; Zuo, Lei; Liu, Ying; Shao, Hong; Ju, Yan; Sun, Chao; Xu, Lei; Zhang, Yan-Min; Wang, Li-Feng; Liu, Li-Wen

    2017-09-02

    We investigated the pathogenesis of MYH7-V878A and CACNA1C-A1594V mutations in a Chinese family with hypertrophic cardiomyopathy. Clinical, electrocardiographic (ECG), echocardiographic, and cardiac magnetic resonance (CMR) examinations of members of a Chinese family were followed by exon and boarding intron analyses of 96 genes in the proband using second-generation sequencing. We confirmed the mutations by bidirectional Sanger sequencing in the members and in 300 healthy controls. We detected MYH7-V878A and CACNA1C-A1594V mutations in this family. The members with both mutations showed inverted T-waves and ST-segment depression in ECG recordings, severe left ventricular (LV) hypertrophy in echocardiography, and myocardial fibrosis in CMR; subject II-11 did not show late gadolinium enhancement. Among those with only the MYH7-V878A mutation, subject III-7 showed abnormal ECG recordings, asymmetric septal hypertrophy, and myocardial fibrosis, and subjects II-13 and III-15 showed some abnormal repolarization, borderline LV wall thickness, and normal CMR findings. Those with only the CACNA1C-A1594V mutation showed nearly normal readings in all examinations. The members with both mutations displayed more severe LV hypertrophy and elevated LV filling pressure than those with 1 or no mutation (p MYH7-V878A and CACNA1C-A1594V mutations may have a cumulative effect. © 2017 S. Karger AG, Basel.

  14. Effects of Calcium Superphosphate Additive on Nitrogen Conservation During Dead-pig Composting

    Directory of Open Access Journals (Sweden)

    LEI Ping

    2017-05-01

    Full Text Available To study the effects of calcium superphosphate additive on nitrogen conservation, an experiment of 30 days dead-pig composting was carried out. Three mixtures were treated with different amount of calcium superphosphate additive of 0%(CK, 5%(T1 and 10%(T2. The results showed that each composte temperature higher than 50 ℃ remained above 10 days, meeting the requirements of hygiene index about the compost rotten. The pH of composting with calcium superphosphate was significantly decreased, while NH4+-N, NH3-N, total nitrogen contents were significant higher than the control. 5% and 10% calcium superphosphate addition increased the total nitrogen contents by 10.7%, 10.1%, respectively. The seed germination index(GI of 5% calcium superphosphate addition was up to 101.4% on the 14th day, which was significant higher than the contrast. It demonstrated that calcium superphosphate could accelerate maturity during dead-pig compositng. Thus, calcium superphosphate as an additive in dead-pig composting could decrease nitrogen losses, which would bring prospects of application in dead-pig composting.

  15. The effects of scaffold architecture and fibrin gel addition on tendon cell phenotype.

    Science.gov (United States)

    Pawelec, K M; Wardale, R J; Best, S M; Cameron, R E

    2015-01-01

    Development of tissue engineering scaffolds relies on careful selection of pore architecture and chemistry of the cellular environment. Repair of skeletal soft tissue, such as tendon, is particularly challenging, since these tissues have a relatively poor healing response. When removed from their native environment, tendon cells (tenocytes) lose their characteristic morphology and the expression of phenotypic markers. To stimulate tendon cells to recreate a healthy extracellular matrix, both architectural cues and fibrin gels have been used in the past, however, their relative effects have not been studied systematically. Within this study, a combination of collagen scaffold architecture, axial and isotropic, and fibrin gel addition was assessed, using ovine tendon-derived cells to determine the optimal strategy for controlling the proliferation and protein expression. Scaffold architecture and fibrin gel addition influenced tendon cell behavior independently in vitro. Addition of fibrin gel within a scaffold doubled cell number and increased matrix production for all architectures studied. However, scaffold architecture dictated the type of matrix produced by cells, regardless of fibrin addition. Axial scaffolds, mimicking native tendon, promoted a mature matrix, with increased tenomodulin, a marker for mature tendon cells, and decreased scleraxis, an early transcription factor for connective tissue. This study demonstrated that both architectural cues and fibrin gel addition alter cell behavior and that the combination of these signals could improve clinical performance of current tissue engineering constructs.

  16. Effect of Incubation Time and Sucrose Addition on the Characteristics of Cheese Whey Yoghurt

    Science.gov (United States)

    Nurhartadi, E.; Utami, R.; Nursiwi, A.; Sari, A. M.; Widowati, E.; Sanjaya, A. P.; Esnadewi, E. A.

    2017-04-01

    The effect of incubation time and concentration of sucrose addition on the characteristics of cheese whey yogurt (lactic acid content, pH, total lactic acid bacteria, antioxidant activity, viscosity) and sensory characteristics (color, odor, flavor, consistency, and overalls) were investigated. The cheese whey yogurt fermentation process was carried out for 24h and 36h with the addition of sucrose 8, 10, and 12% (w/w) of total solid, respectively. The results showed that the lactic acid content, total lactic acid bacteria, antioxidant activity, and viscosity of cheese whey yogurt were affected by the incubation time and sucrose addition. The level of pH of yogurt which was incubated at 24h and 36h were relatively in the same levels, which were 4.51 up to 4.63. Due the sensory characteristic of cheese whey yogurt the panellists gave the high score for the cheese whey yogurt which was incubated at 24h and sucrose addition 12% (w/w) of total solid. The cheese whey yogurt has 0.41% lactic acid content; pH 4.51; 7.09 log total lactic acid bacteria cells / ml; 5.78% antioxidant activity; and 5.97 cP viscosity. The best sensory and physico-chemical characteristic of cheese whey yogurt was achieved by 24h incubation time and 12% concentration of sucrose addition.

  17. The effects of additives on the crystal habit of monosodium L-glutamate monohydrate

    Science.gov (United States)

    Sano, Chiaki; Nagashima, Nobuya; Kawakita, Tetsuya; Iitaka, Yoichi

    1990-01-01

    The effects of various amino acids and organic acids on the habit of MSG crystals have been investigated. The addition of L-alanine (L-Ala) and L-lysine (L-Lys) made the MSG crystals short and thick, but D-glutamic acid (D-Glu), γ-amino butylic acid (γ-ABA) and L-pyrrolidone carboxylic acid (L-PCA) made the crystals long and thin. HPLC analysis of the end and the side faces of the MSG crystals grown with the additives revealed that the concentrations of L-Lys and L-Ala were higher at the end faces than at the side faces; but those of D-Glu, γ-ABA and L-PCA were higher at the side faces than at the end faces. The facts indicate that habit modifications of the MSG crystals, brought about in the presence of these additives, are due to stereo-selective adsorption of the additives on the crystal faces. Finally, the cause leading to the differences in adsorption of the additives on the crystal faces of MSG is discussed in relation to the stacking density of L-Glu molecules and Na ions on each face using the results of the X-ray structure analysis.

  18. Effect of organic additives on positive electrolyte for vanadium redox battery

    Energy Technology Data Exchange (ETDEWEB)

    Li Sha [Department of Functional Materials and Chemistry, School of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China); Huang Kelong, E-mail: lisha_csu@163.com [Department of Functional Materials and Chemistry, School of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China); Liu Suqin; Fang Dong; Wu Xiongwei; Lu Dan; Wu Tao [Department of Functional Materials and Chemistry, School of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China)

    2011-06-30

    Highlights: > Four organics as electrolyte additives of vanadium redox battery. > Changes are examined in the electrochemical properties of vanadium redox battery. > D-sorbitol is a suitable additive to the electrolyte for the vanadium redox battery. > The mechanism of improvement is discussed in detail. - Abstract: Fructose, mannitol, glucose, D-sorbitol are explored as additives in electrolyte for vanadium redox battery (VRB), respectively. The effects of additives on electrolyte are studied by cyclic voltammetry (CV), charge-discharge technique, electrochemical impedance spectroscopy (EIS) and Raman spectroscopy. The results indicate that the vanadium redox cell using the electrolyte with the additive of D-sorbitol exhibits the best electrochemical performance (the energy efficiency 81.8%). The EIS results indicate that the electrochemical activity of the electrolyte is improved by adding D-sorbitol, which can be interpreted as the increase of available (-OH) groups providing active sites for electron transfer. The Raman spectra show that VO{sup 2+} ions take part in forming a complex with the D-sorbitol, which not only improve solubility of V(V) electrolyte, but also provide more activity sites for the V(IV)/V(V) redox reaction.

  19. Origin of mutational effects at the C3 and G8 positions on hammerhead ribozyme catalysis from molecular dynamics simulations.

    Science.gov (United States)

    Lee, Tai-Sung; York, Darrin M

    2008-06-11

    A series of ten 60 ns molecular dynamics (MD) simulations of the native and mutated full length hammerhead ribozymes in the reactant state and in an activated precursor state (G8:2'OH deprotonated) are reported. Mutant simulations include the C3U, G8A, and G8I single mutants and a C3U/G8A double mutant that exhibits an experimental rescue effect. The results provide critical details into the origin of the observed mutation effects and support a mechanism where the 2'OH of G8 acts as a general acid catalyst that is held in position through Watson-Crick hydrogen bonding between G8 and C3.

