Sample records for additive mutational effects

  1. 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. (United States)

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


    Pompe disease is an autosomal recessive lysosomal glycogen storage disorder, characterized by progressive muscle weakness. Deficiency of acid α-glucosidase (EC; can be caused by numerous pathogenic variants in the GAA gene. The Pompe Disease Mutation Database at 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.

  2. MTHFR homozygous mutation and additional risk factors for cerebral infarction in a large Italian family. (United States)

    Del Balzo, Francesca; Spalice, Alberto; Perla, Massimo; Properzi, Enrico; Iannetti, Paola


    Several cases with cerebral infarctions associated with the C677T mutation in the methylenetetrahydrofolate reductase gene (MTHFR) have been reported. Given the large number of asymptomatic individuals with the MTHFR mutation, additional risk factors for cerebral infarction should be considered. This study describes a large family with the MTHFR mutation and a combination of heterozygous factor V Leiden mutations and different additional exogenous and endogenous thrombogenic risk factors. Psychomotor retardation and a left fronto-insular infarct associated with the MTHFR mutation together with diminished factor VII and low level of protein C was documented in the first patient. In the second patient, generalized epilepsy and a malacic area in the right nucleus lenticularis was associated with the MTHFR mutation and a low level of protein C. In the third patient, right hemiparesis and a left fronto-temporal porencephalic cyst were documented, together with the MTHFR mutation and hyperhomocysteinemia. An extensive search of additional circumstantial and genetic thrombogenic risk factors should be useful for prophylaxis and prognosis of infants with cerebral infarctions associated with the MTHFR mutation and of their related family members.

  3. Clinical effects of sulphite additives. (United States)

    Vally, H; Misso, N L A; Madan, V


    Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Topical, oral or parenteral exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however, exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. While contact sensitivity to sulphite additives in topical medications is increasingly being recognized, skin reactions also occur after ingestion of or parenteral exposure to sulphites. Most studies report a 3-10% prevalence of sulphite sensitivity among asthmatic subjects following ingestion of these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. In addition to episodic and acute symptoms, sulphites may also contribute to chronic skin and respiratory symptoms. To date, the mechanisms underlying sulphite sensitivity remain unclear, although a number of potential mechanisms have been proposed. Physicians should be aware of the range of clinical manifestations of sulphite sensitivity, as well as the potential sources of exposure. Minor modifications to diet or behaviour lead to excellent clinical outcomes for sulphite-sensitive individuals.

  4. The Mozart Effect: Additional Data. (United States)

    Hughes, John R.


    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.

  5. Analyzing effects of naturally occurring missense mutations. (United States)

    Zhang, Zhe; Miteva, Maria A; Wang, Lin; Alexov, Emil


    Single-point mutation in genome, for example, single-nucleotide polymorphism (SNP) or rare genetic mutation, is the change of a single nucleotide for another in the genome sequence. Some of them will produce an amino acid substitution in the corresponding protein sequence (missense mutations); others will not. This paper focuses on genetic mutations resulting in a change in the amino acid sequence of the corresponding protein and how to assess their effects on protein wild-type characteristics. The existing methods and approaches for predicting the effects of mutation on protein stability, structure, and dynamics are outlined and discussed with respect to their underlying principles. Available resources, either as stand-alone applications or webservers, are pointed out as well. It is emphasized that understanding the molecular mechanisms behind these effects due to these missense mutations is of critical importance for detecting disease-causing mutations. The paper provides several examples of the application of 3D structure-based methods to model the effects of protein stability and protein-protein interactions caused by missense mutations as well.

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


    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.

  7. Additive Effects on Asymmetric Catalysis. (United States)

    Hong, Liang; Sun, Wangsheng; Yang, Dongxu; Li, Guofeng; Wang, Rui


    This review highlights a number of additives that can be used to make asymmetric reactions perfect. Without changing other reaction conditions, simply adding additives can lead to improved asymmetric catalysis, such as reduced reaction time, improved yield, or/and increased selectivity.

  8. Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations.

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    Liat Rockah-Shmuel


    Full Text Available Systematic mappings of the effects of protein mutations are becoming increasingly popular. Unexpectedly, these experiments often find that proteins are tolerant to most amino acid substitutions, including substitutions in positions that are highly conserved in nature. To obtain a more realistic distribution of the effects of protein mutations, we applied a laboratory drift comprising 17 rounds of random mutagenesis and selection of M.HaeIII, a DNA methyltransferase. During this drift, multiple mutations gradually accumulated. Deep sequencing of the drifted gene ensembles allowed determination of the relative effects of all possible single nucleotide mutations. Despite being averaged across many different genetic backgrounds, about 67% of all nonsynonymous, missense mutations were evidently deleterious, and an additional 16% were likely to be deleterious. In the early generations, the frequency of most deleterious mutations remained high. However, by the 17th generation, their frequency was consistently reduced, and those remaining were accepted alongside compensatory mutations. The tolerance to mutations measured in this laboratory drift correlated with sequence exchanges seen in M.HaeIII's natural orthologs. The biophysical constraints dictating purging in nature and in this laboratory drift also seemed to overlap. Our experiment therefore provides an improved method for measuring the effects of protein mutations that more closely replicates the natural evolutionary forces, and thereby a more realistic view of the mutational space of proteins.

  9. Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations. (United States)

    Rockah-Shmuel, Liat; Tóth-Petróczy, Ágnes; Tawfik, Dan S


    Systematic mappings of the effects of protein mutations are becoming increasingly popular. Unexpectedly, these experiments often find that proteins are tolerant to most amino acid substitutions, including substitutions in positions that are highly conserved in nature. To obtain a more realistic distribution of the effects of protein mutations, we applied a laboratory drift comprising 17 rounds of random mutagenesis and selection of M.HaeIII, a DNA methyltransferase. During this drift, multiple mutations gradually accumulated. Deep sequencing of the drifted gene ensembles allowed determination of the relative effects of all possible single nucleotide mutations. Despite being averaged across many different genetic backgrounds, about 67% of all nonsynonymous, missense mutations were evidently deleterious, and an additional 16% were likely to be deleterious. In the early generations, the frequency of most deleterious mutations remained high. However, by the 17th generation, their frequency was consistently reduced, and those remaining were accepted alongside compensatory mutations. The tolerance to mutations measured in this laboratory drift correlated with sequence exchanges seen in M.HaeIII's natural orthologs. The biophysical constraints dictating purging in nature and in this laboratory drift also seemed to overlap. Our experiment therefore provides an improved method for measuring the effects of protein mutations that more closely replicates the natural evolutionary forces, and thereby a more realistic view of the mutational space of proteins.

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

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    Manrubia Susanna C


    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

  11. Effect of Mutations on HP Lattice Proteins (United States)

    Shi, Guangjie; Vogel, Thomas; Landau, David; Li, Ying; Wüst, Thomas


    Using Wang-Landau sampling with approriate trial moves[2], we investigate the effect of different types of mutations on lattice proteins in the HP model. While exact studies have been carried out for short HP proteins[3], the systems we investigate are of much larger size and hence not accessible for exact enumerations. Based on the estimated density of states, we systematically analyse the changes in structure and degeneracy of ground states of particular proteins and measure thermodynamic quantities like the stability of ground states and the specific heat, for example. Both, neutral mutations, which do not change the structure and stability of ground states, as well as critical mutations, which do change the thermodynamic behavior qualitatively, have been observed. Research supported by NSF

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

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    Dmitriy Yuriyevich Semyonov


    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.

  13. The effect of population bottlenecks on mutation rate evolution in asexual populations. (United States)

    Raynes, Y; Halstead, A L; Sniegowski, P D


    In the absence of recombination, a mutator allele can spread through a population by hitchhiking with beneficial mutations that appear in its genetic background. Theoretical studies over the past decade have shown that the survival and fixation probability of beneficial mutations can be severely reduced by population size bottlenecks. Here, we use computational modelling and evolution experiments with the yeast S. cerevisiae to examine whether population bottlenecks can affect mutator dynamics in adapting asexual populations. In simulation, we show that population bottlenecks can inhibit mutator hitchhiking with beneficial mutations and are most effective at lower beneficial mutation supply rates. We then subjected experimental populations of yeast propagated at the same effective population size to three different bottleneck regimes and observed that the speed of mutator hitchhiking was significantly slower at smaller bottlenecks, consistent with our theoretical expectations. Our results, thus, suggest that bottlenecks can be an important factor in mutation rate evolution and can in certain circumstances act to stabilize or, at least, delay the progressive elevation of mutation rates in asexual populations. Additionally, our findings provide the first experimental support for the theoretically postulated effect of population bottlenecks on beneficial mutations and demonstrate the usefulness of studying mutator frequency dynamics for understanding the underlying dynamics of fitness-affecting mutations.

  14. Islet-intrinsic effects of CFTR mutation. (United States)

    Koivula, Fiona N Manderson; McClenaghan, Neville H; Harper, Alan G S; Kelly, Catriona


    Cystic fibrosis-related diabetes (CFRD) is the most significant extra-pulmonary comorbidity in cystic fibrosis (CF) patients, and accelerates lung decline. In addition to the traditional view that CFRD is a consequence of fibrotic destruction of the pancreas as a whole, emerging evidence may implicate a role for cystic fibrosis transmembrane-conductance regulator (CFTR) in the regulation of insulin secretion from the pancreatic islet. Impaired first-phase insulin responses and glucose homeostasis have also been reported in CF patients. CFTR expression in both human and mouse beta cells has been confirmed, and recent studies have shown differences in endocrine pancreatic morphology from birth in CF. Recent experimental evidence suggests that functional CFTR channels are required for insulin exocytosis and the regulation of membrane potential in the pancreatic beta cell, which may account for the impairments in insulin secretion observed in many CF patients. These novel insights suggest that the pathogenesis of CFRD is more complicated than originally thought, with implications for diabetes treatment and screening in the CF population. This review summarises recent emerging evidence in support of a primary role for endocrine pancreatic dysfunction in the development of CFRD. Summary • CF is an autosomal recessive disorder caused by mutations in the CFTR gene • The vast majority of morbidity and mortality in CF results from lung disease. However CFRD is the largest extra-pulmonary co-morbidity and rapidly accelerates lung decline • Recent experimental evidence shows that functional CFTR channels are required for normal patterns of first phase insulin secretion from the pancreatic beta cell • Current clinical recommendations suggest that insulin is more effective than oral glucose-lowering drugs for the treatment of CFRD. However, the emergence of CFTR corrector and potentiator drugs may offer a personalised approach to treating diabetes in the CF population.

  15. The effect of induced mutations on quantitative traits in Arabidopsis thaliana: Natural versus artificial conditions. (United States)

    Stearns, Frank W; Fenster, Charles B


    Mutations are the ultimate source of all genetic variations. New mutations are expected to affect quantitative traits differently depending on the extent to which traits contribute to fitness and the environment in which they are tested. The dogma is that the preponderance of mutations affecting fitness will be skewed toward deleterious while their effects on nonfitness traits will be bidirectionally distributed. There are mixed views on the role of stress in modulating these effects. We quantify mutation effects by inducing mutations in Arabidopsis thaliana (Columbia accession) using the chemical ethylmethane sulfonate. We measured the effects of new mutations relative to a premutation founder for fitness components under both natural (field) and artificial (growth room) conditions. Additionally, we measured three other quantitative traits, not expected to contribute directly to fitness, under artificial conditions. We found that induced mutations were equally as likely to increase as decrease a trait when that trait was not closely related to fitness (traits that were neither survivorship nor reproduction). We also found that new mutations were more likely to decrease fitness or fitness-related traits under more stressful field conditions than under relatively benign artificial conditions. In the benign condition, the effect of new mutations on fitness components was similar to traits not as closely related to fitness. These results highlight the importance of measuring the effects of new mutations on fitness and other traits under a range of conditions.

  16. Effect of glutathione addition in sparkling wine. (United States)

    Webber, Vanessa; Dutra, Sandra Valduga; Spinelli, Fernanda Rodrigues; Marcon, Ângela Rossi; Carnieli, Gilberto João; Vanderlinde, Regina


    This study aims to evaluate the effect of the addition of glutathione (GSH) on secondary aromas and on the phenolic compounds of sparkling wine elaborated by traditional method. It was added 10 and 20 mg L(-1) of GSH to must and to base wine. The determination of aroma compounds was performed by gas chromatography. Phenolic compounds and glutathione content were analyzed by high performance liquid chromatography. Sparkling wines with addition of GSH to must showed lower levels of total phenolic compounds and hydroxycinnamic acids. Furthermore, the sparkling wine with addition of GSH to must showed higher levels of 2-phenylethanol, 3-methyl-1-butanol and diethyl succinate, and lower concentrations of ethyl decanoate, octanoic and decanoic acids. The GSH addition to the must show a greater influence on sparkling wine than to base wine, however GSH addition to base wine seems retain higher SO2 free levels. The concentration of GSH added showed no significant difference.

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

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    Sook-Kyung Lee


    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. A DSPP mutation causing dentinogenesis imperfecta and characterization of the mutational effect. (United States)

    Lee, Sook-Kyung; Lee, Kyung-Eun; Song, Su Jeong; Hyun, Hong-Keun; Lee, Sang-Hoon; Kim, Jung-Wook


    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.

  19. Maternal filaggrin mutations increase the risk of atopic dermatitis in children: an effect independent of mutation inheritance.

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    Jorge Esparza-Gordillo


    Full Text Available Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental origin, or due to maternal effects reflecting the maternal genome's influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD. We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent-of-origin effects. Beyond the known role of FLG inheritance in AD (R1meta-analysis = 2.4, P = 1.0 x 10-36, we observed a strong maternal FLG genotype effect that was consistent in both independent family sets and for all 4 mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold increased AD risk (S1 = 1.50, Pmeta-analysis = 8.4 x 10-8. Our data point to two independent and additive effects of FLG mutations: i carrying a mutation and ii having a mutation carrier mother. The maternal genotype effect was independent of mutation inheritance and can be seen as a non-genetic transmission of a genetic effect. The FLG maternal effect was observed only when mothers had allergic sensitization (elevated allergen-specific IgE antibody plasma levels, suggesting that FLG mutation-induced systemic immune responses in the mother may influence AD risk in the child. Notably, the maternal effect reported here was stronger than most common genetic risk factors for AD recently identified through genome-wide association studies (GWAS. Our study highlights the power of family-based studies in the identification of new etiological mechanisms and reveals, for the first time, a direct influence of the maternal genotype on the offspring

  20. Sintering of magnesia: effect of additives

    Indian Academy of Sciences (India)

    Satyananda Behera; Ritwik Sarkar


    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 1500 and 1600° C. Sintering was evaluated by per cent densification and microstructural developments were studied by electron microscopy and elemental distribution of the additives in the sintered products was also investigated for their distribution in the matrix. Cr2O3 and TiO2 were found to deteriorate the densification associated with grain growth. Fe2O3 was found to improve the densification and well-compacted grain distribution was observed in the microstructure.

  1. Urinary Tract Effects of HPSE2 Mutations (United States)

    Stuart, Helen M.; Roberts, Neil A.; Hilton, Emma N.; McKenzie, Edward A.; Daly, Sarah B.; Hadfield, Kristen D.; Rahal, Jeffery S.; Gardiner, Natalie J.; Tanley, Simon W.; Lewis, Malcolm A.; Sites, Emily; Angle, Brad; Alves, Cláudia; Lourenço, Teresa; Rodrigues, Márcia; Calado, Angelina; Amado, Marta; Guerreiro, Nancy; Serras, Inês; Beetz, Christian; Varga, Rita-Eva; Silay, Mesrur Selcuk; Darlow, John M.; Dobson, Mark G.; Barton, David E.; Hunziker, Manuela; Puri, Prem; Feather, Sally A.; Goodship, Judith A.; Goodship, Timothy H.J.; Lambert, Heather J.; Cordell, Heather J.; Saggar, Anand; Kinali, Maria; Lorenz, Christian; Moeller, Kristina; Schaefer, Franz; Bayazit, Aysun K.; Weber, Stefanie; Newman, William G.


    Urofacial syndrome (UFS) is an autosomal recessive congenital disease featuring grimacing and incomplete bladder emptying. Mutations of HPSE2, encoding heparanase 2, a heparanase 1 inhibitor, occur in UFS, but knowledge about the HPSE2 mutation spectrum is limited. Here, seven UFS kindreds with HPSE2 mutations are presented, including one with deleted asparagine 254, suggesting a role for this amino acid, which is conserved in vertebrate orthologs. HPSE2 mutations were absent in 23 non-neurogenic neurogenic bladder probands and, of 439 families with nonsyndromic vesicoureteric reflux, only one carried a putative pathogenic HPSE2 variant. Homozygous Hpse2 mutant mouse bladders contained urine more often than did wild-type organs, phenocopying human UFS. Pelvic ganglia neural cell bodies contained heparanase 1, heparanase 2, and leucine-rich repeats and immunoglobulin-like domains-2 (LRIG2), which is mutated in certain UFS families. In conclusion, heparanase 2 is an autonomic neural protein implicated in bladder emptying, but HPSE2 variants are uncommon in urinary diseases resembling UFS. PMID:25145936

  2. Radiation induced dynamic mutations and transgenerational effects. (United States)

    Niwa, Ohtsura


    Many studies have confirmed that radiation can induce genomic instability in whole body systems. Although the molecular mechanisms underlying induced genomic instability are not known at present, this interesting phenomenon could be the manifestation of a cellular fail-safe system in which fidelity of repair and replication is down-regulated to tolerate DNA damage. Two features of genomic instability namely, delayed mutation and untargeted mutation, require two mechanisms of ;damage memory' and ;damage sensing, signal transduction and execution' to induce mutations at a non damaged-site. In this report, the phenomenon of transgenerational genomic instability and possible mechanisms are discussed using mouse data collected in our laboratory as the main bases.

  3. EGFR mutation frequency and effectiveness of erlotinib

    DEFF Research Database (Denmark)

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


    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...

  4. Structural Effects of Oncogenic PI3K alpha Mutations

    Energy Technology Data Exchange (ETDEWEB)

    S Gabelli; C Huang; D Mandelker; O Schmidt-Kittler; B Vogelstein; L Amzel


    Physiological activation of PI3K{alpha} is brought about by the release of the inhibition by p85 when the nSH2 binds the phosphorylated tyrosine of activated receptors or their substrates. Oncogenic mutations of PI3K{alpha} result in a constitutively activated enzyme that triggers downstream pathways that increase tumor aggressiveness and survival. Structural information suggests that some mutations also activate the enzyme by releasing p85 inhibition. Other mutations work by different mechanisms. For example, the most common mutation, His1047Arg, causes a conformational change that increases membrane association resulting in greater accessibility to the substrate, an integral membrane component. These effects are examples of the subtle structural changes that result in increased activity. The structures of these and other mutants are providing the basis for the design of isozyme-specific, mutation-specific inhibitors for individualized cancer therapies.

  5. Structural effects of oncogenic PI3Kα mutations. (United States)

    Gabelli, Sandra B; Huang, Chuan-Hsiang; Mandelker, Diana; Schmidt-Kittler, Oleg; Vogelstein, Bert; Amzel, L Mario


    Physiological activation of PI3Kα is brought about by the release of the inhibition by p85 when the nSH2 binds the phosphorylated tyrosine of activated receptors or their substrates. Oncogenic mutations of PI3Kα result in a constitutively activated enzyme that triggers downstream pathways that increase tumor aggressiveness and survival. Structural information suggests that some mutations also activate the enzyme by releasing p85 inhibition. Other mutations work by different mechanisms. For example, the most common mutation, His1047Arg, causes a conformational change that increases membrane association resulting in greater accessibility to the substrate, an integral membrane component. These effects are examples of the subtle structural changes that result in increased activity. The structures of these and other mutants are providing the basis for the design of isozyme-specific, mutation-specific inhibitors for individualized cancer therapies.

  6. Fitness effects of beneficial mutations: the mutational landscape model in experimental evolution

    DEFF Research Database (Denmark)

    Betancourt, Andrea J.; Bollback, Jonathan Paul


    The mutational landscape model is a theoretical model describing sequence evolution in natural populations. However, recent experimental work has begun to test its predictions in laboratory populations of microbes. Several of these studies have focused on testing the prediction that the effects...

  7. 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)


    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)

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

    NARCIS (Netherlands)

    O.L. Holla; S. Nakken; M. Mattingsdal; T. Ranheim; K.E. Berge; J.C. Defesche; T.P. Leren


    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 ha

  9. Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations

    NARCIS (Netherlands)

    Pomp, Elisabeth R.; Cessie, le Saskia; Rosendaal, Frits R.; Doggen, Carine J.M.


    In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), body weight, height and body mass index (BMI) were evaluated as risk factors. Additionally, the joint effect of obesity together with oral contraceptive use and prothrombotic mutations on the ris

  10. Nurse Scheduling by Cooperative GA with Effective Mutation Operator (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.

  11. Rosiglitazone and Fenofibrate Additive Effects on Lipids

    Directory of Open Access Journals (Sweden)

    Ahmad Slim


    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. The effect of deleterious mutations on neutral molecular variation

    Energy Technology Data Exchange (ETDEWEB)

    Charlesworth, B.; Morgan, M.T.; Charlesworth, D. (Univ. of Chicago, IL (United States))


    Selection against deleterious alleles maintained by mutation may cause a reduction in the amount of genetic variability at linked neutral sites. This is because a new neutral variant can remain in a large population for a long period of time only if it is maintained in gametes that are free of deleterious alleles, and hence are not destined for rapid elimination from the population by selection. Approximate formulas are derived for the reduction below classical neutral values resulting from such background selection against deleterious mutations, for the mean times of fixation and loss of new mutations, nucleotide site diversity, and number of segregating sites. These formulas apply to random-mating populations with no genetic recombination, and to populations reproducing exclusively asexually or by self-fertilization. For a given selection regime and mating system, the reduction is an exponential function of the total mutation rate to deleterious mutations for the section of the genome involved. Simulations show that the effect decreases rapidly with increasing recombination frequency or rate of outcrossing. The mean time to loss of new neutral mutations and the total number of segregating neutral sites are less sensitive to background selection than the other statistics, unless the population size is of the order of a hundred thousand or more. The stationary distribution of allele frequencies at the neutral sites is correspondingly skewed in favor of rare alleles, compared with the classical neutral result. Observed reductions in molecular variation in low recombination genomic regions of sufficiently large size, for instance in the centromere-proximal regions of Drosophila autosomes or in highly selfing plant populations, may be partly due to background selection against deleterious mutations. 58 refs., 3 figs., 6 tabs.

  13. Effect of Single-Site Mutations on HP Lattice Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Guangjie [University of Georgia, Athens, GA; Vogel, Thomas [Los Alamos National Laboratory (LANL); Wuest, Thomas [Swiss Federal Research Institute, Switzerland; Li, Ying Wai [ORNL; Landau, David P [University of Georgia, Athens, GA


    We developed a heuristic method for determining the ground-state degeneracy of hydrophobic-polar (HP) lattice proteins, based on Wang-Landau and multicanonical sampling. It is applied during comprehensive studies of single-site mutations in specific HP proteins with different sequences. The effects in which we are interested include structural changes in ground-states, changes of ground-state energy, degeneracy, and thermodynamic properties of the system. With respect to mutations, both extremely sensitive and insensitive positions in the HP sequence have been found. That is, ground state energies and degeneracies, as well as other thermodynamic and structural quantities may be either largely unaffected or may change significantly due to mutation.

  14. 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.

  15. PSO Algorithm Based on Accumulation Effect and Mutation

    Directory of Open Access Journals (Sweden)

    Ji Wei Dong


    Full Text Available Particle SwarmOptimization (PSO algorithm is a new swarm intelligence optimization   technique, because of its simplicity, fewerparameters and good effects, PSO has been widely used to solve various complexoptimization problems. particle swarm optimization(PSO exist the problems ofpremature and local convergence, we proposed an improved particle swarmoptimization based on aggregation effect and with mutation operator, whichdetermines whether the aggregation occurs in searching, if there is then theGaussian  mutation is detected to theglobal extremum , to overcome particle swarm optimization falling into localoptimal solution defects.  Testing thenew algorithm by a typical test function, the results show that , compared withthe conventional genetic algorithm(SGA, it improves the ability of globaloptimization, but also effectively avoid the premature convergence.

  16. 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;


    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...... 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 ....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...

  17. Antitumor effects and molecular mechanisms of ponatinib on endometrial cancer cells harboring activating FGFR2 mutations. (United States)

    Kim, Do-Hee; Kwak, Yeonui; Kim, Nam Doo; Sim, Taebo


    Aberrant mutational activation of FGFR2 is associated with endometrial cancers (ECs). AP24534 (ponatinib) currently undergoing clinical trials has been known to be an orally available multi-targeted tyrosine kinase inhibitor. Our biochemical kinase assay showed that AP24534 is potent against wild-type FGFR1-4 and 5 mutant FGFRs (V561M-FGFR1, N549H-FGFR2, K650E-FGFR3, G697C-FGFR3, N535K-FGFR4) and possesses the strongest kinase-inhibitory activity on N549H-FGFR2 (IC50 of 0.5 nM) among all FGFRs tested. We therefore investigated the effects of AP24534 on endometrial cancer cells harboring activating FGFR2 mutations and explored the underlying molecular mechanisms. AP24534 significantly inhibited the proliferation of endometrial cancer cells bearing activating FGFR2 mutations (N549K, K310R/N549K, S252W) and mainly induced G1/S cell cycle arrest leading to apoptosis. AP24534 also diminished the kinase activity of immunoprecipitated FGFR2 derived from MFE-296 and MFE-280 cells and reduced the phosphorylation of FGFR2 and FRS2 on MFE-296 and AN3CA cells. AP24534 caused substantial reductions in ERK phosphorylation, PLCγ signaling and STAT5 signal transduction on ECs bearing FGFR2 activating mutations. Akt signaling pathway was also deactivated by AP24534. AP24534 causes the chemotherapeutic effect through mainly the blockade of ERK, PLCγ and STAT5 signal transduction on ECs. Moreover, AP24534 inhibited migration and invasion of endometrial cancer cells with FGFR2 mutations. In addition, AP24534 significantly blocked anchorage-independent growth of endometrial cancer cells. We, for the first time, report the molecular mechanisms by which AP24534 exerts antitumor effects on ECs with FGFR2 activating mutations, which would provide mechanistic insight into ongoing clinical investigations of AP24534 for ECs.

  18. Effectiveness of Low Temperature Additives for Biodiesel Blends (United States)



  19. Fragile X founder effects and new mutations in Finland

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, N.; Smits, B.; Curley, D. [New York State Inst. for Basic Research in Developmental Disabilities, Staten Island, NY (United States)] [and others


    The apparent associations between fragile X mutations and nearby microsatellites may reflect both founder effects and microsatellite instability. To gain further insight into their relative contributions, we typed a sample of 56 unrelated control and 37 fragile X chromosomes from an eastern Finnish population for FMR1 CGG repeat lengths, AGG interspersion patterns, DXS548, FRAXAC1, FRAXE and a new polymorphic locus, Alu-L. In the controls, the most common FMR1 allele was 30 repeats with a range of 20 to 47 and a calculated heterozygosity of 88%. A strong founder effect was observed for locus DXS548 with 95% of fragile X chromosomes having the 21 CA repeat (196 bp) allele compared to 17% of controls, while none of the fragile X but 69% of controls had the 20 repeat allele. Analysis of the combined loci DXS548-FRAXAC1-FRAXE showed three founder haplotypes. Haplotype 21-19-16 was found on 27 (75%) of fragile X chromosomes but on none of controls. Three (8.4%) fragile X chromosomes had haplotypes 21-19-15, 21-19-20, and 21-19-25 differing from the common fragile X haplotype only in FRAXE. These could have arisen by recombination or from mutations of FRAXE. A second haplotype 21-18-17 was found in four (11.1%) fragile X chromosomes but only one (1.9%) control. This may represent a more recent founder mutation. A third haplotype 25-21-15, seen in two fragile X chromosomes (5.6%) and one (1.9%) control, was even less common and thus may represent an even more recent mutation or admixture of immigrant types. Analysis of the AGG interspersions within the FMR1 CGG repeat showed that 7/8 premutation chromosomes lacked an AGG whereas all controls had at least one AGG. This supports the hypothesis that the mutation of AGG to CGG leads to repeat instability and mutational expansion. 43 refs., 3 figs., 7 tabs.

  20. Risk association of hepatocellular carcinoma with S-gene additional N-glycosylation mutation of hepatitis B virus in HBsAg and anti-HBs coexistent patients

    Directory of Open Access Journals (Sweden)

    Yan QIAO


    Full Text Available Objective  To investigate the association of additional N-glycosylation mutation in major hydrophilic region (MHR of hepatitis B virus (HBV S gene with the risk of hepatocellular carcinoma (HCC in HBsAg and anti-HBs coexistent patients. Methods  A total of 284 patients with coexistence of HBsAg and anti-HBs were enrolled in this study, who were admitted in 302 Hospital of PLA from July 2009 to June 2016. HBV DNA was extracted from serum samples and subjected to nested PCR for full-length S-gene sequencing. The association of MHR additional N-glycosylation mutation and clinical parameters with HCC occurrence risk was analyzed. Specifically, the additional N-glycosylation mutation was dynamically analyzed pre-and post-HCC occurrence for 18 patients. Results  Multivariate analysis showed that age >40 years, HBsAg >median, HBeAg negativity, and additional N-glycosylation mutation in MHR were associated with HCC occurrence for the HBsAg and anti-HBs coexistent patients (OR=4.281, 95%CI 1.843-9.941, P=0.001; OR=3.146, 95%CI 1.633-6.060, P=0.001; OR=2.097, 95%CI 1.010-4.357, P=0.047; and OR=4.381, 95%CI 1.842-10.417, P=0.001. In contrast, ALT, anti-HBs, anti-HBe, and HBV DNA levels had no significant association with HCC occurrence. Dynamical analysis showed that the additional N-glycosylation mutation had already developed 1-4 years prior to HCC occurrence in the 8 of 18 observed patients. Conclusion  Additional N-glycosylation mutation in MHR of HBV S gene had close association with HCC occurrence in HBsAg and anti-HBs coexistent patients, suggesting that HBsAg and anti-HBs coexistence and additional N-glycosylation mutation together could serve as a predictive indicator for HCC occurrence in chronic HBV-infected patients. DOI: 10.11855/j.issn.0577-7402.2016.11.08

  1. Effects of some polymeric additives on the cocrystallization of caffeine (United States)

    Chung, Jihae; Kim, Il Won


    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.

  2. Community-wide Evaluation of Methods for Predicting the Effect of Mutations on Protein-Protein Interactions (United States)

    Moretti, Rocco; Fleishman, Sarel J.; Agius, Rudi; Torchala, Mieczyslaw; Bates, Paul A.; Kastritis, Panagiotis L.; Rodrigues, João P. G. L. M.; Trellet, Mikaël; Bonvin, Alexandre M. J. J.; Cui, Meng; Rooman, Marianne; Gillis, Dimitri; Dehouck, Yves; Moal, Iain; Romero-Durana, Miguel; Perez-Cano, Laura; Pallara, Chiara; Jimenez, Brian; Fernandez-Recio, Juan; Flores, Samuel; Pacella, Michael; Kilambi, Krishna Praneeth; Gray, Jeffrey J.; Popov, Petr; Grudinin, Sergei; Esquivel-Rodríguez, Juan; Kihara, Daisuke; Zhao, Nan; Korkin, Dmitry; Zhu, Xiaolei; Demerdash, Omar N. A.; Mitchell, Julie C.; Kanamori, Eiji; Tsuchiya, Yuko; Nakamura, Haruki; Lee, Hasup; Park, Hahnbeom; Seok, Chaok; Sarmiento, Jamica; Liang, Shide; Teraguchi, Shusuke; Standley, Daron M.; Shimoyama, Hiromitsu; Terashi, Genki; Takeda-Shitaka, Mayuko; Iwadate, Mitsuo; Umeyama, Hideaki; Beglov, Dmitri; Hall, David R.; Kozakov, Dima; Vajda, Sandor; Pierce, Brian G.; Hwang, Howook; Vreven, Thom; Weng, Zhiping; Huang, Yangyu; Li, Haotian; Yang, Xiufeng; Ji, Xiaofeng; Liu, Shiyong; Xiao, Yi; Zacharias, Martin; Qin, Sanbo; Zhou, Huan-Xiang; Huang, Sheng-You; Zou, Xiaoqin; Velankar, Sameer; Janin, Joël; Wodak, Shoshana J.; Baker, David


    Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state of predictive methodology. Here we describe a community-wide assessment of methods to predict the effects of mutations on protein-protein interactions. Twenty-two groups predicted the effects of comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders and the results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful methods explicitly considered the effects of mutation on monomer stability in addition to binding affinity, carried out explicit side chain sampling and backbone relaxation, and evaluated packing, electrostatic and solvation effects, and correctly identified around a third of the beneficial mutations. Much room for improvement remains for even the best techniques, and large-scale fitness landscapes should continue to provide an excellent test bed for continued evaluation of methodological improvement. PMID:23843247

  3. Particular Mal de Meleda Phenotypes in Tunisia and Mutations Founder Effect in the Mediterranean Region

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    Mbarka Bchetnia


    Full Text Available Mal de Meleda (MDM is a rare, autosomal recessive form of palmoplantar keratoderma. It is characterized by erythema and hyperkeratosis of the palms and soles that progressively extend to the dorsal surface of the hands and feet. It is caused by mutations in SLURP-1 gene encoding for secreted mammalian Ly-6/uPAR-related protein 1 (SLURP-1. We performed mutational analysis by direct sequencing of SLURP-1 gene in order to identify the genetic defect in three unrelated families (families MDM-12, MDM-13, and MDM-14 variably affected with transgressive palmoplantar keratoderma. A spectrum of clinical presentations with variable features has been observed from the pronounced to the transparent hyperkeratosis. We identified the 82delT frame shift mutation in the SLURP-1 gene in both families MDM-12 and MDM-13 and the missense variation p.Cys99Tyr in family MDM-14. To date, the 82delT variation is the most frequent cause of MDM in the world which is in favour of a recurrent molecular defect. The p.Cys99Tyr variation is only described in Tunisian families making evidence of founder effect mutation of likely Tunisian origin. Our patients presented with very severe to relatively mild phenotypes, including multiple keratolytic pits observed for one patient in the hyperkeratotic area which was not previously reported. The phenotypic variability may reflect the influence of additional factors on disease characteristics. This report further expands the spectrum of clinical phenotypes associated with mutations in SLURP1 in the Mediterranean population.

  4. Effect of additive on the formation of polyacrylonitrile membrane

    Institute of Scientific and Technical Information of China (English)

    YANG Sen; LIU Zhong-zhou


    The effect of additives CaCl2 and CaCl2/H2O on the properties of polyacrylonitrile(PAN) ultrafiltration(UF)membranes prepared by phase inversion process was studied. The dissolving capacity of the casting solution forCaCl2 was enhanced by the addition of H2O. The membranes are characterized in terms of the pure water flux andmolecular weight cut-off( MWCO). The addition of CaCl2 or CaCl2/H2O to the casting solution increases the resultingmembrane permeability.

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


    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.

  6. TERT promoter mutations in skin cancer: the effects of sun exposure and X-irradiation. (United States)

    Pópulo, Helena; Boaventura, Paula; Vinagre, João; Batista, Rui; Mendes, Adélia; Caldas, Regina; Pardal, Joana; Azevedo, Filomena; Honavar, Mrinalini; Guimarães, Isabel; Manuel Lopes, José; Sobrinho-Simões, Manuel; Soares, Paula


    The reactivation or reexpression of telomerase (TERT) is a widespread feature of neoplasms. TERT promoter mutations were recently reported that were hypothesized to result from UV radiation. In this retrospective study, we assessed TERT promoter mutations in 196 cutaneous basal cell carcinomas (BCCs), including 102 tumors from X-irradiated patients, 94 tumors from patients never exposed to ionizing radiation treatment, and 116 melanomas. We sought to evaluate the effects of UV and X-ray irradiation on TERT mutation frequency. TERT mutations were detected in 27% of BCCs from X-irradiated patients, 51% of BCCs from nonirradiated patients, and 22% of melanoma patients. TERT mutations were significantly increased in non-X-irradiated BCC patients compared with X-irradiated BCC patients; the mutations also presented a different mutation signature. In nonirradiated patients, TERT mutations were more frequent in BCCs of sun-exposed skin, supporting a possible causative role of UV radiation. In melanoma, TERT promoter mutations were generally restricted to intermittent sun-exposed areas and were associated with nodular and superficial spreading subtypes, increased thickness, ulceration, increased mitotic rate, and BRAFV600E mutations. Our results suggest that various carcinogenic factors may cause distinct TERT promoter mutations in BCC and that TERT promoter mutations might be associated with a poorer prognosis in melanoma.

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


    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.

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


    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. PMID:26784702

  10. Promotional effects of new types of additives on fat crystallization. (United States)

    Yoshikawa, Shinichi; Kida, Haruyasu; Sato, Kiyotaka


    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.

  11. Contamination effects of drilling fluid additives on cement slurry

    Directory of Open Access Journals (Sweden)

    Youzhi Zheng


    Full Text Available During the cementation of deep wells, contamination at the contact surface between cement slurry and drilling fluid will present a technical challenge, which may threaten operation safety. To deal with the problem, lab tests and analysis were performed specifically on the compatibility of fluids during cementation in Sichuan and Chongqing gas fields. Impacts of commonly used additives for drilling fluids were determined on fluidity and thickening time of conventional cement slurry. Through the infrared spectrum analysis, SEM and XRD, infrared spectrum data of kalium polyacrylamide (KPAM and bio-viscosifier were obtained, together with infrared spectrum, SEM and XRD data of cement slurry with additives. Contamination mechanisms of the cement slurry by conventional additives for drilling fluid were reviewed. Test results show that both KPAM and bio-viscosifier are such high-molecular materials that the long chains in these materials may easily absorb cement particles in the slurry to form mixed network structures; as a result, cement particles were prone to agglomeration and eventually lost their pumpability. Finally, assessment of and testing methods for the contamination effects of drilling fluid additives on cement slurry were further improved to form standards and codes that may help solve the said problems. This study will provide technological supports for the preparation of drilling fluids with desirable properties prior to cementation, the selection of optimal drilling fluids additives, and the development of innovative drilling fluids additives.

  12. Effects of water mist addition on kerosene pool fire

    Institute of Scientific and Technical Information of China (English)

    ZHOU XiaoMeng; QIN Jun; LIAO GuangXuan


    The use of water mist to extinguish fire is a problem of particular interest since the banning of halo-gen-based agents for environmental reasons. This interest is reflected in the large number of re-searches performed on the main fire-extinguishing mechanisms of water mist: heat extraction, oxygen displacement and attenuation of heat fluxes. In contrast, there are still little known about the chemical and some other aspects of water mist addition on the pool fire. In this paper, a phenomenological study was conducted of the effect of water mist addition on the kerosene pool fire through the measurement of the heat release rate, CO, CO2 and O2 species concentration in combustion. The experimental results show that there is a significant enhancement effect at the beginning stage of water mist addition. Then, the flame size was decreased abruptly. By physical suppression effect combined with chemical effect, the experiments' results are explained especially. The study of effects of water mist on pool fire will be useful for optimizing designation of water mist fire-suppression system, improving the fire suppression efficiency and extending their application field.

  13. A novel P106L mutation in EPSPS and an unknown mechanism(s) act additively to confer resistance to glyphosate in a South African Lolium rigidum population. (United States)

    Kaundun, Shiv S; Dale, Richard P; Zelaya, Ian A; Dinelli, Giovanni; Marotti, Ilaria; McIndoe, Eddie; Cairns, Andrew


    Glyphosate resistance evolution in weeds is a growing problem in world agriculture. Here, we have investigated the mechanism(s) of glyphosate resistance in a Lolium rigidum population (DAG1) from South Africa. Nucleotide sequencing revealed the existence of at least three EPSPS homologues in the L. rigidum genome and identified a novel proline 106 to leucine substitution (P106L) in 52% DAG1 individuals. This mutation conferred a 1.7-fold resistance increase to glyphosate at the whole plant level. Additionally, a 3.1-fold resistance increase, not linked to metabolism or translocation, was estimated between wild-type P106-DAG1 and P106-STDS sensitive plants. Point accepted mutation analysis suggested that other amino acid substitutions at EPSPS position 106 are likely to be found in nature besides the P106/S/A/T/L point mutations reported to date. This study highlights the importance of minor mechanisms acting additively to confer significant levels of resistance to commercial field rates of glyphosate in weed populations subjected to high selection pressure.