  20. Stimulatory effects of the flavanol (-)-epicatechin on cardiac angiogenesis: additive effects with exercise.

    Science.gov (United States)

    Ramirez-Sanchez, Israel; Nogueira, Leonardo; Moreno, Aldo; Murphy, Ann; Taub, Pam; Perkins, Guy; Ceballos, Guillermo M; Hogan, Michael; Malek, Moh; Villarreal, Francisco

    2012-11-01

    The consumption of moderate amounts of cocoa products has been associated with reductions in the incidence of cardiovascular diseases. In animal studies, the flavanol (-)-epicatechin (Epi) yields cardioprotection. The effects may be partly due to its capacity to stimulate endothelial nitric oxide synthase (eNOS). The sustained activation of eNOS, as observed with exercise, can serve as a trigger of muscle angiogenesis via the activation of vascular endothelial growth factor (VEGF)-related events. Experiments were pursued to examine the potential of Epi to stimulate myocardial angiogenesis and determine the effects that its combined use with exercise (Ex) may trigger. Hearts obtained from a previous study were used for this purpose. Animals received 1 mg/kg of Epi or water (vehicle) via oral gavage (twice daily). Epi and/or Ex (by treadmill) was provided for 15 days. Results indicate that Ex or Epi significantly stimulate myocardial angiogenesis by ~30% above control levels. The use of Epi-Ex lead to further significant increases (to ~50%). Effects were associated with increases in protein levels and/or activation of canonical angiogenesis pathway associated events (HIF1a, VEGF, VEGFR2, PI3K, PDK, AKT, eNOS, NO, cGMP, MMP-2/-9, Src-1, and CD31). Thus, the use of Epi may represent a safe and novel means to stimulate myocardial angiogenesis.

  1. pH effects of the addition of three biochars to acidic Indonesian mineral soils

    DEFF Research Database (Denmark)

    Martinsen, V; Alling, V; Nurida, N L

    2015-01-01

    Soil acidity may severely reduce crop production. Biochar (BC) may increase soil pH and cation exchange capacity (CEC) but reported effects differ substantially. In a systematic approach, using a standardized protocol on a uniquely large number set of 31 acidic soils, we quantified the effect...... of increasing amounts (0–30%; weight:weight) of three types of field-produced BCs (from cacao (Theobroma cacao. L.) shell, oil palm (Elaeis guineensis. Jacq.) shell and rice (Oryza sativa. L.) husk) on soil pH and CEC. Soils were sampled from croplands at Java, Sumatra and Kalimantan, Indonesia. All BCs caused...... a significant increase in mean soil pH with a stronger response and a greater maximum increase for the cacao shell BC addition, due to a greater acid neutralizing capacity (ANC) and larger amounts of extractable base cations. At 1% BC addition, corresponding to about 30 tons ha−1, the estimated increase in soil...

  2. Effects of Germanium Tetrabromide Addition to Zinc Tetraphenyl Porphyrin / Fullerene Bulk Heterojunction Solar Cells

    Directory of Open Access Journals (Sweden)

    Atsushi Suzuki

    2014-03-01

    Full Text Available The effects of germanium tetrabromide addition to tetraphenyl porphyrin zinc (Zn-TPP/fullerene (C60 bulk heterojunction solar cells were characterized. The light-induced charge separation and charge transfer were investigated by current density and optical absorption. Addition of germanium tetrabromide inserted into active layer of Zn-TPP/C60 as bulk heterojunction had a positive effect on the photovoltaic and optical properties. The photovoltaic mechanism of the solar cells was discussed by experimental results. The photovoltaic performance was due to light-induced exciton promoted by insert of GeBr4 and charge transfer from HOMO of Zn-TPP to LUMO of C60 in the active layer.

  3. Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders

    DEFF Research Database (Denmark)

    Brickman, J M; Clements, M; Tyrell, R

    2001-01-01

    resulting in a single amino acid substitution, Arg160Cys (R160C), is associated with a heritable form of the human condition of septo-optic dysplasia (SOD). We have examined the phenotype of affected members in this pedigree in more detail and demonstrate for the first time a genetic basis for midline...... defects associated with an undescended or ectopic posterior pituitary. A similar structural pituitary abnormality was observed in a second patient heterozygous for another mutation in HESX1, Ser170Leu (S170L). Association of S170L with a pituitary phenotype may be a direct consequence of the HESX1...... mutation since S170L is also associated with a dominant familial form of pituitary disease. However, a third mutation in HESX1, Asn125Ser (N125S), occurs at a high frequency in the Afro-Caribbean population and may therefore reflect a population-specific polymorphism. To investigate the molecular basis...

  4. Effect of additives in reducing ash sintering and slagging in biomass combustion applications

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Liang

    2012-07-01

    formation of low temperature melting potassium rich silicates and phosphates, causing severe sintering of the WCob ash at elevated temperatures. In contrast, both the Pioneer corn cob (PCob) and Surcin corn cob (SCob) contained high contents of Cl, Ca and Mg that promote K release from the ashes to a certain extent and inhibit formation of low temperature melting K rich silicates and phosphates. In addition, abundance of Ca and Mg in the PCob and SCob facilitated formation of high temperature melting Ca/Mg-K-silicates and Ca/Mg-K-phosphates, reducing sintering degrees of ashes derived from these two corn cobs. Utilizing additives is an efficient way to mitigate ash related operational problems in biomass combustion applications. The useful additives can be proximately categorized into Al-Si-based, S-based, calcium-based and phosphorus-based, according to the major chemical composition in the additives. After fed into biomass combustion systems with different approaches, the additives can decrease amounts of problematic ash species through five possible mechanisms, which prevent and/or abate ash related problems consequently. It is interesting to exploit additives from waste materials, which are normally characterized with rather high chemical reactivity, physical adsorption capacity, abundance of refractory compounds themselves and low costs. More detailed studies are needed to clarify effects of these additives on ash transformation during biomass combustion processes. Sintering characteristics of biomass ashes and effects of additives were investigated. The work revealed that severe fusion of wheat straw ash was associated with intensive formation and melting of potassium silicates under heating. Whereas, sintering of wood waste ash was caused by generation of low temperature melting potassium/sodium aluminum silicates and potassium/sodium calcium silicates. The best anti-sintering effect was achieved by using the marble sludge as additive. The dilution effect from the

  5. Which screening strategy should be offered to women with BRCA1 or BRCA2 mutations? A simulation of comparative cost-effectiveness.

    Science.gov (United States)

    de Bock, G H; Vermeulen, K M; Jansen, L; Oosterwijk, J C; Siesling, S; Dorrius, M D; Feenstra, T; Houssami, N; Greuter, M J W

    2013-04-30

    There is no consensus on the most effective strategy (mammography or magnetic resonance imaging (MRI)) for screening women with BRCA1 or BRCA2 mutations. The effectiveness and cost-effectiveness of the Dutch, UK and US screening strategies, which involve mammography and MRI at different ages and intervals were evaluated in high-risk women with BRCA1 or BRCA2 mutations. Into a validated simulation screening model, outcomes and cost parameters were integrated from published and cancer registry data. Main outcomes were life-years gained and incremental cost-effectiveness ratios. The simulation was situated in the Netherlands as well as in the United Kingdom, comparing the Dutch, UK and US strategies with the population screening as a reference. A discount rate of 3% was applied to both costs and health benefits. In terms of life-years gained, the strategies from least to most cost-effective were the UK, Dutch and US screening strategy, respectively. However, the differences were small. Applying the US strategy in the Netherlands, the costs were €43 800 and 68 800 for an additional life-year gained for BRCA1 and BRCA2, respectively. At a threshold of €20 000 per life-year gained, implementing the US strategy in the Netherlands has a very low probability of being cost-effective. Stepping back to the less-effective UK strategy would save relatively little in costs and results in life-years lost. When implementing the screening strategies in the United Kingdom, the Dutch, as well as the US screening strategy have a high probability of being cost-effective. From a cost-effectiveness perspective, the Dutch screening strategy is preferred for screening high-risk women in the Netherlands as well as in the United Kingdom.

  6. Effect of Fruit Addition on the Quality Characteristics of Tahini Halva

    OpenAIRE

    SOYDİNÇ, Hülya; BAŞYİĞİT, Bülent; HAYOĞLU, İbrahim

    2016-01-01

    The purpose of this study was to make Tahini Halva which incorporated with 10, 15 and 20% fruits (raisins and apricots) and to investigate effect on sensory and chemical properties of Tahini halva of addition of fruit during storage. Moreover, tahini halva produced plain compared with halva that added fruits.  Dry matter, ash, crude fiber, protein, sugar, fat, acidity in oil which was extracted, peroxide and refractive index determinations were analyzed in Halva.  According to statistical eva...

  7. Effect of Addition of Cereal Based Beta-glucan on Technological and Functional Properties of Foods

    OpenAIRE

    Nihal Şimşekli; İsmail Sait Doğan

    2015-01-01

    Nowadays usage of dietary fibers in foods has been increasing duo to revealing of health benefits. Beta-glucans found especially in oats and barley, are polysaccharide and source of water-soluble dietary fiber. Positive effects of beta-glucans like healing coronary-heart disease, lowering blood cholesterol level, balancing blood sugar level and preventing obesity, made beta-glucans widespread functional food components for producing various foods. In addition to beneficial physiological effec...

  8. Reduction of the oestrogenic effect of zearalenone in pigs by a feed additive

    Directory of Open Access Journals (Sweden)

    Endre Brydl

    2014-01-01

    Full Text Available Zearalenone is phenolic resorcyclic acid lactone produced by a number of Fusarium species grown on grains, predominantly on maize, in high moisture environment. Due to its oestrogenic effects, feeds contaminated with zearalenone can cause striking negative effects on reproduction primarily in pigs. The aim of the study was to test the efficiency of a feed additive developed for enzymatic decomposition of mycotoxins. A total of sixty 6-week-old conventional Dutch Landrace × Hungarian Large White F1 female pigs weaned at 30 ± 2 days of age were divided into 6 groups of 10 animals. Between 50 and 70 days of age, 4 groups of pigs (experimental were treated with zearalenone (8 or 16 mg/pig dose administered every other day via an oesophageal tube; pigs from the other two groups were not treated with zearalenone and served as controls. Throughout the experiment, the diet of two experimental groups and one control group was supplemented with a feed additive (named: Detoxa Plus at a concentration of 1 kg/tonne; pigs from the other control group received neither zearalenone treatment, nor the feed additive. Pigs’ live weight, weight of ovaries and uterus, histological characteristics of the ovaries, uterus, vagina, spleen and lymph nodes, liver concentrations of zearalenone and its metabolites (α- and β-zearalenol were studied. This study showed the preventive capacity of the feed additive against zearalenone. Positive effects included the prevention of uterine enlargement, beneficial effects on the histopathological scores of ovaries, uterus and vagina and reduced concentration of zearalenone and metabolites in the liver. This study demonstrates for the first time that due to its enzymatic activity Detoxa Plus renders zearalenone contaminated feeds less toxic.

  9. Oxidative treatment of diclofenac via ferrate(VI) in aqueous media: effect of surfactant additives.

    Science.gov (United States)

    Wang, Yingling; Ni, Tianjun; Yuan, Jianmei; Wang, Chunfeng; Liu, Guoguang

    2017-03-01

    The potential reaction of diclofenac (DCF) with ferrate(VI) and influences of coexisting surfactants have not been investigated in depth, and are the focus of this study. The results demonstrated that DCF reacted effectively and rapidly with Fe(VI) and approximately 75% of DCF (0.03 mM) was removed by excess Fe(VI) (0.45 mM) within 10 min. All of the reactions followed pseudo first-order kinetics with respect to DCF and Fe(VI), where the apparent second-order rate constant (kapp) was 5.07 M(-1) s(-1) at pH 9.0. Furthermore, the degradation efficiencies of DCF were clearly dependent on the concentrations of dissolved organic matter additives in the substrate solution. Primarily, inhibitory effects were observed with the samples that contained anionic (sodium dodecyl-benzene sulfonate, SDBS) or non-ionic (Tween-80) surfactants, which have been attributed to the side reactions between Fe(VI) and surfactants, which led to a reduction in the available oxidant for DCF destruction. Furthermore, the addition of a cationic surfactant (cetyltrimethyl ammonium bromide, CTAB) and humic acid (HA) conveyed significantly promotional effects on the DCF-Fe(VI) reaction. The rate enhancement effect for CTAB might be due to micellar surface catalysis, through the Coulomb attraction between the reactants and positively charged surfactants, while the catalytic action for HA resulted from the additional oxidation of Fe(V)/Fe(IV) in the presence of HA. The results provided the basic knowledge required to understand the environmental relevance of DCF oxidation via Fe(VI) in the presence of surfactant additives.

  10. Academic self-concept, autonomous academic motivation, and academic achievement : mediating and additive effects

    OpenAIRE

    Guay, Frédéric; Ratelle, Catherine; Roy, Amélie; Litalien, David

    2010-01-01

    Three conceptual models were tested to examine the relationships among academic self-concept, autonomous academic motivation, and academic achievement. This allowed us to determine whether 1) autonomous academic motivation mediates the relation between academic self-concept and achievement, 2) academic self-concept mediates the relation between autonomous academic motivation and achievement, or 3) both motivational constructs have an additive effect on academic achievement. A total of 925 hig...

  11. Effect of the Addition of Blueberries on Selected Physicochemical and Sensory Properties of Yoghurts

    OpenAIRE

    Asuman Cinbas; Fehmi Yazici

    2008-01-01

    In this research, physicochemical and sensory properties of blueberries and sugar added to yoghurts have been investigated on the first, 10th and 20th day of storage in refrigerator. Samples were analyzed for pH, total solids, protein, fat, ash, viscosity, syneresis, Hunter's L, a, and b values, flavour, body, texture, appearance and colour. Blueberry and sugar mass fractions and storage time had a significant effect on the physicochemical and sensory properties of yoghurts. The addition of b...

  12. Electrolyte addition to nonionic contrast media. Cardiac effects during experimental coronary arteriography.

    Science.gov (United States)

    Pedersen, H K

    1996-01-01

    Although the incidence of serious adverse effects is low during clinical coronary arteriography, life-threatening cardiovascular complications occasionally occur. Ventricular fibrillation (VF) is most often seen during contrast media (CM) injection through a wedged catheter. A simulated wedged catheter model in dogs has therefore been developed. Further, patients with heart failure are at greater risk for CM-related side effects during coronary arteriography. Thus, an acute ischemic heart failure model has been used. The present thesis was designed to investigate the cardiac electrophysiologic and hemodynamic effects of CM during selective coronary arteriography in normal and failing hearts, and in particular the role of electrolyte addition to nonionic CM. The risk of spontaneously induced VF and the arrhythmogenic mechanisms were studied when using iso-osmolal and low-osmolal CM having different contents of electrolytes, and after pretreatment with antiarrhythmic drugs. Further, effects of adding electrolytes to nonionic CM during single and fast repeated injections in normal and failing hearts were studied. Also possible effects of oxygenating CM were studied. CM injection in a wedged catheter situation had a high risk for VF. Probably, VF was due to induced regional electrophysiologic changes in ventricular activation and repolarization. Pretreatment with antiarrhythmic drugs did not prevent VF. However, addition of low concentrations of electrolytes to nonionic CM reduced the risk for VF in a wedged catheter situation. The results indicate that side-effects of CM during coronary arteriography are related mainly to the passive washout of cardiac electrolytes. Electrolyte shifts during coronary arteriography may change the myocardial Na/Ca balance and cellular calcium control. The nonionic, iso-osmolal CM iodixanol, with a balanced content of sodium and calcium and the low-osmolal, nonionic CM iohexol, also with a balanced content of electrolytes, had about the

  13. Effect of Addition of Fennel (Foeniculum vulgare L. on the Quality of Protein Bread

    Directory of Open Access Journals (Sweden)

    Sayed-Ahmad Bouchra

    2017-12-01

    Full Text Available Fennel (Foeniculum vulgare L. is an aromatic plant belonging to Apiaceae family widely cultivated elsewhere for its strongly flavoured leaves and seeds. Fennel seeds are of particular interest as a rich source of both vegetable and essential oils with high amounts of valuable components. However, residual cakes after oil extraction were typically considered as byproducts, in the present framework, the potential added value of these cakes was studied. The aim of this study was to investigate the effect of addition of fennel cake and seeds to protein bread quality. In the current research, a single-screw extruder, which is a solvent-free technique, was used for fennel seed oil extraction. For the protein bread making, fennel seed and cake flour in concentrations from 1 to 6% were used. Moisture, colour L*a*b*, hardness, total phenolic concentration, DPPH radical scavenging activity, and nutritional value of protein bread were determined. The addition of fennel cake and seeds had significant (p < 0.05 effect on bread crumb colour and hardness attribute, whereby the bread became darker and harder in texture than the control. Moreover, higher antioxidant activity and total phenolic concentration were observed for both protein breads enriched with fennel cake and seed flour. The overall results showed that addition of fennel cake and seed had beneficial effects on phenolic concentration, antioxidant activity and quality of protein bread. This result suggests also that added value of fennel seeds oil by-products could be increased by their utilisation in bread production.

  14. Ultrasonic Degradation of Fuchsin Basic in Aqueous Solution: Effects of Operating Parameters and Additives

    Directory of Open Access Journals (Sweden)

    Rui-Jia Lan

    2013-01-01

    Full Text Available Ultrasonic degradation is one of the recent advanced oxidation processes (AOPs and proven to be effective for removing low-concentration organic pollutants from aqueous solutions. In this study, removal of fuchsin basic from aqueous solutions by ultrasound was investigated. The effects of operating parameters such as ultrasound power (200 W–500 W, initial pH (3–6.5, and temperature (15, 22, 35, and 60°C on the ultrasonic degradation were studied. The degradation of fuchsin under ultrasound irradiation basic was found to obey pseudo first-order reaction kinetics. Addition of catalyst Fe(II had a markedly positive effect on degradation. 84.1% extent of degradation was achieved at initial dye concentration 10 μmol L−1, ultrasound power 400 W, ultrasound frequency 25 kHz, dosage of Fe(II 4 mg L−1, initial pH 6.5, and temperature 22°C. But addition of heterogeneous catalyst TiO2 affected degradation slightly. Addition of radical scavenger suppressed fuchsin basic degradation significantly.

  15. [Effects of nitrogen and carbon addition and arbuscular mycorrhiza on alien invasive plant Ambrosia artemisiifolia].

    Science.gov (United States)

    Huang, Dong; Sang, Wei-guo; Zhu, Li; Song, Ying-ying; Wang, Jin-ping

    2010-12-01

    A greenhouse control experiment was conducted to explore the effects of nitrogen and carbon addition and arbuscular mycorrhiza (AM) on the growth of alien invasive plant Ambrosia artemisiifolia (common ragweed). Nitrogen addition had no significant effects on the morphological indices, biomass and its allocation, and absolute growth rate of A. artemisiifolia, but increased the nitrogen content in the aboveground and underground parts of the plant significantly. Carbon addition increased the content of soil available nitrogen. In this case, the biomass allocation in root system for nutrient (nitrogen) absorption promoted, resulting in a remarkable decrease of branch number, total leaf area, specific leaf area (SLA), and leaf mass ratio. As a result, the total biomass decreased significantly. The symbiosis of A. artemisiifolia and AM fungi had great influence on the common ragweed's soil nitrogen acclimation, which enhanced its resource-capture by the increase of SLA, and this effect was more significant when the soil nitrogen content was low. AM fungi played an important role in the growth of A. artemisiifolia in low-nitrogen environment.

  16. Effect of the addition of fibreglass waste on the properties of dried and fired clay bricks

    Science.gov (United States)

    Guzlena, S.; Sakale, G.; Certoks, S.; Grase, L.

    2017-10-01

    The main objective of this study was to investigate the effect of the addition of fibreglass waste on the properties of the dried and fired clay bricks. Different amounts of waste glass (0 – 10 wt %) were added to the original brick clay and fired at 1000 °C. The effects on the technological properties of the bricks such as compressive strength, water absorption and density after firing were investigated. Also cracks and fibreglass influence in dried and fired samples were analysed by digital camera and SEM-EDX analysis.