  14. Effect of arsenic on p53 mutation and occurrence of teratogenic salamanders: their potential as ecological indicators for arsenic contamination. (United States)

    Chang, Jin-Soo; Gu, Man Bock; Kim, Kyoung-Woong


    The p53 mutation in salamanders can be used as an indicator of arsenic contamination. The influence of arsenic exposure was studied on mutation of tumor suppressor gene in salamanders collected from several As-contaminated mine areas in Korea. Salamander eggs and larvae were exposed to arsenic in a toxicity test, and teratogenic salamanders found in heavy metal- and As-contaminated water from As-Bi mines were evaluated using PCR-SSCP to determine if they would be useful as an ecological indicator species. Changes in amino acids were shown to have occurred as a result of an arsenic-accumulating event that occurred after the DNA damage. In addition, both of the Hynobius leechii exposed groups were primarily affected by forms of skin damage, changes in the lateral tail/dorsal flexure and/or abnormality teratogenesis. Single-base sense mutation in codons 346 (AAG: Lys to ATG: Met), 224 (TTT: Phe to TTA: Leu), 211 (ATG: Met to AAG: Lys), 244 (TTT: Phe to TTTG: insertion), 245 (Glu GAG to Gln CAG) and 249 (TGT Cys to TGA stop) of the p53 gene were simultaneously found in mutated salamanders. Based on the results of our data illustrating the effect of arsenic exposure on the p53 mutation of salamanders in arsenic-contaminated mine areas, these mutated salamanders can be used as potential ecological indicators in the arsenic-contaminated ecosystems.

  15. Pleiotropic Effect of tatC Mutation on Metabolism of Pathogen Yesinia enterocolitica

    Institute of Scientific and Technical Information of China (English)


    Objective To analyze the impact of depletion of the twin arginine translocation (TAT) system on virulence and physiology of Yersinia enterocolitica for a better understanding of its pathogenicity. Methods We constructed a △tatC::SpRmutant of Yersinia enterocolitica by P1 phage mediated transduction using Escherichia coli K-12 △tatC::SpR strain as a donor. Results A P1-mediated genetic material transfer was found between the two species of enterobacteria, indicating a great potential of acquisition of antibiotic resistance in emergency of a new threatening pathogen by genetic material exchanges.Periplasmic trimethylamine N-oxidase reductase activity was detected in the wild type Y. enterocolitica strain and translocation of this enzyme was completely abolished by the △tatC::SpR mutation. In addition, the △tatC::SpR mutation showed a pleiotropic effect on the metabolism of Y. enterocolitica. However, the tat mutation did not seem to affect the mobility and virulence of Y.enterocolitica under the conditions used. Conclusion Unlike other pathogenic bacteria studied, the TAT system of Y.enterocolitica might play an important role in the pathogenic process, which is distinct from other pathogens, such as Pseudomonas aeruginosa and enterohemorrhagic E. coli O157:H7.

  16. Effect of Additive on Microstructure of Transparent YAG Ceramics

    Institute of Scientific and Technical Information of China (English)

    Sun Xudong; Wen Lei; Xiu Zhimeng; Huo Di; Li Xiaodong; Chi-Tay Tsai


    Transparent YAG (yttrium aluminum garnet) ceramics were fabricated by solid-state reaction method. Effect of additive (tetraethyl orthosilicate, TEOS) on microstructure of YAG ceramics was investigated. If the addition of TEOS is more than 3% (mass fraction), large amount of liquid phase can be yielded at grain boundaries, resulting in the formation of second phase particles at grain boundaries. If the addition is less than 0.05% (mass fraction), pores are entrapped in the grains. The suitable amount is 0.5% (mass fraction). A fully transparent YAG ceramic was fabricated by vacuum sintering at 1700 ℃ for 5 h. Optical transmittance of the YAG ceramic is 63% in the visible light wavelengths and 70% in the infrared wavelengths.

  17. Effectiveness of various organometallics as antiwear additives in mineral oil (United States)

    Buckley, D. H.


    Sliding friction experiments were conducted with 1045 steel contacting 302 stainless steel and lubricated with various organometallics in mineral oil. Auger emission spectroscopy was used to determine the element present in the wear contact zone. The results indicate that there are organometallics which are as effective an antiwear additives as the commonly used zinc dialkyl dithiophosphate. These include dimethyl cadmium, triphenyl lead thiomethoxide, and triphenyl tin chloride. The additives were examined in concentrations to 1 weight percent. With dimethyl cadmium at concentrations of 0.5 weight percent and above, cadmium was detected in the contact zone. Coincident with the detection of cadmium, a marked decrease in the friction coefficient was observed. All additives examined reduced friction, but only the aforementioned reduced wear to a level comparable to that observed with zinc dialkyl dithiophosphate.

  18. Effects of amino acid additives during hemodialysis of children. (United States)

    Abitbol, C L; Mrozinska, K; Mandel, S; McVicar, M; Wapnir, R A


    The intradialytic losses into the dialysate of free amino acids (AA) and alpha-amino nitrogen were determined during the dialysis of three children. Variations in plasma AA were determined pre- and postdialysis. The effect of these losses with the addition of an Abbott General Amino Acid Mixture to the dialysate in concentrations of 8.5, 17, and 34 mg/100 ml was studied. The major determinant of AA losses was the plasma concentration of the AA before beginning the dialysis treatment. Dialysance of individual AA varied inversely with their molecular weights. A zero flux of alpha-amino nitrogen occurred at a derived concentration of 22 mg/100 ml of the AA additive in the dialysate. Plasma concentrations of nonessential amino acids were little affected by the dialysate additive. In contrast, total essential amino acid nitrogen which fell during baseline dialyses showed significant improvement when the AA solution was added to the dialysate. This study suggests that the addition of AA to the dialysate bath may be effective in decreasing AA nitrogen losses during dialysis.

  19. AHAS herbicide resistance endowing mutations: effect on AHAS functionality and plant growth. (United States)

    Yu, Qin; Han, Heping; Vila-Aiub, Martin M; Powles, Stephen B


    Twenty-two amino acid substitutions at seven conserved amino acid residues in the acetohydroxyacid synthase (AHAS) gene have been identified to date that confer target-site resistance to AHAS-inhibiting herbicides in biotypes of field-evolved resistant weed species. However, the effect of resistance mutations on AHAS functionality and plant growth has been investigated for only a very few mutations. This research investigates the effect of various AHAS resistance mutations in Lolium rigidum on AHAS functionality and plant growth. The enzyme kinetics of AHAS from five purified L. rigidum populations, each homozygous for the resistance mutations Pro-197-Ala, Pro-197-Arg, Pro-197-Gln, Pro-197-Ser or Trp-574-Leu, were characterized and the pleiotropic effect of three mutations on plant growth was assessed via relative growth rate analysis. All these resistance mutations endowed a herbicide-resistant AHAS and most resulted in higher extractable AHAS activity, with no-to-minor changes in AHAS kinetics. The Pro-197-Arg mutation slightly (but significantly) increased the K(m) for pyruvate and remarkably increased sensitivity to feedback inhibition by branched chain amino acids. Whereas the Pro-197-Ser and Trp-574-Leu mutations exhibited no significant effects on plant growth, the Pro-197-Arg mutation resulted in lower growth rates. It is clear that, at least in L. rigidum, these five AHAS resistance mutations have no major impact on AHAS functionality and hence probably no plant resistance costs. These results, in part, explain why so many Pro-197 AHAS resistance mutations in AHAS have evolved and why the Pro-197-Ser and the Trp-574-Leu AHAS resistance mutations are frequently found in many weed species.

  20. Mutational effects of space flight on Zea mays seeds (United States)

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


    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.

  1. 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

  2. Effect of Copper Addition on Electromigration Behavior of Silver Metallization (United States)

    Bhagat, Shekhar; Theodore, N. David; Chenna, Santhosh; Alford, Terry


    This study investigates the effect of Cu alloying on electromigration behavior of Ag metallization. Electromigration tests are performed on pure Ag and Ag (1.5% Cu) samples deposited by e-beam evaporation. The experiments show that Ag (Cu) alloy interconnect has superior elctromigration resistance compared to pure Ag interconnect. X-ray diffraction, four point probe measurements and electron microscopy were used to investigate the test structures and corresponding thin film samples. The Cu improves the lifetime of interconnect test structures by hindering Ag diffusion and increasing 111 texture of Ag. Also, Cu addition seemingly reduces the agglomeration in Ag.

  3. Priming effects in Haplic Luvisol after different substrate additions (United States)

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


    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

  4. Effects of Ca additions on some Mg-alloy hydrides

    Energy Technology Data Exchange (ETDEWEB)

    Lupu, D.; Biris, A.; Indrea, E.; Bucur, R.V.


    The hydrogenation of the alloy of composition CaMg/sub 1/ /sub 8/Ni/sub 0/ /sub 5/ containing CaMg/sub 2/ and MgNi/sub 2/ shows fast activation kinetics. The Mg/sub 2/Ni phase is observed in the dehydrided samples. The three plateaus on the hydrogen desorption isotherms correspond to the most stable magnesium hydrides observed up to now in Mg-alloy ( H = 20 to 24 kcal/mol H/sub 2/). The effects of Ca additions on the hydrogen storage capacity and desorption rates of some Mg-rich alloys have been studied. 16 references, 3 figures, 1 table.

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

    Directory of Open Access Journals (Sweden)

    Andrzej Chwedoruk


    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.

  6. 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)


    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.

  7. A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis. (United States)

    Di Fede, Giuseppe; Catania, Marcella; Morbin, Michela; Rossi, Giacomina; Suardi, Silvia; Mazzoleni, Giulia; Merlin, Marco; Giovagnoli, Anna Rita; Prioni, Sara; Erbetta, Alessandra; Falcone, Chiara; Gobbi, Marco; Colombo, Laura; Bastone, Antonio; Beeg, Marten; Manzoni, Claudia; Francescucci, Bruna; Spagnoli, Alberto; Cantù, Laura; Del Favero, Elena; Levy, Efrat; Salmona, Mario; Tagliavini, Fabrizio


    beta-Amyloid precursor protein (APP) mutations cause familial Alzheimer's disease with nearly complete penetrance. We found an APP mutation [alanine-673-->valine-673 (A673V)] that causes disease only in the homozygous state, whereas heterozygous carriers were unaffected, consistent with a recessive Mendelian trait of inheritance. The A673V mutation affected APP processing, resulting in enhanced beta-amyloid (Abeta) production and formation of amyloid fibrils in vitro. Co-incubation of mutated and wild-type peptides conferred instability on Abeta aggregates and inhibited amyloidogenesis and neurotoxicity. The highly amyloidogenic effect of the A673V mutation in the homozygous state and its anti-amyloidogenic effect in the heterozygous state account for the autosomal recessive pattern of inheritance and have implications for genetic screening and the potential treatment of Alzheimer's disease.

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

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Zhao-Fei; Gou, Xiao-Fan, E-mail:


    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.

  9. Effects of TP53 and PIK3CA mutations in early breast cancer: a matter of co-mutation and tumor-infiltrating lymphocytes. (United States)

    Kotoula, Vassiliki; Karavasilis, Vasilios; Zagouri, Flora; Kouvatseas, George; Giannoulatou, Eleni; Gogas, Helen; Lakis, Sotiris; Pentheroudakis, George; Bobos, Mattheos; Papadopoulou, Kyriaki; Tsolaki, Eleftheria; Pectasides, Dimitrios; Lazaridis, Georgios; Koutras, Angelos; Aravantinos, Gerasimos; Christodoulou, Christos; Papakostas, Pavlos; Markopoulos, Christos; Zografos, George; Papandreou, Christos; Fountzilas, George


    The purpose of this study is to investigate whether the outcome of breast cancer (BC) patients treated with adjuvant chemotherapy is affected by co-mutated TP53 and PIK3CA according to stromal tumor-infiltrating lymphocytes (TILs). Paraffin tumors of all clinical subtypes from 1661 patients with operable breast cancer who were treated within 4 adjuvant trials with anthracycline-taxanes chemotherapy were informative for TP53 and PIK3CA mutation status (semiconductor sequencing genotyping) and for stromal TILs density. Disease-free survival (DFS) was examined. TP53 mutations were associated with higher (p TP53-PIK3CA co-mutations (6 % of all tumors) conferred worst DFS (HR 0.59; 95 % CI 0.44-0.79; p = 0.001 for PIK3CA-only). TP53-only mutations were unfavorable in patients with lower TILs, while patients with lower TILs performed worse if their tumors carried TP53-only mutations (interaction p = 0.046). Multivariate analysis revealed favorable PIK3CA-only mutations in non-LPBC (HR 0.64; 95 % CI 0.47-0.88; p = 0.007), and unfavorable TP53 mutations in ER/PgRpos/HER2neg (HR 1.55; 95 % CI 1.07-2.24; p = 0.021). Mutations did not interact with TILs in non-LP triple-negative and HER2-positive patients. TP53 and PIK3CA mutations appear to have diverse effects on the outcome of early BC patients, according to whether these genes are co-mutated or not, and for TP53 according to TILs density and ER/PgR-status. These findings need to be considered when evaluating the effect of these two most frequently mutated genes in the context of large clinical trials.

  10. Evolution of mutation rates in hypermutable populations of Escherichia coli propagated at very small effective population size. (United States)

    Singh, Tanya; Hyun, Meredith; Sniegowski, Paul


    Mutation is the ultimate source of the genetic variation-including variation for mutation rate itself-that fuels evolution. Natural selection can raise or lower the genomic mutation rate of a population by changing the frequencies of mutation rate modifier alleles associated with beneficial and deleterious mutations. Existing theory and observations suggest that where selection is minimized, rapid systematic evolution of mutation rate either up or down is unlikely. Here, we report systematic evolution of higher and lower mutation rates in replicate hypermutable Escherichia coli populations experimentally propagated at very small effective size-a circumstance under which selection is greatly reduced. Several populations went extinct during this experiment, and these populations tended to evolve elevated mutation rates. In contrast, populations that survived to the end of the experiment tended to evolve decreased mutation rates. We discuss the relevance of our results to current ideas about the evolution, maintenance and consequences of high mutation rates.

  11. 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.

  12. Mortar cohesión. The effect of additives

    Directory of Open Access Journals (Sweden)

    Castro, J. H.


    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.

  13. Effect of chemical additives on flow characteristics of coal slurries

    Energy Technology Data Exchange (ETDEWEB)

    E.S. Mosa; A.-H. M. Saleh; T.A. Taha; A.M. El-Molla [Al-Azhar University, Cairo (Egypt). Mining & Petroleum Engineering Department


    In the present paper, the effect of chemical additives or reagents on rheological characteristics of coal water slurry (CWS) was investigated. The power-law model was applied to determine the non-Newtonian properties of coal slurries. Three types of dispersants namely, sulphonic acid, sodium tripolyphosphate and sodium carbonate were studied and tested at different concentrations ranging from 0.5 to 1.5% by weight from total solids. Sodium salt of carboxymethyl cellulose (Na-CMC) and xanthan gum were tested as stabilizers at concentrations in the range of 0.05 to 0.25% by weight from total solids. It was found that apparent viscosity and flow properties of CWS are sensitive to the use of chemical additives (dispersants and stabilizers). Among studied dispersing agents, sulphonic acid recorded the best performance in modification and reducing CWS viscosity. The best dosage of all tested dispersants was found to be 0.75% by wt of solids. With regard to studied stabilizers, Na-CMC recorded better performance than xanthan gum. The best dosage of investigated stabilizers was found to be as 0.1 % by wt. from total solids. 13 refs., 9 figs., 1 tab.

  14. Effect of different additives on the properties of lithium alanate

    Institute of Scientific and Technical Information of China (English)


    LiAlH4 doped with Ni and Ce(SO4)2 additives and the effect of doping on temperature and hydrogen release were studied by pressure-content-temperature (PCT) experiment and X-ray diffraction (XRD) analysis.It is indicated that doping with Ni induces a significant decrease in temperature in the first step and LiAlH4 doped with 1mol% Ni presents the most absorption of hydrogen.Doping with Ce(SO4)2 also causes a marked decrease,while the amount of hydrogen release changes only slightly.The results from X-ray diffraction analysis show that doping does not cause any structural change; Ni and Ce-containing phases are not observed at room temperature or even at 250℃.

  15. Dual effect on the RET receptor of MEN 2 mutations affecting specific extracytoplasmic cysteines. (United States)

    Chappuis-Flament, S; Pasini, A; De Vita, G; Ségouffin-Cariou, C; Fusco, A; Attié, T; Lenoir, G M; Santoro, M; Billaud, M


    The RET gene encodes a receptor tyrosine kinase whose function is essential during the development of kidney and the intestinal nervous system. Germline mutations affecting one of five cysteines (Cys609, 611, 618, 620 and 634) located in the juxtamembrane domain of the RET receptor are responsible for the vast majority of two cancer-prone disorders, multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC). These mutations lead to the replacement of a cysteine by an alternate amino acid. Mutations of the RET gene are also the underlying genetic cause of Hirschsprung disease (HSCR), a congenital aganglionosis of the hindgut. In a fraction of kindreds, MEN 2A cosegregate with HSCR and affected individuals carry a single mutation at codons 609, 618 or 620. To examine the consequences of cysteine substitution on RET function, we have introduced a Cys to Arg mutation into the wild-type RET at either codons 609, 618, 620, 630 or 634. We now report that each mutation induces a constitutive catalytic activity due to the aberrant disulfide homodimerization of RET. However, mutations 630 and 634 activate RET more strongly than mutations 609, 618 or 620 as demonstrated by quantitative assays in rodent fibroblasts and pheochromocytoma PC12 cells. Biochemical analysis revealed that mutations 618 and 620, and to a lesser extent mutation 609, result in a marked reduction of the level of RET at the cell surface and as a consequence decrease the amount of RET covalent dimer. These findings provide a molecular basis explaining the range of phenotype engendered by alterations of RET cysteines and suggest a novel mechanism whereby mutations of cysteines 609, 618 and 620 exert both activating and inactivating effects.

  16. Predicting Effects of Tropomyosin Mutations on Cardiac Muscle Contraction through Myofilament Modeling

    Directory of Open Access Journals (Sweden)

    Lorenzo Rakesh Sewanan


    Full Text Available Point mutations to the human gene TPM1 have been implicated in the development of both hypertrophic and dilated cardiomyopathies. Such observations have led to studies investigating the link between single residue changes and the biophysical behavior of the tropomyosin molecule. However, the degree to which these molecular perturbations explain the performance of intact sarcomeres containing mutant tropomyosin remains uncertain. Here, we present a modeling approach that integrates various aspects of tropomyosin’s molecular properties into a cohesive paradigm representing their impact on muscle function. In particular, we considered the effects of tropomyosin mutations on (1 persistence length, (2 equilibrium between thin filament blocked and closed regulatory states, and (3 the crossbridge duty cycle. After demonstrating the ability of the new model to capture Ca-dependent myofilament responses during both dynamic and steady-state activation, we used it to capture the effects of hypertrophic cardiomyopathy (HCM related E180G and D175N mutations on skinned myofiber mechanics. Our analysis indicates that the fiber-level effects of the two mutations can be accurately described by a combination of changes to the three tropomyosin properties represented in the model. Subsequently, we used the model to predict mutation effects on muscle twitch. Both mutations led to increased twitch contractility as a consequence of diminished cooperative inhibition between thin filament regulatory units. Overall, simulations suggest that a common twitch phenotype for HCM-linked tropomyosin mutations includes both increased contractility and elevated diastolic tension.

  17. Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin

    Directory of Open Access Journals (Sweden)

    Michael B. Doud


    Full Text Available Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.

  18. Mutations of Vasopressin Receptor 2 Including Novel L312S Have Differential Effects on Trafficking. (United States)

    Tiulpakov, Anatoly; White, Carl W; Abhayawardana, Rekhati S; See, Heng B; Chan, Audrey S; Seeber, Ruth M; Heng, Julian I; Dedov, Ivan; Pavlos, Nathan J; Pfleger, Kevin D G


    Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a genetic disease first described in 2 unrelated male infants with severe symptomatic hyponatremia. Despite undetectable arginine vasopressin levels, patients have inappropriately concentrated urine resulting in hyponatremia, hypoosmolality, and natriuresis. Here, we describe and functionally characterize a novel vasopressin type 2 receptor (V2R) gain-of-function mutation. An L312S substitution in the seventh transmembrane domain was identified in a boy presenting with water-induced hyponatremic seizures at the age of 5.8 years. We show that, compared with wild-type V2R, the L312S mutation results in the constitutive production of cAMP, indicative of the gain-of-function NSIAD profile. Interestingly, like the previously described F229V and I130N NSIAD-causing mutants, this appears to both occur in the absence of notable constitutive β-arrestin2 recruitment and can be reduced by the inverse agonist Tolvaptan. In addition, to understand the effect of various V2R substitutions on the full receptor "life-cycle," we have used and further developed a bioluminescence resonance energy transfer intracellular localization assay using multiple localization markers validated with confocal microscopy. This allowed us to characterize differences in the constitutive and ligand-induced localization and trafficking profiles of the novel L312S mutation as well as for previously described V2R gain-of-function mutants (NSIAD; R137C and R137L), loss-of-function mutants (nephrogenic diabetes insipidus; R137H, R181C, and M311V), and a putative silent V266A V2R polymorphism. In doing so, we describe differences in trafficking between unique V2R substitutions, even at the same amino acid position, therefore highlighting the value of full and thorough characterization of receptor function beyond simple signaling pathway analysis.

  19. Effect of Residue Mutation on the Electrostatic Potential in EcCIC

    Institute of Scientific and Technical Information of China (English)

    ZOU Xianwu; DONG Shuxiang; WANG Xiaoqing; HUANG Shengyou


    The effect of mutation of strongly conserved porelining residues in the chloride channel EcClC on the electrostatic potential and binding free energy of the chloride ion was studied using explicit protein-membrane structures. Electrostatic potential distribution and binding free energy of the chloride ion at different binding sites in the wild-type and mutated EcClC were calculated with APBS. The potential data reveal that the electrostatic potential around the selectivity filter, especially around the site Sext and Scen becomes more negative as the residue R147 was mutated to C147. The electrostatic binding free energy shows that the binding free energy of the chloride ion at all binding sites becomes more positive as R147 was mutated. It follows that mutation of R147 decreases ion stabilization at binding sites and affects channel's gating.

  20. Effect of osteogenesis imperfecta mutations in tropocollagen molecule on strength of biomimetic tropocollagen-hydroxyapatite nanocomposites (United States)

    Dubey, Devendra K.; Tomar, Vikas


    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.

  1. Constant-Pressure Combustion Charts Including Effects of Diluent Addition (United States)

    Turner, L Richard; Bogart, Donald


    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.

  2. 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: [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom)


    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.


    Effect of the Antimutagens Vanillin and Cinnamaldehyde on the / Spontaneous Mutation Spectra of Salmonella TAlO4 Vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutagens that, when added to assay plates, reduced the spontaneous mutant frequency in Salmonella typhi...

  4. MRP1 and P-glycoprotein expression assays would be useful in the additional detection of treatment non-responders in CML patients without ABL1 mutation. (United States)

    Park, Sang Hyuk; Park, Chan-Jeoung; Kim, Dae-Young; Lee, Bo-Ra; Kim, Young Jin; Cho, Young-Uk; Jang, Seongsoo


    We evaluated the ability of the rhodamine-123 efflux assay, multidrug resistance-associated protein-1 (MRP1) expression assay and P-glycoprotein (Pgp) expression assay to discriminate chronic myelogenous leukemia (CML) patients who had failed treatment or were at risk of failure. Each assay was performed in blood samples from CML patients (n=224) treated with tyrosine kinase inhibitors, taken at diagnosis (n=14) and follow-up (n=210). Patient samples were categorized as optimal response (n=120), suboptimal response (n=54), and treatment failure (n=36). Treatment-failed patients had a significantly higher MRP1 expression (5.24% vs. 3.54%, P=0.006) and Pgp expression (5.25% vs. 3.48%, P=0.005) than responders. Both MRP1 (%) and Pgp (%) were highly specific (95.2% and 94.5%) and relatively accurate (83.0% and 82.5%) in the detection of treatment non-responders. Of treatment-failed patients, 41.2% had a positive result in at least one assay and of these patients without ABL1 kinase domain mutation, 51.9% were positive in at least one assay. However, the rhodamine-123 efflux assay failed to discriminate two patient groups. Thus, both MRP1 and Pgp expression assays could be useful for additional identification of treatment non-responders in CML patients without ABL1 mutation.

  5. Differential clinical effects of different mutation subtypes in CALR-mutant myeloproliferative neoplasms (United States)

    Pietra, D; Rumi, E; Ferretti, V V; Buduo, C A Di; Milanesi, C; Cavalloni, C; Sant'Antonio, E; Abbonante, V; Moccia, F; Casetti, I C; Bellini, M; Renna, M C; Roncoroni, E; Fugazza, E; Astori, C; Boveri, E; Rosti, V; Barosi, G; Balduini, A; Cazzola, M


    A quarter of patients with essential thrombocythemia or primary myelofibrosis carry a driver mutation of CALR, the calreticulin gene. A 52-bp deletion (type 1) and a 5-bp insertion (type 2 mutation) are the most frequent variants. These indels might differentially impair the calcium binding activity of mutant calreticulin. We studied the relationship between mutation subtype and biological/clinical features of the disease. Thirty-two different types of CALR variants were identified in 311 patients. Based on their predicted effect on calreticulin C-terminal, mutations were classified as: (i) type 1-like (65%); (ii) type 2-like (32%); and (iii) other types (3%). Corresponding CALR mutants had significantly different estimated isoelectric points. Patients with type 1 mutation, but not those with type 2, showed abnormal cytosolic calcium signals in cultured megakaryocytes. Type 1-like mutations were mainly associated with a myelofibrosis phenotype and a significantly higher risk of myelofibrotic transformation in essential thrombocythemia. Type 2-like CALR mutations were preferentially associated with an essential thrombocythemia phenotype, low risk of thrombosis despite very-high platelet counts and indolent clinical course. Thus, mutation subtype contributes to determining clinical phenotype and outcomes in CALR-mutant myeloproliferative neoplasms. CALR variants that markedly impair the calcium binding activity of mutant calreticulin are mainly associated with a myelofibrosis phenotype. PMID:26449662

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

    Directory of Open Access Journals (Sweden)

    Mota Eduardo


    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.

  7. Parental source effect of inherited mutations in the dystrophin gene of mice and men

    Energy Technology Data Exchange (ETDEWEB)

    Kress, W.; Grimm, T.; Mueller, C.R. [Institute of Human Genetics, Wuerburg (Germany); Bittner, R. [Institute of Anatomy, Wein (Australia)


    Skewed X-inactivation has been suspected the genetic cause for some manifesting female carriers of BMD and DMD. To test whether a parental source effect on the protein expression of the dystrophin gene exists, we have set up backcrosses of mdx mice to wild type strains, enabling us to study the effect of the well-defined origin of the mutation on the dystrophin expression. In skeletal muscle sections the immunohistological staining patterns of dystrophin antibodies were showing a significant difference in the proportion of dystrophin positive versus negative fibers, suggesting a lower expression of paternally inherited mdx mutations. These data are in concordance with the pyruvate kinase (PK) levels in the serum: PK levels were much higher when the mutation was of maternal origin as compared to PK levels in paternally derived mutations. In order to test this {open_quotes}paternal source effect{close_quotes} in humans, we checked obligatory carriers of Becker muscular dystrophy (BMD) for the origin of their mutations. Creatin kinase (CK) levels in 21 carriers with maternally derived mutations were compared to CK values from 8 heterozygotes with mutations of paternal origin: CK (mat) = 140.3 IU/1 versus CK (pat) = 48.6 IU/I. The difference is statistically significant at the 5% level. These observations suggest either a differential X-inactivation or an imprinting of the dystrophin gene in mice and men.

  8. 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.

  9. 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.

  10. Ivermectin plus diethylcarbamazine: an additive effect on early microfilarial clearance. (United States)

    Moulia-Pelat, J P; Nguyen, L N; Glaziou, P; Chanteau, S; Ottesen, E A; Cardines, R; Martin, P M; Cartel, J L


    The effects of ivermectin, diethylcarbamazine (DEC), and the combination of both drugs on levels of microfilaremia (mf) were studied in 30 male Polynesian Wuchereria bancrofti carriers. Microfilarial densities were measured 30 min (H1/2), 1 hr (H1), and 2, 4, 8, 24, and 96 hr (H2, H4, H8, H24, and H96) after supervised single doses of ivermectin plus DEC (400 micrograms/kg plus 1 mg/kg, respectively, 400 micrograms/kg plus 3 mg/kg, respectively, and 400 micrograms/kg plus 6 mg/kg, respectively), DEC (6 mg/kg) alone, and ivermectin (400 micrograms/kg and 100 micrograms/kg, respectively) alone given to six groups of five patients each. The results showed that 1) DEC alone or combined with ivermectin induced a rapid clearance of mf after drug intake; at H1/2, the number of circulating microfilariae was reduced to 16%, 8%, 28%, and 31%, respectively, of pretreatment values in the groups receiving ivermectin plus DEC (400 micrograms/kg plus 1 mg/kg, 400 micrograms/kg plus 3 mg/kg, and 400 micrograms/kg plus 6 mg/kg) and DEC (6 mg/kg) alone; 2) ivermectin alone induced a rapid increase of mf densities during the first 2 hr, followed by a sharp decrease from H4 to H96; and 3) between H8 and H96, mf clearance was almost complete with the combination of ivermectin and DEC. A comparison among groups did not show any synergistic interaction between ivermectin and DEC on the clearance of microfilaria, with the effect of each drug being additive to each another.

  11. Effects of Several Purple Potato Additions on Bread Quality

    Directory of Open Access Journals (Sweden)

    Bădărău Carmen Liliana


    Full Text Available Potato cultivars with purple flesh represent an efficient and natural source of antioxidants, this vegetable having high content in polyphenols (especially anthocyanin pigments. The research goal of this work was to evaluate the anthocyanin and polyphenols content of several Romanian potato varieties (Albastru-Violet de Gălănești and Christian and the effects of these potatoes (add to dough in different proportions on several bread quality indicators. The bread quality depends on physical and chemical properties and on several signs like: flavor and taste, external appearance, crumb porosity and texture, bread’s volume. In this research experiment, beside the total polyphenols and anthocyanin content, the analysis performed on bread (prepared using different potatoes addition 5%, 15% and 30% were sensorial and physic chemical analysis (product volume, crumb porosity, height/diameter ratio, moist and acidity. Experimental results indicated that 15% purple potato cultivar added on the dough was the most indicate proportion to be used in bread processing.

  12. Effect of co-inheritance of β-thalassemia and hemochromatosis mutations on iron overload. (United States)

    López-Escribano, Herminio; Ferragut, Joana F; Parera, Maria M; Guix, Pilar; Castro, José A; Ramon, M Misericòrdia; Picornell, Antònia


    Co-inheritance of mutations in the HFE gene underlying hereditary hemocromatosis (HH) may play a role in the variability of iron status in patients with β-thalassemia (β-thal) minor. Different studies have yielded conflicting results: some suggest iron overload might arise from the interaction of the β-thal trait with homozygosity or even heterozygosity for HFE mutations and others that it was unrelated to the HFE genotype. Because of the high frequency of HFE mutations in the Balearic Islands, where the β-thal trait is also moderately common, it is of interest to evaluate the effect of the co-inheritance of mutations in both genes on the severity of iron loading. A retrospective analysis of 142 individuals heterozygous for β-thal was performed to investigate the effect of HFE mutations on iron status of these patients. No significant differences were detected between β-thal carriers with and without HFE mutations. These results suggest that in the Balearic population the β-thal trait does not tend to be aggravated by the co-inheritance of HFE mutations.

  13. Male mutation bias and possible long-term effects of human activities. (United States)

    Cotton, Samuel; Wedekind, Claus


    The ability of a population to adapt to changing environments depends critically on the amount and kind of genetic variability it possesses. Mutations are an important source of new genetic variability and may lead to new adaptations, especially if the population size is large. Mutation rates are extremely variable between and within species, and males usually have higher mutation rates as a result of elevated rates of male germ cell division. This male bias affects the overall mutation rate. We examined the factors that influence male mutation bias, and focused on the effects of classical life-history parameters, such as the average age at reproduction and elevated rates of sperm production in response to sexual selection and sperm competition. We argue that human-induced changes in age at reproduction or in sexual selection will affect male mutation biases and hence overall mutation rates. Depending on the effective population size, these changes are likely to influence the long-term persistence of a population.

  14. Chemistry of Food Additives: Direct and Indirect Effects. (United States)

    Pauli, George H.


    The primary component(s), impurities, and degradation products of polysorbate 80, nitrate and nitrite salts, and diethylpyrocarbonate (DEPC) are discussed. Safety considerations related to these food additives are also noted. The chick-edema factor which results from an additive in poultry feed is also discussed. (JN)

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

    Directory of Open Access Journals (Sweden)

    Takenobu Michioka


    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.

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

    Directory of Open Access Journals (Sweden)

    Seyed Hossein Khaleghinejad


    Full Text Available Lipases (triacylglycerol acylhydrolase, EC 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.

  17. Effects of hepatitis B virus precore and basal core promoter mutations on the expression of viral antigens: genotype B vs C. (United States)

    Liu, C-J; Cheng, H-R; Chen, C-L; Chen, T-C; Tseng, T-C; Wang, Z-L; Chen, P-J; Liu, C-H; Chen, D-S; Kao, J-H


    Hepatitis B virus (HBV) genotypes/mutants are known to affect natural outcomes. The virologic differences among HBV genotype, precore and basal core promoter (BCP) mutations were investigated. HBV strains were isolated from 18 hepatitis B e antigen (HBeAg)-positive patients (nine genotype B and nine genotype C). All had precore and BCP wild-type sequences. After cloning of full-length HBV genome, the effects of viral genotype, precore and BCP mutations singly or additively on the expression of viral DNA and antigens were investigated by mutagenesis and transfection assays in Huh7 cells. Significant findings included the following: (i) expression of intracellular core protein increased when precore or BCP mutation was introduced in genotype C strains; (ii) expression of intracellular surface protein was lower in genotype C precore wild-type strain compared with genotype B; (iii) precore mutation was associated with a lower extracellular expression level of HBV DNA; (iv) secretion of hepatitis B surface antigen in genotype C was lower than that in genotype B; and (v) secretion of HBeAg in genotype B was lower than that in genotype C. No additive effect was observed by combining precore and BCP mutations. Hence, HBV genotype and precore/BCP mutations correlate with intrahepatic expression of viral antigens in vitro.

  18. VHL missense mutations in the p53 binding domain show different effects on p53 signaling and HIFα degradation in clear cell renal cell carcinoma. (United States)

    Razafinjatovo, Caroline Fanja; Stiehl, Daniel; Deininger, Eva; Rechsteiner, Markus; Moch, Holger; Schraml, Peter


    Clear cell Renal Cell Carcinoma (ccRCC) formation is connected to functional loss of the von Hippel-Lindau (VHL) gene. Recent data identified its gene product, pVHL, as a multifunctional adaptor protein which interacts with HIFα subunits but also with the tumor suppressor p53. p53 is hardly expressed and rarely mutated in most ccRCC. We showed that low and absent p53 expression correlated with the severity of VHL mutations in 262 analyzed ccRCC tissues. In contrast to nonsense and frameshift mutations which abrogate virtually all pVHL functions, missense mutations may rather influence one or few functions. Therefore, we focused on four VHL missense mutations, which affect the overlapping pVHL binding sites of p53 and Elongin C, by investigating their impact on HIFα degradation, p53 expression and signaling, as well as on cellular behavior using ccRCC cell lines and tissues. TP53 mRNA and its effector targets p21, Bax and Noxa, were altered both in engineered cell lines and in tumor tissues which carried the same missense mutations. Two of these mutations were not able to degrade HIFα whereas the remaining two mutations led to HIFα downregulation, suggesting the latter are p53 binding site-specific. The selected VHL missense mutations further enhanced tumor cell survival, but had no effects on cell proliferation. Whereas Sunitinib was able to efficiently reduce cell proliferation, Camptothecin was additionally able to increase apoptotic activity of the tumor cells. It is concluded that systematic characterization of the VHL mutation status may help optimizing targeted therapy for patients with metastatic ccRCC.

  19. The Effect Acid Addition on Characteristic Effervescent Tablet of Tamarillo

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    Fidela Violalita


    Full Text Available The aim of study was to determine the percentage of acid and its influence on characteristic effervescent tablet of tamarillo. The percentages of  acid addition that consist with citric acid and tartaric acid (1:1 were 15%, 20%, 25%, 30% and 35%. Water content, pH solution, vitamin C content, soluble duration, friability of tablet and organoleptic test on colour, aroma and flavour of tamarillo effervescent tablet were determined after addition of acid. The results showed that the difference in percentage of acid addition significantly affected to the water content, pH solution, soluble duration and friability of tablets. Based on organoleptic test, the tablet consist of 25% addition of acid was the best percentage of acid addition. The quality parameters in this percentage were the water content 6.09%, pH solution 4.80,  vitamin C 498.0800 mg/tablet, soluble duration 3.96 minute, friability of tablet 0.11%, while the averages of organoleptic test for colour were 3.40 (ordinary, aroma 3.36 (ordinary, and flavour 3.76 (like.

  20. Differential effects of human L1CAM mutations on complementing guidance and synaptic defects in Drosophila melanogaster.

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    Sirisha Kudumala

    Full Text Available A large number of different pathological L1CAM mutations have been identified that result in a broad spectrum of neurological and non-neurological phenotypes. While many of these mutations have been characterized for their effects on homophilic and heterophilic interactions, as well as expression levels in vitro, there are only few studies on their biological consequences in vivo. The single L1-type CAM gene in Drosophila, neuroglian (nrg, has distinct functions during axon guidance and synapse formation and the phenotypes of nrg mutants can be rescued by the expression of human L1CAM. We previously showed that the highly conserved intracellular FIGQY Ankyrin-binding motif is required for L1CAM-mediated synapse formation, but not for neurite outgrowth or axon guidance of the Drosophila giant fiber (GF neuron. Here, we use the GF as a model neuron to characterize the pathogenic L120V, Y1070C, C264Y, H210Q, E309K and R184Q extracellular L1CAM missense mutations and a L1CAM protein with a disrupted ezrin-moesin-radixin (ERM binding site to investigate the signaling requirements for neuronal development. We report that different L1CAM mutations have distinct effects on axon guidance and synapse formation. Furthermore, L1CAM homophilic binding and signaling via the ERM motif is essential for axon guidance in Drosophila. In addition, the human pathological H210Q, R184Q and Y1070C, but not the E309K and L120V L1CAM mutations affect outside-in signaling via the FIGQY Ankyrin binding domain which is required for synapse formation. Thus, the pathological phenotypes observed in humans are likely to be caused by the disruption of signaling required for both, guidance and synaptogenesis.


    Directory of Open Access Journals (Sweden)

    Hema Shenpagam N.*, D. Kanchana Devi ** and Sinduja G.


    Full Text Available In the present study, the endophytic actinomycetes were collected from three medicinal plants Azadiracta indica, Ocimum sanctum and Phyllanthus amarus. Endophytic actinomycetes were isolated using different media like Starch casein agar, Starch casein nitrate agar, Actinomycetes isolation agar and Soyabean agar, while it showed more colonies in Starch casein agar. The endophytic actinomycetes were stained and biochemical tests were performed. Antimicrobial compound was purified from the filtrate by ethanol extraction method. Antagonistic activities of endophytic actinomycetes isolates were tested against bacterial pathogens (Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa and the fungi Rhizopus. For the selected isolates antibiotic resistance was checked using various antibiotic discs like Amoxycillin, Penicillin, Rifampicin and Ampicillin. The strains which showed efficient antibacterial activity were selected to study the effect of mutation by physical and chemical method. In this study, UV mutated endophytic actinomycetes increase antibiotic production than non-mutated endophytic Actinomycetes, whereas in chemical mutation it does not increase the antibiotic production.

  2. Conservation of CFTR codon frequency through primates suggests synonymous mutations could have a functional effect. (United States)

    Pizzo, Lucilla; Iriarte, Andrés; Alvarez-Valin, Fernando; Marín, Mónica


    Cystic fibrosis is an inherited chronic disease that affects the lungs and digestive system, with a prevalence of about 1:3000 people. Cystic fibrosis is caused by mutations in CFTR gene, which lead to a defective function of the chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Up-to-date, more than 1900 mutations have been reported in CFTR. However for an important proportion of them, their functional effects and the relation to disease are still not understood. Many of these mutations are silent (or synonymous), namely they do not alter the encoded amino acid. These synonymous mutations have been considered as neutral to protein function. However, more recent evidence in bacterial and human proteins has put this concept under revision. With the aim of understanding possible functional effects of synonymous mutations in CFTR, we analyzed human and primates CFTR codon usage and divergence patterns. We report the presence of regions enriched in rare and frequent codons. This spatial pattern of codon preferences is conserved in primates, but this cannot be explained by sequence conservation alone. In sum, the results presented herein suggest a functional implication of these regions of the gene that may be maintained by purifying selection acting to preserve a particular codon usage pattern along the sequence. Overall these results support the idea that several synonymous mutations in CFTR may have functional importance, and could be involved in the disease.


    Directory of Open Access Journals (Sweden)

    Danielly Vieira de Lucena


    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.