  17. Richly parameterized linear models additive, time series, and spatial models using random effects

    CERN Document Server

    Hodges, James S

    2013-01-01

    A First Step toward a Unified Theory of Richly Parameterized Linear ModelsUsing mixed linear models to analyze data often leads to results that are mysterious, inconvenient, or wrong. Further compounding the problem, statisticians lack a cohesive resource to acquire a systematic, theory-based understanding of models with random effects.Richly Parameterized Linear Models: Additive, Time Series, and Spatial Models Using Random Effects takes a first step in developing a full theory of richly parameterized models, which would allow statisticians to better understand their analysis results. The aut

  18. Catalytic effects of eight inorganic additives on pyrolysis of pine wood sawdust by microwave heating

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ming-qiang; Wang, Jun; Zhang, Ming-xu; Chen, Ming-gong; Min, Fan-fei [Department of Chemical and Material Engineering, Anhui University of Science and Technology, Huainan, Anhui 232001 (China); Zhu, Xi-feng [Laboratory of Biomass Clean Energy, University of Science and Technology of China, Hefei 230026 (China); Tan, Zhi-cheng [Thermochemistry Laboratory, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China)

    2008-05-15

    In this paper, pyrolysis of pine wood sawdust was carried out by microwave heating at ca. 470 C under dynamic nitrogen atmosphere. Eight inorganic additives (NaOH, Na{sub 2}CO{sub 3}, Na{sub 2}SiO{sub 3}, NaCl, TiO{sub 2}, HZSM-5, H{sub 3}PO{sub 4}, Fe{sub 2}(SO{sub 4}){sub 3}) were investigated in terms of their catalytic effects on the pyrolysis. All of the eight additives have increased yields of solid products greatly and decreased yields of gaseous products more or less. Yields of liquid products have not subjected to dramatic change. The incondensable gases produced from pyrolysis consist mainly of H{sub 2}, CH{sub 4}, CO and CO{sub 2}. All of the eight additives have made these gases evolve earlier, among which the four sodium additives have the most marked effect. All the additives have made the amount of CH{sub 4} and CO{sub 2} decrease, while all of them except NaCl, TiO{sub 2} and Fe{sub 2}(SO{sub 4}){sub 3} have made that of H{sub 2} increase and all of them except Na{sub 2}SiO{sub 3} and HZSM-5 have made that of CO decrease. Alkaline sodium compounds NaOH, Na{sub 2}CO{sub 3} and Na{sub 2}SiO{sub 3} favor H{sub 2} formation most. The most abundant organic component in the liquid products from pyrolysis of untreated sample and samples treated by all the additives except H{sub 3}PO{sub 4} and Fe{sub 2}(SO{sub 4}){sub 3} is acetol. All the four sodium compounds favor acetol formation reaction and the selection increasing effect follows the order of NaOH > Na{sub 2}CO{sub 3} {approx} Na{sub 2}SiO{sub 3} > NaCl. TiO{sub 2} goes against the formation of acetol, HZSM-5 has no marked effect on acetol formation. The two dominant organic components identified in the liquid products from pyrolysis of H{sub 3}PO{sub 4} and Fe{sub 2}(SO{sub 4}){sub 3} treated samples are both fufural and 4-methyl-2-methoxy-phenol. A possible pathway for acetol formation is tentatively proposed. (author)

  19. [Effect of Point Mutations in the Polymerase Genes of the Influenza A/PR/8/34 (H1N1) Virus on the Immune Response in a Mouse Model].

    Science.gov (United States)

    Kuznetsova, S A; Isakova-Sivak, I N; Kuznetcova, V A; Petukhova, G D; Losev, I V; Donina, S A; Rudenko, L G; Naikhin, A N

    2015-01-01

    The vaccine strains for live attenuated influenza vaccines (LAIVs) have cold-adapted, temperature-sensitive, and attenuated phenotypes, which are guaranteed by the presence of specific mutations from the master donor virus in their internal genes. In this study, we used mutant viruses of the pathogenic A/Puerto Rico/8/34 (H1N1) that contained ts-mutations in PB1 (K265N, V591I), PB2 (V478L), and PA (L28P, V341L) genes along and/or in different combinations to evaluate the impact of these mutations in the immune responses. Sequential addition of tested mutations resulted in the stepwise decrease in virus-specific serum and, to a lesser extent, mucosal antibody levels. We demonstrated strong positive correlation between virus attenuation (virus titer in lung) and antibody titers. The ts-mutations in PB1, PB2, and PA genes are mostly involved in the modulation of the humoral immunity, but also have a moderate effect on the cellular adaptive immune response.

  20. Effects of nitrogen and phosphorus additions on soil methane uptake in disturbed forests

    Science.gov (United States)

    Zheng, Mianhai; Zhang, Tao; Liu, Lei; Zhang, Wei; Lu, Xiankai; Mo, Jiangming

    2016-12-01

    Atmospheric nitrogen (N) deposition is generally thought to suppress soil methane (CH4) uptake in natural forests, and phosphorus (P) input may alleviate this negative effect. However, it remains unclear how N and P inputs control soil CH4 uptake in disturbed forests. In this study, soil CH4 uptake rates were measured in two disturbed forests, including a secondary forest (with previous, but not recent, disturbance) and a plantation forest (with recent continuous disturbance), in southern China for 34 months of N and/or P additions: control, N addition (150 kg N ha-1 yr-1), P addition (150 kg P ha-1 yr-1), and NP addition (150 kg N ha-1 yr-1 plus 150 kg P ha-1 yr-1). Mean CH4 uptake rate in control plots was significantly higher in the secondary forest (24.40 ± 0.81 µg CH4-C m-2 h-1) than in the plantation forest (17.07 ± 0.70 µg CH4-C m-2 h-1). CH4 uptake rate had negative relationships with soil water-filled pore space in both forests. In the secondary forest, N, P, and NP additions significantly decreased CH4 uptake by 39.7%, 27.8%, and 37.6%, respectively, but had no significant effects in the plantation forest, indicating that P input does not alleviate the suppression of CH4 uptake by N deposition. Taken together, our findings suggest that reducing anthropogenic disturbance, including harvesting of forest floor, and anthropogenic N and P inputs will increase soil CH4 uptake in disturbed forests, which is important in view of the increased trends in global warming during recent decades.

  1. The effect of the humic acid and herbal additive supplement on production parameters of broiler chicken

    Directory of Open Access Journals (Sweden)

    Veronika Pistová

    2016-10-01

    Full Text Available In this study the effect of humic acids and dietary herbal additive (clove (Syzygium aromaticum, lavender (Lavendula angustifolia and black pepper (Piper nigrum L. on production parameters of broiler chicken were studied.  A total of 60 Ross 308 broiler chicken were divided into 3 treatments (n=20. The control group of chickens was fed with complete feed mixtures without any additives. Chicken in treatment T1 were fed a diet containing 1% of humic acid and drank a water containing 150 mg/l of herbal additive. Chicken in treatment T2 were fed with complete feed mixture without any additives and drank a water containing 150 mg/l of herbal additive. The body weight, feed intake and feed conversion were evaluated. The results shout that the body weight was significantly higher (P≤0.05 in treatments groups compared to the control group (the order of the groups: 1796.4±188.1; 2052.9±197.9 and 2140.4±300.4 g±SD. The feed intake was in the control group 3.11 kg, in the treatment T1 3.00 kg and in the treatment T2 3.12 kg. Feed conversion for the entire fattening period was in control group 2.19 kg/kg complete feed mixture, in the treatment T1 1.83 kg/kg complete feed mixture and in the treatment T2 1.84 kg/kg complete feed mixture with no significant different (P≥0.05 compared to control group. In conclusion, supplement by humic acid and herbal additive can improve production parameters of broiler chicken.

  2. Effects of carbon nanotube addition on superconductivity in Y-Ba-Cu-O bulk superconductors

    Science.gov (United States)

    Inoue, K.; Miyake, Y.; Miryala, M.; Murakami, M.

    2017-07-01

    Bulk Y-Ba-Cu-O superconductors have significant potential for engineering applications due to high critical current density, which is attributed to the presence of pinning centers such as Y2BaCuO5. The introduction of nano-sized secondary phase is known to act as more effective pinning center than those in micron sizes. The diameter of carbon nanotube (CNT) is close to that of the coherence length of high-temperature superconductors, which is expected to improve the flux pinning performance. We have investigated the effects of CNT addition on the microstructure, superconducting transition temperature (T c), and critical current density (J c) of YBa2Cu3O x (Y123) based bulk superconductors. SEM observation showed the distribution of needle-like particles around 100 nm in length in the Y123 matrix for the CNT added samples. The highly porous texture was also observed for the excess addition of CNT. T c was enhanced from 90.5 K to 91.8 K with increasing CNT addition. It is probable that carbon originated from CNT suppressed oxidation and carrier doping. Jc exhibited the highest value for 0.25 wt% CNT added sample. This suggests that nano-sized needle-like particles act as effective pinning centers. However, a further increase of CNT led to the decline of J c, which suggests that there is an optimum amount of CNT for the improvement of J c. The secondary peak was observed for the sample with 1 wt% CNT addition, where CO3 substitutions with Cu site at the Cu-O chain might induce oxygen vacancies leading to the field induced pinning.

  3. Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice

    Directory of Open Access Journals (Sweden)

    Klaus Fabel

    2009-11-01

    Full Text Available Voluntary physical exercise (wheel running, RUN and environmental enrichment (ENR both stimulate adult hippocampal neurogenesis but do so by different mechanisms. RUN induces precursor cell proliferation, whereas ENR exerts a survival-promoting effect on newborn cells. In addition, continued RUN prevented the physiologically occurring age-related decline in precursor cell in the dentate gyrus but did not lead to a corresponding increase in net neurogenesis. We hypothesized that in the absence of appropriate cognitive stimuli the potential for neurogenesis could not be realized but that an increased potential by proliferating precursor cells due to RUN could actually lead to more adult neurogenesis if an appropriate survival-promoting stimulus follows the exercise. We thus asked whether a sequential combination of RUN and ENR (RUNENR would show additive effects that are distinct from the application of either paradigm alone. We found that the effects of 10 days of RUN followed by 35 days of ENR were additive in that the combined stimulation yielded an approximately 30% greater increase in new neurons than either stimulus alone, which also increased neurogenesis. Surprisingly, this result indicates that although overall the amount of proliferating cells in the dentate gyrus is poorly predictive of net adult neurogenesis, an increased neurogenic potential nevertheless provides the basis for a greater efficiency of the same survival-promoting stimulus. We thus propose that physical activity can “prime” the neurogenic region of the dentate gyrus for increased neurogenesis in the case the animal is exposed to an additional cognitive stimulus, here represented by the enrichment paradigm.

  4. Delayed effects of accelerated heavy ions on the induction of HPRT mutations in V79 hamster cells.

    Science.gov (United States)

    Bláha, Pavel; Koshlan, Nataliya A; Koshlan, Igor V; Petrova, Daria V; Bogdanova, Yulia V; Govorun, Raisa D; Múčka, Viliam; Krasavin, Evgeny A

    2017-10-01

    Fundamental research on the harmful effects of ionizing radiation on living cells continues to be of great interest. Recently, priority has been given to the study of high-charge and high-energy (HZE) ions that comprise a substantial part of the galactic cosmic ray (GCR) spectra that would be encountered during long-term space flights. Moreover, predictions of the delayed genetic effects of high linear energy transfer (LET) exposure is becoming more important as heavy ion therapy use is increasing. This work focuses mainly on the basic research on the delayed effects of HZE ions on V79 Chinese hamster cells, with emphasis on the induction of HPRT mutations after prolonged expression times (ET). The research was conducted under various irradiation conditions with accelerated ions 18 O (E=35.2MeV/n), 20 Ne (E=47.7MeV/n and 51.8MeV/n), and 11 B (E=32.4MeV/n), with LET in the range from 49 to 149 keV/μm and with 60 Co γ-rays. The HPRT mutant fractions (MF) were detected in irradiated cells in regular intervals during every cell culture recultivation (every 3days) up to approximately 40days (70-80 generations) after irradiation. The MF maximum was reached at different ET depending on ionizing radiation characteristics. The position of the maximum was shifting towards longer ET with increasing LET. We speculate that the delayed mutations are created de novo and that they are the manifestation of genomic instability. Although the exact mechanisms involved in genomic instability initiation are yet to be identified, we hypothesize that differences in induction of delayed mutations by radiations with various LET values are related to variations in energy deposition along the particle track. A dose dependence of mutation yield is discussed as well. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Apparent directional selection by biased pleiotropic mutation.

    Science.gov (United States)

    Tanaka, Yoshinari

    2010-07-01

    Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.

  6. Effect of the different level of a dry feed additive on the lupin silage quality

    Directory of Open Access Journals (Sweden)

    Petr Doležal

    2005-01-01

    Full Text Available In the experiment, the effect of additive on the fermentation quality of lupine was examined, by comparing with the untreated control. Fresh green Lupine (Lupines lupine, variete Juno, dry matter content 187.15 g/kg at full waxy stage of maturiy were chopped to the legth of cut ca 30–50 mm. The crop was artificially wilted for a periody 24 h and ensiled as described above. Lupine were ensiled for 98 days in laboratory silos, capacity about 4 L alone or with supplementation of feed additive (5, 10, 20, 30, 40, 50 or 70 kg/tone forage respectively. The composition and as effective substances of this silage ingredient were dry whey (30%, maize meal (40% and dry molases (30%. The silages fermented rapidly and changes in volatile fatty acids (VFA production (P<0.01 and in sum of acids were noted. The different supplementation of additive in our experiment conditions increased significantly (P<0.01 the dry matter content, and decreased statistically significantly (P<0.01 the pH value. The higher DM content was in all experimental silages, but the highest DM content (P<0.01 was in silage with addition of 70 kg/t (231.58Ī0.91 g/kg. All treated silages were well fermented with low levels of ammonia and pH. The different addition of this aditive increased significantly (P<0.01 the contents of lactic acid and total content of acids in comparison with control silage. The experimental silage with higher (5%, resp. 7% feed supplementation was of better quality (significantly higher ratio LA/sum of acids, higher content of lactic acid, lower NH3 content and pH value than the control silage, or silage with lower concentration. In experiment feed additive–treated silages (by groups of 5 or 50 and 70 kg/t had significantly higher alcohol content than untreated silage. It was concluded that feed additive used as a silage additive improved fermentation of lupine, reduced acetic acid and ammonia production and increased silage nutritive value.

  7. Additive effect of heparin on the photoinactivation of Escherichia coli using tricationic P-porphyrins.

    Science.gov (United States)

    Matsumoto, Jin; Suzuki, Kou; Uezono, Hidekazu; Watanabe, Kaho; Yasuda, Masahide

    2017-12-01

    Polycationic porphyrins have received substantial attention in developing singlet oxygen-sensitizers for biological use such as in the photoinactivation of bacteria and photodynamic therapy (PDT) of tumor cells because they have strong binding affinities for DNA and proteins. However, these strong cellular interactions can retard elimination of the drug after PDT. Therefore, the studies on the interactions of porphyrins with other molecules present much interest, in order to modulate the sensitizers' activity or even remove them from the human body after PDT. Here, we studied the additive effect of heparin on the photoinactivation by polycationic porphyrins using Escherichia coli as a model cell. Tricationic P-porphyrin sensitizers substituted with an N-alkylpyridinium group (alkyl = pentyl (1a), hexyl (1b), and heptyl (1c)) or N-hexylammonium (1d) as the axial ligand were used. Additionally, dicationic Sb-porphyrin substituted with an N-hexylpyridinium group (1e) was prepared. We studied the additive effect of heparin on the photoinactivation of E. coli by 1a-1e. The bactericidal activities were evaluated using the half-life (T1/2 in min) of E. coli and the minimum effective concentrations ([P]) of the porphyrin sensitizers. In the absence of heparin, the [P] values were determined to be 0.4-0.5 μM for 1a-1c and 2.0 μM for 1d-1e. The bactericidal activity of 1a-1c was completely retarded by the addition of heparin (1.0 μM). However, the addition of heparin (1.0 μM) could not completely retard the bactericidal activity of 1d-1e whose [P] values were relatively large. It is suggested that tricationic 1a-1c adsorbed onto the anionic heparin through electrostatic interactions. The adsorption of 1 on heparin disturbs the uptake of 1 into E. coli cells. Thus, the addition of heparin was found to be a useful method for retarding photoinactivation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Effect of additives on the anisotropic etching of silicon by using a TMAH based solution

    Science.gov (United States)

    Jun, Ki-Hwa; Kim, Bum-Joon; Kim, Jung-Sik

    2015-09-01

    In this study, the anisotropic etching properties of single crystal silicon were examined using a tetramethyl ammonium hydroxide (TMAH). The variations in the Si etching rate and surface morphology at different etching temperatures and TMAH concentrations were evaluated. The effects of different additives were also examined. As the THAM concentration (10-25 wt. %) decreased, the etching rate increased from 10 μm/h to 70 μm/h at temperatures between 70°C and 90°C. On the other hand, the etched surface roughness became degraded as the hillock density and corner undercut ratio increased. To solve these problems, four additives, pyrazine, ammonium persulfate (AP), ammonium hydrogen sulfate (AHS), and isopropyl alcohol (IPA), were added to the TMAH solution. The experimental results showed that these additives play an important role in increasing the etching rate up to 10-20%. The etched surface was also improved significantly by the decreased hillock density on the surface. The addition of IPA to the TMAH solution showed excellent results in improving the etched surface flatness and the undercutting compensation. On the other hand, one of the characteristics of IPA is the decrease in etching rate with increasing amount of IPA. [Figure not available: see fulltext.

  9. Effects of emulsifier addition on the crystallization and melting behavior of palm olein and coconut oil.

    Science.gov (United States)

    Maruyama, Jessica Mayumi; Soares, Fabiana Andreia Schafer De Martini; D'Agostinho, Natalia Roque; Gonçalves, Maria Inês Almeida; Gioielli, Luiz Antonio; da Silva, Roberta Claro

    2014-03-12

    Two commercial emulsifiers (EM1 and EM2), containing predominantly monoacylglycerols (MAGs), were added in proportiond of 1.0 and 3.0% (w/w) to coconut oil and palm olein. EM1 consisted of approximately 90% MAGs, whereas EM2 consisted of approximately 50% MAGs. The crystallization behavior of these systems was evaluated by differential scanning calorimetry (DSC) and microscopy under polarized light. On the basis of DSC results, it was clear that the addition of EM2 accelerated the crystallization of coconut oil and delayed the crystallization of palm olein. In both oils EM2 addition led to the formation of smaller spherulites, and these effects improved the possibilities for using these fats as ingredients. In coconut oil the spherulites were maintained even at higher temperatures (20 °C). The addition of EM1 to coconut oil changed the crystallization pattern. In palm olein, the addition of 3.0% (w/w) of this emulsifier altered the pattern of crystallization of this fat.

  10. Effect of additional brief counselling after periodic health examination on motivation for health behavior change [corrected].