  4. An effective method, composed of LAMP and dCAPS, to detect different mutations in fenoxaprop-P-ethyl-resistant American sloughgrass (Beckmannia syzigachne Steud.) populations. (United States)

    Pan, Lang; Li, Jun; Xia, Wenwen; Zhang, Di; Dong, Liyao


    The decreased susceptibility of Beckmannia syzigachne to fenoxaprop-P-ethyl is due to the reliance on it to control grass weeds since the 1990s. Loop-mediated isothermal amplification (LAMP), which is a proven simple, rapid, specific, sensitive and inexpensive assay method, has been used to detect the I1781L mutation in B. syzigachne. In the present study, four sets of primers detected four mutations in B. syzigachne, W2027C, I2041A, D2078G and G2096A, using the LAMP method. Additionally, five newly derived cleaved amplified polymorphic sequence (dCAPS) markers were developed to detect five different mutations. With a method composed of LAMP and dCAPS, 19 fenoxaprop-P-ethyl-resistant B. syzigachne populations collected in 2013 were studied. An effective method, composed of LAMP and dCAPS, to detect five mutations, I1781L, W2027C, I2041A, D2078G and G2096A, in B. syzigachne populations was developed. With this method, a B. syzigachne population resistant to fenoxaprop-P-ethyl can be studied to confirm its constitution. And we determined that the resistance level might be relevant to the mutation type and mutation frequency. The type of mutation and its frequency in fenoxaprop-P-ethyl-resistant B. syzigachne populations can be confirmed to provide appropriate herbicide management.

  5. The Escherichia coli modE gene: effect of modE mutations on molybdate dependent modA expression. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Bagheri Homayoun C


    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

  7. Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature. (United States)

    Boucher, Jeffrey I; Bolon, Daniel N A; Tawfik, Dan S


    The last decade has seen a growing number of experiments aimed at systematically mapping the effects of mutations in different proteins, and of attempting to correlate their biophysical and biochemical effects with organismal fitness. While insightful, systematic laboratory measurements of fitness effects present challenges and difficulties. Here, we discuss the limitations associated with such measurements, and in particular the challenge of correlating the effects of mutations at the single protein level ("protein fitness") with their effects on organismal fitness. A variety of experimental setups are used, with some measuring the direct effects on protein function and others monitoring the growth rate of a model organism carrying the protein mutants. The manners by which fitness effects are calculated and presented also vary, and the conclusions, including the derived distributions of fitness effects of mutations, vary accordingly. The comparison of the effects of mutations in the laboratory to the natural protein diversity, namely to amino acid changes that have fixed in the course of millions of years of evolution, is also debatable. The results of laboratory experiments may, therefore, be less relevant to understanding long-term inter-species variations yet insightful with regard to short-term polymorphism, for example, in the study of the effects of human SNPs.

  8. Effects of additive noise on the stability of glacial cycles

    CERN Document Server

    Mitsui, Takahito


    It is well acknowledged that the sequence of glacial-interglacial cycles is paced by the astronomical forcing. However, how much is the sequence robust against natural fluctuations associated, for example, with the chaotic motions of atmosphere and oceans? In this article, the stability of the glacial-interglacial cycles is investigated on the basis of simple conceptual models. Specifically, we study the influence of additive white Gaussian noise on the sequence of the glacial cycles generated by stochastic versions of several low-order dynamical system models proposed in the literature. In the original deterministic case, the models exhibit different types of attractors: a quasiperiodic attractor, a piecewise continuous attractor, strange nonchaotic attractors, and a chaotic attractor. We show that the combination of the quasiperiodic astronomical forcing and additive fluctuations induce a form of temporarily quantised instability. More precisely, climate trajectories corresponding to different noise realiza...

  9. Investigation of Fuel Additive Effects on Sooting Flames (United States)


    material to be analyzed i, illuminated with a beam of soft x-rays. These cause both photo- and Auger-electrons to be emitted from surface layer atoms. controlled sputtering away of surface material with energetic argon cations done in sequence with the ESCA procedure described above. The ESCA...may not always be estimated accurately. This difficulty’ rn-y be overcome, how., vver , by making anI additional Rayleigh measurement of’ scattered

  10. The Effect of Fluorocarbon Surfactant Additives on the Effective Viscosity of Acetone Solutions of Cellulose Diacetate, (United States)



  11. The fitness effects of a point mutation in Escherichia coli change with founding population density. (United States)

    Cao, Huansheng; Plague, Gordon R


    Although intraspecific competition plays a seminal role in organismal evolution, little is known about the fitness effects of mutations at different population densities. We identified a point mutation in the cyclic AMP receptor protein (CRP) gene in Escherichia coli that confers significantly higher fitness than the wildtype at low founding population density, but significantly lower fitness at high founding density. Because CRP is a transcription factor that regulates the expression of nearly 500 genes, we compared global gene expression profiles of the mutant and wildtype strains. This mutation (S63F) does not affect expression of crp itself, but it does significantly affect expression of 170 and 157 genes at high and low founding density, respectively. Interestingly, acid resistance genes, some of which are known to exhibit density-dependent effects in E. coli, were consistently differentially expressed at high but not low density. As such, these genes may play a key role in reducing the crp mutant's fitness at high density, although other differentially expressed genes almost certainly also contribute to the fluctuating fitness differences we observed. Whatever the causes, we suspect that many mutations may exhibit density-dependent fitness effects in natural populations, so the fate of new mutations may frequently depend on the effective population size when they originate.

  12. Cognitive Effects of Greek Affiliation in College: Additional Evidence (United States)

    Pascarella, Ernest T.; Flowers, Lamont; Whitt, Elizabeth J.


    Previous research published in this journal found broad-based negative effects of Greek affiliation on standardized measures of cognitive development after 1 year of college. Following the same sample, and employing essentially the same research design and analytic model, the present study found that the negative effects of Greek affiliation were…

  13. In silico investigation of molecular effects caused by missense mutations in creatine transporter protein (United States)

    Zhang, Zhe; Schwatz, Charles; Alexov, Emil


    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.

  14. Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice (United States)

    Kim, Mi-Jung; Hacker, Timothy A.; Vermulst, Marc; Weindruch, Richard; Prolla, Tomas A.


    Mitochondrial DNA (mtDNA) mutations are thought to have a causative role in age-related pathologies. We have shown previously that mitochondrial mutator mice (PolgD257A/D257A), harboring a proofreading-deficient version of the mtDNA polymerase gamma (POLG), accumulate mtDNA mutations in multiple tissues and display several features of accelerated aging. Calorie restriction (CR) is known to delay the onset of age-related diseases and to extend the lifespan of a variety of species, including rodents. In the current study we investigated the effects of CR on the lifespan and healthspan of mitochondrial mutator mice. Long-term CR did not increase the median or maximum lifespan of PolgD257A/D257A mice. Furthermore, CR did not reduce mtDNA deletions in the heart and muscle, accelerated sarcopenia, testicular atrophy, nor improve the alterations in cardiac parameters that are present in aged mitochondrial mutator mice. Therefore, our findings suggest that accumulation of mtDNA mutations may interfere with the beneficial action of CR in aging retardation. PMID:28158260

  15. Effects of an additional dimension in the Young experiment

    Energy Technology Data Exchange (ETDEWEB)

    Barros, Allan Kardec, E-mail:


    The results of the Young experiment can be analyzed either by classical or Quantum Physics. The later one though leads to a more complete interpretation, based on two different patterns that appear when one works either with single or double slits. Here we show that the two patterns can be derived from a single principle, in the context of General Relativity, if one assumes an additional spatial dimension to the four known today. The found equations yield the same results as those in Quantum Mechanics.

  16. Effects of an additional dimension in the Young experiment

    CERN Document Server

    Barros, Allan Kardec


    The results of the Young experiment can be analyzed either by classical or Quantum Physics. The later one though leads to a more complete interpretation, based on two different patterns that appear when one works either with single or double slits. Here we show that the two patterns can be derived from a single principle, in the context of General Relativity, if one assumes an additional spatial dimension to the four known today. The found equations yield the same results as those in Quantum Mechanics.

  17. Effect of hydrogen addition on autoignited methane lifted flames

    KAUST Repository

    Choin, Byung Chul


    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.

  18. Obstructive Sleep Apnea, Hypertension, and Their Additive Effects on Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Mario Francesco Damiani


    Full Text Available Background and Aims. It is widely accepted that obstructive sleep apnea (OSA is independently associated with atherosclerosis. Similar to OSA, hypertension (HTN is a condition associated with atherosclerosis. However, to date, the impact of the simultaneous presence of OSA and HTN on the risk of atherosclerosis has not been extensively studied. The aim of this study was to evaluate the consequences of the coexistence of OSA and HTN on carotid intima-media thickness (IMT and on inflammatory markers of atherosclerosis (such as interleukin- [IL-] 6 and pentraxin- [PTX-] 3. Methods. The study design allowed us to define 4 groups: (1 controls (n=30; (2 OSA patients without HTN (n=30; (3 HTN patients without OSA (n=30; (4 patients with OSA and HTN (n=30. In the morning after portable monitoring (between 7 am and 8 am, blood samples were collected, and carotid IMT was measured. Results. Carotid IMT, IL-6, and PTX-3 in OSA normotensive patients and in non-OSA HTN subjects were significantly higher compared to control subjects; in addition, in OSA hypertensive patients they were significantly increased compared to OSA normotensive, non-OSA HTN, or control subjects. Conclusions. OSA and HTN have an additive role in the progression of carotid atherosclerosis and in blood levels of inflammatory markers for atherosclerosis, such as interleukin-6 and pentraxin-3.

  19. Effects of new mutations on fitness: insights from models and data. (United States)

    Bataillon, Thomas; Bailey, Susan F


    The rates and properties of new mutations affecting fitness have implications for a number of outstanding questions in evolutionary biology. Obtaining estimates of mutation rates and effects has historically been challenging, and little theory has been available for predicting the distribution of fitness effects (DFE); however, there have been recent advances on both fronts. Extreme-value theory predicts the DFE of beneficial mutations in well-adapted populations, while phenotypic fitness landscape models make predictions for the DFE of all mutations as a function of the initial level of adaptation and the strength of stabilizing selection on traits underlying fitness. Direct experimental evidence confirms predictions on the DFE of beneficial mutations and favors distributions that are roughly exponential but bounded on the right. A growing number of studies infer the DFE using genomic patterns of polymorphism and divergence, recovering a wide range of DFE. Future work should be aimed at identifying factors driving the observed variation in the DFE. We emphasize the need for further theory explicitly incorporating the effects of partial pleiotropy and heterogeneity in the environment on the expected DFE.

  20. 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:


    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.

  1. Effect of mutated IκBα transfection on multidrug resistance in hilar cholangiocarcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Ru-Fu Chen; Zhi-Hua Li; Xian-He Kong; Ji-Sheng Chen


    AIM: To explore the expression effect of mutated IκBαtransfection on multidrug resistance gene (MDR-1) in hilar cholangiocarcinoma cells by inhibiting the activity of nuclear transcription factor-κB (NF-κB).METHODS: We used the mutated IκBα plasmid to transfect QBC939HCVC+ cells and QBC939 cells, and electrophoretic gel mobility shift assay (EMSA) to detect the binding activity of NF-κB DNA and the effect of the transfrecting mutated IκBα plasmid on multidrug resistance gene (MDR-1) in hilar cholangiocarcinoma cells and its expression protein (P-GP).RFSULTS: Plasmid DNA was digested by restriction enzymes Xbal and Hand Ⅲ, and its product after electrophoresis showed two bands with a big difference in molecular weight,with a size of 4.9 kb and 1.55 kb respectively, which indicated that the carrier was successfully constructed and digested with enzymes. The radioactivity accumulation of QBC939HCVC+and QBC939 cells transfected with mutated IκBα plasmid was significantly lower than that of the control group not transfected with mutated IκBα plasmid. Double densimeter scanning showed that the relative signal density between the tansfection group and non-transfection group was significantly different, which proved that the mutated IκBα plasmid could inhibit the binding activity of NF-κB DNA in hilar cholangiocarcinoma cells. Compared to control group not transfected with m IκBα plasmid, the expression level of MDR-1mRNA in the QBC939 and QBC939HCVC+ cells transfected with mutated IκBα plasmid was lower. The expression intensity of P-GP protein in QBC939 and QBC939HCVC+ cells transfected with mutated IκBα was significantly lower than that of the control group not transfected with mutated IκBα plasmid.CONCLUSION: The mutated IκBα plasmid transfection can markedly reverse the multidrug resistance of hilar cholangiocarcinoma cells. Interruption of NF-κB activity may become a new target in gene therapy for hilar cholangiocarcinogenesic carcinoma.

  2. [Effective prevention through nutritional and food additives: barriers and resistance]. (United States)

    Lux, R; Walter, U


    The population-wide and individual preventive potentials of nutritional and food additives such as vitamins and trace elements are generally accepted in the international literature. Iodisation and fluoridation were and are a main focus of activity. The enrichment of food with folic acid is also partly population-related. Until now, however, the theoretical possibilities of nutritional supplementations have not been fully exploited. Various barriers and resistances arise in programme development and implementation. Interviews with key stakeholders and community groups can clarify decade-long discussions in the literature and the media. The study on hand is based on a structural analysis. It shows the various arguments as well as beneficial and impeding factors for a population-wide prevention programme, for specific target groups and individuals. The findings of this research could also be applied to other Public Health challenges.

  3. 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


    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.

  4. Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations (United States)

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


    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.

  5. Mutational effects of γ-rays and carbon ion beams on Arabidopsis seedlings (United States)

    Yoshihara, Ryouhei; Nozawa, Shigeki; Hase, Yoshihiro; Narumi, Issay; Hidema, Jun; Sakamoto, Ayako N.


    To assess the mutational effects of radiation on vigorously proliferating plant tissue, the mutation spectrum was analyzed with Arabidopsis seedlings using the plasmid-rescue method. Transgenic plants containing the Escherichia coli rpsL gene were irradiated with γ-rays and carbon ion beams (320-MeV 12C6+), and mutations in the rpsL gene were analyzed. Mutant frequency increased significantly following irradiation by γ-rays, but not by 320-MeV 12C6+. Mutation spectra showed that both radiations increased the frequency of frameshifts and other mutations, including deletions and insertions, but only γ-rays increased the frequency of total base substitutions. These results suggest that the type of DNA lesions which cause base substitutions were less often induced by 320-MeV 12C6+ than by γ-rays in Arabidopsis seedlings. Furthermore, γ-rays never increased the frequencies of G:C to T:A or A:T to C:G transversions, which are caused by oxidized guanine; 320-MeV 12C6+, however, produced a slight increase in both transversions. Instead, γ-rays produced a significant increase in the frequency of G:C to A:T transitions. These results suggest that 8-oxoguanine has little effect on mutagenesis in Arabidopsis cells. PMID:23728320

  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


    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. Gamma radiation effects on siloxane-based additive manufactured structures (United States)

    Schmalzer, Andrew M.; Cady, Carl M.; Geller, Drew; Ortiz-Acosta, Denisse; Zocco, Adam T.; Stull, Jamie; Labouriau, Andrea


    Siloxane-basedadditive manufactured structures prepared by the direct ink write (DIW) technology were exposed to ionizing irradiation in order to gauge radiolysis effects on structure-property relationships. These well-defined 3-D structures were subjected to moderate doses of gamma irradiation in an inert atmosphere and characterized by a suite of experimental methods. Changes in thermal, chemical, microstructure, and mechanical properties were evaluated by DSC, TGA, FT-IR, mass spectroscopy, EPR, solvent swelling, SEM, and uniaxial compressive load techniques. Our results demonstrated that 3-D structures made from aromatic-free siloxane resins exhibited hardening after being exposed to gamma radiation. This effect was accompanied by gas evolution, decreasing in crystallization levels, decreasing in solvent swelling and damage to the microstructure. Furthermore, long-lived radiation-induced radicals were not detected by EPR methods. Our results are consistent with cross-link formation being the dominant degradation mechanism over chain scission reactions. On the other hand, 3-D structures made from high phenyl content siloxane resins showed little radiation damage as evidenced by low off gassing.

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

    Directory of Open Access Journals (Sweden)

    Asem Hussein


    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.

  9. Effect of inoculating addition on machinability of gray cast iron

    Institute of Scientific and Technical Information of China (English)

    REN Fengzhang; LI Fengjun; LIU Weiming; MA Zhanhong; TIAN Baohong


    Gray cast irons were inoculated with FeSi75+RE and FeSi75+Sr inoculants. The changes of apex angle of the drills before and af-ter being used were used to evaluate machinability of gray cast irons. Effect of FeSi75+RE and FeSi75+Sr inoculants on mechanical proper-ties, machinability and sensibility of gray cast iron used in cylinder block were investigated. Experimental results showed that gray cast iron treated with 60%FeSi75+40% RE inoculants exhibited tensile strength consistently at about 295 MPa along with good hardness and im-proved metallurgical quality. While gray cast iron inoculated with 20%FeSi75+80% Sr inoculants exhibited the best machinability, the low-est cross-section sensibility and the least microhardness difference. The tool flank wear of the drill increased correspondingly with the in-crease of the microhardness difference of the matrix, indicating the great effect of homogeneity of the matrix on the machinability of gray cast iron.

  10. The CFTR frameshift mutation 3905insT and its effect at transcript and protein level. (United States)

    Sanz, Javier; von Känel, Thomas; Schneider, Mircea; Steiner, Bernhard; Schaller, André; Gallati, Sabina


    Cystic fibrosis (CF) is one of the most common genetic diseases in the Caucasian population and is characterized by chronic obstructive pulmonary disease, exocrine pancreatic insufficiency, and elevation of sodium and chloride concentrations in the sweat and infertility in men. The disease is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes a protein that functions as chloride channel at the apical membrane of different epithelia. Owing to the high genotypic and phenotypic disease heterogeneity, effects and consequences of the majority of the CFTR mutations have not yet been studied. Recently, the frameshift mutation 3905insT was identified as the second most frequent mutation in the Swiss population and found to be associated with a severe phenotype. The frameshift mutation produces a premature termination codon (PTC) in exon 20, and transcripts bearing this PTC are potential targets for degradation through nonsense-mediated mRNA decay (NMD) and/or for exon skipping through nonsense-associated alternative splicing (NAS). Using RT-PCR analysis in lymphocytes and different tissue types from patients carrying the mutation, we showed that the PTC introduced by the mutation does neither elicit a degradation of the mRNA through NMD nor an alternative splicing through NAS. Moreover, immunocytochemical analysis in nasal epithelial cells revealed a significantly reduced amount of CFTR at the apical membrane providing a possible molecular explanation for the more severe phenotype observed in F508del/3905insT compound heterozygotes compared with F508del homozygotes. However, further experiments are needed to elucidate the fate of the 3905insT CFTR in the cell after its biosynthesis.

  11. Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease. (United States)

    Goriely, Anne; Wilkie, Andrew O M


    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.


    Directory of Open Access Journals (Sweden)



    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.

  13. Effect of bovine lactoferrin addition to milk in yogurt manufacturing. (United States)

    Franco, I; Castillo, E; Pérez, M D; Calvo, M; Sánchez, L


    The aim of this work was to study the effect of milk supplementation with lactoferrin of different iron saturation on the manufacturing and characteristics of yogurt. Bovine lactoferrin was added at concentrations of 0.5, 1, and 2 mg/mL in the holo (iron saturated) and apo (without iron) forms. Some physicochemical properties, such as pH, concentration of lactic acid, and texture of supplemented yogurts, were determined throughout the shelf-life period storage (28 d) at 4°C. We also evaluated the stability of lactoferrin in supplemented yogurt throughout the storage time. The supplementation of milk with bovine lactoferrin did not greatly affect the physical properties of the yogurt, though apo-lactoferrin slightly delayed the decrease of pH. This could be attributed to the partial inhibition observed on the growth of Streptococcus thermophilus. The integrity and immunoreactive concentration of lactoferrin, determined by Western blotting and noncompetitive ELISA, respectively, remained constant throughout the shelf life of yogurt.

  14. 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)


    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)

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

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    Colombo Elisa A


    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

  16. Effect of extracellular calcium on the additive effect of theophylline on the cardiac response to catecholamine

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    Shamkuwar Prashant


    Full Text Available At different extracellular calcium concentrations, the positive inotropic effect of isoproterenol and isoproterenol in combination with theophylline, a phosphodiesterase inhibitor have been evaluated in the isolated frog heart and the isolated guinea pig left atria to investigate whether extracellular calcium produces any effect on the additive effect of the theophylline on the cardiac response to catecholamine. Cumulative dose response study of isoproterenol and isoproterenol in presence of theophylline at different extracellular calcium concentration was performed. The study revealed an increase in additive effect of theophylline on the cardiac response to catecholamine with increase in extracellular calcium concentration, but increase in extracellular calcium concentration decreased the myocardial responsiveness to additive effect of theophylline and isoproterenol combination. The mechanism of positive inotropic effect of isoproterenol and in combination with theophylline involves increase in intracellular cAMP by different pathways and extracellular calcium produces positive inotropic effect by initiating the interaction between the contractile proteins actin and myosin. The study revealed that an increase in the concentration of extracellular calcium increased the additive effect of theophylline and isoproterenol combination, but a decrease in the myocardial responsiveness was observed.

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

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    Warispreet Singh


    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. Effects of Mutations on Structure-Function Relationships of Matrix Metalloproteinase-1. (United States)

    Singh, Warispreet; Fields, Gregg B; Christov, Christo Z; Karabencheva-Christova, Tatyana G


    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.


    Institute of Scientific and Technical Information of China (English)

    韩永年; 张欣欣; 陆志檬; 张东华


    Objective To explore the effects of mutations in tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif of the polymerase in the hepatitis B virus ( HBV) genome on lamivudine antiviral therapy. Methods Partial HBV DNA segment containing the YMDD motif in the P gene was obtained through amplification by polymerase chain reaction ( PCR ) from 19 chronic hepatitis B patients with serum HBV DNA positive at the 48th week treatment with lamivudine and subjected to automatic sequencing. Influences of variants with YMDD mutations on lamivudine therapy were seen by observing the dynamic changes of serum HBV DNA and ALT levels. Results Serum HBV DNA breakthrough was found in 3 out of 10 individuals with detection of the YMDD mutations at the 48th week and in 5 at the 52th week, 2 of the 5 patients accompanied by serum ALT re-elevation, whereas of 9 subjects without YMDD mutations, 2 experienced an HBV DNA breakthrough at the 48th week and 1 of them had a conversion from HBV DNA positive to negative at the 52th week. Patients with detectable HBV DNA level had a fluctuating level of serum ALT all time during the treatment. Conclusion Detection of mutations in the YMDD motif of polyrnerase gene in HBV genome during the lamivudine therapy will be helpful to monitoring its therapeutic outcomes.

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

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    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))


    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.

  1. Effect of single-site mutations on hydrophobic-polar lattice proteins (United States)

    Shi, Guangjie; Vogel, Thomas; Wüst, Thomas; Li, Ying Wai; Landau, David P.


    We developed a heuristic method for determining the ground-state degeneracy of hydrophobic-polar (HP) lattice proteins, based on Wang-Landau and multicanonical sampling. It is applied during comprehensive studies of single-site mutations in specific HP proteins with different sequences. The effects in which we are interested include structural changes in ground states, changes of ground-state energy, degeneracy, and thermodynamic properties of the system. With respect to mutations, both extremely sensitive and insensitive positions in the HP sequence have been found. That is, ground-state energies and degeneracies, as well as other thermodynamic and structural quantities, may be either largely unaffected or may change significantly due to mutation.

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

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    Gentilcore Giusy


    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.

  3. Joint effects of heavy metal binary mixtures on seed germination, root and shoot growth, bacterial bioluminescence, and gene mutation

    Institute of Scientific and Technical Information of China (English)

    In Chul Kong


    This investigation was to assess the joint effects of metal binary mixtures on seed germination,root and shoot growth,bacterial bioluminescence,and gene mutation based on the one toxic unit (1 TU) approach.Different sensitivities and orders of toxicity of metal mixtures were observed among the bioassays.In general,mostly additive or antagonistic effects were observed,while almost no synergistic effects by the binary metal mixtures in all bioassays.Therefore,the combined effects of heavy metals in the different bioassays were difficult to generalize since they were dependent on both chemical type and the organism used in each bioassay.However,these results indicate that a battery of bioassays with mixture chemicals as opposed to just a single assay with single metal is a better strategy for the bioassessment of environmental pollutants.

  4. 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


    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)

  5. Gaucher disease: Pseudoreversion of a disease mutation`s effects--implications for structure/function and genotype/phenotype correlations

    Energy Technology Data Exchange (ETDEWEB)

    Ponce, E.; Mear, J; Grabowski, G.A. [Children`s Hospital Research Foundation, Cincinnati, OH (United States)


    Numerous mutations ({approximately}45) of the acid {beta}-glucosidase gene have been identified in patients with Gaucher disease. Many of these have been characterized by partial sequencing of cDNAs derived by RT-PCR or PCR of genomic DNA. In addition, genotype/phenotype correlations have been based on screening for known mutations. Thus, only a part of the gene is characterized in any population of affected patients. Several Gaucher disease alleles contain multiple, authentic point mutations that raises concern about conclusions based on only partial genetic characterization. Several wild-type cDNAs for acid {beta}-glucosidase have been sequenced. One contained a cloning artifact encoding R495H. We expressed this cDNA and showed that the R495H enzyme had normal kinetic and stability properties. A disease-associated allele encoding R496H has been found by several groups. The close association and similarities of these two substitutions led us to question the disease casuality of the R496H allele. To evaluate this, we created and/or expressed cDNAs encoding R495, R496 (wild-type), (R495H, R496), (R495, R496H) and (R495H, R496H). The (wild-type) and (R495H, R496) enzymes had indistinguishable properties whereas the (R495, R496H) enzyme was essentially inactive. The introduction of both mutations (R495H, R496H) produced an enzyme whose activity was 25 to 50% of the wild-type. These results indicate that a pseudoreversion to a functional enzyme can occur by introducing a functionally neutral mutation together with a severe mutation. These results have major implications to structure/function and genotype/phenotype correlations in this disease.

  6. Prevalence of dominant mutations in Spain: effect of changes in maternal age distribution. (United States)

    Martínez-Frías, M L; Herranz, I; Salvador, J; Prieto, L; Ramos-Arroyo, M A; Rodríguez-Pinilla, E; Cordero, J F


    We studied the birth prevalence of autosomal dominant mutations in Spain and estimated how a decrease in maternal age distribution may lead to reduction in dominant mutations. The data were collected by the Estudio Colaborativo Español de Malformaciones Congénitas from April, 1976, to December, 1985. Among 553,270 liveborn infants monitored during the period, 66 infants with autosomal dominant conditions were identified. These included Apert, Crouzon, Hay-Wells, Treacher-Collins, Robinow, Stickler, Adams-Oliver, and the blepharophimosis syndromes, achondroplasia, cleidocranial dysostosis, and thanatophoric dysplasia. The overall rate of autosomal dominant conditions was 1.2 per 10,000 liveborn infants. Thirteen (20%) had an affected relative, and 52 (79%) had a negative family history. One case was excluded because of insufficient family data. The rate of autosomal dominant mutations was 0.9 per 10,000 liveborn infants, or 47 per 1 million gametes. A reduction in the maternal age distribution of mothers age 35 years and older from the current 10.8% to 4.9%, as in Atlanta, Georgia, would reduce the rate of Down syndrome in Spain by 33% and through a change in parternal age distribution may lead to a reduction in dominant mutations of about 9.6%. This suggests that a public health campaign to reduce older maternal age distribution in Spain may also lead to a reduction in dominant mutations and emphasizes the potential that a direct campaign for fathers to complete their families before age 35 years may have a small, but measurable, effect in the primary prevention of dominant mutations.

  7. The Mutation Breeding and Mutagenic Effect of Air Plasma on Penicillium Chrysogenum

    Institute of Scientific and Technical Information of China (English)

    桂芳; 王辉; 王鹏; 刘会; 蔡晓春; 胡以华; 袁成凌; 郑之明


    Low temperature air plasma was used as the mutation tool for penicillin-producing strain Penicillium chrysogenum. The discharge conditions were RF power of 360 W, temperature of 40℃ in a sealed chamber, and pressure of 10 Pa to 30 Pa. The result showed that the kinetics of the survival rate followed a typical saddle-shaped curve. Based on a statistic analysis, at the treating duration of 10 min, the positive mutation rate was as high as 37.5% while the negative mutation rate was low. The colonial morphology changed obviously when the plasma treating duration reached or exceeded 45 min. After both primary and secondary screening, a mutant designated as aPc051310 with high productivity of penicillin was obtained, and a strong mutagenic effect on P. chrysogenurn was observed in the process. It was proved that after five generations, the mutant aPc051310 still exhibits a high productivity. All the results prove that the plasma mutation method could be developed as a convenient and effective tool to breed high-yield strains in the fermentation industry, while expanding the plasm application at the same time.

  8. a/alpha-specific effect on the mms3 mutation on ultraviolet mutagenesis in Saccharomyces cerevisiae. (United States)

    Martin, P; Prakash, L; Prakash, S


    A new gene involved in error-prone repair of ultraviolet (UV) damage has been identified in Saccharomyces cerevisiae by the mms3-1 mutation. UV-induced reversion is reduced in diploids that are homozygous for mms3-1, only if they are also heterozygous (MATa/MAT alpha) at the mating type locus. The mms3-1 mutation has no effect on UV-induced reversion either in haploids or MATa/MATa or MAT alpha/MAT alpha diploids. The mutation confers sensitivity to UV and methyl methane sulfonate in both haploids and diploids. Even though mutation induction by UV is restored to wild-type levels in MATa/MATa mms3-1/mms3-1 or MAT alpha/MAT alpha mms3-1/mms3-1 diploids, such strains still retain sensitivity to the lethal effects of UV. Survival after UV irradiation in mms3-1 rad double mutant combinations indicates that mms3-1 is epistatic to rad6-1 whereas non-epistatic interactions are observed with rad3 and rad52 mutants. When present in the homozygous state in MATa/MAT alpha his1-1/his1-315 heteroallelic diploids, mms3-1 was found to lower UV-induced mitotic recombination.

  9. Measuring epistasis in fitness landscapes: The correlation of fitness effects of mutations. (United States)

    Ferretti, Luca; Schmiegelt, Benjamin; Weinreich, Daniel; Yamauchi, Atsushi; Kobayashi, Yutaka; Tajima, Fumio; Achaz, Guillaume


    Genotypic fitness landscapes are constructed by assessing the fitness of all possible combinations of a given number of mutations. In the last years, several experimental fitness landscapes have been completely resolved. As fitness landscapes are high-dimensional, simple measures of their structure are used as statistics in empirical applications. Epistasis is one of the most relevant features of fitness landscapes. Here we propose a new natural measure of the amount of epistasis based on the correlation of fitness effects of mutations. This measure has a natural interpretation, captures well the interaction between mutations and can be obtained analytically for most landscape models. We discuss how this measure is related to previous measures of epistasis (number of peaks, roughness/slope, fraction of sign epistasis, Fourier-Walsh spectrum) and how it can be easily extended to landscapes with missing data or with fitness ranks only. Furthermore, the dependence of the correlation of fitness effects on mutational distance contains interesting information about the patterns of epistasis. This dependence can be used to uncover the amount and nature of epistatic interactions in a landscape or to discriminate between different landscape models.

  10. The Mutation Breeding and Mutagenic Effect of Air Plasma on Penicillium Chrysogenum (United States)

    Gui, Fang; Wang, Hui; Wang, Peng; Liu, Hui; Cai, Xiaochun; Hu, Yihua; Yuan, Chengling; Zheng, Zhiming


    Low temperature air plasma was used as the mutation tool for penicillin-producing strain Penicillium chrysogenum. The discharge conditions were RF power of 360 W, temperature of 40°C in a sealed chamber, and pressure of 10 Pa to 30 Pa. The result showed that the kinetics of the survival rate followed a typical saddle-shaped curve. Based on a statistic analysis, at the treating duration of 10 min, the positive mutation rate was as high as 37.5% while the negative mutation rate was low. The colonial morphology changed obviously when the plasma treating duration reached or exceeded 45 min. After both primary and secondary screening, a mutant designated as aPc051310 with high productivity of penicillin was obtained, and a strong mutagenic effect on P. chrysogenum was observed in the process. It was proved that after five generations, the mutant aPc051310 still exhibits a high productivity. All the results prove that the plasma mutation method could be developed as a convenient and effective tool to breed high-yield strains in the fermentation industry, while expanding the plasm application at the same time.

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

    Directory of Open Access Journals (Sweden)

    Kapoor S


    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

  12. Long-Range Structural Effects of a Charcot-Marie-Tooth Disease-Causing Mutation in Human Glycyl-TRNA Synthetase

    Energy Technology Data Exchange (ETDEWEB)

    Xie, W.; Nangle, L.A.; Zhang, W.; Schimmel, P.; Yang, X.-L.


    Functional expansion of specific tRNA synthetases in higher organisms is well documented. These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system. At least 10 disease-causing mutant alleles of GlyRS have been annotated. These mutations scatter broadly across the primary sequence and have no apparent unifying connection. Here we report the structure of wild type and a CMT-causing mutant (G526R) of homodimeric human GlyRS. The mutation is at the site for synthesis of glycyl-adenylate, but the rest of the two structures are closely similar. Significantly, the mutant form diffracts to a higher resolution and has a greater dimer interface. The extra dimer interactions are located {approx}30 {angstrom} away from the G526R mutation. Direct experiments confirm the tighter dimer interaction of the G526R protein. The results suggest the possible importance of subtle, long-range structural effects of CMT-causing mutations at the dimer interface. From analysis of a third crystal, an appended motif, found in higher eukaryote GlyRSs, seems not to have a role in these long-range effects.

  13. MHC class IIB additive and non-additive effects on fitness measures in the guppy Poecilia reticulata. (United States)

    Fraser, B A; Neff, B D


    The genetic architecture of fitness at the class IIB gene of the major histocompatibility complex (MHC) in the guppy Poecilia reticulata was analysed. Diversity at the MHC is thought to be maintained by some form of balancing selection; heterozygote advantage, frequency-dependent selection or spatially and temporally fluctuating selection. Here these hypotheses are evaluated by using an algorithm that partitions the effect of specific MHC allele and genotypes on fitness measures. The effect of MHC genotype on surrogate measures of fitness was tested, including growth rate (at high and low bulk food diets), parasite load following a parasite challenge and survival. The number of copies of the Pore_a132 MHC allele was inversely related to infection by Gyrodactylus flukes and it appeared to be positively related to faster growth. Also, genotypes combining the Pore_a132 or other relatively common alleles paired with rare MHC alleles produced both advantageous and detrimental non-additive effects. Thus, the genetic architecture underlying fitness at the MHC is complex in the P. reticulata.

  14. Transcription-induced mutational strand bias and its effect on substitution rates in human genes. (United States)

    Mugal, Carina F; von Grünberg, Hans-Hennig; Peifer, Martin


    If substitution rates are not the same on the two complementary DNA strands, a substitution is considered strand asymmetric. Such substitutional strand asymmetries are determined here for the three most frequent types of substitution on the human genome (C --> T, A --> G, and G --> T). Substitution rate differences between both strands are estimated for 4,590 human genes by aligning all repeats occurring within the introns with their ancestral consensus sequences. For 1,630 of these genes, both coding strand and noncoding strand rates could be compared with rates in gene-flanking regions. All three rates considered are found to be on average higher on the coding strand and lower on the transcribed strand in comparison to their values in the gene-flanking regions. This finding points to the simultaneous action of rate-increasing effects on the coding strand--such as increased adenine and cytosine deamination--and transcription-coupled repair as a rate-reducing effect on the transcribed strand. The common behavior of the three rates leads to strong correlations of the rate asymmetries: Whenever one rate is strand biased, the other two rates are likely to show the same bias. Furthermore, we determine all three rate asymmetries as a function of time: the A --> G and G --> T rate asymmetries are both found to be constant in time, whereas the C --> T rate asymmetry shows a pronounced time dependence, an observation that explains the difference between our results and those of an earlier work by Green et al. (2003. Transcription-associated mutational asymmetry in mammalian evolution. Nat Genet. 33:514-517.). Finally, we show that in addition to transcription also the replication process biases the substitution rates in genes.

  15. Variation in the fitness effects of mutations with population density and size in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Huansheng Cao

    Full Text Available The fitness effects of mutations are context specific and depend on both external (e.g., environment and internal (e.g., cellular stress, genetic background factors. The influence of population size and density on fitness effects are unknown, despite the central role population size plays in the supply and fixation of mutations. We addressed this issue by comparing the fitness of 92 Keio strains (Escherichia coli K12 single gene knockouts at comparatively high (1.2×10(7 CFUs/mL and low (2.5×10(2 CFUs/mL densities, which also differed in population size (high: 1.2×10(8; low: 1.25×10(3. Twenty-eight gene deletions (30% exhibited a fitness difference, ranging from 5 to 174% (median: 35%, between the high and low densities. Our analyses suggest this variation among gene deletions in fitness responses reflected in part both gene orientation and function, of the gene properties we examined (genomic position, length, orientation, and function. Although we could not determine the relative effects of population density and size, our results suggest fitness effects of mutations vary with these two factors, and this variation is gene-specific. Besides being a mechanism for density-dependent selection (r-K selection, the dependence of fitness effects on population density and size has implications for any population that varies in size over time, including populations undergoing evolutionary rescue, species invasions into novel habitats, and cancer progression and metastasis. Further, combined with recent advances in understanding the roles of other context-specific factors in the fitness effects of mutations, our results will help address theoretical and applied biological questions more realistically.

  16. Segregation pattern and biochemical effect of the G3460A mtDNA mutation in 27 members of LHON family. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Rajkumar Revathi


    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.

  18. Cochlear implantation effect on deaf children with gap junction protein beta 2 gene mutation

    Institute of Scientific and Technical Information of China (English)

    KONG Ying; LIU Sha; WANG Su-ju; Li Shu-jing; LIANG Shuang


    Background The popularization and promotion of gene diagnosis technology makes it possible to detect deafness genes for children with congenital hearing impairment,and the proportion of gap junction protein beta 2 (GJB2) gene mutations in cochlear implant patients is 26.5% We did follow-up evaluation on auditory rehabilitation effect for all 31 deaf children with GJB2 gene mutation after cochlear implantation to provide a reference for such patients.Methods Application of “the genetic deafness gene chip detection kit” and “gene complete sequence analysis” were applied to conduct detection on common genetic deafness gene mutation hotspots of the hearing impaired children with cochlear implantation.To conduct auditory rehabilitation effect evaluation on all 31 cases of patients with GJB2 genetic deafness after 3,6 and 12 months of the operation respectively.The single factor repeated measure analysis of variance (ANOVA) was applied to analysis whether there were significant difference among the results of initial consonant of a Chinese syllable recognition at 3 different stages after the operation,the results of vowel of a Chinese syllable recognition at 3 different stages after the operation,and the results of two-syllable recognition at 3 different stages after the operation.Results The 235delC is the high-incidence mutational site in 31 cases of patients with GJB2 genetic deafness,and the total detection rate is up to 90.3% (28/31).There were significant differences in the initial consonant and the vowel of a Chinese syllable recognition rate,and the two-syllable recognition rates at 3,6,and 12 months after the operation (P<0.01).Conclusion Cochlear implantation is a safe and effective measure for auditory reconstruction,enabling patients with GJB2 hereditary severe sensorineural deafness to achieve auditory speech recognition effectively.

  19. In silico analysis of alpha1-antitrypsin variants: the effects of a novel mutation

    Directory of Open Access Journals (Sweden)

    Sabri Denden


    Full Text Available Alpha1-antitrypsin (AAT is a highly polymorphic protein with more than 120 variants that are classified as normal (normal protein secretion, deficient (reduced circulating AAT level caused by defective secretion or null (no protein secretion. Alpha1-antitrypsin deficiency, one of the most common genetic disorders, predisposes adults to pulmonary emphysema and, to a lesser extent, chronic liver disease and cirrhosis. In this report, we provide additional sequence data for alpha1-antitrypsin based on the characterization of a novel variant detected in a 53-year-old heterozygous patient with chronic obstructive pulmonary disease. The mutation occurred on a PI*M2 base allele and was characterized by a T → C transition at nt 97 in exon II that led to the replacement of phenylalanine by leucine (F33L. Since the mutation was found in the heterozygous state with the expression of a normally secreted variant (PI*M1 it was not possible to assess the pattern of F33L secretion. However, computational analyses based on evolutionary, structural and functional information indicated a reduction of 23 ų in the side chain volume and the creation of a cavity in the protein hydrophobic core that likely disturbed the tridimensional structure and folding of AAT. The accuracy of the in silico prediction was confirmed by testing known mutations.

  20. Profound Effects of Aggregatibacter actinomycetemcomitans Leukotoxin Mutation on Adherence Properties Are Clarified in in vitro Experiments. (United States)

    Velusamy, Senthil Kumar; Sampathkumar, Vandana; Godboley, Dipti; Fine, Daniel H


    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 (Phard 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) some caution should be used when interpreting the effect attributed to targeted gene mutations when seen in a competitive in vivo environment.