    Science.gov (United States)

    Son, Ki Young; Lee, Cheol Min; Cho, BeLong; Lym, Youl Lee; Oh, Seung Won; Chung, Wonjoo; Lee, Jin-Seok; Park, DuShin; Kim, Han Suk

    2012-11-01

    This study was to evaluate the effect of additional brief counseling by a primary care physician on lifestyle modification of examinees after a periodic health examination. 1,000 participants of the 2007 Korean national health screening program were asked to note any variation in their health behavior after participating in the screening program. The degree of comprehensive motivation for lifestyle modification was assessed in terms of stages of health behavior change. We calculated odds ratio of positive change (enhanced stage of change) with multiple logistic regression analysis and age-adjusted proportion of positive changers. Of 989 respondents, 486 and 503 received the basic and additional programs, respectively. Additional group were more likely to be positive changer than basic group (adjusted OR 1.78; 95% CI 1.19-2.65), and this was more prominent in older age group (adjusted OR 2.38, 95% CI 1.23-4.58). The age-adjusted proportions of positive changers were 22.7% (95% CI, 17.9-28.3) and 36.2% (95% CI, 30.4-42.4) in the basic and additional groups, respectively (P health examination. Thus, such a consultation should be considered when designing a health-screening program.

  11. phuR intergenic mutation results in pleiotropic effects on global gene expression

    DEFF Research Database (Denmark)

    Khademi, Seyed Mohammad Hossein; Wassermann, Tina; Ciofu, Oana

    2015-01-01

    We have previously found a positive selection for promoter mutations in Pseudomonas aeruginosa DK2 leading to increased expression of the phu (Pseudomonas heme utilization) system. By mimicking conditions of the CF airways in vitro, we experimentally demonstrated that increased expression of phuR...

  12. Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia

    Science.gov (United States)

    TET2 enzymatically converts 5-methyl-cytosine to 5-hydroxymethyl-cytosine, possibly leading to loss of DNA methylation. TET2 mutations are common in myeloid leukemia and were proposed to contribute to leukemogenesis through DNA methylation. To expand on this concept, we studied chronic myelomonocyti...

  13. Effects of electron beam radiation on trait mutation in azuki bean ...

    African Journals Online (AJOL)

    Dry seeds of azuki bean (Vigna angularisi), Jingnong 6 and Hebei 801 varieties were irradiated by electron beam of 100, 300, 600, 700 and 900 Gy, respectively. Mutations of leaf shape and color, seed size and shape, trailing, more branching, dwarfing, early or late flowering time and high yield were created in M2 and M3 ...

  14. Effects of mutations at the stambh A locus of Drosophila melanogaster

    Indian Academy of Sciences (India)

    We report novel findings on the cytogenetic location, functional complexity and maternal and germline roles of the stambh A locus of Drosophila melanogaster. stmA is localized to polytene bands 44D1.2 on 2R. stmA mutations are of two types: temperature-sensitive (ts) adult and larval paralytic or unconditional embryonic ...

  15. Epidemiology of isoniazid resistance mutations and their effect on tuberculosis treatment outcomes

    NARCIS (Netherlands)

    Huyen, Mai N. T.; Cobelens, Frank G. J.; Buu, Tran N.; Lan, Nguyen T. N.; Dung, Nguyen H.; Kremer, Kristin; Tiemersma, Edine W.; van Soolingen, Dick

    2013-01-01

    Isoniazid resistance is highly prevalent in Vietnam. We investigated the molecular and epidemiological characteristics and the association with first-line treatment outcomes of the main isoniazid resistance mutations in Mycobacterium tuberculosis in codon 315 of the katG and in the promoter region

  16. Epidemiology of isoniazid resistance mutations and their effect on tuberculosis treatment outcomes.

    NARCIS (Netherlands)

    Huyen, M.N.; Cobelens, F.G.; Buu, T.N.; Lan, N.T.; Dung, N.H.; Kremer, K.; Tiemersma, E.W.; Soolingen, D. van

    2013-01-01

    Isoniazid resistance is highly prevalent in Vietnam. We investigated the molecular and epidemiological characteristics and the association with first-line treatment outcomes of the main isoniazid resistance mutations in Mycobacterium tuberculosis in codon 315 of the katG and in the promoter region

  17. The effect of mutations in the AmpC promoter region on β-lactam ...

    African Journals Online (AJOL)

    Analysis of the ampC promoter and attenuator regions of the isolate showed that the isolate had mutations in the promoter region and this included insertions of nucleotides in ... The insertion of an extra nucleotide in the spacer region between the -10 and -35 boxes affects the resistance of bacteria to β-lactam antibiotics.

  18. Pleiotropic effect of his gene mutations on nitrogen fixation in Klebsiella pneumoniae

    DEFF Research Database (Denmark)

    Jensen, Jens Stougaard; Kennedy, C

    1982-01-01

    Several his mutations were found to influence nitrogen fixation in Klebsiella pneumoniae: hisB, hisC, and hisD mutants had 50% of wild-type levels of nitrogenase activity when supplied with 30 mug or less histidine/ml although this concentration did not limit protein synthesis and the mutants...

  19. Effect of combined herbal feed additives on methane, total gas production and rumen fermentation.

    Science.gov (United States)

    Chaturvedi, Indu; Dutta, Tapas Kumar; Singh, Pawan Kumar; Sharma, Ashwani

    2015-01-01

    The present study was to evaluate effect of herbal feed additives on methane and total gas production during the rumen fermentation for environment and animal health concern. Different parts of the five medicinal plants were selected such as leaf and small stems of Ocimum sanctum (Tulsi), roots of Curcuma longa (Haldi), fruits of Emblica officinalis (Amla), leaves of Azadirachta indica (Neem) and leaves and small stem of Clerodendrum phlomidis (Arni) for our study. Addition of different herbal additive combinations did not influence IVDMD and total gas production however methane production (mg/g of substrate DM) was significantly (P<0.05) reduced in Amla: Neem and Neem: Arni combinations. Total nitrogen significantly (P<0.01) increased in the combinations of Tulsi: Haldi and Amla: Neem. TCA-ppt-N is significantly (P<0.01) increased in Tulsi: Haldi, Haldi: Amla, Amla: Neem and Neem: Arni however NH3-N (mg/dl) significantly decreased in all treatments. We conclude that the screening of plant combinations, Amla: Neem and Neem: Arni have potential to decrease methane production and our herbal feed supplements have no side-effects on the ruminant in small amount.

  20. Effect of the La alloying addition on the antibacterial capability of 316L stainless steel.

    Science.gov (United States)

    Yuan, J P; Li, W; Wang, C

    2013-01-01

    316L stainless steel is widely used for fashion jewelry but it can carry a large number of bacteria and cause the potential risk of infection since it has no antimicrobial ability. In this paper, La is used as an alloying addition. The antibacterial capability, corrosion resistance and processability of the La-modified 316L are investigated by microscopic observation, thin-film adhering quantitative bacteriostasis, electrochemical measurement and mechanical test. The investigations reveal that the La-containing 316L exhibits the Hormesis effect against Staphylococcus aureus ATCC 25923 and Escherichia coli DH5α, 0.05 wt.% La stimulates their growth, as La increases, the modified 316L exhibits the improved antibacterial effect. The more amount of La is added, the better antibacterial ability is achieved, and 0.42 wt.% La shows excellent antibacterial efficacy. No more than 0.11 wt.% La addition improves slightly the corrosion resistance in artificial sweat and has no observable impact on the processability of 316L, while a larger La content degrades them. Therefore, the addition of La alone in 316L is difficult to obtain the optimal combination of corrosion resistance, antibacterial capability and processability. In spite of that, 0.15 wt.% La around is inferred to be the trade-off for the best overall performance. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. The effect of hydrophilicity of graphene oxide as additive towards performance of polysulfone membrane

    Science.gov (United States)

    Jamalludin, Mohd Riduan; Harun, Zawati; Zakaria, M. S.; Rahim, Wan Mohd Faizal Wan Abd; Khor, C. Y.; Rosli, M. U.; Ishak, Muhammad Ikman; Nawi, M. A. M.; Shahrin, Suhaimi

    2017-09-01

    This study investigates the effect of hydrophilicity of graphene oxide as additive towards properties and performance on polysulfone (PSf) membrane. A polysulfone (PSf) membrane containing graphene oxide (GO) with different content was prepared via phase inversion technique. Characterization on the fabricated membrane were water contact angle measurement, porosity and mean pore size. The effects of PSf/GO were further investigated in terms of permeation test, rejection test and antifouling test. Based on the result obtained, PSf membrane incorporating with GO additive shows better capability to permeate more water compared to unfilled PSf membrane. The PSf/GO membrane were able to increase the permeate rate rapidly with the highest value is given by sample 4 (consist of 0.7 g of GO) at 571.78 J/m2h. Furthermore, water contact angle confirmed the hydrophilicity of this membrane at 62°. The transmembrane fouling activity showed that GO embedded in PSf membrane has improved tremendously. In addition, this study revealed that 0.7g of GO had the highest permeation test, rejection test and antifouling test.

  2. The effect of self-serving attribution on attraction in additive- and conjunctive-task groups.

    Science.gov (United States)

    Uraz, G; Aydin, O

    1995-04-01

    The prediction that the effect of self-serving attribution on personal attraction will vary according to task type was tested. Twenty-four groups of Turkish students, each consisting of 1 participant and 3 confederates, received success feedback after having performed either an additive or a conjunctive task. Two of the confederates made either self-serving or group-serving attributions, whereas the 3rd confederate attributed success to the collective efforts of all group members. Following these attributions, the participants filled out a form to indicate the degree to which they preferred each member as a friend and a work mate. Self-serving attributors in the conjunctive-task condition were less preferred as friends than the self-serving attributors in the additive-task condition. Also, the additive-task participants' ratings for other group members were systematically higher than those of the conjunctive-task participants. Thus, there was a main effect of task type for both friends and workmates.