  1. Effect of pathogenic mutations on the structure and dynamics of Alzheimer's A beta 42-amyloid oligomers. (United States)

    Kassler, Kristin; Horn, Anselm H C; Sticht, Heinrich


    Converging lines of evidence suggest that soluble A beta-amyloid oligomers play a pivotal role in the pathogenesis of Alzheimer's disease, and present direct effectors of synaptic and cognitive dysfunction. Three pathological E22-A beta-amyloid point mutants (E22G, E22K, E22Q) and the deletion mutant E22 Delta exhibit an enhanced tendency to form prefibrillar aggregates. The present study assessed the effect of these four mutations using molecular dynamics simulations and subsequent structural and energetic analyses. Our data shows that E22 plays a unique role in wild type A beta, since it has a destabilising effect on the oligomer structure due to electrostatic repulsion between adjacent E22 side chains. Mutations in which E22 is replaced by an uncharged residue result in higher oligomer stability. This effect is also observed to a lesser extent for the E22K mutation and is consistent with its lower pathogenicity compared to other mutants. Interestingly, deletion of E22 does not destroy the amyloid fold but is compensated by local changes in the backbone geometry that allow the preservation of a structurally important salt bridge. The finding that all mutant oligomers investigated exhibit higher internal stability than the wild type offers an explanation for the experimentally observed enhanced oligomer formation and stability.

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

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


    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. Sequence context of indel mutations and their effect on protein evolution in a bacterial endosymbiont. (United States)

    Williams, Laura E; Wernegreen, Jennifer J


    Indel mutations play key roles in genome and protein evolution, yet we lack a comprehensive understanding of how indels impact evolutionary processes. Genome-wide analyses enabled by next-generation sequencing can clarify the context and effect of indels, thereby integrating a more detailed consideration of indels with our knowledge of nucleotide substitutions. To this end, we sequenced Blochmannia chromaiodes, an obligate bacterial endosymbiont of carpenter ants, and compared it with the close relative, B. pennsylvanicus. The genetic distance between these species is small enough for accurate whole genome alignment but large enough to provide a meaningful spectrum of indel mutations. We found that indels are subjected to purifying selection in coding regions and even intergenic regions, which show a reduced rate of indel base pairs per kilobase compared with nonfunctional pseudogenes. Indels occur almost exclusively in repeat regions composed of homopolymers and multimeric simple sequence repeats, demonstrating the importance of sequence context for indel mutations. Despite purifying selection, some indels occur in protein-coding genes. Most are multiples of three, indicating selective pressure to maintain the reading frame. The deleterious effect of frameshift-inducing indels is minimized by either compensation from a nearby indel to restore reading frame or the indel's location near the 3'-end of the gene. We observed amino acid divergence exceeding nucleotide divergence in regions affected by frameshift-inducing indels, suggesting that these indels may either drive adaptive protein evolution or initiate gene degradation. Our results shed light on how indel mutations impact processes of molecular evolution underlying endosymbiont genome evolution.

  4. The novel R347g pathogenic mutation of aromatic amino acid decarboxylase provides additional molecular insights into enzyme catalysis and deficiency. (United States)

    Montioli, Riccardo; Paiardini, Alessandro; Kurian, Manju A; Dindo, Mirco; Rossignoli, Giada; Heales, Simon J R; Pope, Simon; Voltattorni, Carla Borri; Bertoldi, Mariarita


    We report here a clinical case of a patient with a novel mutation (Arg347→Gly) in the gene encoding aromatic amino acid decarboxylase (AADC) that is associated with AADC deficiency. The variant R347G in the purified recombinant form exhibits, similarly to the pathogenic mutation R347Q previously studied, a 475-fold drop of kcat compared to the wild-type enzyme. In attempting to unravel the reason(s) for this catalytic defect, we have carried out bioinformatics analyses of the crystal structure of AADC-carbidopa complex with the modelled catalytic loop (residues 328-339). Arg347 appears to interact with Phe103, as well as with both Leu333 and Asp345. We have then prepared and characterized the artificial F103L, R347K and D345A mutants. F103L, D345A and R347K exhibit about 13-, 97-, and 345-fold kcat decrease compared to the wild-type AADC, respectively. However, unlike F103L, the R347G, R347K and R347Q mutants as well as the D345A variant appear to be more defective in catalysis than in protein folding. Moreover, the latter mutants, unlike the wild-type protein and the F103L variant, share a peculiar binding mode of dopa methyl ester consisting of formation of a quinonoid intermediate. This finding strongly suggests that their catalytic defects are mainly due to a misplacement of the substrate at the active site. Taken together, our results highlight the importance of the Arg347-Leu333-Asp345 hydrogen-bonds network in the catalysis of AADC and reveal the molecular basis for the pathogenicity of the variants R347. Following the above results, a therapeutic treatment for patients bearing the mutation R347G is proposed.

  5. Multiple oncogenic mutations related to targeted therapy in nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian-Wei Zhang; Hong-Yuan Zhao; Yu-Xiang Ma; Zhi-Huang Hu; Pei-Yu Huang; Li Zhang; Tao Qin; Shao-Dong Hong; Jing Zhang; Wen-Feng Fang; Yuan-Yuan Zhao; Yun-Peng Yang; Cong Xue; Yan Huang


    Introduction:An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related oncogenic mutations have not been fully evaluated. This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC. Methods:By using the SNaPshot assay, a rapid detection method, 19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients. The associations between oncogenic mutations and clinicopathologic factors were analyzed. Results:Among 70 patients, 12 (17.1%) had mutations in 5 oncogenes:7 (10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation, 2 (2.8%) had epidermal growth factor receptor (EGFR) mutation, 1 (1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, 1 (1.4%) had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and 1 (1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. No significant differences were observed between oncogenic mutations and clinicopathologic characteristics. Additionally, these oncogenic mutations were not associated with tumor recurrence and metastasis. Conclusions:Oncogenic mutations are present in NPC patients. The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.

  6. Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases

    NARCIS (Netherlands)

    Lenz, Tobias L; Deutsch, Aaron J; Han, Buhm; Hu, Xinli; Okada, Yukinori; Eyre, Stephen; Knapp, Michael; Zhernakova, Alexandra; Huizinga, Tom W J; Abecasis, Gonçalo; Becker, Jessica; Boeckxstaens, Guy E; Chen, Wei-Min; Franke, Andre; Gladman, Dafna D; Gockel, Ines; Gutierrez-Achury, Javier; Martin, Javier; Nair, Rajan P; Nöthen, Markus M; Onengut-Gumuscu, Suna; Rahman, Proton; Rantapää-Dahlqvist, Solbritt; Stuart, Philip E; Tsoi, Lam C; van Heel, David A; Worthington, Jane; Wouters, Mira M; Klareskog, Lars; Elder, James T; Gregersen, Peter K; Schumacher, Johannes; Rich, Stephen S; Wijmenga, Cisca; Sunyaev, Shamil R; de Bakker, Paul I W; Raychaudhuri, Soumya


    Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the

  7. The effects of expression of an activated rasG mutation on the differentiation of Dictyostelium. (United States)

    Thiery, R; Robbins, S; Khosla, M; Spiegelman, G B; Weeks, G


    Dictyostelium discoideum contains two ras genes, rasG and rasD, that are expressed during growth and differentiation, respectively. It was shown previously that Dictyostelium transformants expressing an activated rasD gene (a mutation producing a change in amino acid 12 from glycine to threonine) developed abnormally. When developed on filters these transformants formed multitipped aggregates, which did not go on to produce final fruiting bodies, but in a submerged culture assay on a plastic surface they either formed small aggregates or did not aggregate. In this study we transformed cells with the rasG gene, mutated to change amino acid 12 from glycine to threonine. The resulting transformants developed normally on filters, but aggregation under other conditions was impaired. In particular, in submerged culture on a plastic surface they either produced very small aggregates or did not aggregate, one of the phenotypes exhibited by the activated rasD transformants. Molecular analysis of the transformants revealed the presence of high copy numbers of the mutated rasG gene, but the level of expression of the mutant gene never exceeded the level of expression of the endogenous gene. These results indicate a powerful dominant effect of a relatively small amount of the activated RasG protein in Dictyostelium.

  8. Conformational Effects of the A21G Flemish Mutation on the Aggregation of Amyloid β Peptide. (United States)

    Yagi-Utsumi, Maho; Dobson, Christopher M


    Among the various hereditary mutants of amyloid β (Aβ) in familial Alzheimer's disease (AD), the A21G Flemish-type mutant has unique properties showing a low aggregation propensity but progressive deposition in vascular walls. Moreover, in contrast to other familial AD cases that show extensive Aβ1-42 deposition in the brain, patients with Flemish AD predominantly exhibit the deposition of the Aβ1-40 isoform. Here we report the structural characterization of the Flemish-type mutant (A21G) in comparison with the wild-type Aβ1-40 peptide to examine the possible effects of the A21G mutation on the conformation of the Aβ1-40 isoform. The kinetic analysis of the aggregation of the peptides monitored by thioflavin T fluorescence measurement indicates that the mutation precludes the initial nucleation process of amyloid fibril formation by Aβ1-40. Spectroscopic data indicate that the Flemish-type mutant bound to aqueous micelles composed of lyso-GM1, in which the mobile N-terminal segment is tethered through the C-terminal helical segment, has reduced α-helical structure compared to the wild-type peptide. Our findings suggest that the mutational perturbation to the membrane binding properties is coupled with the changes in nucleation behavior of Aβ during its fibril formation.

  9. A study on effective use of heat transfer additives in the process of steam condensation

    Energy Technology Data Exchange (ETDEWEB)

    Vemuri, Srinivas; Kim, Kwang J. [Department of Mechanical Engineering, University of Nevada, Reno, NV 89557 (United States); Kang, Yong Tae [Department of Mechanical and Industrial Systems Engineering, KyungHee University, KyungHee (Korea, Republic of)


    It is well known that the additives in absorption chillers play a significant role in increasing absorber performance. Realizing that the additives in absorption chillers circulate throughout the system including the condensers, we investigated the effect of additives in the condenser. Reported herein are the results of the experimental and theoretical investigations done by using effective heat transfer additives for enhancing heat transfer coefficient in condensation of steam over a horizontal copper (99.9% Cu, 0.1% P) tube surface. By using effective additives, the condensation heat transfer coefficient can be enhanced as much as 1.47 times when compared to filmwise condensation. The steam condensation, which occurred in our experiments while using effective additives, was mostly pseudo-dropwise like. In our experiments, we noted that the use of heat transfer additive such as 2-ethoxyethanol for steam condensation was highly effective. This increase in heat transfer coefficient can be attributed to concept of Marangoni effect. It is understood that this surface convection is caused by local variations in the interfacial tension. So far there has been very little noted literature available on the theoretical aspect of surface tension effect on enhancing heat transfer rate in steam condensation. In the current research we try to explain the surface tension effect for enhancing heat transfer rate in steam condensation using effective heat transfer additives. (author)

  10. Effect of point mutations on Herbaspirillum seropedicae NifA activity

    Directory of Open Access Journals (Sweden)

    B. Aquino


    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.

  11. 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)


    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.

  12. The additive and interactive effects of parenting and children's personality on externalizing behaviour

    NARCIS (Netherlands)

    Prinzie, P; Onghena, P; Hellinckx, W; Grietens, H; Ghesquiere, P; Colpin, H


    Parenting practices have been previously linked to childhood externalizing behaviour However little attention has been given to the potential effect of individual personality differences among children on this relation. The current study assesses the additive effects of children's personality charac

  13. Effect of small additions of vanadium and niobium on structure and mechanical properties of ductile iron

    Directory of Open Access Journals (Sweden)

    Fraś E.


    Full Text Available Results of investigations of influence of small additions of vanadium (up to 0,15 % V and niobium (up to 0,04% Nb on structure of ductile iron is presented in this work. Effect of these additions on distribution of graphite nodule diameter, nodule count, fraction and carbide count have been determined. Investigations of effect of small additions of vanadium and niobium on mechanical properties taking into account tensile strength, yield strength and elongation have also been made.

  14. Effect of Y220C mutation on p53 and its rescue mechanism: a computer chemistry approach. (United States)

    Rauf, Shah Md Abdur; Endou, Akira; Takaba, Hiromitsu; Miyamoto, Akira


    Mutation causes inactivation of 'p53' tumor suppressor protein in almost fifty percent of cancers in humans. Outside the DNA-binding surface of p53, Y220C is the most common cancerous mutation. Previous studies have shown that a surface cavity is created by this mutation which destabilizes p53. PhiKan083, a carbazole derivative capable of binding with that cavity, and slows down its thermal denaturation rate. We investigated, theoretically, on mechanisms of structural stability loss due to Y220C mutation and mechanisms of stability restoration by PhiKan083 at the atomic level. From this study it is found that in Tp53C, Tyr220 has five electrostatic interactions with residues Val 147, Prol51, Pro153 and Pro223 located on S3/S4 loop and S7/S8 loop. The S7/S8 loop is stabilized by these electrostatic interactions. Due to the Y220C mutation all these electrostatic interactions are lost. As a result the structural fluctuation occurs at S7/S8 loop, and the loop is displaced from its original position after 6 ns MD simulation. When PhiKan083 is present (inserted) at the mutation site it provides five electrostatic interactions with Pro155, Glu221 and Thr230, and two hydrogen bonds with Leu145 and Asp228, respectively. These interactions provided by Pkikan083 stabilized the S7/S8 loop, and as a result it couldn't be displaced. Our results showed that due to Y220C mutation p53 became destabilized through structural fluctuations surrounding the mutation site. When PhiKan083 is present at the Y220C mutation site (in 2vuk), it provides electrostatic and hydrogen bonding interactions among residue-220, its neighboring residues and PhiKan08. These interactions give additional stability to Y220C mutant p53, thus Y220C mutant p53 doesn't destabilize.

  15. Specific effects of BCL10 Serine mutations on phosphorylations in canonical and noncanonical pathways of NF-κB activation following carrageenan (United States)

    Bhattacharyya, Sumit; Borthakur, Alip; Anbazhagan, Arivarasu N.; Katyal, Shivani; Dudeja, Pradeep K.


    To determine the impact of B cell leukemia/lymphoma (BCL) 10 on the phosphorylation of crucial mediators in NF-κB-mediated inflammatory pathways, human colonic epithelial cells were exposed to carrageenan (CGN), a sulfated polysaccharide commonly used as a food additive and known to induce NF-κB nuclear translocation by both canonical and noncanonical pathways. Phosphorylations of intermediates in inflammatory cascades, including NF-κB-inducing kinase (NIK) at Thr559, transforming growth factor-β-activating kinase (TAK) 1 at Thr184, Thr187, and Ser192, and inhibitory factor κBα (IκBα) at Ser32, were examined following mutation of BCL10 at Ser138 and at Ser218. Specific phosphoantibodies were used for detection by enzyme-linked immunosorbent assay, immunoblot, and confocal microscopy of differences in phosphorylation following transfection by mutated BCL10. Both mutations demonstrated dominant-negative effects, with inhibition of phospho(Ser32)-IκBα to less than control levels. Both of the BCL10 mutations reduced the CGN-induced increases in nuclear RelA and p50, but only the Ser138 mutation inhibited the CGN-induced increases in nuclear RelB and p52 and in NIK Thr559 phosphorylation. Hence, the phosphorylation of BCL10 Ser138, but not Ser218, emerged as a critical event in activation of the noncanonical pathway of NF-κB activation. Either BCL10 Ser138 or Ser218 mutation inhibited the phosphorylation of TAK1 at Thr184 and at Thr187, but not at Ser192. These findings indicate that BCL10 phosphorylations act upstream of phosphorylations of NIK, TAK1, and IκBα and differentially affect the canonical and noncanonical pathways of NF-κB activation. PMID:21700900

  16. Concrete with the addition of a high level of fly ash and effect of the additive on the concrete

    Energy Technology Data Exchange (ETDEWEB)

    Salcedo Lorente, A.J.


    Flyash is usually considered an acceptable substitute for Portland cement in concrete mixtures. However, this article is studying a type of concrete in which flyash makes up between 40 and 80% of the total weight of the conglomerate material, being considered as an additional ingredient to Portland cement, aggregates and water as well as requiring different proportions. 42 refs., 9 figs., 7 tabs.

  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;


    , 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...

  18. 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

  19. Primary congenital glaucoma and Rieger's anomaly: extended haplotypes reveal founder effects for eight distinct CYP1B1 mutations


    Chavarria-Soley, G.; Michels-Rautenstrauss, K.; Pasutto, F; Flikier, D.; Flikier, P.; Cirak, S; Bejjani, B.; Winters, D.; Lewis, R; Mardin, C.; Reis, A; Rautenstrauss, B.


    PURPOSE: Mutations in the cytochrome P450 1B1 (CYP1B1) gene are a frequent cause of primary congenital glaucoma (PCG) in different ethnic groups. Cytochrome P450 proteins are monooxygenases, which catalyze many reactions involved in the metabolism of drugs as well as steroids and other lipids. The repeated occurence of several mutations in various ethnic groups raises the question if founder effects or mutation-prone sites in CYP1B1 are the cause for this observation.METHODS: A total of 30 in...

  20. The Mutational Robustness of Influenza A Virus (United States)

    McCrone, John T.; Lauring, Adam S.


    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. PMID:27571422

  1. Modeling tissue- and mutation- specific electrophysiological effects in the long QT syndrome: role of the Purkinje fiber.

    Directory of Open Access Journals (Sweden)

    Vivek Iyer

    Full Text Available Congenital long QT syndrome is a heritable family of arrhythmias caused by mutations in 13 genes encoding ion channel complex proteins. Mounting evidence has implicated the Purkinje fiber network in the genesis of ventricular arrhythmias. In this study, we explore the hypothesis that long QT mutations can demonstrate different phenotypes depending on the tissue type of expression. Using computational models of the human ventricular myocyte and the Purkinje fiber cell, the biophysical alteration in channel function in LQT1, LQT2, LQT3, and LQT7 are modeled. We identified that the plateau potential was important in LQT1 and LQT2, in which mutation led to minimal action potential prolongation in Purkinje fiber cells. The phenotype of LQT3 mutation was dependent on the biophysical alteration induced as well as tissue type. The canonical ΔKPQ mutation causes severe action potential prolongation in both tissue types. For LQT3 mutation F1473C, characterized by shifted channel availability, a more severe phenotype was seen in Purkinje fiber cells with action potential prolongation and early afterdepolarizations. The LQT3 mutation S1904L demonstrated striking effects on action potential duration restitution and more severe action potential prolongation in Purkinje fiber cells at higher heart rates. Voltage clamp simulations highlight the mechanism of effect of these mutations in different tissue types, and impact of drug therapy is explored. We conclude that arrhythmia formation in long QT syndrome may depend not only on the basis of mutation and biophysical alteration, but also upon tissue of expression. The Purkinje fiber network may represent an important therapeutic target in the management of patients with heritable channelopathies.

  2. Probing the effect of MODY mutations near the co-activator-binding pocket of HNF4α. (United States)

    Rha, Geun Bae; Wu, Guangteng; Chi, Young-In


    HNF4α (hepatocyte nuclear factor 4α) is a culprit gene product for a monogenic and dominantly inherited form of diabetes, referred to as MODY (maturity onset diabetes of the young). As a member of the NR (nuclear receptor) superfamily, HNF4α recruits transcriptional co-activators such as SRC-1α (steroid receptor co-activator-1α) and PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) through the LXXLL-binding motifs for its transactivation, and our recent crystal structures of the complex provided the molecular details and the mechanistic insights into these co-activator recruitments. Several mutations have been identified from the MODY patients and, among these, point mutations can be very instructive site-specific measures of protein function and structure. Thus, in the present study, we probed the functional effects of the two MODY point mutations (D206Y and M364R) found directly near the LXXLL motif-binding site by conducting a series of experiments on their structural integrity and specific functional roles such as overall transcription, ligand selectivity, target gene recognition and co-activator recruitment. While the D206Y mutation has a subtle effect, the M364R mutation significantly impaired the overall transactivation by HNF4α. These functional disruptions are mainly due to their reduced ability to recruit co-activators and lowered protein stability (only with M364R mutation), while their DNA-binding activities and ligand selectivities are preserved. These results confirmed our structural predictions and proved that MODY mutations are loss-of-function mutations leading to impaired β-cell function. These findings should help target selective residues for correcting mutational defects or modulating the overall activity of HNF4α as a means of therapeutic intervention.

  3. Rifampicin-Resistance Mutations in the rpoB Gene in Bacillus velezensis CC09 have Pleiotropic Effects (United States)

    Cai, Xun-Chao; Xi, Huan; Liang, Li; Liu, Jia-Dong; Liu, Chang-Hong; Xue, Ya-Rong; Yu, Xiang-Yang


    Rifampicin resistance (Rifr) mutations in the RNA polymerase β subunit (rpoB) gene exhibit pleiotropic phenotypes as a result of their effects on the transcription machinery in prokaryotes. However, the differences in the effects of the mutations on the physiology and metabolism of the bacteria remain unknown. In this study, we isolated seven Rifr mutations in rpoB, including six single point mutations (H485Y, H485C, H485D, H485R, Q472R, and S490L) and one double point mutation (S490L/S617F) from vegetative cells of an endophytic strain, Bacillus velezensis CC09. Compared to the wild-type (WT) strain (CC09), the H485R and H485D mutants exhibited a higher degree of inhibition of Aspergillus niger spore germination, while the H485Y, S490L, Q472R, and S490L/S617F mutants exhibited a lower degree of inhibition due to their lower production of the antibiotic iturin A. These mutants all exhibited defective phenotypes in terms of pellicle formation, sporulation, and swarming motility. A hierarchical clustering analysis of the observed phenotypes indicated that the four mutations involving amino acid substitutions at H485 in RpoB belonged to the same cluster. In contrast, the S490L and Q472R mutations, as well as the WT strain, were in another cluster, indicating a functional connection between the mutations in B. velezensis and phenotypic changes. Our data suggest that Rifr mutations cannot only be used to study transcriptional regulation mechanisms, but can also serve as a tool to increase the production of bioactive metabolites in B. velezensis. PMID:28243227

  4. The state of the art on zinc addition effect in the nuclear reactor coolant system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, U. C.; Sung, K. W.; Kim, K. R.; Paek, S.; Maeng, W. Y


    Zinc addition to the primary coolant appears promising with regard to reducing radiation dose rate, and is being used in several plants. Zinc acts to inhibit the corrosion of stainless steel by forming a thin protective film. This oxide film, with no associated increase in cobalt concentration within the film, thereby lowers the dose rate. This report on the state of art presents an overview of the zinc addition to the reactor coolant to reduce the primary system dose rate. This report discusses the effect of zinc addition for BWRs and PWRs, the thermodynamic of zinc chemistry, and the effect of zinc addition on material corrosion. (author)

  5. Structural and energetic effects of A2A adenosine receptor mutations on agonist and antagonist binding.

    Directory of Open Access Journals (Sweden)

    Henrik Keränen

    Full Text Available To predict structural and energetic effects of point mutations on ligand binding is of considerable interest in biochemistry and pharmacology. This is not only useful in connection with site-directed mutagenesis experiments, but could also allow interpretation and prediction of individual responses to drug treatment. For G-protein coupled receptors systematic mutagenesis has provided the major part of functional data as structural information until recently has been very limited. For the pharmacologically important A(2A adenosine receptor, extensive site-directed mutagenesis data on agonist and antagonist binding is available and crystal structures of both types of complexes have been determined. Here, we employ a computational strategy, based on molecular dynamics free energy simulations, to rationalize and interpret available alanine-scanning experiments for both agonist and antagonist binding to this receptor. These computer simulations show excellent agreement with the experimental data and, most importantly, reveal the molecular details behind the observed effects which are often not immediately evident from the crystal structures. The work further provides a distinct validation of the computational strategy used to assess effects of point-mutations on ligand binding. It also highlights the importance of considering not only protein-ligand interactions but also those mediated by solvent water molecules, in ligand design projects.

  6. 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.

  7. Differential effects of genistein on prostate cancer cells depend on mutational status of the androgen receptor. (United States)

    Mahmoud, Abeer M; Zhu, Tian; Parray, Aijaz; Siddique, Hifzur R; Yang, Wancai; Saleem, Mohammad; Bosland, Maarten C


    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.

  8. L30A Mutation of Phospholemman Mimics Effects of Cardiac Glycosides in Isolated Cardiomyocytes. (United States)

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


    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.

  9. The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation. (United States)

    Molenaar, Remco J; Radivoyevitch, Tomas; Maciejewski, Jaroslaw P; van Noorden, Cornelis J F; Bleeker, Fonnet E


    Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key events in the development of glioma, acute myeloid leukemia (AML), chondrosarcoma, intrahepatic cholangiocarcinoma (ICC), and angioimmunoblastic T-cell lymphoma. They also cause D-2-hydroxyglutaric aciduria and Ollier and Maffucci syndromes. IDH1/2 mutations are associated with prolonged survival in glioma and in ICC, but not in AML. The reason for this is unknown. In their wild-type forms, IDH1 and IDH2 convert isocitrate and NADP(+) to α-ketoglutarate (αKG) and NADPH. Missense mutations in the active sites of these enzymes induce a neo-enzymatic reaction wherein NADPH reduces αKG to D-2-hydroxyglutarate (D-2HG). The resulting D-2HG accumulation leads to hypoxia-inducible factor 1α degradation, and changes in epigenetics and extracellular matrix homeostasis. Such mutations also imply less NADPH production capacity. Each of these effects could play a role in cancer formation. Here, we provide an overview of the literature and discuss which downstream molecular effects are likely to be the drivers of the oncogenic and survival-prolonging properties of IDH1/2 mutations. We discuss interactions between mutant IDH1/2 inhibitors and conventional therapies. Understanding of the biochemical consequences of IDH1/2 mutations in oncogenesis and survival prolongation will yield valuable information for rational therapy design: it will tell us which oncogenic processes should be blocked and which "survivalogenic" effects should be retained.

  10. Effect of urea addition on giant reed ensilage and subsequent methane production by anaerobic digestion. (United States)

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


    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.

  11. Non-additive effects of intra- and interspecific competition between two larval salamanders. (United States)

    Anderson, Thomas L; Whiteman, Howard H


    Assessment of the relative strengths of intra- and interspecific competition has increased in recent years and is critical to understanding the importance of competition. Yet, whether intra- and interspecific competition can have non-additive effects has rarely been tested. The resulting fitness consequences of such non-additive interactions are important to provide the context necessary to advance our understanding of competition theory. We compared the strength of additive and non-additive intra- and interspecific competition by manipulating densities of a pair of larval salamanders (Ambystoma talpoideum and A. maculatum) in experimental mesocosms within a response surface design. Intraspecific density had the strongest effect on the strength of competition for both species, and few observed comparisons indicated interspecific competition was an important factor in predicting body size, growth or larval period length of either species. Non-additive effects of intra- and interspecific competition influenced some response variables, including size and mass at metamorphosis in A. maculatum, but at a reduced strength compared to intraspecific effects alone. Intraspecific competition was thus the dominant biotic interaction, but non-additive effects also impact the outcome of competition in these species, validating the importance of testing for and incorporating non-additive density effects into competition models.

  12. Differential effects of the Huntington's disease CAG mutation in striatum and cerebellum are quantitative not qualitative. (United States)

    Fossale, Elisa; Seong, Ihn Sik; Coser, Kathryn R; Shioda, Toshi; Kohane, Isaac S; Wheeler, Vanessa C; Gusella, James F; MacDonald, Marcy E; Lee, Jong-Min


    Huntington's disease (HD) involves marked early neurodegeneration in the striatum, whereas the cerebellum is relatively spared despite the ubiquitous expression of full-length mutant huntingtin, implying that inherent tissue-specific differences determine susceptibility to the HD CAG mutation. To understand this tissue specificity, we compared early mutant huntingtin-induced gene expression changes in striatum to those in cerebellum in young Hdh CAG knock-in mice, prior to onset of evident pathological alterations. Endogenous levels of full-length mutant huntingtin caused qualitatively similar, but quantitatively different gene expression changes in the two brain regions. Importantly, the quantitatively different responses in the striatum and cerebellum in mutant mice were well accounted for by the intrinsic molecular differences in gene expression between the striatum and cerebellum in wild-type animals. Tissue-specific gene expression changes in response to the HD mutation, therefore, appear to reflect the different inherent capacities of these tissues to buffer qualitatively similar effects of mutant huntingtin. These findings highlight a role for intrinsic quantitative tissue differences in contributing to HD pathogenesis, and likely to other neurodegenerative disorders exhibiting tissue-specificity, thereby guiding the search for effective therapeutic interventions.

  13. Inhibitory effects of a novel Val to Thr mutation on the distal heme of human catalase. (United States)

    Mashhadi, Zahra; Boeglin, William E; Brash, Alan R


    True catalases efficiently breakdown hydrogen peroxide, whereas the catalase-related enzyme allene oxide synthase (cAOS) is completely unreactive and instead metabolizes a fatty acid hydroperoxide. In cAOS a Thr residue adjacent to the distal His restrains reaction with H2O2 (Tosha et al. (2006) J. Biol. Chem. 281:12610; De Luna et al. (2013) J. Phys. Chem. B 117: 14635) and its mutation to the consensus Val of true catalases permits the interaction. Here we investigated the effects of the reciprocal experiment in which the Val74 of human catalase is mutated to Thr, Ser, Met, Pro, or Ala. The Val74Thr substitution decreased catalatic activity by 3.5-fold and peroxidatic activity by 3-fold. Substitution with Ser had similar negative effects (5- and 3-fold decreases). Met decreased catalatic activity 2-fold and eliminated peroxidatic activity altogether, whereas the Val74Ala substitution was well tolerated. (The Val74Pro protein lacked heme). We conclude that the conserved Val74 of true catalases helps optimize catalysis. There are rare substitutions of Val74 with Ala, Met, or Pro, but not with Ser of Thr, possibly due their hydrogen bonding affecting the conformation of His75, the essential distal heme residue for activity in catalases.

  14. Effectiveness of the Touch Math Technique in Teaching Basic Addition to Children with Autism (United States)

    Yikmis, Ahmet


    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…

  15. Parental Anxiety and Child Symptomatology: An Examination of Additive and Interactive Effects of Parent Psychopathology (United States)

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


    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…

  16. Site-specific mutations of FtsZ - effects on GTPase and in vitro assembly

    Directory of Open Access Journals (Sweden)

    Stricker Jesse


    Full Text Available Abstract Background FtsZ, the major cytoskeletal protein in bacterial cytokinesis, assembles in vitro into protofilaments, which can further associate into sheets, bundles or tubes. We have constructed 16 site-directed mutants of E. coli ftsZ, and tested them for GTP hydrolysis and assembly in vitro, and for their ability to complement the temperature sensitive ftsZ84 mutation in E. coli. Results The mutants were grouped into three classes. Benign mutants, which mapped mostly to the front and back surface of the protofilament, were able to complement ftsZ84 in vivo and showed normal assembly in vitro. GTP contact mutations had less than 10% of wild type GTPase activity. They could all assemble in vitro, and several of these mutants could complement ftsZ84. A third, and newly discovered, class of mutations mapped to the sides of the protofilaments. These lateral mutants had mostly normal GTPase and assembly in vitro, but none of them complemented ftsZ84. The non-complementing mutants showed greatly reduced expression from the pBS58 vector, suggesting possible dominant negative effects. Conclusions Several mutants with greatly reduced GTPase could still complement ftsZ84, suggesting that the high level of GTPase observed in vitro is not essential for in vivo function. All of the lateral mutants failed to complement ftsZ84, which suggests that these surfaces of the protofilaments are important for function in cell division. These lateral surfaces may mediate association of FtsZ protofilaments into pairs or small sheets, although their structure is apparently different from the sheets assembled in DEAE dextran or calcium.

  17. 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.


    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.

  18. Additives effects on crystallization and morphology in a novel caustic aluminate solution decomposition process

    Institute of Scientific and Technical Information of China (English)

    Ying ZHANG; Sbili ZHENG; Yifei ZHANG; Hongbin XU; Yi ZHANG


    A novel process of caustic aluminate solution decomposition by alcohol medium was developed by the Institute of Process Engineering, Chinese Academy of Sciences in order to solve the problem of low decomposi-tion ratio in the traditional Bayer seeded hydrolysis process. In this research, effects of additives on the crystallization ratio, secondary particle size and morphol-ogy of aluminum hydroxide in the new process were studied to obtain high-quality products. On the basis of primary selection of additives, an orthogonal design L9(34)was used as a chemometric method to investigate the effects of additives. The studied parameters include the reaction style, quantity of additives, caustic soda concen-tration, as well as the combination manner. The crystal-lization ratios of sodium aluminate solution and crystal size of aluminum hydroxide, determined by ICP-OES, SEM and MLPSA (Malvern Laser Particle Size Analyzer), were used to evaluate the effects of the additives. The results showed that different combination manners could promote agglomeration or dispersion. An additive composed by Tween 80 and PEG 200 could promote agglomeration,while a spot of PEG species had a relatively strong dispersion effect. However, the additives had little effects on the crystallization ratios. According to the Raman spectra result, the added alcohol medium might serve as a kind of solvent.

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

    Directory of Open Access Journals (Sweden)

    Jing Bi


    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.

  20. The Effects of Non—Metal Additives on Hydration Reisitance of MgO—C Bricks

    Institute of Scientific and Technical Information of China (English)

    OUYAGNG; WANGRuikun; 等


    The general method of solving the problem of hydration of MgO-C brick is by adding with metal Si,Mg or compround metal additives,but metal additives have bad effect on the MgO-C brick,The test tried adding non-metal additives to matrix material.The results showed that a suitable amount of this kind of additives not only inhibits hydration of MgO-C brick and does not affect corrosion resistance and avoids thermal expansion,but also can improve oxidation resistance.

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

    Directory of Open Access Journals (Sweden)

    A. Vadiraj


    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.

  2. Effects of Ta Addition on NiTi Shape Memory Alloys

    Institute of Scientific and Technical Information of China (English)


    @@The effect of Ta addition on the martensitic transformation characteristics and the X-ray visibility on NiTi shape memory alloy have been studied in (Ni51Ti49)1-xTax system. It was found that the transformation temperatures of the Ni51Ti49 binary alloy increased drastically by an addition of 0~4 at. pct Ta, but only slightly when the concentration exceeded 4 at. pct; the addition of Ta greatly decreases the sensitivity of the martensitic transformations to the variation in the Ni-Ti ratio. The addition of Ta to the NiTi binary alloy can improve its X-ray visibility.

  3. Effect of fluorapatite additive on the mechanical properties of tricalcium phosphate-zirconia composites (United States)

    Sallemi, I.; Ben Ayed, F.; Bouaziz, J.


    The effect of fluorapatite addition on the mechanical properties of tricalcium phosphate - 50 wt% zirconia composites was investigated during the sintering process. The Brazilian test was used to measure the mechanical resistance of bioceramics. The mechanical properties of composites increase with the sintering temperature and with fluorapatite additive. At 1400°C, the fluorapatite additive ameliorates the densification and the mechanical resistance of tricalcium phosphate - 50 wt% zirconia composites. The 31P magic angle spinning nuclear magnetic resonance analysis of tricalcium phosphate - zirconia composites sintered with fluorapatite additives reveals the presence of tetrahedral P sites.

  4. 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


    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.

  5. Study on mutation induced effect of gamma ray and DES on black bean phaseolus vulgaris

    Energy Technology Data Exchange (ETDEWEB)

    Le Thi Dinh; Pham Le Ha; Nguyen Van Toan; Le Xuan Tham [Nuclear Research Institute, Radiobiology Department, Dalat (Viet Nam)


    The study on mutation induced effect of gamma ray and DES on black bean Phaseolus vulgaris was carried out at Radiobiology Department, Nuclear Research Institute of Dalat. Dry seeds of variety No.1847 - Bonita - Cuba in set of 13 black bean varieties were irradiated with gamma ray from {sup 60}Co source at dose range from 150 Gy to 350 Gy and treated with DES at concentration from 0.1% to 0.3% in 2 hours for experiments in laboratory. The doses of 200, 250, 300 Gy and concentration of 0.2% DES in 2 hours were selected to treat dry seeds for experiments on the field. In populations of M{sub 1} generation, the height, number of branches and fruits per plant, number of seeds per fruit were decreased with increasing of irradiation doses. In populations of M{sub 2} generation, individual variants in leaf shape, chlorophyll, short stem, dwarf, early maturity, flowering in very short time were obtained and selected in all treatment cases. Mutation frequency at dose of 300 Gy was higher than that in other treatment cases, but ratio of sterility is also largest. The mutant lines of early maturity and short stem with flowering in very short time are promised materials for further studies. (author)

  6. Dynamical network of residue-residue contacts reveals coupled allosteric effects in recognition, catalysis, and mutation. (United States)

    Doshi, Urmi; Holliday, Michael J; Eisenmesser, Elan Z; Hamelberg, Donald


    Detailed understanding of how conformational dynamics orchestrates function in allosteric regulation of recognition and catalysis remains ambiguous. Here, we simulate CypA using multiple-microsecond-long atomistic molecular dynamics in explicit solvent and carry out NMR experiments. We analyze a large amount of time-dependent multidimensional data with a coarse-grained approach and map key dynamical features within individual macrostates by defining dynamics in terms of residue-residue contacts. The effects of substrate binding are observed to be largely sensed at a location over 15 Å from the active site, implying its importance in allostery. Using NMR experiments, we confirm that a dynamic cluster of residues in this distal region is directly coupled to the active site. Furthermore, the dynamical network of interresidue contacts is found to be coupled and temporally dispersed, ranging over 4 to 5 orders of magnitude. Finally, using network centrality measures we demonstrate the changes in the communication network, connectivity, and influence of CypA residues upon substrate binding, mutation, and during catalysis. We identify key residues that potentially act as a bottleneck in the communication flow through the distinct regions in CypA and, therefore, as targets for future mutational studies. Mapping these dynamical features and the coupling of dynamics to function has crucial ramifications in understanding allosteric regulation in enzymes and proteins, in general.

  7. Effect of bentonite addition on residual strength of microwave-hardened waterglass-containing moulding sands

    Directory of Open Access Journals (Sweden)

    M. Stachowicz


    Full Text Available The paper presents results of a preliminary research of the effect of bentonite addition on residual strength of microwave-hardened moulding sands, containing sodium waterglass. Strength was determined at ambient temperature, on cylindrical specimens baked in an oven. Moulding sands for examinations were based on high-silica sand with addition of 2.5 % of non-modified, domestic-made waterglass grade 145. The prepared standard cylindrical specimens were hardened using the innovative microwave heating process and next baked for 30 minutes at temperatures between 100 and 1200 °C. Strength parameters of the specimens were determined on the specimens cooled- down to ambient temperature. The obtained results were compared with literature data to evaluate the effect of the applied hardening method and of the special additive on residual strength as a function of baking temperature. A favourable effect was found of both the innovative heating process and the applied bentonite addition.

  8. Mutation analysis of presenilin-1 gene in Alzheimer’s disease patients and the effects of its mutation on expression of presenilin-1 and amyloid precursor protein

    Institute of Scientific and Technical Information of China (English)



    Objective To analyze the presenilin-1(PS-1) gene mutations in Alzheimer’s disease(AD) patients and investigate the influence of the initiation codon mutation on the mRNA expression of PS-1 and amyloid precursor protein

  9. The Effect of F877L and T878A Mutations on Androgen Receptor Response to Enzalutamide. (United States)

    Prekovic, Stefan; van Royen, Martin E; Voet, Arnout R D; Geverts, Bart; Houtman, Rene; Melchers, Diana; Zhang, Kam Y J; Van den Broeck, Thomas; Smeets, Elien; Spans, Lien; Houtsmuller, Adriaan B; Joniau, Steven; Claessens, Frank; Helsen, Christine


    Treatment-induced mutations in the ligand-binding domain of the androgen receptor (AR) are known to change antagonists into agonists. Recently, the F877L mutation has been described to convert enzalutamide into an agonist. This mutation was seen to co-occur in the endogenous AR allele of LNCaP cells, next to the T878A mutation. Here, we studied the effects of enzalutamide on the F877L and T878A mutants, as well as the double-mutant AR (F877L/T878A). Molecular modeling revealed favorable structural changes in the double-mutant AR that lead to a decrease in steric clashes for enzalutamide. Ligand-binding assays confirmed that the F877L mutation leads to an increase in relative binding affinity for enzalutamide, but only the combination with the T878A mutation resulted in a strong agonistic activity. This correlated with changes in coregulator recruitment and chromatin interactions. Our data show that enzalutamide is only a very weak partial agonist of the AR F877L, and a strong partial agonist of the double-mutant AR. Mol Cancer Ther; 15(7); 1702-12. ©2016 AACR.

  10. The ups and downs of mutation frequencies during aging can account for the Apert syndrome paternal age effect. (United States)

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


    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.

  11. 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


    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.

  12. 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


    Directory of Open Access Journals (Sweden)

    Arvind KUMAR


    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.

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

    Directory of Open Access Journals (Sweden)

    YANG Yan


    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.

  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


    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. Estimation of direct effects for survival data by using the Aalen additive hazards model

    DEFF Research Database (Denmark)

    Martinussen, T.; Vansteelandt, S.; Gerster, M.


    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...

  17. HER2 missense mutations have distinct effects on oncogenic signaling and migration (United States)

    Zabransky, Daniel J.; Yankaskas, Christopher L.; Cochran, Rory L.; Wong, Hong Yuen; Croessmann, Sarah; Chu, David; Kavuri, Shyam M.; Red Brewer, Monica; Rosen, D. Marc; Dalton, W. Brian; Cimino-Mathews, Ashley; Cravero, Karen; Button, Berry; Kyker-Snowman, Kelly; Cidado, Justin; Erlanger, Bracha; Parsons, Heather A.; Manto, Kristen M.; Bose, Ron; Lauring, Josh; Arteaga, Carlos L.; Konstantopoulos, Konstantinos; Park, Ben Ho


    Recurrent human epidermal growth factor receptor 2 (HER2) missense mutations have been reported in human cancers. These mutations occur primarily in the absence of HER2 gene amplification such that most HER2-mutant tumors are classified as “negative” by FISH or immunohistochemistry assays. It remains unclear whether nonamplified HER2 missense mutations are oncogenic and whether they are targets for HER2-directed therapies that are currently approved for the treatment of HER2 gene-amplified breast cancers. Here we functionally characterize HER2 kinase and extracellular domain mutations through gene editing of the endogenous loci in HER2 nonamplified human breast epithelial cells. In in vitro and in vivo assays, the majority of HER2 missense mutations do not impart detectable oncogenic changes. However, the HER2 V777L mutation increased biochemical pathway activation and, in the context of a PIK3CA mutation, enhanced migratory features in vitro. However, the V777L mutation did not alter in vivo tumorigenicity or sensitivity to HER2-directed therapies in proliferation assays. Our results suggest the oncogenicity and potential targeting of HER2 missense mutations should be considered in the context of cooperating genetic alterations and provide previously unidentified insights into functional analysis of HER2 mutations and strategies to target them. PMID:26508629

  18. Cardiac effects of the c.1583 C→G LMNA mutation in two families with Emery-Dreifuss muscular dystrophy. (United States)

    Zhang, Li; Shen, Hongrui; Zhao, Zhe; Bing, Qi; Hu, Jing


    The present study aimed to examine and analyze cardiac involvement in two Emery‑Dreifuss muscular dystrophy (EDMD) pedigrees caused by the c.1583 C→G mutation of the lamin A/C gene (LMNA). The clinical and genetic characteristics of members of two families with EDMD were evaluated by performing neurological examinations, skeletal muscle biopsies, cardiac evaluations, including electrocardiography, 24 h Holter, ultrasound cardiography and 99TcM‑MIBI‑gated myocardiac perfusion imaging, and genomic DNA sequencing. Family history investigations revealed an autosomal dominant transmission pattern of the disease in Family 1 and a sporadic case in Family 2. The three affected patients exhibited typical clinical features of EDMD, including joint contractures, muscle weakness and cardiac involvement. Muscle histopathological investigation revealed dystrophic features. In addition, each affected individual exhibited either cardiac arrhythmia, which was evident as sinus tachycardia, atrial flutter or complete atrioventricular inhibition. Cardiac imaging revealed dilated cardiomyopathy in two of the individuals, one of whom was presented with heart failure. The second patient presented with no significant abnormalities in cardiac structure or function. The three affected individuals exhibited a heterozygous missense mutation in the LMNA gene (c.1583 C→G), which caused a T528R amino acid change in the LMNA protein. In conclusion, the present study identified three patients with EDMD, exhibiting the same dominant LMNA mutation and presenting with a spectrum of severe cardiac abnormalities, including cardiac conduction system defects, cardiomyopathy and heart failure. As LMNA mutations have been associated with at least six clinical disorders, including EDMD, the results of the present study provide additional mutational and functional data, which may assist in further establishing LMNA mutational variation and disease pathogenesis.

  19. Thermogravimetric Analysis of Effects of High-Content Limstone Addition on Combustion Characteristics of Taixi Anthracite

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong; LI Mei; SUN Min; WEI Xian-yong


    Combustion characteristics of Taixi anthracite admixed with high content of limestone addition were investigated with thermogravimetric analysis. The results show that limestone addition has a little promoting effect on the ignition of raw coals as a whole. The addition of limestone is found to significantly accelerate the combustion and burnout of raw coals. The higher the sample mass is, the more significant the effect will be. The results also show that the change of limestone proportion between 45%-80% has little effect on ignition temperatures of coal in the blended samples. Increasing limestone content lowers the temperature corresponding to the maximum weight loss. Although higher maximum mass loss rates are observed with higher limestone content, the effect is found not ascribed to changing limestone addition, but to the decrease of absolute coal mass in the sample. The change of limestone proportion has little effect on its burnout temperature. Mechanism analysis indicates that these phenomena result mainly from improved heat conduction due to limestone addition.

  20. Effects of magnetic ion-exchange resin addition during coagulation on floc properties and membrane filtration. (United States)

    Choi, Yang Hun; Kweon, Ji Hyang; Jeong, Young Mi; Kwon, Soonbuhm; Kim, Hyung-Soo


    The application of magnetic ion-exchange resin (MIEX) during chemical coagulation was investigated for the removal of organic matters responsible for fouling in membrane processes. Two different coagulants were used-polyaluminium chloride (PAC1) and polyaluminum chloride silicate (PACS). The MIEX addition during coagulation with both PAC1 and PACS considerably enhanced removal of dissolved organic carbon. Coagulation with MIEX treatment substantially removed all portions of natural organic matter (NOM), while the MIEX treatment alone effectively removed the hydrophobic and transphilic portions of NOM. The enhanced NOM removal by PAC1 coagulation with the addition of MIEX had positive effects on membrane flux at moderate transmembrane pressure conditions. However, the almost identical flux patterns were reported in the experiments of coagulation with PACS and PACS with MIEX addition. The results of the specific cake resistances indicated that the MIEX addition substantially decreased the resistances. The larger size distributions of PAC1 with MIEX corresponded well with the flux improvement.

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

    Directory of Open Access Journals (Sweden)

    V. Sajith


    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. Effect of Additives on Sintering of Cr2O3 in Reductive Atmosphere

    Institute of Scientific and Technical Information of China (English)

    LIANGYonghe; SUNChengxu; 等


    The influence of additives TiO2,Y2O3 and composite rare earth on sintering of Cr2O3 in reductive atmosphere was studied.Results show that TiO2 can effectively increase the sinteed density at low temperature,As the increase of sintering temperature,such kind of effect becomes more and more unobvious and finaly disappear at 1550℃.Moreover,Y2O3 and composite rare earth have negative effect on sintering.

  3. Effect of addition of ethyl alcohol on gelation and viscoelasticity of tissue conditioners


    Murata, Hiroshi; Hamada, Taizo; Harshini,; Toki, Kazuhito; Nikawa, Hiroki


    The clinical effectiveness of tissue conditioners is influenced by their gelation characteristics and viscoelastic properties after gelation. The purpose of this study was to evaluate the effect of addition of ethyl alcohol (EtOH) on these properties, and to compare the effect of EtOH with that of the powder/liquid (P/L) ratio. Three tissue conditioners were used in this study. The gelation times were obtained with an oscillating rheometer. The viscoelastic properties after gelation were also...

  4. Effect of zinc and cerium addition on property of copper-based adsorbents for phosphine adsorption

    Institute of Scientific and Technical Information of China (English)

    宁平; 易红宏; 余琼粉; 唐晓龙; 杨丽萍; 叶智青


    A series of copper-based activated carbon (AC) adsorbents were prepared in order to investigate the effect of Zn, Ce addition on Cu-based AC adsorbent for phosphine (PH3) adsorption removal from yellow phosphorous tail gas. N2 adsorption isotherm and X-ray diffrac-tion (XRD) results suggested that the addition of Zn could increase the adsorbent ultramicropores, decrease the adsorbent supermicropores and the adsorbent average pore diameter. Therefore it enhanced the PH3 adsorption capacity. Appropriate amoun...

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

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


    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. 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: [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)


    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.

  7. The effect of phosphate additives on the lubrication of rolling element bearings in a refrigerant environment

    Energy Technology Data Exchange (ETDEWEB)

    Tuomas, Roger; Isaksson, Ove [Luleaa University of Technology, Division of Machine Elements, SE-971 87 Luleaa (Sweden)


    Chlorine free replacement refrigerants, HFC (hydrofluorocarbons) and HC (hydrocarbons), have shown less lubricating properties. Phosphate based additives were used to improve the lubricity with refrigerant R-134a, demonstrating positive effects. In the present paper, the ability to form lubricating film and wear of two additives, phosphate ester and acid phosphate, was investigated in a bearing test apparatus. The results show that phosphate additive in polyolester oil, in an R-134a environment, increases the lubricating film and reduce wear. Surface topography during the initial run-in changes to a more favorable profile with lower RMS angle and longer wavelengths that promote load-carrying capacity and film build-up. (author)

  8. Effect of addition of CO2 to raw milk on quality of UHT-treated milk


    Vianna, PCB; Walter, EHM; Dias, MEF; Faria, JAF; Netto, FM; Gigante, ML


    The objective of this study was to evaluate the effect of addition of CO2 to raw milk on UHT milk quality during storage. Control milk (without CO2 addition) and treated milk (with CO2 addition up to pH 6.2) were stored in bulk tanks at 4°C for 6d. After storage, both samples were UHT processed using indirect heating (140°C for 5s). Samples were aseptically packed in low-density polyethylene pouches and stored in the dark at room temperature. Raw milk was evaluated upon receipt for physicoche...

  9. Effects of additional food in a delayed predator-prey model. (United States)

    Sahoo, Banshidhar; Poria, Swarup


    We examine the effects of supplying additional food to predator in a gestation delay induced predator-prey system with habitat complexity. Additional food works in favor of predator growth in our model. Presence of additional food reduces the predatory attack rate to prey in the model. Supplying additional food we can control predator population. Taking time delay as bifurcation parameter the stability of the coexisting equilibrium point is analyzed. Hopf bifurcation analysis is done with respect to time delay in presence of additional food. The direction of Hopf bifurcations and the stability of bifurcated periodic solutions are determined by applying the normal form theory and the center manifold theorem. The qualitative dynamical behavior of the model is simulated using experimental parameter values. It is observed that fluctuations of the population size can be controlled either by supplying additional food suitably or by increasing the degree of habitat complexity. It is pointed out that Hopf bifurcation occurs in the system when the delay crosses some critical value. This critical value of delay strongly depends on quality and quantity of supplied additional food. Therefore, the variation of predator population significantly effects the dynamics of the model. Model results are compared with experimental results and biological implications of the analytical findings are discussed in the conclusion section.

  10. Effect of ensiling and silage additives on fatty acid composition of ryegrass and corn experimental silages. (United States)

    Alves, S P; Cabrita, A R J; Jerónimo, E; Bessa, R J B; Fonseca, A J M


    Two experiments were conducted using laboratory mini-silos to study the effect of ensiling and silage additives on fatty acid (FA) composition, including minor or unusual FA, of ryegrass and corn silages. Ryegrass was ensiled for 12 wk with no additives, with the addition of a bacterial inoculant or formic acid. Corn was ensiled for 9 wk without additives, with the addition of a bacterial inoculant or calcium formate. Ensiling affected both total FA content and FA composition of ryegrass silages. Total FA concentration increased (P 0.05) by ensiling. However, their concentration (mg/g of DM) in silages was greater (P=0.017 and P=0.001, respectively) than in fresh ryegrass. Two 18:2 FA (trans-11,cis-15 and cis-9,cis-15) that were not originally present in the fresh ryegrass were detected in silages. Silage additives affected the FA composition of ryegrass silages, mostly by increasing the proportions of SFA, but not on total FA concentration. Ensiling did not affect (P=0.83) total FA content of corn silages; however, FA composition was affected, mostly by decreasing the proportions of 18:2n-6 and 18:3n-3. Silage additives had no effect on corn silage FA composition. Exposing corn silages to air resulted in no oxidation of FA or reduction in total FA content or composition.

  11. Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases (United States)

    Lenz, Tobias L.; Deutsch, Aaron J.; Han, Buhm; Hu, Xinli; Okada, Yukinori; Eyre, Stephen; Knapp, Michael; Zhernakova, Alexandra; Huizinga, Tom W.J.; Abecasis, Goncalo; Becker, Jessica; Boeckxstaens, Guy E.; Chen, Wei-Min; Franke, Andre; Gladman, Dafna D.; Gockel, Ines; Gutierrez-Achury, Javier; Martin, Javier; Nair, Rajan P.; Nöthen, Markus M.; Onengut-Gumuscu, Suna; Rahman, Proton; Rantapää-Dahlqvist, Solbritt; Stuart, Philip E.; Tsoi, Lam C.; Van Heel, David A.; Worthington, Jane; Wouters, Mira M.; Klareskog, Lars; Elder, James T.; Gregersen, Peter K.; Schumacher, Johannes; Rich, Stephen S.; Wijmenga, Cisca; Sunyaev, Shamil R.; de Bakker, Paul I.W.; Raychaudhuri, Soumya


    Human leukocyte antigen (HLA) genes confer strong risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen binding repertoires between a heterozygote’s two expressed HLA variants may result in additional non-additive risk effects. We tested non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (RA, Ncases=5,337), type 1 diabetes (T1D, Ncases=5,567), psoriasis vulgaris (Ncases=3,089), idiopathic achalasia (Ncases=727), and celiac disease (Ncases=11,115). In four out of five diseases, we observed highly significant non-additive dominance effects (RA: P=2.5×1012; T1D: P=2.4×10−10; psoriasis: P=5.9×10−6; celiac disease: P=1.2×10−87). In three of these diseases, the dominance effects were explained by interactions between specific classical HLA alleles (RA: P=1.8×10−3; T1D: P=8.6×1027; celiac disease: P=6.0×10−100). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (RA: 1.4%, T1D: 4.0%, and celiac disease: 4.1%, beyond a simple additive model). PMID:26258845

  12. [Effects of superphosphate addition on NH3 and greenhouse gas emissions during vegetable waste composting]. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Su Yang Lee


    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.

  14. Effect of additives on isothermal crystallization kinetics and physical characteristics of coconut oil. (United States)

    Chaleepa, Kesarin; Szepes, Anikó; Ulrich, Joachim


    The effect of lauric acid and low-HLB sucrose esters (L-195, S170) on the isothermal crystallization of coconut oil was investigated by differential scanning calorimetry. The fundamental crystallization parameters, such as induction time of nucleation and crystallization rate, were obtained by using the Gompertz equation. The Gibb's free energy of nucleation was calculated via the Fisher-Turnbull equation based on the equilibrium melting temperature. All additives, investigated in this work, proved to have an inhibition effect on nucleation and crystallization kinetics of coconut oil. Our results revealed that the inhibition effect is related to the dissimilarity of the molecular characteristics between coconut oil and the additives. The equilibrium melting temperature (T(m) degrees ) of the coconut oil-additive mixtures estimated by the Hoffman-Weeks method was decreased with the addition of lauric acid and increased by using sucrose esters as additives. Micrographs showing simultaneous crystallization of coconut oil and lauric acid indicated that strong molecular interaction led to the increase in lamellar thickness resulting in the T(m) degrees depression of coconut oil. The addition of L-195 modified the crystal morphology of coconut oil into large, dense, non-porous crystals without altering the polymorphic occurrence of coconut oil. The enhancement in lamellar thickness and crystal perfection supported the T(m) degrees elevation of coconut oil.

  15. Effect of UVM induction on mutation fixation at non-pairing and mispairing DNA lesions. (United States)

    Rahman, M S; Dunman, P M; Wang, G; Murphy, H S; Humayun, M Z


    Mutation fixation at an ethenocytosine (epsilon C) residue borne on transfected M13 single-stranded DNA is significantly enhanced in response to pretreatment of Escherichia coli cells with UV, alkylating agents or hydrogen peroxide, a phenomenon that we have called UVM for UV modulation of mutagenesis. The UVM response does not require the E. coli SOS or adaptive responses, and is observed in cells defective for oxyR, an oxidative DNA damage-responsive regulatory gene. UVM may represent either a novel DNA-repair phenomenon, or an unrecognized feature of DNA replication in damaged cells that affects a specific class of non-coding DNA lesions. To explore the range of DNA lesions subject to the UVM effect, we have examined mutation fixation at 3,N4-ethenocytosine and 1,N6-ethenoadenine, as well as at O6-methylguanine (O6mG). M13 viral single-stranded DNA constructs bearing a single mutagenic lesion at a specific site were transfected into cells pretreated with UV or 1-methyl-3-nitro-1-nitroso-guanidine (MNNG). Survival of transfected viral DNA was measured as transfection efficiency, and mutagenesis at the lesion site was analysed by a quantitative multiplex sequence analysis technology. The results suggest that the UVM effect modulates mutagenesis at the two etheno lesions, but does not appear to significantly affect mutagenesis at O6mG. Because the modulation of mutagenesis is observed in cells incapable of the SOS response, these data are consistent with the notion that UVM may represent a previously unrecognized DNA damage-inducible response that affects the fidelity of DNA replication at certain mutagenic lesions in Escherichia coli.

  16. [Effects of menthol as an additive in tobacco products and the need for regulation]. (United States)

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


    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.

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

    KAUST Repository

    Carreja, B


    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.


    Directory of Open Access Journals (Sweden)



    Full Text Available The effects of four different additive formulations namely 5748, 801, 264 and 261 on the viscosity index of two lubricating oils (base oils namely 150N and 500N at two temperatures 400C and 1000C wereinvestigated. The base oils were blended with the additives in three different proportions of 100/4. 100/8 and 100/12. The results gave a viscosity index of 96 and 98 respectively for 150N and 500N withoutadditives. On the other hand, the addition of 12g of 261 additive formulations to 100cm3 of both base oils gave about 180% increase in kinematic viscosity at 400C, about 161% increase and 146% increase at1000C for 150N and 500N respectively. About 60% in viscosity index was achieved by 100/12 blend of 261 additives in 150N. The results revealed that 261 additive formulations gave the highest increase inviscosity in all proportions increasing as the weight of the additive increases. Generally, all the four additive formulations used mproved the viscosities of all the blends in all the proportions and at both temperatures. The blends can be classified as very high viscosity index being above 110. This means that they will undergo very little change in viscosity with temperature extremes and so can be considered to have stable viscosity.

  19. Analysis of error-prone survival data under additive hazards models: measurement error effects and adjustments. (United States)

    Yan, Ying; Yi, Grace Y


    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.

  20. Effects of site substitution and metal ion addition on doped manganites

    CERN Document Server

    Pradhan, A K; Roul, B K; Sahu, D R; Muralidhar, M


    We report transport, magnetization and transmission electron microscopy studies of the effects of A-and B-site substitution, and the addition of metal ions such as Pt, Ag and Sr, on doped ABO sub 3 perovskites, where A = La, Pr etc and B = Mn. Disorder induced by such substitution changes the behaviour of the charge-ordered (CO) state significantly. A-and B-site substitution suppresses the CO phase due to size mismatch and disorder produced by inhomogeneity. On the other hand, addition of metal ions such as Pt and Ag improves several colossal-magnetoresistance properties significantly due to microstructural effects and enhanced current percolation through grain boundaries.

  1. Effects of Additives on Sintering and Characterization of Calcium Phosphate Ceramics

    Institute of Scientific and Technical Information of China (English)


    Calcium phosphate precursory powders containing Na and Mg have been prepared by the citric acid sol-gel combustion method. The elements of Na and Mg were introduced from component of CaO- P2O5-Na2 O-MgO. The effect of sintering additives on the phase composition was characterized by XRD. The effect of sintering additives on sintering of materials was also characterized by linear shrinkage, TEM and SEM. Finally the microstructure of porous calcium phosphate ceramic was determined by SEM.

  2. The effect of tailor-made additives on crystal growth of methyl paraben: Experiments and modelling (United States)

    Cai, Zhihui; Liu, Yong; Song, Yang; Guan, Guoqiang; Jiang, Yanbin


    In this study, methyl paraben (MP) was selected as the model component, and acetaminophen (APAP), p-methyl acetanilide (PMAA) and acetanilide (ACET), which share the similar molecular structure as MP, were selected as the three tailor-made additives to study the effect of tailor-made additives on the crystal growth of MP. HPLC results indicated that the MP crystals induced by the three additives contained MP only. Photographs of the single crystals prepared indicated that the morphology of the MP crystals was greatly changed by the additives, but PXRD and single crystal diffraction results illustrated that the MP crystals were the same polymorph only with different crystal habits, and no new crystal form was found compared with other references. To investigate the effect of the additives on the crystal growth, the interaction between additives and facets was discussed in detail using the DFT methods and MD simulations. The results showed that APAP, PMAA and ACET would be selectively adsorbed on the growth surfaces of the crystal facets, which induced the change in MP crystal habits.

  3. Dissociating compatibility effects and distractor costs in the additional singleton paradigm. (United States)

    Folk, Charles L


    The interpretation of identity compatibility effects associated with irrelevant items outside the nominal focus of attention has fueled much of the debate over early versus late selection and perceptual load theory. However, compatibility effects have also played a role in the debate over the extent to which the involuntary allocation of spatial attention (i.e., attentional capture) is completely stimulus-driven or whether it is contingent on top-down control settings. For example, in the context of the additional singleton paradigm, irrelevant color singletons have been found to produce not only an overall cost in search performance but also significant compatibility effects. This combination of search costs and compatibility effects has been taken as evidence that spatial attention is indeed allocated in a bottom-up fashion to the salient but irrelevant singletons. However, it is possible that compatibility effects in the additional singleton paradigm reflect parallel processing of identity associated with low perceptual load rather than an involuntary shift of spatial attention. In the present experiments, manipulations of load were incorporated into the traditional additional singleton paradigm. Under low-load conditions, both search costs and compatibility effects were obtained, replicating previous studies. Under high-load conditions, search costs were still present, but compatibility effects were eliminated. This dissociation suggests that the costs associated with irrelevant singletons may reflect filtering processes rather than the allocation of spatial attention.

  4. 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: [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada)


    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.

  5. The effect of lactic acid bacterial starter culture and chemical additives on wilted rice straw silage. (United States)

    Wang, Yan-Su; Shi, Wei; Huang, Lin-Ting; Ding, Cheng-Long; Dai, Chuan-Chao


    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.

  6. Effect of Mixed Solvents and Additives on the Habit Modification of 6-APA Crystals

    Institute of Scientific and Technical Information of China (English)

    GONG Junbo; WANG Jingkang; WEI Hongyuan


    6-aminopenicillanic acid (6-APA) crystals obtained under different physical and chemical conditions of the solutions may present different habits. The habits of diamond-shaped plates are desirable compared with other habits of 6-APA crystals. To obtain ideal 6-APA crystals, the effects of the mixed solvents and additives on 6-APA crystal habits were investigated. Ethanol or acetone was used as the organic solvent, and impurities existing in the 6-APA purification process were used as the additives. 6-APA growth habits were changed when the concentrations of ethanol, acetone or phenyl acetic acid were increased to exceed their critical concentration. The observed results show that the dominant face on 6-APA crystals was identified to be {020}, but the overall habit was controlled by the relative growth rates of the {101} and {002} faces. Crystal growth rates and habits can be appreciably changed by specific adsorption of additives on crystal faces.In some cases solvent molecules can act in a similar way and may be regarded as bulk additives. The effects of additives and organic solvents on 6-APA crystal habits were the results of adsorption effect, which fitted the experimental results quite well.

  7. Effect of GdL Addition on Physico-chemical Properties of Fermented Sausages during Ripening. (United States)

    Yim, Dong-Gyun; Jang, Kyoung-Hwan; Chung, Ku-Young


    This study investigated the effects of glucono-δ-lactone (GdL) addition on physicochemical and microbiological characteristics of fermented sausages during ripening and drying. Five batches of sausages were produced under ripening conditions: without GdL and with 0, 0.1, 0.25, 0.5 and 0.75% of GdL addition. Samples from each treatment were taken for physicochemical and microbiological analyses on the 0, 1, 3, 5, 7, 10, 15, 20 and 25th day of ripening. Chemical analysis showed a significant decrease in moisture content of sausages with increasing amounts of GdL added (pfermented sausages showed the highest in T4 (psausages were increased on the 25th day compared to day 0 (psausages. The addition of 0.75% GdL was effective in controlling bacteria counts. Addition of GdL in sausages resulted in the physicochemical and microbiological attributes equal to or better than no addition of GdL without any harmful effect.

  8. Mutation effects of C{sup 2+} ion irradiation on the greasy Nitzschia sp

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Y.N., E-mail: [School of Chemistry and Environment, Beihang University, 37th Xueyuan Road, Haidian District, P.O. Box 106, 100191 Beijing (China); Liu, C.L.; Wang, Y.K. [School of Chemistry and Environment, Beihang University, 37th Xueyuan Road, Haidian District, P.O. Box 106, 100191 Beijing (China); Xue, J.M. [State Key Lab of Nuclear Physics and Nuclear Technology, Peking University, 100084 Beijing (China)


    Highlights: • The optimal conditions of C{sup 2+} ion irradiation on Nitzschia sp. were discussed. • Get the “saddle type” survival curve. • One mutant whose lipid content improved significantly was selected. • The C{sup 2+} ion irradiation didn’t change the algae's morphology and growth rate. - Abstract: Screening and nurturing algae with high productivity, high lipid content and strong stress resistance are very important in algae industry. In order to increase the lipid content, the Nitzschia sp. was irradiated with a 3 MeV C{sup 2+} beam. The sample pretreatment method was optimized to obtain the best mutagenic condition and the survival ratio curve. The positive mutants with a significant improvement in lipid content were screened and their C{sup 2+} mutagenic effects were analyzed by comparing the greasiness and growth characteristics with the wild type algae. Results showed that when the Nitzschia sp. was cultivated in nutritious medium containing 10% glycerol solution, and dried on the filter for 5 min after centrifugation, the realization of the microalgae heavy ion mutagenesis could be done. The survival ratio curve caused by C{sup 2+} irradiation was proved to be “saddle-shaped”. A positive mutant was screened among 20 survivals after irradiation, the average lipid content of the mutation increased by 9.8% than the wild type after 4 generations. But the growth rate of the screened mutation didn’t change after the heavy ion implantation compared to the wild type algae.

  9. Effect of fructo-oligosaccharide and isomalto-oligosaccharide addition on baking quality of frozen dough. (United States)

    Park, Eun Young; Jang, Sung-Bum; Lim, Seung-Taik


    The baking quality of frozen doughs containing different levels of fructo-oligosaccharides (FO) or isomalto-oligosaccharides (IMO) (3-9%, w/w flour), and stored for 0-8weeks at -18°C, was examined. The addition of FO or IMO increased the proof volume of the dough and the loaf volume of bread prepared from frozen dough. A 6% addition of FO or IMO was optimum, giving the highest proof volume and bread loaf volume, but a higher concentration than 6% induced low baking quality including lower proof volume and bread loaf volume. The bread crumb was moister and softer after the addition of FO or IMO before, and even after, frozen storage. Darker crumb colour was observed in the bread after the addition of FO or IMO. The oligosaccharides added to the frozen dough were effective in improving the quality of bread made from frozen dough, except for resulting in a darker bread crumb.


    Directory of Open Access Journals (Sweden)

    Karoon Fangsuwannarak


    Full Text Available The purpose of this study is to perform comparative analysis of the effect of the different fuel additives as polymer based-bio-solution, natural organic based-bio-solution and nano-titanium metalloid (TiO2 compound on the performance parameters and exhuast emissions of a pickup Diesel engine, operating on commercial Diesel fuel (D and B5 palm biodiesel (95% D+5% palm oil. The basic properties of the fuel blended with TiO2 metalloid compound and bio-solution based additives were measured according to ASTM standard. Engine performance of a pickup diesel engine was investigated by testing on a chassis dynamometer with the simulation of road load condition. It was found that TiO2 based-additive is more effective for improving engine power than pure Diesel and B5 fuels by 7.78% and 1.36%, respectively. Meanwhile, with using TiO2 additive, the maximum engine torque on average increased by 1.01% and 1.53% in the wide range between 1,700 and 3,000 rpm as compared with Diesel and B5 fuels, respectively. The TiO2 and natural organic additives is significantly effective on Diesel fuel for reducing brake specific fuel consumption reached by 13.22% and 10.01%, respectively as compared with pure Diesel. Moreover, the exhuast emissions (NOx, CO and CO2 decreased from the engine using the TiO2 additive in Diesel fuel and natural organic additive in Diesel fuel.

  11. Effects of Ga Addition on Interfacial Reactions Between Sn-Based Solders and Ni (United States)

    Wang, Chao-Hong; Li, Kuan-Ting


    The use of Ga as a micro-alloying element in Sn-based solders can change the microstructure of solder joints to improve the mechanical properties, and even suppress the interfacial intermetallic compound (IMC) growth. This research investigated the effects of Ga addition (0.2-1 wt.%Ga) on the IMC formation and morphological evolution in the Sn-based solder joints with Ni substrate. In the soldering reaction at 250°C and with less than 0.2 wt.%Ga addition, the formed phase was Ni3Sn4. When the Ga addition increased to 0.5 wt.%, it changed to a thin Ni2Ga3 layer of ˜1 μm thick, which stably existed at the interface in the initial 1-h reaction. Subsequently, the whole Ni2Ga3 layer detached from the Ni substrate and drifted into the molten solder. The Ni3Sn4 phase became dominant in the later stage. Notably, the Ga addition significantly reduced the grain size of Ni3Sn4, resulting in the massive spalling of Ni3Sn4 grains. With 1 wt.%Ga addition, the Ni2Ga3 layer remained very thin with no significant growth, and it stably existed at the interface for more than 10 h. In addition, the solid-state reactions were examined at temperatures of 160°C to 200°C. With addition of 0.5 wt.%Ga, the Ni3Sn4 phase dominated the whole reaction. By contrast, with increasing to 1 wt.%Ga, only a thin Ni2Ga3 layer was found even after aging at 160°C for more than 1200 h. The 1 wt.%Ga addition in solder can effectively inhibit the Ni3Sn4 formation in soldering and the long-term aging process.

  12. Effects of Ga Addition on Interfacial Reactions Between Sn-Based Solders and Ni (United States)

    Wang, Chao-Hong; Li, Kuan-Ting


    The use of Ga as a micro-alloying element in Sn-based solders can change the microstructure of solder joints to improve the mechanical properties, and even suppress the interfacial intermetallic compound (IMC) growth. This research investigated the effects of Ga addition (0.2-1 wt.%Ga) on the IMC formation and morphological evolution in the Sn-based solder joints with Ni substrate. In the soldering reaction at 250°C and with less than 0.2 wt.%Ga addition, the formed phase was Ni3Sn4. When the Ga addition increased to 0.5 wt.%, it changed to a thin Ni2Ga3 layer of ˜1 μm thick, which stably existed at the interface in the initial 1-h reaction. Subsequently, the whole Ni2Ga3 layer detached from the Ni substrate and drifted into the molten solder. The Ni3Sn4 phase became dominant in the later stage. Notably, the Ga addition significantly reduced the grain size of Ni3Sn4, resulting in the massive spalling of Ni3Sn4 grains. With 1 wt.%Ga addition, the Ni2Ga3 layer remained very thin with no significant growth, and it stably existed at the interface for more than 10 h. In addition, the solid-state reactions were examined at temperatures of 160°C to 200°C. With addition of 0.5 wt.%Ga, the Ni3Sn4 phase dominated the whole reaction. By contrast, with increasing to 1 wt.%Ga, only a thin Ni2Ga3 layer was found even after aging at 160°C for more than 1200 h. The 1 wt.%Ga addition in solder can effectively inhibit the Ni3Sn4 formation in soldering and the long-term aging process.

  13. Synthetic Effect of Vivid Shark Skin and Polymer Additive on Drag Reduction Reinforcement

    Directory of Open Access Journals (Sweden)

    Huawei Chen


    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.

  14. Additional Interventions to Enhance the Effectiveness of Individual Placement and Support: A Rapid Evidence Assessment

    Directory of Open Access Journals (Sweden)

    Naomi Boycott


    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.

  15. Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome

    DEFF Research Database (Denmark)

    Delpón, Eva; Cordeiro, Jonathan M; Núñez, Lucía


    (to)) is thought to play a prominent role in the expression of the syndrome, mutations in I(to)-related genes have not been identified as yet. METHODS AND RESULTS: One hundred and five probands with BrS were screened for ion channel gene mutations using single strand conformation polymorphism (SSCP...

  16. Effects of 16S rRNA gene mutations on tetracycline resistance in Helicobacter pylori

    NARCIS (Netherlands)

    M.M. Gerrits (Monique); M. Berning; A.H.M. van Vliet (Arnoud); E.J. Kuipers (Ernst); J.G. Kusters (Johannes)


    textabstractThe triple-base-pair 16S rDNA mutation AGA(926-928)-->TTC mediates high-level tetracycline resistance in Helicobacter pylori. In contrast, single- and double-base-pair mutations mediated only low-level tetracycline resistance and decreased growth rates in the presence o

  17. Epidemiology of isoniazid resistance mutations and their effect on tuberculosis treatment outcomes. (United States)

    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


    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 of the inhA gene. Mycobacterium tuberculosis strains with phenotypic resistance to isoniazid from consecutively diagnosed smear-positive tuberculosis patients in rural Vietnam were subjected to Genotype MTBDRplus testing to identify katG and inhA mutations. Treatment failure and relapse were determined by sputum culture. In total, 227 of 251 isoniazid-resistant strains (90.4%) had detectable mutations: 75.3% in katG codon 315 (katG315) and 28.2% in the inhA promoter region. katG315 mutations were significantly associated with pretreatment resistance to streptomycin, rifampin, and ethambutol but not with the Beijing genotype and predicted both unfavorable treatment outcome (treatment failure or death) and relapse; inhA promoter region mutations were only associated with resistance to streptomycin and relapse. In tuberculosis patients, M. tuberculosis katG315 mutations but not inhA mutations are associated with unfavorable treatment outcome. inhA mutations do, however, increase the risk of relapse, at least with treatment regimens that contain only isoniazid and ethambutol in the continuation phase.

  18. The effect of SERPINF1 in-frame mutations in osteogenesis imperfecta type VI. (United States)

    Al-Jallad, Hadil; Palomo, Telma; Roughley, Peter; Glorieux, Francis H; McKee, Marc D; Moffatt, Pierre; Rauch, Frank


    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.

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

    Directory of Open Access Journals (Sweden)

    Escámez María-José


    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.

  20. 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)


    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)

  1. The Effectiveness of an Additional Stretching Exercise Program in Improving Flexibility Level among Preschool Boys (United States)

    Lee, Wee Akina Sia Seng; Rengasamy, Shabeshan A/L; Raju, Subramaniam A/L


    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…

  2. 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.


    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 withou

  3. The Effects of CO2 Addition on the Partial Oxidation of Heptane for Hydrogen Generation

    Institute of Scientific and Technical Information of China (English)

    Ran RAN; Guo Xing XIONG; Shi Shan SHENG; Wei Shen YANG


    The effects of CO2 on the partial oxidation of heptane for hydrogen generation have been studied. Based on the experimental results and thermodynamic equilibrium calculations, the validity of CO2 addition to weaken the hot spots, and the feasibility of the autothermal operation are discussed.

  4. Effects of DCD addition to slurry on nitrate leaching in sandy soils

    NARCIS (Netherlands)

    Corré, W.J.; Zwart, K.B.


    The effects of the addition of the nitrification inhibitor dicyandiamide (DCD) to cattle slurry, applied in autumn to an arable sandy soil, were investigated in a three-year field experiment in the Netherlands. Treatments included application of slurry with DCD in November and December, application

  5. 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.


    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 non-pharma

  6. The Effect of Enzyme Addition on Anaerobic Digestion of Jose Tall Wheat Grass (United States)

    The effects of the addition of enzyme products containing cellulase, hemicellulase, and Beta-glucosidase to anaerobic digestion systems were studied. Anaerobic digestion tests were performed using batch reactors operated at 35°C. The application of enzyme products in three digestion configurations w...

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


    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.

  8. Positional effect of mutations in 5'UTR of hepatitis C virus4a on patients' response to therapy

    Institute of Scientific and Technical Information of China (English)

    Mostafa K El Awady; Hassan M Azzazy; Ahmed M Fahmy; Sherif M Shawky; Noha G Badreldin; Samar S Yossef; Moataza H Omran; Abdel Rahman N Zekri; Said A Goueli


    AIM:To investigate the effects of mutations in domain Ⅲ of the hepatitis C virus (HCV) internal ribosome entry sequences (IRES) on the response of chronic HCV genotype 4a patients to interferon therapy. METHODS:HCV RNA was extracted from 19 chronic HCV 4a patients receiving interferon/ribavirin therapy who showed dramatic differences in their response to combination therapy after initial viral clearance. IRES domain Ⅲ was cloned and 15 clones for each patient were sequenced. The obtained sequences were aligned with genotype 4a prototype using the ClustalW program and mutations scored. Prediction of stem-loop secondary structure and thermodynamic stability of the major quasispecies in each patient was performed using the MFOLD 3.2 program with Turner energies and selected constraints on base pairing. RESULTS:Analysis of RNA secondary structure revealed that insertions in domain Ⅲ altered Watson- Crick base pairing of stems and reduced molecular stability of RNA, which may ultimately reduce binding affinity to ribosomal proteins. Insertion mutations in domain Ⅲ were statistically more prevalent in sustained viral response patients (SVR, n = 14) as compared to breakthrough (BT, n = 5) patients. CONCLUSION:The influence of mutations within domain Ⅲ on the response of HCV patients to combination therapy depends primarily on the position, but not the frequency, of these mutations within IRES domain Ⅲ.

  9. Long-range effects and functional consequences of stabilizing mutations in the ankyrin repeat domain of IκBα. (United States)

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


    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.

  10. Modelling the effects of selection temperature and mutation on the prisoner's dilemma game on a complete oriented star. (United States)

    Ren, Jianguo; Xu, Yonghong


    This paper models the prisoner's dilemma game based on pairwise comparison in finite populations on a complete oriented star (COS). First, we derive a linear system on a COS for calculating the corresponding fixation probabilities that imply dependence of the selection temperature and mutation. Then we observe and analyze the effects of two parameters on fixation probability under different population sizes. In particular, it is found through the experimental results that (1) high mutation is more sensitive to the fixation probability than the low one when population size is increasing, while the opposite is the case when the number of cooperators is increasing, and (2) selection temperature demotes the fixation probability.

  11. The R304X mutation of the Aryl hydrocarbon receptor Interacting Protein gene in familial isolated pituitary adenomas: mutational Hot-Spot or founder effect?


    Occhi, G.; Jaffrain-Rea, M. L.; Trivellin, G.; Albiger, N; Ceccato, F.; De Menis, E.; Angelini, M.; Ferasin, S; Beckers, Albert; F. Mantero; Scaroni, C.


    Background: Mutations in the Aryl hydrocarbon receptor Interacting Protein (AIP) gene have been described in about 15% of kindreds with Familial Isolated Pituitary Adenomas (FIPA) and in a minority of early onset sporadic pituitary adenomas (PA). Among the AIP mutations reported so far, the R304X (AIPR304X) represents, together with the "Finnish mutation" Q14X, the most common one. Methods: Three AIPR304X Italian families, including a newly reported kindred, have been genotyped for 12 genetic...

  12. Effect of PTPRD rs2279776 gene and interaction with hepatitis B virus mutations on the risk of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)



    Objective To investigate the effect of rs2279776 at the PTPRD and its interactions on hepatitis B virus(HBV)mutations as well as related risk on hepatocellular carcinoma(HCC).Methods A total of 3023 individ-uals,including 1012 healthy controls,990 HCC-free HBV-infected subjects,and 1021 HBV-caused hepatocellular carcinoma patients(HCC)

  13. Sensitivity of the distribution of mutational fitness effects to environment, genetic background, and adaptedness: a case study with Drosophila. (United States)

    Wang, Alethea D; Sharp, Nathaniel P; Agrawal, Aneil F


    Heterogeneity in the fitness effects of individual mutations has been found across different environmental and genetic contexts. Going beyond effects on individual mutations, how is the distribution of selective effects, f(s), altered by changes in genetic and environmental context? In this study, we examined changes in the major features of f(s) by estimating viability selection on 36 individual mutations in Drosophila melanogaster across two different environments in two different genetic backgrounds that were either adapted or nonadapted to the two test environments. Both environment and genetic background affected selection on individual mutations. However, the overall distribution f(s) appeared robust to changes in genetic background but both the mean, E(s), and the variance, V(s) were dependent on the environment. Between these two properties, V(s) was more sensitive to environmental change. Contrary to predictions of fitness landscape theory, the match between genetic background and assay environment (i.e., adaptedness) had little effect on f(s).

  14. 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;


    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...... founder effect, and to study the mechanism of loss of function of the mutant receptor....

  15. [Effect of the female genotype on the yield of dominant lethal mutations induced by thiophosphamide in mature mouse spermia]. (United States)

    Korogodina, Iu V


    On crossing of thiophosphamide treated CBA males to untreated A/He, C57BL/6, C57BL/Mib and fidget females the lowest output of dominant lethal mutations was found in progeny of C57BL/Mib females. It is suggested that the ceparation of premutational lesions is most effective in egg cells of this strain.

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

    Energy Technology Data Exchange (ETDEWEB)

    Matney, T.S.