  3. Effectiveness of additional trunk exercises on gait performance: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Van Criekinge, Tamaya; Saeys, Wim; Hallemans, Ann; Vereeck, Luc; De Hertogh, Willem; Van de Walle, Patricia; Vaes, Nathalie; Lafosse, Christophe; Truijen, Steven

    2017-06-02

    Evidence is lacking concerning the effect of additional trunk rehabilitation on gait performance. Investigating gait performance by both clinical and biomechanical outcome measures might lead to new scientific insights into the importance of the trunk during gait rehabilitation in people suffering from stroke. This protocol was written according to the SPIRIT 2013 Statement. An assessor-blinded randomized controlled trial will be conducted in patients with impaired trunk control after stroke. A total of 60 patients will be randomly allocated to the control or the experimental group by means of sealed opaque envelopes. They will receive either 16 h of additional trunk exercises (experimental group) or cognitive exercises (controls) for 1 h a day, 4 days a week for 4 weeks. Patients will also receive 2 h of standard care consisting of physiotherapy and occupational therapy. Gait performance will be assessed clinically by the Tinetti Test and biomechanically by means of a full body gait analysis. In addition, the effect of the exercise protocol on the trunk itself and trunk activities of daily living will be assessed by the Trunk Impairment Scale and the Barthel Index. Despite the evidence demonstrating the importance of trunk control after stroke, studies about the effects of trunk rehabilitation on gait performance are inconsistent. In the current study, a more sophisticated treatment protocol will be used to enlarge therapeutic improvements, the relationship between clinical and biomechanical measures of gait performance can be investigated, and the sustainability of the effects of trunk exercises over time will be examined. Since clinical improvements are of greater importance to patients and physiotherapists, clinical assessment scales will be used as primary outcome measures. ClinicalTrials.gov, ID: NCT02708888 . Registered on 2 March 2016.

  4. Effect of the Y955C mutation on mitochondrial DNA polymerase nucleotide incorporation efficiency and fidelity.

    Science.gov (United States)

    Estep, Patricia A; Johnson, Kenneth A

    2011-07-26

    The human mitochondrial DNA polymerase (pol γ) is responsible for the replication of the mitochondrial genome. Mutation Y955C in the active site of pol γ results in early onset progressive external ophthalmoplegia, premature ovarian failure, and Parkinson's disease. In single-turnover kinetic studies, we show that the Y955C mutation results in a decrease in the maximal rate of polymerization and an increase in the K(m) for correct incorporation. The mutation decreased the specificity constant for correct incorporation of dGTP, TTP, and ATP to values of 1.5, 0.35, and 0.044 μM(-1) s(-1), respectively, representing reductions of 30-, 110-, and 1300-fold, respectively, relative to the value for the wild-type enzyme. The fidelity of incorporation was reduced 6-130-fold, largely because of the significant decrease in the specificity constant for correct dATP:T incorporation. For example, k(cat)/K(m) for forming a TTP:T mismatch was decreased 10-fold from 0.0002 to 0.00002 μM(-1) s(-1) by the Y955C mutant, but the 1300-fold slower incorporation of the correct dATP:T relative to that of the wild type led to a 130-fold lower fidelity. While correct incorporation of 8-oxo-dGTP was largely unchanged, the level of incorporation of 8-oxo-dG with dA in the template strand was reduced 500-fold. These results support a role for Y955 in stabilizing A:T base pairs at the active site of pol γ and suggest that the severe clinical symptoms of patients with this mutation may be due, in part, to the reduced efficiency of incorporation of dATP opposite T, and that the autosomal dominant phenotype may arise from the resulting higher mutation frequency. © 2011 American Chemical Society

  5. Differentiation-specific effects of LHON mutations introduced into neuronal NT2 cells.

    Science.gov (United States)

    Wong, Alice; Cavelier, Lucia; Collins-Schramm, Heather E; Seldin, Michael F; McGrogan, Michael; Savontaus, Marja-Liisa; Cortopassi, Gino A

    2002-02-15

    Inheritance of one of three primary mutations at positions 11778, 3460 or 14484 of the mitochondrial genome in subunits of Complex I causes Leber's Hereditary Optic Neuropathy (LHON), a specific degeneration of the optic nerve, resulting in bilateral blindness. It has been unclear why inheritance of a systemic mitochondrial mutation would result in a specific neurodegeneration. To address the neuron-specific degenerative phenotype of the LHON genotype, we have created cybrids using a neuronal precursor cell line, Ntera 2/D1 (NT2), containing mitochondria from patient lymphoblasts bearing the most common LHON mutation (11778) and the most severe LHON mutation (3460). The undifferentiated LHON-NT2 mutant cells were not significantly different from the parental cell control in terms of mtDNA/nDNA ratio, mitochondrial membrane potential, reactive oxygen species (ROS) production or the ability to reduce Alamar Blue. Differentiation of NT2s resulted in a neuronal morphology and neuron-specific pattern of gene expression, and a 3-fold reduction in mtDNA/nDNA ratio in both mutant and control cells; however, the differentiation protocol yielded significantly less LHON cells than controls, by 30%, indicating either a decreased proliferative potential or increased cell death of the LHON-NT2 cells. Differentiation of the cells to the neuronal form also resulted in significant increases in ROS production in the LHON-NT2 neurons versus controls, which is abolished by rotenone, a specific inhibitor of Complex I. We infer that the LHON genotype requires a differentiated neuronal environment in order to induce increased mitochondrial ROS, which may be the cause of the reduced NT2 yield; and suggest that the LHON degenerative phenotype may be the result of an increase in mitochondrial superoxide which is caused by the LHON mutations, possibly mediated through neuron-specific alterations in Complex I structure.

  6. Effects of maternally exposed food coloring additives on laryngeal histology in rats.

    Science.gov (United States)

    Başak, Kayhan; Doguç, Duygu Kumbul; Aylak, Firdevs; Karadayi, Nimet; Gültekin, Fatih

    2014-01-01

    Experimental reports showed carcinogenic effects of artificial food colors and additives (AFCAs) on many organs, including the head and neck region. We aimed to investigate the effect of AFCAs on laryngeal histomorphology and immunohistochemical expression in maternally exposed rats. "No observable adverse effect levels" of commonly used AFCAs as a mixture were given to female rats before and during gestation. Histopathological and immunohistochemical findings were evaluated in their offspring. Significant decreasing in goblet cell count and cilia loss were observed with AFCAs in maternally exposed rats (p<0.05). Immunohistochemically, the Ki67 index was significantly increased and villin expression was significantly reduced in laryngeal epithelium in the study group (p<0.05), whereas expression of cyclooxygenase type 2, Muc-2, Muc-5AC, p53, and epidermal growth factor receptors did not differ between the groups. This study demonstrated that maternal exposure of AFCAs plays a role in the mucosal defense system and possibly in carcinogenesis.

  7. Combined Effect of the Cfr Methyltransferase and Ribosomal Protein L3 Mutations on Resistance to Ribosome-Targeting Antibiotics

    DEFF Research Database (Denmark)

    Pakula, Kevin K; Hansen, Lykke H; Vester, Birte

    2017-01-01

    Several groups of antibiotics inhibit bacterial growth by binding to bacterial ribosomes. Mutations in ribosomal protein L3 have been associated with resistance to linezolid and tiamulin, which both bind at the peptidyl transferase center in the ribosome. Resistance to these and other antibiotics...... also occurs through methylation of 23S rRNA at position A2503 by the methyltransferase Cfr. The mutations in L3 and the cfr gene have been found together in clinical isolates, raising the question of whether they have a combined effect on antibiotic resistance or growth. We transformed a plasmid...... seen. This study underscores the complex interplay between various resistance mechanisms and cross-resistance, even from antibiotics with overlapping binding sites....

  8. Synergistic effects of sorafenib in combination with gemcitabine or pemetrexed in lung cancer cell lines with K-ras mutations

    Directory of Open Access Journals (Sweden)

    Shu Wang

    2016-03-01

    Full Text Available K-ras is currently accepted as the most frequently mutated oncogene in non-small cell lung cancer (NSCLC, including squamous carcinoma, adenocarcinoma, and large cell carcinoma. NSCLC patients with the K-ras mutation appear to be refractory to the majority of systemic therapies. In the present study, the in vitro antitumor effects and correlated molecular mechanisms of sorafenib combined with gemcitabine or pemetrexed were explored in the K-ras mutation-positive NSCLC A549 cell line. Sorafenib was seen to exhibit dose-dependent growth inhibition in the A549 cells, while sorafenib combined with pemetrexed demonstrated a greater synergism compared with sorafenib combined with gemcitabine. Sorafenib arrested the cell cycle at the G1 phase, while gemcitabine and pemetrexed caused arrest at the S phase. The molecular mechanism of this synergism was due to the downstream signalling pathways, which were efficiently suppressed by sorafenib, therefore increasing the incidence of the entry of the chemotherapeutic drugs into the apoptotic pathways. Moreover, sorafenib and pemetrexed demonstrated stronger synergism, demonstrating that inhibiting the Ras/Raf/Mek/Erk and Ras/PI3K/Akt pathways concurrently may achieve improved antitumor effects.

  9. Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir.

    Science.gov (United States)

    Yu, Yuqi; Wang, Jinan; Shao, Qiang; Shi, Jiye; Zhu, Weiliang

    2015-05-27

    Molecular dynamics simulations are performed to investigate the dynamic properties of wild-type HIV-1 protease and its two multi-drug-resistant variants (Flap + (L10I/G48V/I54V/V82A) and Act (V82T/I84V)) as well as their binding with APV and DRV inhibitors. The hydrophobic interactions between flap and 80 s (80's) loop residues (mainly I50-I84' and I50'-I84) play an important role in maintaining the closed conformation of HIV-1 protease. The double mutation in Act variant weakens the hydrophobic interactions, leading to the transition from closed to semi-open conformation of apo Act. APV or DRV binds with HIV-1 protease via both hydrophobic and hydrogen bonding interactions. The hydrophobic interactions from the inhibitor is aimed to the residues of I50 (I50'), I84 (I84'), and V82 (V82') which create hydrophobic core clusters to further stabilize the closed conformation of flaps, and the hydrogen bonding interactions are mainly focused with the active site of HIV-1 protease. The combined change in the two kinds of protease-inhibitor interactions is correlated with the observed resistance mutations. The present study sheds light on the microscopic mechanism underlying the mutation effects on the dynamics of HIV-1 protease and the inhibition by APV and DRV, providing useful information to the design of more potent and effective HIV-1 protease inhibitors.