    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)

  17. Effect of mutations in the pea genes Sym33 and Sym40. I. Arbuscular mycorrhiza formation and function. (United States)

    Jacobi, Lidia M; Petrova, Olesia S; Tsyganov, Viktor E; Borisov, Alexey Y; Tikhonovich, Igor A


    Two pea (Pisum sativum L.) symbiotic mutants SGEFix(-)-1 (sym40) and SGEFix(-)-2 (sym33) with abnormalities in infection thread development and function in symbiotic root nodules have been characterised in terms of mycorrhizal colonisation of roots, shoot and root biomass accumulation and shoot and root phosphorus (P) content. The mutation in gene sym33 decreased mycorrhizal colonisation of roots (except arbuscule abundance in mycorrhizal root fragments, which increased) but did not change the effectiveness of mycorrhiza function. The mutation in sym40 did not affect either of these processes. Both mutants showed differences in plant development compared with the wild-type line SGE. The mutants had delayed flowering and pod ripening, and shoot/root biomass ratios and P accumulation also differed from those of SGE. These observations suggest that the gene mutations cause systemic changes in plant development.

  18. Effect of mutations in the A site of 16 S rRNA on aminoglycoside antibiotic-ribosome interaction

    DEFF Research Database (Denmark)

    Recht, M I; Douthwaite, S; Dahlquist, K D


    Decoding of genetic information occurs upon interaction of an mRNA codon-tRNA anticodon complex with the small subunit of the ribosome. The ribosomal decoding region is associated with highly conserved sequences near the 3' end of 16 S rRNA. The decoding process is perturbed by the aminoglycoside...... of universally conserved nucleotides at 1406 to 1408 and 1494 to 1495 in the decoding region of plasmid-encoded bacterial 16 S rRNA. Phenotypic changes range from the benign effect of U1406-->A or A1408-->G substitutions, to the highly deleterious 1406G and 1495 mutations that assemble into 30 S subunits...... but are defective in forming functional ribosomes. Changes in the local conformation of the decoding region caused by these mutations were identified by chemical probing of isolated 30 S subunits. Ribosomes containing 16 S rRNA with mutations at positions 1408, 1407+1494, or 1495 had reduced affinity...

  19. Effect of three different anti-mycotoxin additives on broiler chickens exposed to aflatoxin B1

    Directory of Open Access Journals (Sweden)

    AA Oliveira


    Full Text Available The growth of filamentous fungi on food often causes, aside from its deterioration, the mycotoxin production which determines economic losses in poultry industry, such as decreased productivity and injuries on poultry's carcass. Adsorbents based on yeast cell wall from Saccharomyces cerevisiae, which contain esterified glucomannan, are an alternative to reduce the mycotoxins bioavailability. The aim of this study was to compare in vitro and in vivo the performance of new three anti-mycotoxin additives (AMA based on yeast cell wall from Saccharomyces cerevisiae. The adsorption process was quantified in vitro, and the data obtained when plotted with Hill's equation indicated a cooperative process. Then, the three different AMA were tested for its ability to reduce the effects of aflatoxins in the diet of growing broiler chickens. The addition of 1 mg kg-1 aflatoxin B1 to the diets of broilers caused a negative change on the performance parameters besides increasing liver weight, fatty degeneration and liver necrosis. The addition of two different kinds of AMA (0.2% could reverse such effects. In conclusion, AMA 1 and 2 are additives with good potential for application on animal production. The AMA 3 ingredients must be re-tested alone for its adsorption capacity. These are the first data reported from Brazil anti-mycotoxin additives with preliminary isothermal analysis. Since beneficial characteristics of S. cerevisiae cell wall in animal industry are strain dependent, this study suggests two new promising alternatives to ameliorate mycotoxin problem.

  20. The Blazhko effect and additional excited modes in RR Lyrae stars

    CERN Document Server

    Benkő, J M


    Recent photometric space missions, such as CoRoT and Kepler revealed that many RR Lyrae stars pulsate -- beyond their main radial pulsation mode -- in low amplitude modes. Space data seem to indicate a clear trend, namely overtone (RRc) stars and modulated fundamental (RRab) RR Lyrae stars ubiquitously show additional modes, while non-Blazhko RRab stars never do. Two Kepler stars (V350 Lyr and KIC 7021124), however, apparently seemed to break this rule: they were classified as non-Blazhko RRab stars showing additional modes. We processed Kepler pixel photometric data of these stars. We detected small amplitude, but significant Blazhko effect for both stars by using the resulted light curves and O$-$C diagrams. This finding strengthens the apparent connection between the Blazhko effect and the excitation of additional modes. In addition, it yields a potential tool for detecting Blazhko stars through the additional frequency patterns even if we have only short but accurate time series observations. V350 Lyr sho...

  1. The Effect of Silicon and Aluminum Additions on the Oxidation Resistance of Lean Chromium Stainless Steels

    Energy Technology Data Exchange (ETDEWEB)

    Dunning, J.S.; Alman, D.E.; Rawers, J.C.


    The effect of Si and Al additions on the oxidation of lean chromium austenitic stainless steels has been studied. A baseline composition of Fe-16Cr-16Ni-2Mn-1Mo was selected to allow combined Si and Al additions of up to 5 wt. pct. in a fully austenitic alloy. The baseline composition was selected using a net Cr equivalent equation to predict the onset of G-ferrite formation in austenite. Cyclic oxidation tests in air for 1000 hours were carried out on alloys with Si only or combined Si and Al additions in the temperature range 700 C to 800 C. Oxidation resistance of alloys with Si only additions were outstanding, particularly at 800 C. It was evident that different rate controlling mechanisms for oxidation were operative at 700 C and 800 C in the Si alloys. In addition, Si alloys pre-oxidized at 800 C, showed a zero weight gain in subsequent testing for 1000 hours at 700 C. The rate controlling mechanism in alloys with combined Si and Al addition for oxidation at 800 C was also different than alloys with Si only. SEM and ESCA analysis of the oxide films and base material at the oxide/base metal interface were conducted to study potential rate controlling mechanisms.

  2. Experimental investigation of effects of bio-additives on fuel economy of the gasoline engine

    Institute of Scientific and Technical Information of China (English)

    YAO ChunDe; ZHANG ZhiHui; XU YuanLi; HUANG Yu


    The matter extracted from palm oil was considered as gasoline additive. The effect of various percentages (0.2%, 0.4% and 0.6%) of the bio-additives on fuel economy of SI engine respectively running on prime gasoline, gasoline with known compo-nents, ethanol gasoline, and methanol gasoline under typical urban operation condition 2000 r/min was investigated. The results showed that the bio-additives can remarkably improve the fuel economy of Sl engine while operating on all kinds of fuel. The optimal ratio of bio-additive to gasoline depends on the fuel used and on the different engine operating conditions. Besides, the experiments of constant volume combustion bomb, analysis of in cylinder processes, the synchrotron re-dietion and high-temperature friction were conducted to probe into the mechanism of the bio-additive impact on fuel economy. It indicated that the bio-additives can increase the maximum cylinder combustion pressure, improve exhaust emissions and largely reduce the frication coefficient.

  3. Experimental investigation of effects of bio-additives on fuel economy of the gasoline engine

    Institute of Scientific and Technical Information of China (English)


    The matter extracted from palm oil was considered as gasoline additive. The effect of various percentages (0.2%, 0.4% and 0.6%) of the bio-additives on fuel economy of SI engine respectively running on prime gasoline, gasoline with known compo- nents, ethanol gasoline, and methanol gasoline under typical urban operation condition 2000 r/min was investigated. The results showed that the bio-additives can remarkably improve the fuel economy of SI engine while operating on all kinds of fuel. The optimal ratio of bio-additive to gasoline depends on the fuel used and on the different engine operating conditions. Besides, the experiments of constant volume combustion bomb, analysis of in cylinder processes, the synchrotron ra- diation and high-temperature friction were conducted to probe into the mechanism of the bio-additive impact on fuel economy. It indicated that the bio-additives can increase the maximum cylinder combustion pressure, improve exhaust emissions and largely reduce the frication coefficient.

  4. Effect of Ingredient Loading on Surface Migration Kinetics of Additives in Vulcanized Natural Rubber Compounds

    Directory of Open Access Journals (Sweden)

    Bryan B. Pajarito


    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.

  5. Effect of Dodecylbenzene Sulfonic Acid Used as Additive on Residue Hydrotreating

    Institute of Scientific and Technical Information of China (English)

    Sun Yudong; Yang Chaohe


    The effect of additive—dodecylbenzene sulfonic acid (DBSA)—on residue hydrotreating was studied in the au-toclave. The results showed that the additive improved stabilization of the colloid system of residue, which could delay the aggregation and coke formation from asphaltenes on the catalyst, and make heavy components transformed into light oil. The residue conversion in the presence of this additive increased by 1.94%, and the yield of light oil increased by 1.53% when the reaction time was 90 min. The surface properties of the catalyst in the presence of this additive were better than that of the blank test within a very short time (30 min) and deteriorated rapidly after a longer reaction time due to higher conversion and coke deposition. Compared with the blank test, the case using the said additive had shown that the structure of hydrotreated asphaltene units was smaller and the condensation degrees were higher. The test results indicated that the additive could improve the hydrotreating reactivity of residue via permeation and depolymerization, the heavier components could be transformed into light oil more easily, and the light oil yield and residue conversion were higher for the case using the said additive in residue hydrotreating process.

  6. Species composition and fire: non-additive mixture effects on ground fuel flammability

    Directory of Open Access Journals (Sweden)

    Cassandra eVan Altena


    Full Text Available Biodiversity effects on many aspects of ecosystem function have been well documented. However, fire is an exception: fire experiments have mainly included single species, bulk litter, or vegetation, and, as such, the role of biodiversity as a determinant of flammability, a crucial aspect of ecosystem function, is poorly understood. This study is the first to experimentally test whether flammability characteristics of two-species mixtures are non-additive, i.e. differ from expected flammability based on the component species in monoculture. In standardized fire experiments on ground fuels, including monocultures and mixtures of five contrasting subarctic plant fuel types in a controlled laboratory environment, we measured flame speed, flame duration and maximum temperature. Broadly half of the mixture combinations showed non-additive effects for these flammability indicators; these were mainly enhanced dominance effects, where the fuel types with the more flammable value for a characteristic determined the flammability of the whole mixture. The high incidence of species non-additive effects on ground fuel flammability suggest that the combinations of fuel types may have important effects on ground fire regimes in vegetations differing or changing in species composition.

  7. Categorical and continuous - disentangling the neural correlates of the carry effect in multi-digit addition

    Directory of Open Access Journals (Sweden)

    Dressel Katharina


    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.

  8. 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.

  9. Effect of indium addition in U-Zr metallic fuel on lanthanide migration (United States)

    Kim, Yeon Soo; Wiencek, T.; O'Hare, E.; Fortner, J.; Wright, A.; Cheon, J. S.; Lee, B. O.


    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.

  10. Effect of Addition of Cereal Based Beta-glucan on Technological and Functional Properties of Foods

    Directory of Open Access Journals (Sweden)

    Nihal Şimşekli


    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.

  11. Effect of cerium addition on microstructures of carbon-alloyed iron aluminides

    Indian Academy of Sciences (India)

    S Sriram; R Balasubramaniam; M N Mungole; S Bharagava; R G Baligidad


    The effect of Ce addition on the microstructure of carbon-alloyed Fe3Al-based intermetallic has been studied. Three different alloys of composition, Fe–18.5Al–3.6C, Fe–20.0Al–2.0C and Fe–19.2Al–3.3C–0.07Ce (in at%), were prepared by electroslag remelting process. Their microstructures were characterized using optical and scanning electron microscopies. Stereological methods were utilized to understand the observed microstructures. All the alloys exhibited a typical two-phase microstructure consisting of Fe3AlC carbides in an iron aluminide matrix. In the alloy without Ce addition, large bulky carbides were equally distributed throughout the matrix with many smaller precipitates interspersed in between. In the alloy with Ce addition, the carbide grain sizes were finer and uniformly distributed throughout the matrix. The effect of Ce addition on the carbide morphology has been explained based on the known effect of Ce in modifying carbide morphology in cast irons.

  12. Assessment of the Low Alloy Cast Steel Inoculation Effects with Chosen Additives

    Directory of Open Access Journals (Sweden)

    D. Bartocha


    Full Text Available Structure, and thus the mechanical properties of steel are primarily a function of chemical composition and the solidification process which can be influenced by the application of the inoculation treatment. This effect depends on the modifier used. The article presents the results of studies designed to assess the effects of structural low alloy steel inoculation by selected modifying additives. The study was performed on nine casts modeled with different inoculants, assessment of the procedure impact was based on the macrostructure of made castings. The ratio of surface area equivalent to the axial zone of the crystals and columnar crystals zone was adopted as a measure of the inoculation effect.

  13. The effect of Y2O3 addition on thermal shock behavior of magnesium aluminate spinel

    Directory of Open Access Journals (Sweden)

    Pošarac Milica


    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.

  14. The Additive Risk Model for Estimation of Effect of Haplotype Match in BMT Studies

    DEFF Research Database (Denmark)

    Scheike, Thomas; Martinussen, T; Zhang, MJ


    leads to a missing data problem. We show how Aalen's additive risk model can be applied in this setting with the benefit that the time-varying haplomatch effect can be easily studied. This problem has not been considered before, and the standard approach where one would use the expected-maximization (EM......) algorithm cannot be applied for this model because the likelihood is hard to evaluate without additional assumptions. We suggest an approach based on multivariate estimating equations that are solved using a recursive structure. This approach leads to an estimator where the large sample properties can...

  15. Solvent additive effects on small molecule crystallization in bulk heterojunction solar cells probed during spin casting

    KAUST Repository

    Pérez, Louis A.


    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.

  16. Addition of alarm pheromone components improves the effectiveness of desiccant dusts against Cimex lectularius. (United States)

    Benoit, Joshua B; Phillips, Seth A; Croxall, Travis J; Christensen, Brady S; Yoder, Jay A; Denlinger, David L


    We demonstrate that the addition of bed bug, Cimex lectularius, alarm pheromone to desiccant formulations greatly enhances their effectiveness during short-term exposure. Two desiccant formulations, diatomaceous earth (DE) and Dri-die (silica gel), were applied at the label rate with and without bed bug alarm pheromone components, (E)-2-hexenal, (E)-2-octenal, and a (E)-2-hexenal:(E)-2-octenal blend. First-instar nymphs and adult females were subjected to 10-min exposures, and water loss rates were used to evaluate the response. Optimal effectiveness was achieved with a pheromone concentration of 0.01 M. With Dri-die alone, the water loss was 21% higher than in untreated controls, and water loss increased nearly two times with (E)-2-hexenal and (E)-2-octenal and three times with the (E)-2-hexenal: (E)-2-octenal blend. This shortened survival of first-instar nymphs from 4 to 1 d, with a similar reduction noted in adult females. DE was effective only if supplemented with pheromone, resulting in a 50% increase in water loss over controls with the (E)-2-hexenal:(E)-2-octenal blend, and a survival decrease from 4 to 2 d in first-instar nymphs. Consistently, the addition of the pheromone blend to desiccant dust was more effective than adding either component by itself or by using Dri-die or DE alone. Based on observations in a small microhabitat, the addition of alarm pheromone components prompted bed bugs to leave their protective harborages and to move through the desiccant, improving the use of desiccants for control. We concluded that short exposure to Dri-die is a more effective treatment against bed bugs than DE and that the effectiveness of the desiccants can be further enhanced by incorporation of alarm pheromone. Presumably, the addition of alarm pheromone elevates excited crawling activity, thereby promoting cuticular changes that increase water loss.

  17. Additive scales in degenerative disease - calculation of effect sizes and clinical judgment

    Directory of Open Access Journals (Sweden)

    Riepe Matthias W


    Full Text Available Abstract Background The therapeutic efficacy of an intervention is often assessed in clinical trials by scales measuring multiple diverse activities that are added to produce a cumulative global score. Medical communities and health care systems subsequently use these data to calculate pooled effect sizes to compare treatments. This is done because major doubt has been cast over the clinical relevance of statistically significant findings relying on p values with the potential to report chance findings. Hence in an aim to overcome this pooling the results of clinical studies into a meta-analyses with a statistical calculus has been assumed to be a more definitive way of deciding of efficacy. Methods We simulate the therapeutic effects as measured with additive scales in patient cohorts with different disease severity and assess the limitations of an effect size calculation of additive scales which are proven mathematically. Results We demonstrate that the major problem, which cannot be overcome by current numerical methods, is the complex nature and neurobiological foundation of clinical psychiatric endpoints in particular and additive scales in general. This is particularly relevant for endpoints used in dementia research. 'Cognition' is composed of functions such as memory, attention, orientation and many more. These individual functions decline in varied and non-linear ways. Here we demonstrate that with progressive diseases cumulative values from multidimensional scales are subject to distortion by the limitations of the additive scale. The non-linearity of the decline of function impedes the calculation of effect sizes based on cumulative values from these multidimensional scales. Conclusions Statistical analysis needs to be guided by boundaries of the biological condition. Alternatively, we suggest a different approach avoiding the error imposed by over-analysis of cumulative global scores from additive scales.

  18. 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; 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 BRCA1

  19. Effect of Prior Bilateral Oophorectomy on the Presentation of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers

    Directory of Open Access Journals (Sweden)

    Metcalfe Kelly A


    Full Text Available Abstract Purpose To compare the presentation of invasive breast cancer in BRCA1 and BRCA2 mutation carriers with and without prior bilateral oophorectomy. Patients and methods Women with a BRCA1 or BRCA2 mutation with the diagnosis of invasive breast cancer were identified from ten cancer genetics clinics. The medical history, medical treatment records and pathology reports for the breast cancers were reviewed. Information was abstracted from medical charts, including history (and date of oophorectomy, date of breast cancer diagnosis, stage of disease, and pathologic characteristics of the breast cancer. Women with prior bilateral oophorectomy were matched by age, year of diagnosis, and mutation with one or more women who had two intact ovaries at the time of breast cancer diagnosis. Characteristics of the breast tumours were compared between the two groups. Results Women with prior bilateral oophorectomy presented with smaller tumours on average compared to women without prior oophorectomy (mean size 1.50 cm vs. 1.95 cm; p = 0.01. Additionally, although not statistically significant, women with intact ovaries were more likely to have high-grade tumour (70% vs. 54%: p = 0.10 and to have positive lymph nodes (34% vs. 18%; p = 0.11 compared to women with prior bilateral oophorectomy. Conclusions Bilateral oophorectomy prior to breast cancer appears to favourably influence the biological presentation of breast cancer in BRCA1 and BRCA2 mutation carriers.

  20. Neighboring-Nucleotide Effects on the Mutation Patterns of the Rice Genome

    Institute of Scientific and Technical Information of China (English)

    Hui Zhao; Qi-Zhai Li; Chang-Qing Zeng; Huan-Ming Yang; Jun Yu


    DNA composition dynamics across genomes of diverse taxonomy is a major subject of genome analyses. DNA composition changes are characteristics of both replication and repair machineries. We investigated 3,611,007 single nucleotide polymorphisms (SNPs) generated by comparing two sequenced rice genomes from distant inbred lines (subspecies), including those from 242,811 introns and 45,462 protein-coding sequences (CDSs). Neighboring-nucleotide effects (NNEs) of these SNPs are diverse, depending on structural content-based classifications (genomewide, intronic, and CDS) and sequence context-based categories (A/C, A/G, A/T,C/G, C/T, and G/T substitutions) of the analyzed SNPs. Strong and evident NNEs and nucleotide proportion biases surrounding the analyzed SNPs were observed in 1-3 bp sequences on both sides of an SNP. Strong biases were observed around neighboring nucleotides of protein-coding SNPs, which exhibit a periodicity of three in nucleotide content, constrained by a combined effect of codon-related rules and DNA repair mechanisms. Unlike a previous finding in the human genome,we found negative correlation between GC contents of chromosomes and the magnitude of corresponding bias of nucleotide C at -1 site and G at +1 site. These results will further our understanding of the mutation mechanism in rice as well as its evolutionary implications.

  1. Classification of suppressor additives based on synergistic and antagonistic ensemble effects

    Energy Technology Data Exchange (ETDEWEB)

    Broekmann, P., E-mail: [BASF SE, Global Business Unit Electronic Materials, 67056 Ludwigshafen (Germany); Department of Chemistry and Biochemistry, University of Bern, Bern (Switzerland); Fluegel, A.; Emnet, C.; Arnold, M.; Roeger-Goepfert, C.; Wagner, A. [BASF SE, Global Business Unit Electronic Materials, 67056 Ludwigshafen (Germany); Hai, N.T.M. [Department of Chemistry and Biochemistry, University of Bern, Bern (Switzerland); Mayer, D. [BASF SE, Global Business Unit Electronic Materials, 67056 Ludwigshafen (Germany)


    Highlights: > Three fundamental types of suppressor additives for copper electroplating could be identified by means of potential transient measurements. > These suppressor additives differ in their synergistic and antagonistic interplay with anions that are chemisorbed on the metallic copper surface during electrodeposition. > In addition these suppressor chemistries reveal different barrier properties with respect to cupric ions and plating additives (Cl, SPS). - Abstract: Three fundamental types of suppressor additives for copper electroplating could be identified by means of potential transient measurements. These suppressor additives differ in their synergistic and antagonistic interplay with anions that are chemisorbed on the metallic copper surface during electrodeposition. In addition these suppressor chemistries reveal different barrier properties with respect to cupric ions and plating additives (Cl, SPS). While the type-I suppressor selectively forms efficient barriers for copper inter-diffusion on chloride-terminated electrode surfaces we identified a type-II suppressor that interacts non-selectively with any kind of anions chemisorbed on copper (chloride, sulfate, sulfonate). Type-I suppressors are vital for the superconformal copper growth mode in Damascene processing and show an antagonistic interaction with SPS (Bis-Sodium-Sulfopropyl-Disulfide) which involves the deactivation of this suppressor chemistry. This suppressor deactivation is rationalized in terms of compositional changes in the layer of the chemisorbed anions due to the competition of chloride and MPS (Mercaptopropane Sulfonic Acid) for adsorption sites on the metallic copper surface. MPS is the product of the dissociative SPS adsorption within the preexisting chloride matrix on the copper surface. The non-selectivity in the adsorption behavior of the type-II suppressor is rationalized in terms of anion/cation pairing effects of the poly-cationic suppressor and the anion-modified copper

  2. Effects of different additives on bimetallic Au-Pt nanoparticles electrodeposited onto indium tin oxide electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Ballarin, Barbara, E-mail: ballarin@ms.fci.unibo.i [Dipartimento di Chimica Fisica ed Inorganica, Universita di Bologna, V.le Risorgimento, 4, 40136-Bologna (Italy)] [INSTM, UdR Bologna (Italy); Gazzano, Massimo [ISOF-CNR, V. Selmi, 40126-Bologna (Italy); Tonelli, Domenica [Dipartimento di Chimica Fisica ed Inorganica, Universita di Bologna, V.le Risorgimento, 4, 40136-Bologna (Italy)] [INSTM, UdR Bologna (Italy)


    Bimetallic Au-Pt nanoparticles (Au-Pt{sub NPs}) have been synthesized using an electrochemical reduction approach. The effects of the addition of different additives in the electrodeposition bath namely KI, 1-nonanesulfonic acid sodium salt and Triton X-100 have been investigated. The structural characterization of the bimetallic nanoparticles has been carried out using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), UV-vis spectroscopy, X-ray diffraction (XRD) and cyclic voltammetry (CV). The Au-Pt{sub NPs} prepared in the presence of KI and Triton X-100 characterized by a relatively narrow size distribution as well as a higher particle density and surface coverage whereas no changes in the morphology were observed. These results suggest a dependence of the size and distribution of the bimetallic nanoparticles from the type and concentration of the additives employed.

  3. Effect of cerium and lanthanum additives on plasma electrolytic oxidation of AZ31 magnesium alloy

    Institute of Scientific and Technical Information of China (English)

    沈德久; 马豪杰; 郭长虹; 蔡景瑞; 李国龙; 何东磊; 杨庆祥


    Plasma electrolytic oxidation (PEO) coatings on AZ31 magnesium (Mg) alloy were developed using the aqueous solution with alkaline silicate and sodium hydroxide as a base electrolyte system. The effects of cerium (Ce) nitrate and lanthanum (La) nitrate additives on the voltage response, microstructure, compositions and corrosion resistance of PEO coatings were investigated by scan-ning electron microscopy (SEM), energy-dispersive spectrum (EDS), X-ray diffraction (XRD) and potentiodynamic polarization tests, etc. The results showed that Ce and La additives increased the stable voltage and compactness of the PEO coatings, while, those did not change the compositions of the PEO coatings. The corrosion resistance of the PEO coating obtained in solutions with La nitrate of 0.1 g/L was the best, followed by that with Ce nitrate of 0.1 g/L and that without additives.

  4. 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


    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...

  5. Effect of TiC whisker addition on properties of YG1OF alloy

    Institute of Scientific and Technical Information of China (English)


    The cemented carbide material (YG10F) with different additions of TiC whisker (0%, 0.3%, 0.6%, mass fraction) was prepared by different techniques. The effect of TiC whisker addition on the density, microhardness and toughness of the experimental material was investigated. The results indicate that after the wet-milling for 8 h and sintering in vacuum at 1 440 ℃, the toughness of YG10F is remarkably improved and meanwhile higher microhardness is obtained by 0.3% TiC whisker addition. Preliminary analysis suggests that the main toughening mechanism of TiC whisker in YG10F is whisker pull-out and bridging phenomena.

  6. Effect of Ca addition on the corrosion behavior of Mg-Al-Mn alloy (United States)

    Yang, Jiang; Peng, Jian; Nyberg, Eric A.; Pan, Fu-sheng


    The microstructures and corrosion resistance of magnesium-5 wt% aluminum-0.3 wt% manganese alloys (Mg-Al-Mn) with different Ca additions (0.2-4 wt%) were investigated. Results showed that with increasing Ca addition, the grain of the alloys became more refined, whereas the corrosion resistant ability of the alloys initially increased and then decreased. The alloy with 2 wt% Ca addition exhibited the best corrosion resistance, attributed to the effect of the oxide film and (Mg,Al)2Ca phases which were discontinuously distributed on the grain boundaries. These phases acted as micro-victims, they preferentially corroded to protect the α-Mg matrix. The oxide film formed on the alloy surface can hinder the solution further to protect the α-Mg matrix.

  7. Effect of bauxite addition on densification and mullitization behaviour of West Bengal clay

    Indian Academy of Sciences (India)

    N S Raut; P Biswas; T K Bhattacharya; K Das


    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 present in bauxite and clay formed liquid phase which helped in particle diffusion to aid densification. The X-ray diffraction of sample fired at 1500°C showed cristoballite phase gradually disappearing and at the same time mullite and -Al2O3 phase appearing at a higher level of bauxite addition. The in situ nascent alumina formed was reactive that facilitated the formation of secondary mullite by solution precipitation mechanism. The presence of bauxite also changed the morphology of the mullite particles. Two types of mullite were distinctly observed in the SEM photographs: elongated primary mullite and equiaxed secondary mullite.

  8. 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.


    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...

  9. Assessment of Site Specific Mutational Effect on Transcription Initiation at Escherichia coli Promoter

    Directory of Open Access Journals (Sweden)

    S. Kannan


    Full Text Available Problem statement: It is widely accepted thought that the weak promoters control the RNA synthesis and play regulatory role in complex genetic networks in bacterial system. An experiment had been designed to address whether mutations in the -16/-17 region affect the rate of transcription at an activator-independent promoter in E. coli or not? Approach: The aim of this study was to determine whether mutations in the -16/-17 region affect the rate of expression at an activator-dependent promoter in JM109 strain of E. coli. Primers were constructed to amplify the mutant promoter genes through PCR. The amplified PCR product was checked and then inserted into the MCS region of pAA128 plasmid. Further the plasmid vector was transformed into JM109 strain of E. coli and then cloned the selected transformats. Finally, the plasmid from each mutant colony was then sequenced using the protocol supplied with the Amersham Pharmacia Biotech T7 sequencing Kit. The JM109 cultures for which the sequences were determined, then assayed for ß-galactosidase activity to assess the rate of gene expression from the altered promoters. Results: The present investigation revealed that the extended-10 promoter region has a substantial effect on the rate of transcription at weak promoter sequence and also bearing little resemblance to the consensus sequence recognized by RNA. The expression of the genetically engineered plasmid proved that the 2 bps (-16 and -17 base pair found adjacently upstream of the extended-10 promoter have an effect on the level of transcription. This was achieved by site specific base substitutions into the weak promoter of a modified lac operon lacking any activator or repressor binding sites. The results from gene expression assays of several mutants showed a distinct preference for either GG or TT located adjacently upstream of the extended promoter element. Thus the present study emphasized that

  10. Effect of rhenium addition on tungsten fuzz formation in helium plasmas (United States)

    Khan, Aneeqa; De Temmerman, Gregory; Morgan, Thomas W.; Ward, Michael B.


    The effect of the addition of rhenium to tungsten on the formation of a nanostructure referred to as 'fuzz' when exposed to helium plasmas at fusion relevant ion fluxes was investigated in the Magnum and Pilot PSI devices at the FOM Institute DIFFER. The effect rhenium had on fuzz growth was seen to be dependent on time, temperature and flux. Initial fuzz growth was seen to be highly dependent on grain orientation, with rhenium having little effect. Once the fuzz was fully developed, the effect of grain orientation disappeared and the rhenium had an inhibiting effect on growth. This could be beneficial for inhibiting fuzz growth in a future fusion reactor, where transmutation of tungsten to rhenium is expected. It also appears that erosion or annealing of the fuzz is limiting growth of fuzz at higher temperatures in the range of ∼1340 °C.

  11. Effects of Nitrogen and Phosphorus Additions on Carbon Cycling of Tropical Mountain Rainforests in Hainan, China (United States)

    Lai, J.


    Nitrogen (N) and Phosphorus (P) deposition is projected to increase significantly in tropical regions in the coming decades, which has changed and will change the structure and function of ecosystems, and affects on ecosystem Carbon (C) cycle. As an important part in global C cycle, how the C cycle of tropical rainforests will be influenced by the N and P deposition should be focused on. This study simulated N and P deposition in a primary and secondary forest of tropical mountain rainforest in Jianfengling, Hainan, China, during five-year field experiment to evaluate the effects of N and P deposition on C cycling processes and relate characteristics. Six levels of N and P treatments were treated: Control, Low-N, Medium-N, High-N, P and N+P. The relative growth rates (RGR) of tree layer in treatment plots were different from that in control plots after years of N and P addition. Simulated N and P deposition also increased ANPP in primary forest. N and P addition changed the growth of trees by altering soil nutrient and microbial activities. N and P addition increased soil organic carbon (SOC) and total N (TN) content, and significantly increased soil total P (TP) content, not changing soil pH. During the whole process of N and P addition, as net nitrification rate and net N mineralization rate were promoted by N and P addition, and effective N content (nitrate) of soil increased in the plot treated with N treatments compared to the control treatment. The microbial P content was increased by N and P addition, and microbial N was not changed. The increasing N deposition may enhance soil nutrient and stimulate growth of trees, which will lead to an increase of the C sequestration.

  12. Coexposure to phytoestrogens and bisphenol a mimics estrogenic effects in an additive manner. (United States)

    Katchy, Anne; Pinto, Caroline; Jonsson, Philip; Nguyen-Vu, Trang; Pandelova, Marchela; Riu, Anne; Schramm, Karl-Werner; Samarov, Daniel; Gustafsson, Jan-Åke; Bondesson, Maria; Williams, Cecilia


    Endocrine-disrupting chemicals (EDC) are abundant in our environment. A number of EDCs, including bisphenol A (BPA) can bind to the estrogen receptors (ER), ERα and ERβ, and may contribute to estrogen-linked diseases such as breast cancer. Early exposure is of particular concern; many EDCs cross the placenta and infants have measurable levels of, eg, BPA. In addition, infants are frequently fed soy-based formula (SF) that contains phytoestrogens. Effects of combined exposure to xeno- and phytoestrogens are poorly studied. Here, we extensively compared to what extent BPA, genistein, and an extract of infant SF mimic estrogen-induced gene transcription and cell proliferation. We investigated ligand-specific effects on ER activation in HeLa-ERα and ERβ reporter cells; on proliferation, genome-wide gene regulation and non-ER-mediated effects in MCF7 breast cancer cells; and how coexposure influenced these effects. The biological relevance was explored using enrichment analyses of differentially regulated genes and clustering with clinical breast cancer profiles. We demonstrate that coexposure to BPA and genistein, or SF, results in increased functional and transcriptional estrogenic effects. Using statistical modeling, we determine that BPA and phytoestrogens act in an additive manner. The proliferative and transcriptional effects of the tested compounds mimic those of 17β-estradiol, and are abolished by cotreatment with an ER antagonist. Gene expression profiles induced by each compound clustered with poor prognosis breast cancer, indicating that exposure may adversely affect breast cancer prognosis. This study accentuates that coexposure to BPA and soy-based phytoestrogens results in additive estrogenic effects, and may contribute to estrogen-linked diseases, including breast cancer.

  13. Priming effects in aggregate size fractions induced by glucose addition and grinding (United States)

    Tian, Jing; Blagodatskaya, Evgenia; Pausch, Johanna; Kuzaykov, Yakov


    It is widely recognized that soil organic matter (SOM) mineralization can be accelerated (positive priming) or retarded (negative priming) by addition of easily available substrates to soil. SOM is a heterogeneous mixture, which contains numerous compounds with different degradability and turnover rates times. Nevertheless, so far, there is still lack of knowledge on identifying single fractions of the SOM as the source of C and N released by priming effects. The aim of this study was to determine the priming effect as related to different aggregate fractions, aggregate disruption and the amounts of substrate. In a 49 days incubation experiment, the soil samples were separated into three aggregate fractions (>2 mm, 2-0.25 mm and 0.25 mm) than in the microaggregates (priming effect increased as added glucose increased in all intact aggregate size, and highest priming effect was observed in >2 mm fraction. However, the magnitude of priming effect response to glucose addition depended on the aggregate size after grinding. This study demonstrates that substrate amounts, aggregate fractionation and grinding can have obvious impacts on priming effect, indicating important implications for understanding SOM cycling and stability.

  14. Effect of titanium addition on thermal stability of hydroxyapatite/zirconia nanocomposite

    Directory of Open Access Journals (Sweden)

    Wang L.I.


    Full Text Available HA/ZrO2 composite nanpowder with various addition of titanium (0.2-2.4wt% were synthesized via wet chemical method using ZrOCl2.8H2O, H3PO4, Ca(OH2 and tetraethylorthotitanate as precursor materials. The composites were then sintered at 900-1200ºC for 2h, respectively. Effect of titanium addition to the composite on the phase composition and thermal stability during thermal treatment was investigated. The results suggested that as the sintering temperature increased from 900°C to 1200ºC and with the addition of titanium to the composite below 0.8wt%, main phases were HA and ZrO2. As the sintering temperature increased to 1200°C and with the addition of titanium to the composite above 0.8wt%, main phases were HA, ZrO2 and a small amount of dicalcium phosphate (DCP. There were still no tricalcium phosphate (β-TCP and CaZrO3 phases observed, which indicated that the addition of titanium restrained decomposition of HA and thermal reaction between HA and ZrO2. It also suggested that the addition of 0.8wt% titanium to the composite was optimum for producing HA/ZrO2 composite nanopowder with expected main phases. With the addition of 0.8wt% titanium to the composite, SEM images showed that the individual particles of the two materials were still visible, which also implied that the reaction between HA and ZrO2 did not occur.

  15. 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


    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.


    Institute of Scientific and Technical Information of China (English)

    M.C.Chaturvedi; Y.L.Wang; N.L.Richards


    Four alloys TMS-75 (Base), Base+B, Base+C and TMD-103 (Base+B+C) with varying levels of B, C were directionally solidified (DS), and their weldability was investigated by bead-onplate electron beam welding.It was found that cracking occurred in the weld-metal, as well as in the heat affected zone (HAZ).Both γ/γ' and/or γ/carbide eutectic contributed to the weld-metal cracking, and the γ/γ' eutectic was found to be mainly responsible for cracking in HAZ However, constitutional liquation of carbides seems to have made some contribution also.The B addition had a detrimental effect on HAZ cracking susceptibility, while C addition improved it appreciably even in the presence of B.In addition, no obvious differences were observed in cracking susceptibility of weld-metal in the four alloys.The cracking modes and mechanisms underlying the effect of B and C addition on weldability could be explained on the basis of microstructures of the four alloys.

  17. Effect of several variables in the polymer toys additive migration to saliva. (United States)

    Noguerol-Cal, R; López-Vilariño, J M; González-Rodríguez, M V; Barral-Losada, L


    Capacity to migrate of a representative group of polymeric additives, dyes, antioxidants, hindered amine light stabilizers (HALS) or antistatics, from plastic toys to saliva was analyzed to protect children in their habits of sucking and biting. Most of target additives appear no-regulated in toys normative but adverse effects on human health of some of them have been demonstrated and their presence in others commercial articles normative has been included. In order to offer an effective and easy tool to perform these controls, migration tests by dynamic and static contact, followed by a preconcentration step by liquid-liquid extraction (LLE) and ultra performance liquid chromatographic analysis with ultraviolet-visible and evaporative light scattering detections (UPLC-UV/Vis-ELSD) have been optimized to evaluate the migrated amounts of the additives in saliva simulant. The detection limits of the migration methodologies were ranged from 8.68 × 10(-2) to 1.30 × 10(-3)mg migrated (L simulant)(-1). Influence of several variables on this mass transport, as time, temperature and friction, was also analyzed to achieve the most aggressive methodology to protect consumers. Migration of several studied additives, whose presence has been demonstrated in several purchased commercial toys, has been observed.

  18. Co-digestion of manure and industrial waste--The effects of trace element addition. (United States)

    Nordell, Erik; Nilsson, Britt; Nilsson Påledal, Sören; Karisalmi, Kaisa; Moestedt, Jan


    Manure is one of the most common substrates for biogas production. Manure from dairy- and swine animals are often considered to stabilize the biogas process by contributing nutrients and trace elements needed for the biogas process. In this study two lab-scale reactors were used to evaluate the effects of trace element addition during co-digestion of manure from swine- and dairy animals with industrial waste. The substrate used contained high background concentrations of both cobalt and nickel, which are considered to be the most important trace elements. In the reactor receiving additional trace elements, the volatile fatty acids (VFA) concentration was 89% lower than in the control reactor. The lower VFA concentration contributed to a more digested digestate, and thus lower methane emissions in the subsequent storage. Also, the biogas production rate increased with 24% and the biogas production yield with 10%, both as a result of the additional trace elements at high organic loading rates. All in all, even though 50% of the feedstock consisted of manure, trace element addition resulted in multiple positive effects and a more reliable process with stable and high yield.

  19. Effect of the BSCCO superconducting properties by tiny Y2O3 addition (United States)

    Dong, Yan; Sun, Aimin; Xu, Bin; Zhang, Hongtao; Zhang, Meng


    In this paper, the effect of tiny Y2O3 addition in (Bi,Pb)-2223 superconductor prepared by solid state reaction technique was studied. The properties of samples have been investigated via X-ray diffraction (XRD), resistance-temperature (R-T) curve, scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS). XRD data indicated that all samples are multiphase and the major phases are high-temperature phases and low-temperature phases. The volume fraction of (Bi,Pb)-2223 is not great change with tiny Y2O3 addition. All samples exhibit superconducting phase with the critical transition temperature and one-step transition, however, the transition width was decreased with the Y2O3 addition up to 0.04 wt.% and sharp increased with the excessive oxide addition. SEM pictures show that the Y2O3 appeared on the flake-type grains surface obviously, but the number and size of the hole between grains are decreased in the 0.04 wt.% addition.

  20. CAN Canopy Addition of Nitrogen Better Illustrate the Effect of Atmospheric Nitrogen Deposition on Forest Ecosystem? (United States)

    Zhang, Wei; Shen, Weijun; Zhu, Shidan; Wan, Shiqiang; Luo, Yiqi; Yan, Junhua; Wang, Keya; Liu, Lei; Dai, Huitang; Li, Peixue; Dai, Keyuan; Zhang, Weixin; Liu, Zhanfeng; Wang, Faming; Kuang, Yuanwen; Li, Zhian; Lin, Yongbiao; Rao, Xingquan; Li, Jiong; Zou, Bi; Cai, Xian; Mo, Jiangming; Zhao, Ping; Ye, Qing; Huang, Jianguo; Fu, Shenglei


    Increasing atmospheric nitrogen (N) deposition could profoundly impact community structure and ecosystem functions in forests. However, conventional experiments with understory addition of N (UAN) largely neglect canopy-associated biota and processes and therefore may not realistically simulate atmospheric N deposition to generate reliable impacts on forest ecosystems. Here we, for the first time, designed a novel experiment with canopy addition of N (CAN) vs. UAN and reviewed the merits and pitfalls of the two approaches. The following hypotheses will be tested: i) UAN overestimates the N addition effects on understory and soil processes but underestimates those on canopy-associated biota and processes, ii) with low-level N addition, CAN favors canopy tree species and canopy-dwelling biota and promotes the detritus food web, and iii) with high-level N addition, CAN suppresses canopy tree species and other biota and favors rhizosphere food web. As a long-term comprehensive program, this experiment will provide opportunities for multidisciplinary collaborations, including biogeochemistry, microbiology, zoology, and plant science to examine forest ecosystem responses to atmospheric N deposition.

  1. 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: [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)


    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.

  2. Effect of additives on size and shape of lithium carbonate crystals (United States)

    Taborga, P.; Brito, I.; Graber, T. A.


    Generally, properties such internal structure, shape, and size distribution influence the reactivity, fluidity and wettability of the crystals, and may be modified by the use of additives such as polyelectrolytes or surfactants. The aim of this study was to investigate the effect of different additives on the size and morphology of lithium carbonate crystals obtained by reactive crystallization from solutions of LiCl and Na2CO3. The additives used were: polyethylenimine (PEI), polyethylene glycol (PEG), poly (4-styrenesulfonic acid), (P4SA), polyacrylic acid (PAA), sodium dodecyl sulfate (SDS), and sodium dodecyl benzenesulfonate (SDBS). Obtained crystals were observed using scanning electron microscopy, the crystal size distribution was determined by a size image analyzer, and the crystal structure were analyzed by X-ray diffraction. The results showed that the presence of PEI, PEG and P4SA, increased the length of the lithium carbonate particles. The presence of SDS decreases the crystals size. Using SDBS as additive, the crystals had a needle-like shape, Finally PAA allowed the production of Li2CO3 spherulites. Crystal structure of lithium carbonate did not change in the presence of the tested additives.

  3. Distinct conformational and functional effects of two adjacent pathogenic mutations in cardiac troponin I at the interface with troponin T. (United States)

    Akhter, Shirin; Jin, J-P


    The α-helix in troponin I (TnI) at the interface with troponin T (TnT) is a highly conserved structure. A point mutation in this region, A116G, was found in human cardiac TnI in a case of cardiomyopathy. An adjacent dominantly negative mutation found in turkey cardiac TnI (R111C, equivalent to K117C in human and K118C in mouse) decreased diastolic function and blunted beta-adrenergic response in transgenic mice. To investigate the functional importance of the TnI-TnT interface and pathological impact of the cardiac TnI mutations, we engineered K118C and A117G mutations in mouse cardiac TnI for functional studies. Despite their adjacent locations, A117G substitution results in faster mobility of cardiac TnI in SDS-PAGE whereas K118C decreases gel mobility, indicating significant and distinct changes in overall protein conformation. Consistently, monoclonal antibody epitope analysis demonstrated distinct local and remote conformational alterations in the two mutant proteins. Protein binding assays showed that K118C, but not A117G, decreased the relative binding affinity of cardiac TnI for TnT. K118C mutation decreased binding affinity for troponin C in a Ca(2+)-dependent manner, whereas A117G had a similar but less profound effect. Protein kinase A phosphorylation or truncation to remove the cardiac specific N-terminal extension of cardiac TnI resulted in similar conformational changes in the region interfacing with TnT and minimized the functional impacts of the mutations. The data demonstrate potent conformational and functional impacts of the TnT-interfacing helix in TnI and suggest a role of the N-terminal extension of cardiac TnI in modulating TnI-TnT interface functions.

  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. Effect Of The Gadolinium Oxide Addition On The Electrical Properties Of Tetragonal Zirconium Dioxide

    Directory of Open Access Journals (Sweden)

    Cyran J.


    Full Text Available The aim of this work was examination of gadolinium-doped 3YSZ electrical and structural properties. Such materials may be used as electrolytes in intermediate temperature solid oxide fuel cells (IT-SOFC. First step of the research was synthesis of 3YSZ with different contents of gadolinium (0.25; 0.5; 1.0 at %. Prepared materials were characterized by high porosity. No effect of gadolinium addition on grain size was observed. The experimentally determined values of grain interiors electrical conductivities for gadolinium doped samples are comparable to grain interior conductivities of gadolinium free tetragonal zirconia. On the other hand, a clear effect of gadolinium addition on electrical conductivity of grain boundaries was observed. It was found that 3YSZ containing 0.25 at. % Gd was the most promising from the investigated materials as a solid electrolyte for IT SOFC.


    Institute of Scientific and Technical Information of China (English)

    H.M. Geng; X.C. Wu; Y.A. Min; H.B. Wang; H.K. Zhang


    Experiments conducted to determine the effect of copper addition on the machinability of plastic mold steel, 4Cr16Mo, were presented. The machinability of mold steel 4Cr16Mo was visibly improved by adding Cu. The top wear of 4Cr16Mo with copper was less than that without copper. The Cu-rich phase had the effect of a lubricant and the heat conductivity, which reduced cutting-tool wear, improved machinability, and increased the service life of the cutting-tool. Increasing of copper addition decreased the hot-working character of 4Cr16Mo. The optimal hot-working parameters for 4Cr16Mo with copper were determined by the tensile test and the compression test. The rate of deformation should be adopted as 0.6 s-1. The heating-up temperature, initial forging temperature, and terminal forging temperature were 1200℃, 1150℃, and 950℃, respectively.

  7. Health Effects Associated with Inhalation Exposure to Diesel Emission Generated with and without CeO2 Nano Fuel Additive (United States)

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Addition of nano cerium (Ce) oxide additive to diesel fuel (DECe) increases fuel burning efficiency resulting in altered emission characteristics and potentially altered health effects. We hypothesized that inh...

  8. Effect of additives on mycelial growth and fructification of Pleurotus squarrosulus (Polyporales: Polyporaceae)


    Kadiri, Mukaila


    The effects of dungs (cow, horse. poultry), yam peels, rice bran, chaff (Sorghum, maize) and several sugars on mycelial growth and fructification of Pleurolus squarrosulus (Mant.). Singer were investigated. The concentrations were 5%, 10% and 15% (for sugars: 1%,3% and 5%). The substrate raw materials were maize and rice straw and cotton waste (substrates without the additives used as controls). Optirnum mycelial growth was obtained with 10% rice bran, or Sorghum or maize chaff, 5% dung (any)...

  9. The effect of Y2O3 addition on thermal shock behavior of magnesium aluminate spinel


    Pošarac Milica; Devečerski A.; Volkov-Husović T.; Matović B.; Minić D.M.


    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...

  10. Effect of cerium addition on microstructure and texture of aluminum foil for electrolytic capacitors

    Institute of Scientific and Technical Information of China (English)

    王海燕; 李文学; 任慧平; 黄丽颖; 王向阳


    Anode foil of aluminum electrolytic capacitor,which requires large surface area for high capacitance,were prepared by rolling,annealing and electrochemical etching.Effects of cerium addition on the capacitance of aluminum electrolytic capacitors were investigated.Microstructure of the aluminum foil surface was observed by optical microscopy(OM) and scanning electron microscopy(SEM).Electron back scattered diffraction(EBSD) was also employed to reveal texture evolvement of cold-rolled aluminum foil after ann...

  11. Homogeneous Gold Catalysis through Relativistic Effects: Addition of Water to Propyne

    CERN Document Server

    Lein, Matthias; Schwerdtfeger, Peter


    In the catalytic addition of water to propyne the Au(III) catalyst is not stable under non-relativistic conditions and dissociates into a Au(I) compound and Cl2. This implies that one link in the chain of events in the catalytic cycle is broken and relativity may well be seen as the reason why Au(III) compounds are effective catalysts.

  12. Effect of alumina particle additions of the aging kinetics of 6061 aluminum matrix composites


    Allen, Susan Marie.


    Approved for public release, distribution is unlimited Differential scanning calorimetry (DSC) was conducted using a monolithic 6061 aluminum material and two 6061 aluminum matrix composite materials. The composite materials were reinforced with 10 volume percent and 15 volume percent alumina particles. Electrical resistivity and hardness measurements during isothermal aging treatments were also conducted. The effects of prior aging and alumina particle additions on the growth kinetics and...


    Energy Technology Data Exchange (ETDEWEB)

    White, T


    The effectiveness of three dispersants to modify rheology was examined using rheology measurements and laser scanning confocal microscopy (LSCM) in simulated waste solutions. All of the dispersants lowered the yield stress of the slurries below the baseline samples. The rheology curves were fitted reasonably to a Bingham Plastic model. The three-dimensional LSCM images of simulants showed distinct aggregates were greatly reduced after the addition of dispersants leading to a lowering of the yield stress of the simulated waste slurry solutions.

  14. Effectivity of Aloe vera bioactives as feed additive for broilers reared on deep litter


    A.P Sinurat; T Purwadaria; T Pasaribu; W Rakhmani; J Dharma; J Rosida; S Sitompul; Udjianto


    There are plenty of Indonesian plants contain usefull bioactive components. One of them is Aloe vera. Previous experiment showed that Aloe vera bioactives reduced aerob bacteria in the intestinal and improved feed efficiency in broilers reared in cages. The results however, gave some variations, may be due to variation in rearing the chickens. Two experiments were carried out to study the effectivity of Aloe vera bioactives as feed additives for broilers reared on deep litter. In the first st...

  15. Effects of Sodium Sulfate as Electrolyte Additive on Electrochemical Performance of Lead Electrode

    Institute of Scientific and Technical Information of China (English)

    YU Jin-yu; QIAN Zhao-hong; ZHAO Meng; WANG Yu-jie; NIU Lin


    Sodium sulfate as an electrolyte additive was studied via electrochemical methods including linear sweep voltammetry(LSV),cyclic voltammetry(CV) and electrochemical impedance spectroscopy(EIS) to deeply understand its effect on the hydrogen evolution current and overpotential as well as the formation and structure of anodic passivation films on lead surface during the redox processes.The results achieved will be valuable to improve the cycle life and maintenance-free properties of lead-acid batteries.

  16. Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders

    DEFF Research Database (Denmark)

    Brickman, J M; Clements, M; Tyrell, R


    The homeobox gene Hesx1/HESX1 has been implicated in the establishment of anterior pattern in the central nervous system (CNS) in a number of vertebrate species. Its role in pituitary development has been documented through loss-of-function studies in the mouse. A homozygous missense point mutation...... 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...

  17. The Nonlinear Structure of the Desmoplakin Plakin Domain and the Effects of Cardiomyopathy-Linked Mutations

    NARCIS (Netherlands)

    C. Al-Jassar; T. Knowles; M. Jeeves; K. Kami; E. Behr; H. Bikker; M. Overduin; M. Chidgey


    Desmoplakin is a cytoplasmic desmosomal protein that plays a vital role in normal intercellular adhesion. Mutations in desmoplakin can result in devastating skin blistering diseases and arrhythmogenic right ventricular cardiomyopathy, a heart muscle disorder associated with ventricular arrhythmias,

  18. Effect of the chlortetracycline addition method on methane production from the anaerobic digestion of swine wastewater. (United States)

    Huang, Lu; Wen, Xin; Wang, Yan; Zou, Yongde; Ma, Baohua; Liao, Xindi; Liang, Juanboo; Wu, Yinbao


    Effects of antibiotic residues on methane production in anaerobic digestion are commonly studied using the following two antibiotic addition methods: (1) adding manure from animals that consume a diet containing antibiotics, and (2) adding antibiotic-free animal manure spiked with antibiotics. This study used chlortetracycline (CTC) as a model antibiotic to examine the effects of the antibiotic addition method on methane production in anaerobic digestion under two different swine wastewater concentrations (0.55 and 0.22mg CTC/g dry manure). The results showed that CTC degradation rate in which manure was directly added at 0.55mg CTC/g (HSPIKE treatment) was lower than the control values and the rest of the treatment groups. Methane production from the HSPIKE treatment was reduced (pmethane production under different antibiotic addition methods might be explained by the microbial activity and the concentrations of antibiotic intermediate products and metabolites. Because the primary entry route of veterinary antibiotics into an anaerobic digester is by contaminated animal manure, the most appropriate method for studying antibiotic residue effects on methane production may be using manure from animals that are given a particular antibiotic, rather than adding the antibiotic directly to the anaerobic digester.

  19. Effect of Skimmed-Milk and Starter Addition on Lactic Acid Formation in Soyghurt

    Directory of Open Access Journals (Sweden)

    Yanna Syamsuddin


    Full Text Available Research on Effect of Skimmed-Milk and Starter Addition on Lactic Acid Formation in Soyghurt has been done. Soyghurt is a probiotic drinking product made from soy-milk produced by fermentation process using lactic acid bacteria. The bacteria used as starter was Lactobacillus bulgaricus and Streptococcus thermophillus. The objective of this research was to evaluate the effect of skimmed-milk and starter addition on the formation of lactic acid. Variables used in this research was skimmed-milk concentration of 5, 10, and 15% and starter concentration of 3, 5, and 7%, based on volume of soy-milk used as raw material. The soy-milk used was analyzed for its carbohydrate and protein content, and the soyghurt produced was analyzed for its lactic acid, pH and syneresis. The result showed that carbohydrate and protein content in soy-milk was 122.39 mg/L and 2.75%, respectively. The best condition of this process was the addition of 15% skimmed-milk and 5% starter, which yielded the highest lactic acid of 15% with pH of 4.23 and syneresis of 15%. It can be concluded that increasing skimmed-milk concentration cause the increase in lactic acid formation and decrease pH and syneresis. While effect of starter concentration on product analysis was influenced by the amount of nutrition contain in soy-milk.

  20. Effect of mutation and genetic background on drug resistance in Mycobacterium tuberculosis. (United States)

    Fenner, Lukas; Egger, Matthias; Bodmer, Thomas; Altpeter, Ekkehardt; Zwahlen, Marcel; Jaton, Katia; Pfyffer, Gaby E; Borrell, Sonia; Dubuis, Olivier; Bruderer, Thomas; Siegrist, Hans H; Furrer, Hansjakob; Calmy, Alexandra; Fehr, Jan; Stalder, Jesica Mazza; Ninet, Béatrice; Böttger, Erik C; Gagneux, Sebastien


    Bacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistant Mycobacterium tuberculosis isolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains, katG mutations were associated with high-level and inhA promoter mutations with low-level drug resistance. Only katG(S315T) (65.6% of all isoniazid-resistant strains) and inhA promoter -15C/T (22.7%) were found in molecular clusters. M. tuberculosis lineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6; P mutations (OR, 6.4; 95% CI, 2.0 to 20.7; P = 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages; P tuberculosis drug resistance mutations were associated with various levels of drug resistance and transmission, and M. tuberculosis lineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds in M. tuberculosis drug resistance.

  1. Richly parameterized linear models additive, time series, and spatial models using random effects

    CERN Document Server

    Hodges, James S


    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

  2. Microscopic Studies Of The Effect Of Some Food Additives On The Kidney Of Albino Rat


    Abd El-Tawab M. Ismail - Ashraf M.Moustafa


    Recently the use of synthetic food coloring additives was increased and the levels of human exposure to such agents are very broad, thus feeding over long periods may continually possess potential hazards to the human health. Also most of the food colors tested in the conventional toxicity experiments showed toxic effects at very high level of intake i.e. 1-5 % in the diet. The aim of this study was to evaluate the histological and histochemical effects of some of these substances (Sodium nit...

  3. Micellar Effects on Nucleophilic Addition Reaction and Applicability of Enzyme Catalysis Model

    Directory of Open Access Journals (Sweden)

    R. K. London Singh


    Full Text Available This study describes the effect of anionic and cationic micelles on nucleophilic addition reaction of rosaniline hydrochloride (RH with hydroxide under pseudo-first order condition. Strong inhibitory effect is observed due to SDS micelle, whereas CTAB catalysed the reaction. This is explained on the basis of electrostatic and hydrophobic interactions which are simultaneously operating in the reaction system. The kinetic data obtained is quantitatively analysed by applying the positive cooperativity model of enzyme catalysis. Binding constants and influence of counterions on the reaction have also been investigated.

  4. Effects of V addition on recrystallization resistance of 7150 aluminum alloy after simulative hot deformation

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Jing; Shi, Cangji; Chen, X.-Grant, E-mail:


    The effects of different V contents (0.01 to 0.19 wt.%) on the recrystallization resistance of 7150 aluminum alloys during post-deformation heat treatment were investigated. The microstructural evolutions at as-cast, as-homogenized conditions and after post-deformation annealing were studied using optical, scanning electron and transmission electron microscopes and using the electron backscattered diffraction technique. The precipitation of Al{sub 21}V{sub 2} dispersoids was observed in alloys containing 0.11 to 0.19 wt.% V after homogenization. The dispersoids were mainly distributed in the dendrite cells, and the precipitate-free zones occurred in the interdendritic regions and near grain boundaries. V addition could significantly enhance the recrystallization resistance during post-deformation annealing, particularly in the presence of a great number of Al{sub 21}V{sub 2} dispersoids. Recrystallized grain growth was effectively restricted because of the dispersoid pinning effect. The alloy containing 0.15 wt.% V exhibited the highest recrystallization resistance amongst all V-containing alloys studied. - Highlights: • Investigated the effect of V level on microstructure and flow stress of 7150 alloys • Characterized microstructures using optical microscopy, SEM, TEM and EBSD • Described the precipitation behavior of V-dispersoids in the dendritic structure • Studied the V effect on recrystallization resistance during post heat treatment • V addition greatly enhanced the recrystallization resistance during annealing.

  5. Predicting the Effect of Mutations on Protein-Protein Binding Interactions through Structure-Based Interface Profiles. (United States)

    Brender, Jeffrey R; Zhang, Yang


    The formation of protein-protein complexes is essential for proteins to perform their physiological functions in the cell. Mutations that prevent the proper formation of the correct complexes can have serious consequences for the associated cellular processes. Since experimental determination of protein-protein binding affinity remains difficult when performed on a large scale, computational methods for predicting the consequences of mutations on binding affinity are highly desirable. We show that a scoring function based on interface structure profiles collected from analogous protein-protein interactions in the PDB is a powerful predictor of protein binding affinity changes upon mutation. As a standalone feature, the differences between the interface profile score of the mutant and wild-type proteins has an accuracy equivalent to the best all-atom potentials, despite being two orders of magnitude faster once the profile has been constructed. Due to its unique sensitivity in collecting the evolutionary profiles of analogous binding interactions and the high speed of calculation, the interface profile score has additional advantages as a complementary feature to combine with physics-based potentials for improving the accuracy of composite scoring approaches. By incorporating the sequence-derived and residue-level coarse-grained potentials with the interface structure profile score, a composite model was constructed through the random forest training, which generates a Pearson correlation coefficient >0.8 between the predicted and observed binding free-energy changes upon mutation. This accuracy is comparable to, or outperforms in most cases, the current best methods, but does not require high-resolution full-atomic models of the mutant structures. The binding interface profiling approach should find useful application in human-disease mutation recognition and protein interface design studies.

  6. Mutational effects and population dynamics during viral adaptation challenge current models. (United States)

    Miller, Craig R; Joyce, Paul; Wichman, Holly A


    Adaptation in haploid organisms has been extensively modeled but little tested. Using a microvirid bacteriophage (ID11), we conducted serial passage adaptations at two bottleneck sizes (10(4) and 10(6)), followed by fitness assays and whole-genome sequencing of 631 individual isolates. Extensive genetic variation was observed including 22 beneficial, several nearly neutral, and several deleterious mutations. In the three large bottleneck lines, up to eight different haplotypes were observed in samples of 23 genomes from the final time point. The small bottleneck lines were less diverse. The small bottleneck lines appeared to operate near the transition between isolated selective sweeps and conditions of complex dynamics (e.g., clonal interference). The large bottleneck lines exhibited extensive interference and less stochasticity, with multiple beneficial mutations establishing on a variety of backgrounds. Several leapfrog events occurred. The distribution of first-step adaptive mutations differed significantly from the distribution of second-steps, and a surprisingly large number of second-step beneficial mutations were observed on a highly fit first-step background. Furthermore, few first-step mutations appeared as second-steps and second-steps had substantially smaller selection coefficients. Collectively, the results indicate that the fitness landscape falls between the extremes of smooth and fully uncorrelated, violating the assumptions of many current mutational landscape models.

  7. Effect of HIV-1 Subtype C integrase mutations implied using molecular modeling and docking data (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


    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.

  8. Structural and protein interaction effects of hypertrophic and dilated cardiomyopathic mutations in alpha-tropomyosin

    Directory of Open Access Journals (Sweden)

    Audrey N. Chang


    Full Text Available The potential alterations to structure and associations with thin filament proteins caused by the dilated cardiomyopathy (DCM associated tropomyosin (Tm mutants E40K and E54K, and the hypertrophic cardiomyopathy (HCM associated Tm mutants E62Q and L185R, were investigated. In order to ascertain what the cause of the known functional effects may be, structural and protein-protein interaction studies were conducted utilizing actomyosin ATPase activity measurements and spectroscopy. In actomyosin ATPase measurements, both HCM mutants and the DCM mutant E54K caused increases in Ca2+-induced maximal activities, while E40K caused a decrease. Investigation of Tm’s ability to inhibit actomyosin ATPase in the absence of troponin showed that HCM-associated mutant Tms did not inhibit as well as wildtype, whereas the DCM associated mutant E40K inhibited better. E54K did not inhibit the actomyosin ATPase activity at any concentration of Tm tested. Thermal denaturation studies by circular dichroism and molecular modeling of the mutations in Tm showed that in general, the DCM mutants caused destabilization within the Tm, while the HCM mutants resulted in increased stability. These findings demonstrate that the structural alterations in Tm observed here may affect the regulatory function of Tm on actin, thereby directly altering the ATPase rates of myosin.

  9. Effect of the dnaN mutation on the growth of small DNA phages. (United States)

    Taketo, A


    The effect of the dnaN mutation on the growth of single-stranded DNA phages was studied by burst experiments. In HC138 dnaN cells exposed to 42.5 degrees C at 5 min before infection, growth of spherical (microvirid or isometric) phages such as alpha 3, phi Kh-1 and phi X174 was partially reduced at the nonpermissive temperature. When infection was performed at 30 min after temperature shift-up, viral replication was completely inhibited at 42.5 degrees C in the dnaN strain but not in a dna+ revertant. At 41 degrees C, multiplication of filamentous (inovirid) phages M13 and fd was restricted specifically in HC138 F+ dnaN bacteria. When dnaN cells lysogenic for lambda i21 were grown at 42.5 degrees C for 60 min and then shifted down to 33 degrees C, a burst of lambda i21 occurred with concomitant cellular lysis, manifesting induction of the prophage development.

  10. The effects of Tmc1 Beethoven mutation on mechanotransducer channel function in cochlear hair cells. (United States)

    Beurg, Maryline; Goldring, Adam C; Fettiplace, Robert


    Sound stimuli are converted into electrical signals via gating of mechano-electrical transducer (MT) channels in the hair cell stereociliary bundle. The molecular composition of the MT channel is still not fully established, although transmembrane channel-like protein isoform 1 (TMC1) may be one component. We found that in outer hair cells of Beethoven mice containing a M412K point mutation in TMC1, MT channels had a similar unitary conductance to that of wild-type channels but a reduced selectivity for Ca(2+). The Ca(2+)-dependent adaptation that adjusts the operating range of the channel was also impaired in Beethoven mutants, with reduced shifts in the relationship between MT current and hair bundle displacement for adapting steps or after lowering extracellular Ca(2+); these effects may be attributed to the channel's reduced Ca(2+) permeability. Moreover, the density of stereociliary CaATPase pumps for Ca(2+) extrusion was decreased in the mutant. The results suggest that a major component of channel adaptation is regulated by changes in intracellular Ca(2+). Consistent with this idea, the adaptive shift in the current-displacement relationship when hair bundles were bathed in endolymph-like Ca(2+) saline was usually abolished by raising the intracellular Ca(2+) concentration.

  11. Effects of nitrogen and phosphorus additions on soil methane uptake in disturbed forests (United States)

    Zheng, Mianhai; Zhang, Tao; Liu, Lei; Zhang, Wei; Lu, Xiankai; Mo, Jiangming


    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.

  12. Effect of silver addition on the properties of nickel-titanium alloys for dental application. (United States)

    Oh, Keun-Taek; Joo, Uk-Hyon; Park, Gee-Ho; Hwang, Chung-Ju; Kim, Kyoung-Nam


    Equiatomic and near-equiatomic nickel-titanium alloys exhibit a shape-memory effect and superelasticity. However, the properties of such alloys are extremely sensitive to the precise nickel-titanium ratio and the addition of alloying elements. High corrosion resistance is necessary for biomedical applications, especially orthodontic. The purpose of this study was to investigate the effect of silver addition to nickel-titanium alloys for dental and medical application. Arc melting, homogenization, hot rolling, and solution heat treatment were performed to prepare the nickel-titanium-silver (NiTi-Ag) specimens. The properties of the ternary NiTi-Ag alloys such as phase-transformation temperature, microstructure, microhardness, corrosion resistance, and cytotoxicity were investigated. The NiTi-Ag alloys showed low silver recovery rate for the cast alloy, due to silver's low evaporation temperature, and low silver solubility in nickel-titanium. Silver addition to nickel-titanium increased the transition temperature range to 100 degrees C and stabilized the martensitic phase (monoclinic structure) at room temperature, because the martensitic transformation starting temperature (Ms) was above room temperature. Martensitic and austenitic phases existed in X-ray diffraction patterns of solution-annealed NiTi-Ag alloys. The silver addition was considered to improve the corrosion resistance and form a stable passive film. Significantly, the mechanical properties of the silver-added alloys were dependent upon the amount of alloying addition. There was no toxicity in the NiTi-Ag alloys, as the response index showed none or mild levels.

  13. Synergistic effect between nano-ceramic lubricating additives and electroless deposited Ni-W-P coating (United States)

    Chen, Min; Cheng, Wushan; Zhao, Zuxin; Huang, Xiaobo


    The major solving ways for the material wear are surface modification and lubrication. Currently, the researches at home and abroad are all limited to the single study of either nano-lubricating oil additive or electroless deposited coating. The surface coating has high hardness and high wear resistance, however, the friction reduction performance of the coating with high hardness is not good, the thickness of the coating is limited, and the coating can not regenerate after wearing. The nano-lubricating additives have good tribological performance and self-repair function, but under heavy load, the self-repair rate to the worn surface with the nano-additives is smaller than the wearing rate of the friction pair. To solve the above problems, the Ni-W-P alloy coating and deposition process with excellent anti-wear, and suitable for industrial application were developed, the optimum bath composition and process can be obtained by studying the influence of the bath composition, temperature and PH value to the deposition rate and the plating solution stability. The tribological properties as well as anti-wear and friction reduction mechanism of wear self-repair nano-ceramic lubricating additives are also studied. The ring-block abrasion testing machine and energy dispersive spectrometer are used to explore the internal relation between the coating and the nano-lubricating oil additives, and the tribology mechanism, to seek the synergetic effect between the two. The test results show that the wear resistance of Ni-W-P alloy coating (with heat treatment and in oil with nano-ceramic additives) has increased hundreds times than 45 steel as the metal substrate in basic oil, the friction reduction performance is improved. This research breaks through the bottleneck of previous separate research of the above-mentioned two methods, and explores the combination use of the two methods in industrial field.

  14. The effect of the humic acid and herbal additive supplement on production parameters of broiler chicken

    Directory of Open Access Journals (Sweden)

    Veronika Pistová


    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.

  15. Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice

    Directory of Open Access Journals (Sweden)

    Klaus Fabel


    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.

  16. Comparison of the genetic effects of equimolar doses of ENU and MNU: While the chemicals differ dramatically in their mutagenicity in stem-cell spermatogonia, both elicit very high mutation rates in differentiating spermatogonia

    Energy Technology Data Exchange (ETDEWEB)

    Russell, Liane B. [Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6420 (United States)]. E-mail:; Hunsicker, Patricia R. [Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6420 (United States); Russell, William L. [Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6420 (United States)


    Mutagenic, reproductive, and toxicity effects of two closely related chemicals, ethylnitrosourea (ENU) and methylnitrosourea (MNU), were compared at equimolar and near-equimolar doses in the mouse specific-locus test in a screen of all stages of spermatogenesis and spermiogenesis. In stem-cell spermatogonia (SG), ENU is more than an order of magnitude more mutagenic than MNU. During post-SG stages, both chemicals exhibit high peaks in mutation yield when differentiating spermatogonia (DG) and preleptotene spermatocytes are exposed. The mutation frequency induced by 75 mg MNU/kg during this peak interval is, to date, the highest induced by any single-exposure mutagenic treatment - chemical or radiation - that allows survival of the exposed animal and its germ cells, producing an estimated 10 new mutations per genome. There is thus a vast difference between stem cell and differentiating spermatogonia in their sensitivity to MNU, but little difference between these stages in their sensitivity to ENU. During stages following meiotic metaphase, the highest mutation yield is obtained from exposed spermatids, but for both chemicals, that yield is less than one-quarter that obtained from the peak interval. Large-lesion (LL) mutations were induced only in spermatids. Although only a few of the remaining mutations were analyzed molecularly, there is considerable evidence from recent molecular characterizations of the marker genes and their flanking chromosomal regions that most, if not all, mutations induced during the peak-sensitive period did not involve lesions outside the marked loci. Both ENU and MNU treatments of post-SG stages yielded significant numbers of mutants that were recovered as mosaics, with the proportion being higher for ENU than for MNU. Comparing the chemicals for the endpoints studied and additional ones (e.g., chromosome aberrations, toxicity to germ cells and to animals, teratogenicity) revealed that while MNU is generally more effective, the opposite

  17. Comparison of the genetic effects of equimolar doses of ENU and MNU: While the chemicals differ dramatically in their mutagenicity in stem-cell spermatogonia, both elicit very high mutation rates in differentiating spermatogonia

    Energy Technology Data Exchange (ETDEWEB)

    Russell, Liane B [ORNL; Hunsicker, Patricia R [ORNL; Russell, William [Deceased


    Mutagenoic, reproductive, and toxicity effects of two closely related chemicals, ethylnitrosourea (ENU) and methylnitrosourea (MNU), were compared at equimolar and near-equimolar doses in the mouse specific-locus test in a screen of all stages of spermatogenesis and spermiogenesis. In stem cell spermatogonial (SG), ENU is more than an order of magnitude more mutagenic than MNU. During post-SG stages, both chemicals exhibit high peaks in mutation yield when differentiating spermatogonial (DG) and preleptotene spermatocytes are exposed. The mutation frequency induced by 75 mg MNU/kg during this peak interval is, to date, the highest induced by any single- xposure mutagenic treatment chemical or radiation that allows survival of the exposed animal and its germ cells, producing an estimated 10 new mutations per genome. There is thus a vast difference between stem cell and differentiating spermatogonial in their sensitivity to MNU, but little difference between these stages in their sensitivity to ENU. During stages following meiotic metaphase, the highest mutation yield is obtained from exposed spermatids, but for both chemicals, that yield is less than one-quarter that obtained from the peak interval. Large-lesion (LL) mutations were induced only in spermatids. Although only a few of the remaining mutations were analyzed molecularly, there is considerable evidence from recent molecular characterizations of the marker genes and their flanking chromosomal regions that most, if not all, mutations induced during the peak-sensitive period did not involve lesions outside the marked loci. Both ENU and MNU treatments of post-SG stages yielded significant numbers of mutants that were recovered as mosaics, with the proportion being higher for ENU than for MNU. Comparing the chemicals for the endpoints studied and additional ones (e.g., chromosome aberrations, toxicity to germ cells and to animals, teratogenicity) revealed that while MNU is generally more effective, the opposite

  18. Rheological behavior and organoleptic effects of ovalbumin addition in yogurt mousse production. (United States)

    Menéndez, M; Paredes, B; Iglesias, O; Rendueles, M; Díaz, M


    Yogurt mousse is a novel, high added-value dairy product that has been well received by the market. This paper presents a study of the effect of the addition of ovalbumin to the product on its rheological and organoleptic qualities. The ovalbumin was previously separated from egg white with a high grade of purity using an ion exchange resin synthesized by the authors. Diverse rheological tests at different temperatures and corresponding sensorial assessments were conducted to compare samples without and with added ovalbumin. The obtained results confirm that the product is viscoelastic and combines the properties of foams and emulsions; the elastic component is greater than the viscous component. Moreover, at temperatures ranging from 5 to 15 degrees C, a usual interval of consumption, the product behaves rheologically in a similar way. Conversely, the addition of ovalbumin under the assayed conditions also makes the elastic character of the product increase at a given temperature. Finally, the sensorial assessment tests and determinations of stability and volume yield enabled us to verify that the addition of ovalbumin at an amount of 1.3% hardly alters the stability, resistance to shear stress, or the texture and improves the degree of foaming. Therefore, the product with additive is of good commercial quality.

  19. Effects of beta-glucan addition to a probiotic containing yogurt. (United States)

    Vasiljevic, T; Kealy, T; Mishra, V K


    This study investigated the effects of addition of beta-glucan from 2 different cereal sources (oat and barley) on growth and metabolic activity of Bifidobacterium animalis ssp. lactis (Bb-12) as determined by plating on a selective medium in yogurt during prolonged cold storage. These yogurt batches were compared to unsupplemented and inulin supplemented controls. All batches were also assessed for syneresis. Oat beta-glucan addition resulted in improved probiotic viability and stability comparable to that of inulin. It also enhanced lactic and propionic acid production. The barley beta-glucan addition suppressed proteolytic activity more than that from oat. These improvements were hindered by greater syneresis caused likely by thermodynamic incompatibility. Small amplitude oscillatory measurements of acidified model mixture of beta-glucan/skim milk solids showed formation of casein gel within the beta-glucan network. Binary mixtures of beta-glucan and skim milk solids had apparent pseudoplastic and non-Newtonian behavior governed mainly by beta-glucan contribution. Above critical concentrations, the mixtures underwent phase separation with the lower phase rich in protein. The phase diagram also showed that the addition of beta-glucan may be possible at or below 0.24 w/w%.

  20. Effects of emulsifier addition on the crystallization and melting behavior of palm olein and coconut oil. (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


    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.

  1. Effects of rare earth elements addition on microstructures, tensile properties and fractography of A357 alloy

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Wenming, E-mail: [State Key Lab of Materials Processing and Die and Mould Technology, Huazhong University of Science and Technology, Wuhan 430074 (China); School of Mechanical and Electrical Engineering, Wuhan Institute of Technology, Wuhan 430073 (China); Fan, Zitian; Dai, Yucheng; Li, Chi [State Key Lab of Materials Processing and Die and Mould Technology, Huazhong University of Science and Technology, Wuhan 430074 (China)


    The effects of rare earth (RE) containing Ce and La elements addition on the microstructures characteristics, tensile properties and fracture behavior of A357 alloy under as-cast and T6 conditions were systematically investigated in this study. Obtained results showed that the addition of RE obviously reduced the sizes of the α-Al primary phase and eutectic silicon particles as well as SDAS value and improved the morphology of eutectic silicon particles. The optimum level of added RE content were 0.2 wt%, and the aspect ratio of eutectic silicon particles of the A357 modified alloy under as-cast and T6 conditions decreased 142% and 174%, respectively, compared with the unmodified alloy. In addition, the addition of RE greatly improved the tensile properties of A357 alloy as result of the significant improvement in microstructure, especially in elongation under T6 condition. The fracture surfaces of the A357 unmodified alloy tensile samples showed a clear brittle fracture nature, and its fracture path passed through the eutectic silicon particles and displayed a transgranular fracture mode, leading to poorer ductility. The fracture path of the A357 modified alloys passed through the eutectic phase along the grain boundaries of the α-Al primary phase, and the fracture generated by dimple rupture with cracked eutectic silicon particles, and it showed an intergranular fracture mode, resulting in superior ductility.

  2. Effect of Additives on Melting Point of LATS Refining Ladle Slag

    Institute of Scientific and Technical Information of China (English)

    WANG Hong-ming; LI Gui-rong; DING Zhen-tao; DAI Qi-xun; LI Bo


    To avoid slag sticking on the ladle immersion cover during the LATS refining and alloying process, the effect of Al2O3 on the melting point of the ladle slag was studied and the additives including CaF2, B2O3, Li2O, and CaO were used to decrease the melting point of the ladle slag. The melting point was measured using the hemisphere method. The results show that the addition of Al2O3 to the ladle slag increases the melting point. The fluxing action is not remarkable if only CaF2 or CaO is used as the additive. The fluxing action of the composite additive obtained by the mixing of CaO and CaF2 in the mass proportion of wCaO∶wCaF2=2∶1 is preferred. The fluxing action of B2O3 is also notable. When the B2O3 content in mass percent is in the range from 2% to 10%, the corresponding melting point is 1 380 ℃ to 1 290 ℃. The fluxing action of Li2O is the most remarkable. When the Li2O content is up to 5%, the melting point of the slag is lower than 1 300 ℃.

  3. Effects of AI Addition on the Thermoelectric Properties of Zn-Sb Based Alloys

    Institute of Scientific and Technical Information of China (English)

    CUI Jiaolin; LIU Xianglian; YANG Wei; CHEN Dongyong; MAO Liding; QIAN Xin


    The β-Zn4Sb3, emerged as a compelling p-type thermoelectric material, is widely used in heat-electricity conversion in the 400-650 K range. In order to probe the effects of slight doping on the crystal structure and physical properties, we prepared the samples of Al-added Zn-Sb based alloys by spark plasma sintering and evaluated their microstructures and thermoelectric properties. After a limited Al addition into the Zn-Sb based alloys we observed many phases in the alloys, which include a major phase β-Zn4Sb3,intermetallic phases ZnSb and AISb. The major β-Zn4Sb3 phase plays a fundamental role in controlling the thermoelectric performance, the precipitated phases ZnSb and AISb are of great importance to tailor the transport properties, such as the gradual enhancement of lattice thermal conductivity, in spite of an increased phonon scattering in additional grain boundaries. The highest thermoelectric figure of merit of 0.55 is obtained for the alloy with a limited AI addition at 653 K, which is 0.08 higher than that of un-doped β-Zn4Sb3 at the corresponding temperature. Physical property experiments indicate that there is a potentiality for the improvement of thermoelectric properties if a proper elemental doping is carried out into the Zn-Sb based alloys, which was confirmed by AI addition in the present work.

  4. Effect of the Additives on the Desulphurization Rate of Flash Hydrated and Agglomerated CFB Fly Ash (United States)

    Li, D. X.; Li, H. L.; Xu, M.; Lu, J. F.; Liu, Q.; Zhang, J. S.; Yue, G. X.

    CFB fly ash from separators was mixed with water or the mixture of water and additives under the temperature of 363K by use of a blender. Then, this compound of fly ash and water or additives was pumped into a CFB combustion chamber by a sludge pump. Because the temperature of flue gas was high in CFB, the fly ash was hydrated fast and agglomerated in the same time. Through this process, the size of agglomerating fly ash is larger than the original particle and the relative residence time of agglomerated fly ash in CFB becomes longer. Therefore, the rate of utility of calcium in fly ash improves and the content of carbon in fly ash decreases. This results in a low Ca/S and low operational cost for CFB boiler. The additive is one key factor, which affects the rate of desulfurization of agglomerated fly ash. Effect of different additives on rate of desulfurization is not same. Cement and limestone are beneficiated to sulfur removal of agglomerated fly ash, but sodium silicate does not devote to the rate of sulfur removal of agglomerated fly ash.

  5. Effect of phosphor addition on eutectic solidification and microstructure of an Al-13%Si alloy

    Directory of Open Access Journals (Sweden)

    Liao Hengcheng


    Full Text Available As the refiner or modifier, the master alloys containing high concentration phosphor are widely used in preparing eutectic or hypereutectic Al-Si alloys. To study the effect of phosphor addition on the eutectic solidification and microstructure of the Al-13%Si alloy, an investigation has been undertaken by means of thermal analysis and micro/macro-structure observation. Results indicate that addition of phosphor in near eutectic Al-Si alloy promotes the nucleation of eutectic but has little refinement impact on primary Si particles as expected. Conversely, both primary Si particles and eutectic Si flakes become slightly coarser in P-rich alloys. The coarsening of eutectic Si flakes ties closely to the increased eutectic growth temperature with phosphor addition. The eutectic solidification of the alloy proceeds from the near mold zone towards the center, and it is also found that a few independent nucleation regions emerge in liquid at the solidification front due to the addition of phosphor.

  6. Effect of a bacterial inoculum and additive on dry matter in situ degradability of sugarcane silage

    Institute of Scientific and Technical Information of China (English)

    Jos A Reyes-Gutirrez; Oziel D Montaez-Valdez; Ramn Rodrguez-Macias; Mario Ruz-Lpez; Eduardo Salcedo-Prez; Cndido E Guerra-Medina


    The objective of this study was to evaluate the effect of adding a bacterial inoculum and a handmade additive to sugarcane silage (SCS) on the in situ digestibility of dry matter (DM). The treatments were:T1) sugarcane silage (SCS) and T2) sugar-cane silage with 1%inoculum and 1%additive (SCS+). The bacterial inoculum consisted of 10.0%molasses, 1.0%yogurt, 5.0%chicken manure, 0.5%urea, and 83.0%water, and the additive was formulated with 1.0%urea, 0.1%ammonium sulfate, and 0.25%phosphorus. In situ dry matter digestibility (DMD) was determined using the nylon bag technique with four cows equipped with ruminal ifstulas. Cows were fed with ensiled sugarcane supplemented with 1 kg of commercial concentrate. 5 g of ground sample for each sugarcane treatment were weighted in nylon bags and incubated for 4, 8, 12, 24, 48, and 72 h in a completely randomized design with six replicates. The DMD (%) was higher (P<0.05) for SCS+for al incubation times when compared with SCS. There were no differences in ruminal pH between the treatments for al the incubation times. The data suggested that the sugarcane silage with bacterial inoculum and additive could be an alternative for providing forage for ruminants during the season of low growth and quality grass.