  10. Consanguinity and founder effect for Gaucher disease mutation G377S in a population from Tabuleiro do Norte, Northeastern Brazil.

    Science.gov (United States)

    Chaves, R G; Pereira, L da Veiga; de Araújo, F T; Rozenberg, R; Carvalho, M D F; Coelho, J C; Michelin-Tirelli, K; Chaves, M de Freitas; Cavalcanti, G B

    2015-10-01

    Gaucher's disease (GD) is caused by a β-glucocerebrosidase deficiency, leading to the accumulation of glucocerebroside in the reticuloendothelial system. The prevalence of GD in Tabuleiro do Norte (TN) (1:4000) is the highest in Brazil. The purpose of this study was to present evidence of consanguinity and founder effect for the G377S mutation (c.1246G>A) among GD patients in TN based on enzyme, molecular and genealogical studies. Between March 2009 and December 2010, 131 subjects at risk for GD (GC in dried blood ≤2.19 nmol/h/ml) and 5 confirmed GD patients from the same community were submitted for molecular analysis to characterize the genetic profile of the population. Based on the enzymatic and molecular analysis, the subjects were classified into three categories: affected (n = 5), carrier (n = 20) and non-carrier (n = 111). All carriers were (G377S/wt). Affected subjects were homozygous (G377S/G377S). The identification of a single mutation in carriers and homozygotes from different generations, the history of the community and the genealogy study suggest that the high prevalence of GD in this population may be due to a combination of consanguinity and founder effect for the G377S mutation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Effect of degassing addition on the solidification segregation of nickel aluminum bronze

    Science.gov (United States)

    Syazwan, F.; Kavinjr, M.; Maghribi, S.; Ashraf, N.; Hadi, A.; Shayfull, Z.; Rashidi, M. M.

    2017-09-01

    The effect of degassing agent addition on the solidification segregation of Nickel Aluminum Bronze was investigated. The complex relationship between the development of the solidification microstructures and buildup of microsegregation in Nickel Aluminum Bronze was obtained by using microstructure analysis and EDS analysis. This experiment describes the characterization of microsegregation in Nickel Aluminum Bronze which was made using point to count microanalysis along the microstructure. With this method, the differences of elements distribution in alloys solidified in the microstructure were clearly evidenced. The results show a microstructure directly affected by segregation of elements in Nickel Aluminum Bronze matrix. There is segregation of elements in the Late To Freeze (LTF) region after solidification from melting. As for degassing treatment, higher degassing addition on the Nickel Aluminum Bronze increased the elements segregation.

  12. Effects of additives on the stability of electrolytes for all-vanadium redox flow batteries

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jianlu; Li, Liyu; Nie, Zimin; Chen, Baowei; Vijayakumar, M.; Kim, Soowhan; Wang, Wei; Schwenzer, Birgit; Liu, Jun; Yang, Zhenguo

    2011-10-01

    The stability of the electrolytes for all-vanadium redox flow battery was investigated with ex-situ heating/cooling treatment and in-situ flow-battery testing methods. The effects of inorganic and organic additives have been studied. The additives containing the ions of potassium, phosphate, and polyphosphate are not suitable stabilizing agents because of their reactions with V(V) ions, forming precipitates of KVSO6 or VOPO4. Of the chemicals studied, polyacrylic acid and its mixture with CH3SO3H are the most promising stabilizing candidates which can stabilize all the four vanadium ions (V2+, V3+, VO2+, and VO2+) in electrolyte solutions up to 1.8 M. However, further effort is needed to obtain a stable electrolyte solution with >1.8 M V5+ at temperatures higher than 40 °C.

  13. Studies for understanding effects of additions on the strength of cement concrete

    Science.gov (United States)

    Bucur, R. D.; Barbuta, M.; Konvalina, P.; Serbanoiu, A. A.; Bernas, J.

    2017-09-01

    The paper analyzes the effects of different types of additions introduced in concrete mix on the compressive strength. The current studies show that additions contribute to improve some characteristics of concrete and to reduce the cement dosage, so it can obtain concretes which are cheaper and friendlier with environment. In the experimental mixes were introduced: crushed natural aggregates, slag aggregates, silica fume, fly ash, chopped tire, polystyrene granule, glass fibers and metallic fibers. The experimental values of compressive strengths were compared for two concrete grades (C20/25 and C25/30). The study shown that near the well-known possibilities of improving mechanical strengths of cement concrete by increasing cement dosage and strength, by using crushed aggregates and by reducing the water/cement ratio, there are other methods in which less cement is used by replacing it with different wastes or by adding fiber.

  14. The Effectiveness of the Additional Vocational Education and Staff Development for Industrial Enterprises

    Directory of Open Access Journals (Sweden)

    Y. S. Kalabina

    2012-01-01

    Full Text Available In the course of the Russian economy modernization, developing the effec- tive system of vocational training and further professional training appears to be the main condition for the dynamic competitive advantage of industrial enterprises. The paper inves- tigates the urgent issue of developing the system of additional vocational training and staff development with the reference to the ever-changing institutional logic controlling the em- ployee – employer relations. The paper presents the review of theoretic approaches to the system of additional vocational training, as well as the economic analysis and estimates of return on investment in different forms of vocational training. The methodological approach to the system efficiency estimation is given along with the factors determining the forma- tion and development of vocational training system. Based on the research findings, the recommendations integrating the staff development policy are given aimed at promoting the effectiveness of the employee – employer relations. 

  15. Effect of the Addition of Blueberries on Selected Physicochemical and Sensory Properties of Yoghurts

    Directory of Open Access Journals (Sweden)

    Asuman Cinbas

    2008-01-01

    Full Text Available In this research, physicochemical and sensory properties of blueberries and sugar added to yoghurts have been investigated on the first, 10th and 20th day of storage in refrigerator. Samples were analyzed for pH, total solids, protein, fat, ash, viscosity, syneresis, Hunter's L, a, and b values, flavour, body, texture, appearance and colour. Blueberry and sugar mass fractions and storage time had a significant effect on the physicochemical and sensory properties of yoghurts. The addition of blueberries to yoghurt formula resulted in an increase in the syneresis and a decrease in the pH, fat, protein, ash, viscosity and whiteness values. The addition of sugar improved only the flavour of yoghurts. Panelists favoured samples with 25 % blueberries and 4 % sugar in terms of flavour, body, texture, appearance and colour.

  16. Additive effects of physical stress and herbivores on intertidal seaweed biodiversity.

    Science.gov (United States)

    Williams, Susan L; Bracken, Matthew E S; Jones, Emily

    2013-05-01

    Patterns in rocky intertidal seaweed biodiversity influence the resilience and functioning of these important primary producer communities. In turn, seaweed biodiversity patterns are the result of many ecological factors. We determined the influences of thermal and desiccation stress, herbivory, and nutrients on seaweed biodiversity on a northern California rocky shoreline. In a fully crossed design at two tidal heights at wave-protected and exposed sites, we deployed screens to reduce stress, removed herbivores, and added nutrients for 18 months. The treatments reduced temperature, increased relative humidity, decreased herbivore abundances, and increased nitrogen in both seawater and seaweeds. Seaweed abundance and biodiversity (cover, biomass, species richness, diversity, evenness, and community composition) were influenced by tidal height, physical stress, and herbivores. Wave exposure affected all response variables except biomass and evenness. Stress and herbivores had independent additive effects on seaweed abundance and diversity. Physical stress did not make the community as a whole more susceptible to herbivores, and screens had overarching positive effects on seaweed biodiversity even though they also had positive effects on herbivore abundance. Nutrients had virtually no effect on seaweed biodiversity, and we observed no bottom-up effects of nutrient addition on herbivore density or biomass. Small green algae and diatoms were important contributors to overall algal cover and to changes in composition across treatments, but larger macroalgae dominated the species richness response. The striking absence of interactions between stress and herbivory highlights how seaweed communities can respond independently to important drivers of biodiversity. Thus, nonadditive, potentially synergistic effects do not necessarily complicate the understanding of how seaweed biodiversity responds to environmental change.

  17. Anaerobic digestion of Jatropha curcas L. press cake and effects of an iron-additive.

    Science.gov (United States)

    Schmidt, Thomas

    2011-11-01

    Oil production from Jatropha curcas L. seeds generates large amounts of Jatropha press cake (JPC) which can be utilized as a substrate for biogas production. The objective of this work was to investigate anaerobic mono-digestion of JPC and the effects of an iron additive (IA) on gas quality and process stability during the increase of the organic loading rate (OLR). With the increase of the OLR from 1.3 to 3.2 g(VS) L(-1) day(-1), the biogas yield in the reference reactor (RR) without IA decreased from 512 to 194 L(N) kg(VS) (-1) and the CH₄ concentration decreased from 69.3 to 44.4%. In the iron additive reactor (IAR), the biogas yield decreased from 530 to 462 L(N) kg(VS) (-1) and the CH₄ concentration decreased from 69.4 to 61.1%. The H₂S concentration in the biogas was reduced by addition of the IA to values below 258 ppm in the IAR while H₂S concentration in the RR increased and exceeded the detection limit of 5000 ppm. The acid capacity (AC) in the RR increased to more than 20 g L(-1), indicating an accumulation of organic acids caused by process instability. AC values in the IAR remained stable at values below 5 g L(-1). The results demonstrate that JPC can be used as sole substrate for anaerobic digestion up to an OLR of 2.4 g(VS) l(-1) day(-1). The addition of IA has effectively decreased the H(2)S content in the biogas and has improved the stability of the anaerobic process and the biogas quality.

  18. Effect of phosphate additi