  7. Superior MgH2 Kinetics with MgO Addition: A Tribological Effect

    Directory of Open Access Journals (Sweden)

    Kondo-Francois Aguey-Zinsou


    Full Text Available The kinetics of hydrogen absorption/desorption in magnesium can be improved without any catalysis assistance and MgO was found to be more effective than the best catalyst reported so far, i.e., Nb2O5. Herein, a quantitative analysis of the hydrogen kinetics in magnesium modified with MgO was performed in order to identify possible rate controlling mechanisms. While hydrogen absorption was found to be diffusion controlled as commonly reported, hydrogen desorption evolved from nucleation and growth to an interface controlled process depending on the desorption temperature. Comparison with the effect of Nb2O5 indicates that similar rate limiting steps occur regardless of the oxide additive. These findings are reconciled by considering the tribological effect of solid oxide additives, as a correlation between oxides electronegativity and improvement in hydrogen kinetics was found. Such a correlation clearly highlights the mechanical effect of solid oxides in facilitating the grinding and stabilisation of small magnesium particles for efficient and fast hydrogen kinetics.

  8. Combined effect of sourdough lactic acid bacteria and additives on bread firmness and staling. (United States)

    Corsetti, A; Gobbetti, M; De Marco, B; Balestrieri, F; Paoletti, F; Russi, L; Rossi, J


    The effect of various sourdoughs and additives on bread firmness and staling was studied. Compared to the bread produced with Saccharomyces cerevisiae 141, the chemical acidification of dough fermented by S. cerevisiae 141 or the use of sourdoughs increased the volume of the breads. Only sourdough fermentation was effective in delaying starch retrogradation. The effect depended on the level of acidification and on the lactic acid bacteria strain. The effect of sourdough made of S. cerevisiae 141-Lactobacillus sanfranciscensis 57-Lactobacillus plantarum 13 was improved when fungal alpha-amylase or amylolytic strains such as L. amylovorus CNBL1008 or engineered L. sanfranciscensis CB1 Amy were added. When pentosans or pentosans, endoxylanase enzyme, and L. hilgardii S32 were added to the same sourdough, a greater delay of the bread firmness and staling was found. When pentosans were in part hydrolyzed by the endoxylanase enzyme, the bread also had the highest titratable acidity, due to the fermentation of pentoses by L. hilgardii S32. The addition of the bacterial protease to the sourdough increased the bread firmness and staling.

  9. Effects of feed additives on rumen and blood profiles during a starch and fructose challenge. (United States)

    Golder, H M; Celi, P; Rabiee, A R; Lean, I J


    We evaluated the effect of feed additives on the risk of ruminal acidosis in Holstein heifers (n = 40) fed starch and fructose in a challenge study. Heifers were randomly allocated to feed additive groups (n = 8 heifers/group): (1) control (no additives); (2) virginiamycin (VM); (3) monensin + tylosin (MT); (4) monensin + live yeast (MLY); and (5) sodium bicarbonate + magnesium oxide (BUF). Heifers were fed 2.5% of body weight (BW) dry matter intake (DMI) per day of a total mixed ration (62:38 forage:concentrate) and feed additives for a 20-d adaptation period. Fructose (0.1% of BW/d) was included for the last 10d of the adaptation period. On d 21, heifers were fed to target a DMI of 1.0% of BW of wheat, fructose at 0.2% of BW, and their feed additives. Rumen fluid samples obtained by stomach tube and blood samples were collected weekly as well as during a 3.6-h period on challenge day (d 21). Virginiamycin and BUF groups maintained a consistently high DMI across the 20-d adaptation period. The MLY heifers had low DMI of the challenge ration. Average daily gain and feed conversion ratio were not affected by feed additives. All rumen and plasma measures changed weekly over adaptation and over the challenge sampling period with the exception of rumen total lactate and histamine concentrations, plasma oxidative stress index, and ceruloplasmin. Substantial within- and between-group variation was observed in rumen and plasma profiles at challenge sampling. No significant group changes were observed in rumen total volatile fatty acids, propionate, acetate-to-propionate ratio, isobutyrate, caproate, isovalerate, total lactate, d- and l-lactate, and pH measures on challenge day. Acetate concentration was increased in the BUF and control groups on challenge day. Butyrate concentration was lower in the MLY and MT groups compared with other groups at challenge. Valerate concentrations were lowest in the control, VM, and BUF groups and lactate concentrations were numerically


    Institute of Scientific and Technical Information of China (English)

    Wang Xishu; Zhang Yihe; Fu Shaoyun; Feng Xiqiao


    Tensile deformation and fracture characteristics of polyimide/montmorillonite nanocomposite films are investigated to enhance the particular mechanical properties and understand the effective factors in dominating the mechanical properties of nanocomposites, such as the nanolayer, matrix and nanolayer/matrix interface. How to contribute to the mechanical properties of nanocomposite film is a very complex problem. In this paper, these factors are analyzed based on the addition amount and fracture mechanics. The results indicate that the specimen at 20 wt% MMT breaks prematurely with a fracture strength (σb=78 MPa) much lower than that (σb = 128 MPa) at the 1wt% MMT. However, the Young's modulus (3.2 GPa) of the former is higher than that (1.9 GPa) of the latter. Fractography also indicates that the brittle cracking formed in high content addition is the main cause of failure but microscopically ductile fracture morphology still exists locally. And for the trace element addition, the smaller threading slipping veins are evenly distributed on the entire fracture section of these films. Therefore, these characteristics would presumably be associated with both the concentration effects of size of nanocomposite sheets and the increasing deformation harmony in nanolayers.

  11. Additive effect of cysteinyl leukotriene or thromboxane modifiers to inhaled corticosteroids in asthmatic patients

    Directory of Open Access Journals (Sweden)

    Shigeharu Myou


    Full Text Available Bronchial asthma is a chronic inflammatory disease of the conducting airways. Current asthma treatment guidelines recommend inhaled corticosteroids (ICS as the first-line maintenance therapy for mild to severe persistent asthma, because ICS are the most efficacious anti-inflammatory medication. Despite treatment with ICS, suppression of inflammation is often incomplete and blockade by ICS of cysteinyl leukotriene (CysLT and thromboxane (TX A2 biosynthesis is limited. The addition of a CysLT1 receptor antagonist to an ICS represents a reasonable alternative therapeutic approach for the treatment of asthma patients whose symptoms remain uncontrolled on ICS alone. Indeed, CysLT1 receptor antagonists are demonstrated both to have an additive effect to ICS therapy and to allow the reduction of ICS dosage. Thromboxane modifiers also have an additive effect with low- to moderate-dose ICS. Although the long-term usefulness of add-on therapy of CysLT or TX modifiers (vs long-acting β2-adrenergic receptor agonists to ICS is unclear, these alternatives are worthy of further consideration.

  12. Effect of additive on synthesis of MnZn ferrite nanocrystal by hydrothermal crystallization

    Institute of Scientific and Technical Information of China (English)

    桑商斌; 古映莹; 黄可龙


    The effect of additive RCOONa on the formation of MnZn ferrite homogeneous coprecipitation precursor was studied in this paper. The action of additive in the MnZn ferrite hydrothermal crystallization process was investigated according to crystal field theory and crystal growth unit theory. And the growth unit formation process was presented and its structure was illustrated. The results show that the precursor of MnZn ferrite is a colloidal mixture composed of Zn(OH)2, Fe(OH)2, Mn(OH)2, MnO(OH) , MnO2 @ xH2O and so on, and dissolves in solution in the form of hydroxyl coordination tetrahedron and octahedron such as Zn(OH)2-4,Fe(OH)2-4 , Fe(OH)4-6 ,Fe(OH)-4 , Fe(OH)3-6 ,Mn(OH)2-4 ,Mn(OH)3-6 etc. , and the growth unit is formed by combination of the coordination polyhedra subsequently in the hydrothermal precess. The additive is beneficial to the formation of homogeneous precursor and has dispersive effect on the aggregation of the crystal growth unit by forming associate with hydrogen bond,which is beneficial to the synthesis of the pure product with a tiny size and a narrow size distribution.

  13. Effect of the La alloying addition on the antibacterial capability of 316L stainless steel. (United States)

    Yuan, J P; Li, W; Wang, C


    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.

  14. 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.

  15. Paget disease of bone-associated UBA domain mutations of SQSTM1 exert distinct effects on protein structure and function (United States)

    Goode, Alice; Long, Jed E.; Shaw, Barry; Ralston, Stuart H.; Visconti, Micaela Rios; Gianfrancesco, Fernando; Esposito, Teresa; Gennari, Luigi; Merlotti, Daniela; Rendina, Domenico; Rea, Sarah L.; Sultana, Melanie; Searle, Mark S.; Layfield, Robert


    SQSTM1 mutations are common in patients with Paget disease of bone (PDB), with most affecting the C-terminal ubiquitin-associated (UBA) domain of the SQSTM1 protein. We performed structural and functional analyses of two UBA domain mutations, an I424S mutation relatively common in UK PDB patients, and an A427D mutation associated with a severe phenotype in Southern Italian patients. Both impaired SQSTM1's ubiquitin-binding function in pull-down assays and resulted in activation of basal NF-κB signalling, compared to wild-type, in reporter assays. We found evidence for a relationship between the ability of different UBA domain mutants to activate NF-κB signalling in vitro and number of affected sites in vivo in 1152 PDB patients from the UK and Italy, with A427D-SQSTM1 producing the greatest level of activation (relative to wild-type) of all PDB mutants tested to date. NMR and isothermal titration calorimetry studies were able to demonstrate that I424S is associated with global structural changes in the UBA domain, resulting in 10-fold weaker UBA dimer stability than wild-type and reduced ubiquitin-binding affinity of the UBA monomer. Our observations provide insights into the role of SQSTM1-mediated NF-κB signalling in PDB aetiology, and demonstrate that different mutations in close proximity within loop 2/helix 3 of the SQSTM1 UBA domain exert distinct effects on protein structure and stability, including indirect effects at the UBA/ubiquitin-binding interface. PMID:24642144

  16. Effect of calcium chloride addition on ice cream structure and quality. (United States)

    Costa, F F; Resende, J V; Abreu, L R; Goff, H D


    The influence of calcium fortification by the addition of calcium chloride on quality parameters of ice cream based on physical properties was investigated, as was the effect of kappa-carrageenan at modifying the effects of this calcium fortification. Four ice cream mixes of conventional composition, with added kappa-carrageenan (0 or 0.025%) and added calcium chloride (0 or 4.4 g L(-1) = 40 mM of added Ca(2+)), were prepared. Modulated temperature-differential scanning calorimetry was used to investigate the effect of calcium chloride on the nucleation temperature, enthalpy of melting, and freezing point depression. The protein composition of 15.4% (wt/wt) reconstituted skim milk powder solutions with or without 4.4 g L(-1) added CaCl(2) and in the supernatant after ultracentrifugation was determined. Fat particle size distributions in ice cream were characterized by light scattering. Ice crystal sizes before and after temperature cycling were determined by cold-stage light microscopy. The results demonstrated that the addition of calcium chloride led to a substantial increase in ice crystal sizes and in fat partial coalescence, which were exacerbated by the addition of kappa-carrageenan. These results can be explained by the interaction between Ca(2+) ions and casein micelles, rather than any effects on freezing point depression. The calcium ions led to a more compact micelle, less serum beta-casein, and high fat destabilization, all of which would be expected to reduce macromolecular structure and volume occupancy in the unfrozen phase, which led to increased rates of ice recrystallization.

  17. Effects of mutated replicase and movement protein genes on attenuation of tobacco mosaic virus

    Institute of Scientific and Technical Information of China (English)

    杨恭; 邱并生; 魏军亚; 刘广超


    Our previous reports showed that one opal mutation (UGA) and one ochre mutation (UAA) respectively located in the replicase and movement protein (MP) genes of the attenuated tomato mosaic virus K(ToMV-K) contribute to the viral attenuation. To explore a wider application of this attenuation pattern to other plant viruses, we have constructed three mutants which respectively contain one opal mutation of the replicase gene and/or one ochre mutation of the MP using PCR-mediated site-directed mutagenesis from a virulent tobacco mosaic virus isolated from China (TMV-Cv). Plant infection performed by in vitro transcripts revealed that the MP truncated mutant TMV-Cvmp and the replicase-MP truncated mutant TMV-Cvrase-mp were infectious on both local lesion (Nicotiana tabacum cv. Xanthi NC) and systemic (N. tabacum cv. K326) host plants, while the replicase truncated mutant TMV-Cvrase was non-infectious. The K326 plant infected by TMV- Cvrease-mp displayed only a little mild mosaic. By electronic microscopy (EM), plant re-inoculation, RNA Dot-blot, RT-PCR and sequencing we demonstrated that the progeny viruses of TMV-Cvmp and TMV-Cvrease-mp shared similar morphological character with TMV-Cv, owned the abilities to infect, replicate and propagate in the assayed plants, and maintained the mutated sites during infection. These data showed that both the opal and the ochre mutations are able to cooperatively induce the attenuated phenotypes of TMV-Cvrase-mp on plants, indicating that the mutation pattern of ToMV-K could be used to attenuate other virulent plant viruses.

  18. Trends in lignin modification: a comprehensive analysis of the effects of genetic manipulations/mutations on lignification and vascular integrity (United States)

    Anterola, Aldwin M.; Lewis, Norman G.


    activities. Such enzymes thus fulfill subsidiary processing roles, with all (except CCOMT) apparently being bifunctional for both H and G substrates. Their severe downregulation does, however, predictably result in impaired monolignol biosynthesis, reduced lignin deposition/vascular integrity, (upstream) metabolite build-up and/or shunt pathway metabolism. There was no evidence for an alternative acid/ester O-methyltransferase (AEOMT) being involved in lignin biosynthesis.The G/S lignin pathway networks are operative in specific cell types in angiosperms and employ two additional biosynthetic steps to afford the corresponding S components, i.e. through introduction of an hydroxyl group at C-5 and its subsequent O-methylation. [These enzymes were originally classified as ferulate-5-hydroxylase (F5H) and caffeate O-methyltransferase (COMT), respectively.] As before, neither step has apparently any role in carbon allocation to the pathway; hence their individual downregulation/manipulation, respectively, gives either a G enriched lignin or formation of the well-known S-deficient bm3 "lignin" mutant, with cell walls of impaired vascular integrity. In the latter case, COMT downregulation/mutation apparently results in utilization of the isoelectronic 5-hydroxyconiferyl alcohol species albeit in an unsuccessful attempt to form G-S lignin proper. However, there is apparently no effect on overall G content, thereby indicating that deposition of both G and S moieties in the G/S lignin forming cells are kept spatially, and presumably temporally, fully separate. Downregulation/mutation of further downstream steps in the G/S network [i.e. utilizing 4CL, CCR and CAD isoforms] gives predictable effects in terms of their subsidiary processing roles: while severe downregulation of 4CL gave phenotypes with impaired vascular integrity due to reduced monolignol supply, there was no evidence in support of increased growth and/or enhanced cellulose biosynthesis. CCR and CAD downregulation/mutations

  19. Effect of Sc addition on microstructure and mechanical properties of 1460 alloy

    Directory of Open Access Journals (Sweden)

    Juan Ma


    Full Text Available The effect of minor addition of Sc on microstructure, age hardening behavior, tensile properties and fracture morphology of 1460 alloy have been studied. It is found that Sc content increase from 0.11 wt% to 0.22 wt% is favorable for grain refinement in as-cast alloy but results in a coarsening of Cu-rich particles. The alloy with 0.11 wt% Sc exhibits enhanced mechanical properties and age hardening effect. Transmission electron microscopy (TEM investigations on the alloy with 0.11 wt% Sc have suggested that a large amount of Al3(Sc, Zr particles precipitated at the earlier aging may inhibit recrystallization effectively.

  20. A germ-line-selective advantage rather than an increased mutation rate can explain some unexpectedly common human disease mutations. (United States)

    Choi, Soo-Kyung; Yoon, Song-Ro; Calabrese, Peter; Arnheim, Norman


    Two nucleotide substitutions in the human FGFR2 gene (C755G or C758G) are responsible for virtually all sporadic cases of Apert syndrome. This condition is 100-1,000 times more common than genomic mutation frequency data predict. Here, we report on the C758G de novo Apert syndrome mutation. Using data on older donors, we show that spontaneous mutations are not uniformly distributed throughout normal testes. Instead, we find foci where C758G mutation frequencies are 3-4 orders of magnitude greater than the remaining tissue. We conclude this nucleotide site is not a mutation hot spot even after accounting for possible Luria-Delbruck "mutation jackpots." An alternative explanation for such foci involving positive selection acting on adult self-renewing Ap spermatogonia experiencing the rare mutation could not be rejected. Further, the two youngest individuals studied (19 and 23 years old) had lower mutation frequencies and smaller foci at both mutation sites compared with the older individuals. This implies that the mutation frequency of foci increases as adults age, and thus selection could explain the paternal age effect for Apert syndrome and other genetic conditions. Our results, now including the analysis of two mutations in the same set of testes, suggest that positive selection can increase the relative frequency of premeiotic germ cells carrying such mutations, although individuals who inherit them have reduced fitness. In addition, we compared the anatomical distribution of C758G mutation foci with both new and old data on the C755G mutation in the same testis and found their positions were not correlated with one another.

  1. Effects on stress rupture life and tensile strength of tin additions to Inconel 718 (United States)

    Dreshfield, R. L.; Johnson, W.


    Because Inconel 718 represents a major use of columbium and a large potential source of columbium for aerospace alloys could be that of columbium derived from tin slags, the effects of tin additions to Inconel 718 at levels which might be typical of or exceed those anticipated if tin slag derived columbium were used as a melting stock were investigated. Tin was added to 15 pound Inconel 718 heats at levels varying from none added to approximately 10,000 ppm (1 wt%). Limited 1200 F stress rupture testing was performed at stresses from 68,000 to 115,000 psi and a few tensile tests were performed at room temperature, 800 and 1200 F. Additions of tin in excess of 800 ppm were detrimental to ductility and stress rupture life.

  2. Effects of lanthanum addition on corrosion resistance of hot-dipped galvalume coating

    Institute of Scientific and Technical Information of China (English)

    YANG Dong; CHEN Jianshe; HAN Qing; LIU Kuiren


    Effects of La addition on corrosion resistance of hot-dipped galvalume coating steel wire were investigated. The corrosion resistance of Zn-Al-Si-La alloy coatings containing 0, 0.02wt.%, 0.05wt.%, 0.1wt.% and 0.2wt.% La were evaluated by various tests such as copper-accelerated acetic acid salt spray testing (CASS), immersion test in 3.5% NaCl solution, electrochemical tests including weak polarization curves and electrochemical impedance spectroscopy (EIS) tests, scanning electron microscope (SEM) test and X-ray diffraction (XRD) test. It was found that the corrosion resistance of galvalume coating could be improved by adding proper amounts of La. Meanwhile, the mechanism of the improvement of corrosion resistance by La addition was discussed.

  3. Effect of red mud addition on the corrosion parameters of reinforced concrete evaluated by electrochemical methods

    Directory of Open Access Journals (Sweden)

    D.V. Ribeiro

    Full Text Available Red mud, the main waste generated in aluminum and alumina production from bauxite ore by the Bayer process, is considered "hazardous" due to its high pH. The high pH also provides greater protection of rebars, which is reflected in the low corrosion potential and high electrical resistivity (filler effect of concrete. The corrosion potential was monitored by electrochemical measurements and the electrical resistivity was evaluated using sensors embedded in concrete test specimens. The results showed that the addition of red mud is beneficial to concrete, reducing its corrosion potential and increasing its electrical resistivity. Red mud proved to be a promising additive for concrete to inhibit the corrosion process.

  4. The Effectiveness of the Additional Vocational Education and Staff Development for Industrial Enterprises

    Directory of Open Access Journals (Sweden)

    Y. S. Kalabina


    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. 

  5. Effect of boron addition on the microstructure and stress-rupture properties of directionally solidified superalloys

    Institute of Scientific and Technical Information of China (English)

    Bao-ping Wu; Lin-han Li; Jian-tao Wu; Zhen Wang; Yan-bin Wang; Xing-fu Chen; Jian-xin Dong; Jun-tao Li


    This study is focused on the effect of boron addition, in the range of 0.0007wt% to 0.03wt%, on the microstructure and stress-rupture properties of a directionally solidified superalloy. With increasing boron content in the as-cast alloys, there is an increase in the fraction of theγ′/γ eutectic and block borides precipitate around theγ′/γ eutectic. At a high boron content of 0.03wt%, there is precipitation of lamellar borides. Upon heat treatment, fine block borides tend to precipitate at grain boundaries with increasing boron content. Overall, the rupture life of the directionally solidified superalloy is significantly improved with the addition of nominal content of boron. However, the rupture life decreases when the boron content exceeds 0.03wt%.

  6. Effect of Additives on Magnetic Properties of High Frequency MnZn Power Ferrite

    Institute of Scientific and Technical Information of China (English)

    YU Zhong; LAN Zhongwen; WANG Jingmei; ZHANG Yidong; WANG Haocai


    The effect of additives,such as CaO and V2O5 on the magnetic properties of high frequency MnZn power ferrite is studied by the conventional ceramic process.As a result,the grain boundary resistivity increases and the power loss declines with the addition of CaO enriched at the grain boundary.By adding an optimum amount of V2O5 which acts indirectly via liquid phase formation and influences the microstructural development during sintering,the crystalline grain of ferrite was refined,the porosity decreases,the amount of grain boundary and the grain boundary resistivity increased,so the power loss is suppressed.

  7. Renormalization and additional degrees of freedom within the chiral effective theory for spin-1 resonances

    CERN Document Server

    Kampf, Karol; Trnka, Jaroslav


    We study in detail various aspects of the renormalization of the spin-1 resonance propagator in the effective field theory framework. First, we briefly review the formalisms for the description of spin-1 resonances in the path integral formulation with the stress on the issue of propagating degrees of freedom. Then we calculate the one-loop 1-- meson self-energy within the Resonance chiral theory in the chiral limit using different methods for the description of spin-one particles, namely the Proca field, antisymmetric tensor field and the first order formalisms. We discuss in detail technical aspects of the renormalization procedure which are inherent to the power-counting non-renormalizable theory and give a formal prescription for the organization of both the counterterms and one-particle irreducible graphs. We also construct the corresponding propagators and investigate their properties. We show that the additional poles corresponding to the additional one-particle states are generated by loop corrections...

  8. Effect of Additive on Sulfur-fixation Process of Sulfur-fixation Agent

    Institute of Scientific and Technical Information of China (English)

    XIE Jun-lin; QIU Jian-rong; ZHAO Gai-ju; LOU Jin-ping; HAN Chun-hua


    The crystallization behavior of desulfurization product is directly related to its high-temperatureresistant ability. Effects of the additive on the sulfur-fixation efficiency of the Ba-sulfur-fixation agent and also on the crystallization behavior of the sulfur-fixation product were studied when CaCO3 and BaCO3 were used as the desulfurization agent and MgO and SrCO3 used as the assistant sulfur-fixation agent. The result shows that increase of sulfur-fixation capability for the additive is not owe to their directly react to form sulfate or interact with CaCO3 and BaCO3 to form composite mineral heat-resistant in high temperature, but owe to their activation to sulfur-fixation reaction of the sulfur-fixation agent.

  9. Advanced analysis of a cryptochrome mutation's effects on the robustness and phase of molecular cycles in isolated peripheral tissues of Drosophila

    Directory of Open Access Journals (Sweden)

    Hall Jeffrey C


    Full Text Available Abstract Background Previously, we reported effects of the cryb mutation on circadian rhythms in period and timeless gene expression within isolated peripheral Drosophila tissues. We relied on luciferase activity driven by the respective regulatory genomic elements to provide real-time reporting of cycling gene expression. Subsequently, we developed a tool kit for the analysis of behavioral and molecular cycles. Here, we use these tools to analyze our earlier results as well as additional data obtained using the same experimental designs. Results Isolated antennal pairs, heads, bodies, wings and forelegs were evaluated under light-dark cycles. In these conditions, the cryb mutation significantly decreases the number of rhythmic specimens in each case except the wing. Moreover, among those specimens with detectable rhythmicity, mutant rhythms are significantly weaker than cry+ controls. In addition, cryb alters the phase of period gene expression in these tissues. Furthermore, peak phase of luciferase-reported period and timeless expression within cry+ samples is indistinguishable in some tissues, yet significantly different in others. We also analyze rhythms produced by antennal pairs in constant conditions. Conclusions These analyses further show that circadian clock mechanisms in Drosophila may vary in a tissue-specific manner, including how the cry gene regulates circadian gene expression.


    Institute of Scientific and Technical Information of China (English)

    YANG Ji-song; LIU Jing-shuang; YU Jun-bao; WANG Jin-da; QIN Sheng-jin; LI Xin-hua


    Soil respiration is a main dynamic process of carbon cycle in wetland. It is important to contribute to global climate changes. Water table and nutritious availability are significant impact factors to influence responses of CO2 emission from wetland soil to climate changes. Twenty-four wetland soil monoliths at 4 water-table positions and in 3 nitrogen status have been incubated to measure rates of CO2 emission from wetland soils in this study.Three static water-table controls and a fluctuant water-table control, with 3 nitrogen additions in every water-table control,were carried out. In no nitrogen addition treatment, high CO2 emissions were found at a static low water table ( Ⅰ )and a fluctuant water table (Ⅳ),averaging 306.7mg/(m2·h) and 307.89mg/(m2·h), respectively, which were 51%-57% higher than that at static high water table ( Ⅱ and Ⅲ). After nitrogen addition, however, highest CO2 emission was found at Ⅱ and lowest emission at Ⅲ. The results suggested that nutritious availability of wetland soil might be important to influence the effect of water table on the CO2 emission from the wetland soil. Nitrogen addition led to enhancing CO2 emissions from wetland soil, while the highest emission was found in 1N treatments other than in 2N treatments. In 3 nutritious treatments,low CO2 emissions at high water tables and high CO2 emissions at low water tables were also observed when water table fluctuated. Our results suggested that both water table changes and nutritious imports would effect the CO2 emission from wetland.

  11. Anaerobic digestion of Jatropha curcas L. press cake and effects of an iron-additive. (United States)

    Schmidt, Thomas


    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.

  12. Effect of metallic additives on in situ combustion of Huntington Beach crude experiments

    Energy Technology Data Exchange (ETDEWEB)

    Baena, C.J.; Castanier, L.M.; Brigham, W.E.


    The economics and applicability of an in-situ combustion process for the recovery of crude oil are dictated to a large extent by the nature and the amount of fuel formed during the process. The aim of this work is to use combustion tube studies to determine on a quantitative basis, how the nature and the amount of fuel formed could be changed by the presence of metallic additives. These experiments follow from the qualitative observations on the effect of metallic additives on the in-situ combustion of Huntington Beach crude oil made by De los Rios (1987) at SUPRI. He performed kinetic studies on the oxidation of Huntington Beach crude in porous media and showed that the nature of the fuel formed changed when metallic additives were present. Combustion tube runs were performed using the metallic additives: ferrous chloride (FeCl{sub 2{center dot}}4H{sub 2}O), zinc chloride (ZnCl{sub 2}) and stannic chloride (SnCl{sub 4{center dot}}5H{sub 2}O). Unconsolidated cores were prepared by mixing predetermined amounts of an aqueous solution of the metal salt, Huntington Beach crude oil, Ottawa sand and clay in order to achieve the desired fluid saturations. The mixture was then tamped into the combustion tube. Dry air combustion tube runs were performed keeping the conditions of saturation, air flux and injection pressure approximately the same during each run. The nature of the fuel formed and its impact on the combustion parameters were determined and compared with a control run -- an experiment performed with no metallic additive. 30 refs., 33 figs., 6 tabs.

  13. Spatial interpolation of hourly rainfall – effect of additional information, variogram inference and storm properties

    Directory of Open Access Journals (Sweden)

    A. Verworn


    Full Text Available Hydrological modelling of floods relies on precipitation data with a high resolution in space and time. A reliable spatial representation of short time step rainfall is often difficult to achieve due to a low network density. In this study hourly precipitation was spatially interpolated with the multivariate geostatistical method kriging with external drift (KED using additional information from topography, rainfall data from the denser daily networks and weather radar data. Investigations were carried out for several flood events in the time period between 2000 and 2005 caused by different meteorological conditions. The 125 km radius around the radar station Ummendorf in northern Germany covered the overall study region. One objective was to assess the effect of different approaches for estimation of semivariograms on the interpolation performance of short time step rainfall. Another objective was the refined application of the method kriging with external drift. Special attention was not only given to find the most relevant additional information, but also to combine the additional information in the best possible way. A multi-step interpolation procedure was applied to better consider sub-regions without rainfall.

    The impact of different semivariogram types on the interpolation performance was low. While it varied over the events, an averaged semivariogram was sufficient overall. Weather radar data were the most valuable additional information for KED for convective summer events. For interpolation of stratiform winter events using daily rainfall as additional information was sufficient. The application of the multi-step procedure significantly helped to improve the representation of fractional precipitation coverage.

  14. Spatial interpolation of hourly rainfall – effect of additional information, variogram inference and storm properties

    Directory of Open Access Journals (Sweden)

    A. Verworn


    Full Text Available Hydrological modelling of floods relies on precipitation data with a high resolution in space and time. A reliable spatial representation of short time step rainfall is often difficult to achieve due to a low network density. In this study hourly precipitation was spatially interpolated with the multivariate geostatistical method kriging with external drift (KED using additional information from topography, rainfall data from the denser daily networks and weather radar data. Investigations were carried out for several flood events in the time period between 2000 and 2005 caused by different meteorological conditions. The 125 km radius around the radar station Ummendorf in northern Germany covered the overall study region. One objective was to assess the effect of different approaches for estimation of semivariograms on the interpolation performance of short time step rainfall. Another objective was the refined application of the method kriging with external drift. Special attention was not only given to find the most relevant additional information, but also to combine the additional information in the best possible way. A multi-step interpolation procedure was applied to better consider sub-regions without rainfall.

    The impact of different semivariogram types on the interpolation performance was low. While it varied over the events, an averaged semivariogram was sufficient overall. Weather radar data were the most valuable additional information for KED for convective summer events. For interpolation of stratiform winter events using daily rainfall as additional information was sufficient. The application of the multi-step procedure significantly helped to improve the representation of fractional precipitation coverage.

  15. Thermodynamic Effect of Platinum Addition to beta-NiAl: An Initial Investigation (United States)


    An initial investigation was conducted to determine the effect of platinum addition on the activities of aluminum and nickel in beta-NiAl(Pt) over the temperature range 1354 to 1692 K. These measurements were made with a multiple effusion-cell configured mass spectrometer (multi-cell KEMS). The results of this study show that Pt additions act to decreased alpha(Al) and increased the alpha(Ni) in beta-NiAl(Pt) for constant X(sub Ni)/X(sub Al) approx. = 1.13, while at constant X(sub Al) the affect of Pt on Al is greatly reduced. The measured partial enthalpies of mixing indicate Al-atoms have a strong self interaction while Ni- and Pt-atoms in have similar interactions with Al-atoms. Conversely the binding of Ni-atoms in beta-NiAl decreases with Pt addition independent of Al concentration. These initial results prove the technique can be applied to the Ni-Al-Pt system but more activity measurements are required to fully understand the thermodynamics of this system and how Pt additions improved the scaling behavior of nickel-based superalloys. In addition, with the choice of a suitable oxide material for the effusion-cell, the "closed" isothermal nature of the effusion-cell allows the direct investigation of an alloy-oxide equilibrium which resembles the "local-equilibrium" description of the metal-scale interface observed during high temperature oxidation. It is proposed that with an Al(l) + Al2O3(s) experimental reference state together with the route measurement of the relative partial-pressures of Al(g) and Al2O(g) allows the activities of O and Al2O3 to be determined along with the activities of Ni and Al. These measurements provide a direct method of investigating the thermodynamics of the metal-scale interface of a TGO-scale.

  16. Effects of temperature and chemical addition on the formation of bromoorganic DBPs during ozonation. (United States)

    Zhang, Xiangru; Echigo, Shinya; Lei, Hongxia; Smith, Michael E; Minear, Roger A; Talley, Jeffrey W


    The effects of temperature and addition of OH radical scavengers/enhancers or HOBr scavenger on the formation of bromoorganic disinfection byproducts (DBPs) from ozonation of six raw waters were studied in true batch reactors. The formation of bromoorganic DBPs during ozonation generally increased with the increase of temperature, but might also decrease for the waters with somewhat higher values of specific UV absorbance (SUVA). The addition of hydrogen peroxide, ethanol, or ammonium dramatically decreased the formation of bromoorganic DBPs; t-butanol addition significantly increased the formation of bromoorganic DBPs; bicarbonate addition might increase or decrease bromoorganic DBP formation depending on the water source. For all the waters treated with the chemical addition, the level of total organic bromine (TOBr) varied with the same pace as that of ozone exposure (CT), which suggests that TOBr formed during ozonation may be used to estimate the CT, a measure for the achieved degree of disinfection. The results demonstrate that for each water, the correlation between TOBr and CT was less affected by the change of chemical composition of the water than that between BrO(3)(-) and CT; for a given chemical composition and temperature of a water, there generally were well-defined relationships between TOBr and CT, and bromoform and CT just as that between BrO(3)(-) and CT. The possible mechanisms behind the linear functions of TOBr or BrO(3)(-) versus CT were given. Further study is needed to examine whether the trends found in this research can be applicable for the high SUVA waters.

  17. Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions. (United States)

    Suzuki, Masao; Tsuruoka, Chizuru; Kanai, Tatsuaki; Kato, Takeshi; Yatagai, Fumio; Watanabe, Masami


    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.

  18. Effect of Sodium Alginate Addition to Resveratrol on Acute Gouty Arthritis

    Directory of Open Access Journals (Sweden)

    Peng Wang


    Full Text Available Objective: Resveratrol has been shown to exert anti-inflammatory and antioxidant effects, while sodium alginate is a common pharmaceutic adjuvant with antioxidative and immunomodulatory properties. We performed an animal study to investigate the effect of sodium alginate addition to resveratrol on acute gouty arthritis. Methods: Twenty-four SPF Wistar mice were randomized to four groups receiving the combination of sodium alginate and resveratrol, resveratrol alone, colchicine, and placebo, respectively. Acute gouty arthritis was induced by injection of 0.05 ml monosodium urate (MSU solution (25g/mL into ankle joint cavity. IL-1β, CCR5, and CXCL10 levels in both serum and synovial fluid were measured using ELISA. NLRP3 expression in the synovial tissues was measured using western plot. Results: The combination of sodium alginate and resveratrol significantly reduced synovial levels of IL-1β, CCR5, and CXCL10 when compared with colchicines, and all P values were less than 0.0001. The combination of sodium alginate and resveratrol was also superior to resveratrol in terms of both serum levels and synovial levels of IL-1β, CCR5, and CXCL10. In addition, resveratrol, with or without sodium alginate, could reduce NLRP3 expression obviously in the synovial tissues. Conclusion: The combination of sodium alginate and resveratrol has better effect over colchicines in treating MSU-induced acute gouty arthritis.

  19. Comparison of image quality and effective dose by additional filtration on digital chest tomosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kye Sun [Dept. of Dignostic Radiology, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Sung Chul [Dept. of Radiological Science, Gachon University, Sungnam (Korea, Republic of)


    The purpose of this study is to suggest proper additional filtration by comparisons patient dose and image quality among additional filters in digital chest tomosynthesis (DTS). We measured the effective dose, dose area product (DAP) by changing thickness of Cu, Al and Ni filter to compare image quality by CD curve and SNR, CNR. Cu, Al and Ni exposure dose were similar thickness 0.3 mm, 3 mm and 0.3 mm respectively. The exposure dose using filter was decreased average about 33.1% than non filter. The DAP value of 0.3 mm Ni were decreased 72.9% compared to non filter and the lowest dose among 3 filter. The effective dose of 0.3 mm Ni were decreased 48% compared to 0.102 mSv effective dose of non filter. At the result of comparison of image quality through CD curve there were similar aspect graph among Cu, Al and Ni. SNR was decreased average 19.07%, CNR was average decreased 18.17% using 3 filters. In conclusion, Ni filtration was considered to be most suitable when considered comprehensive thickness, character, sort of filter, dose reduction and image quality evaluation in DTS.

  20. Effect of zirconium addition on the recrystallization behaviour of a commercial Al–Cu–Mg alloy

    Indian Academy of Sciences (India)

    K T Kashyap


    It is well known that the second phase particles have an effect on recrystallization and grain growth behaviour of an alloy. Particularly the bimodal distribution of second phase particles has an effect which is opposite in sense where coarse second phase particles (> 1 m) stimulate nucleation while fine particles exhibit Zener drag. In the literature, the effect of zirconium addition to aluminium alloys has been well documented in order to produce superplasticity by giving ultra fine grain size to the alloy. Addition of zirconium produces Al3Zr particles which pin the grain boundaries during recrystallization and grain growth. In the present work, zirconium was added to a commercial Al–Cu–Mg alloy and by heat treatment Al3Zr particles were precipitated and after forging, the grain size was an order of magnitude lower than the alloy without zirconium. Transmission electron microscopy was employed to characterize the second phase particles, i.e. Al3Zr particles and found to be rod shaped and identified to be cubic ordered 12 phase with a lattice parameter of 0.408 nm. Further, it was observed that fine (100 nm) Al3Zr particles promote only continuous recrystallization which is polygonization of subgrains and subgrain growth. It was found that the fine dispersion of Al3Zr particles inhibits both recrystallization and grain growth in the commercial Al–Cu–Mg alloy.

  1. The Effect of the Addition of Encapsulated Collagen Hydrolysate on Some Quality Characteristics of Sucuk (United States)


    The effect of addition commercial fish collagen hydrolysate and encapsulated fish collagen hydrolysate on the quality characteristics of sucuk (a traditional Turkish dry-fermented sausage) was investigated. Fish collagen hydrolysates were encapsulated with maltodextrin (MD) which has two different dextrose equivalent (12DE and 19 DE), with two different types of core/coating material ratios (10% peptide : 90% MD, 20% peptide : 80% MD). Than six group of sucuk dough (control, peptide, MD1210, MD1220, MD1910, MD1920) prepared and naturally fermented. The effects of the ripening period (28 d), treatment (peptide and encapsulated peptide addition) ‘ripening period × treatment’ interaction on sucuk’s pH, lactic acid contents, aw values and moisture contents were statistically significant (pfermentation for both activities. Antioxidant activity of encapsulated peptide added (%39.56-40.48) groups were higher than control (34.28%) and peptide added (33.99%) groups except MD1920 (38.30%). The effect of the ripening period of the sucuk samples on TBA values was found to be statistically significant (p<0.01) while treatment and ‘ripening period × treatment’ interaction were not to be significant (p<0.05). The value of hardness was the highest in the encapsulated peptide added groups (29.27, 35.83 N), and it was 20.40 N and 15.41 N in the peptide added group and the control group respectively. PMID:28115893

  2. Choosing components in the additive main effect and multiplicative interaction (AMMI models

    Directory of Open Access Journals (Sweden)

    Dias Carlos Tadeu dos Santos


    Full Text Available The additive main effect and multiplicative interaction (AMMI models allows analysts to detect interactions between rows and columns in a two-way table. However, there are many methods proposed in the literature to determine the number of multiplicative components to include in the AMMI model. These methods typically give different results for any particular data set, so the user needs some guidance as to which methods to use. In this paper we compare four commonly used methods using simulated data based on real experiments, and provide some general recommendations.

  3. The Effect of Chelating Copolymer Additive on the Yttrium Iron Garnet Nanoparticle Formation

    Institute of Scientific and Technical Information of China (English)

    Wang; Cheng-chien


    1 Results Yttrium iron garnet (YIG) is a well-known ferromagnetic garnet material and has widely used in electronic devices[1].A new acrylic chelating polymer was developed to act as the additive of the preparation of YIG precursor in our previous study[2].The sintering temperature of YIG nanocrystal obtained by this YIG precursor (ACP) was magnificently descended from 1 000 to 600 ℃.In this study,we were further to study the effect of amount of chelating polymer and the compositions of chelating polyme...

  4. Inhibition of Aluminium Corrosion in Hydrochloric Acid Using Nizoral and the Effect of Iodide Ion Addition

    Directory of Open Access Journals (Sweden)

    I. B. Obot


    Full Text Available The effect of nizoral (NZR on the corrosion inhibition of aluminium alloy AA 1060 in 2 M HCl solution was investigated using the mylius thermometric technique. Results of the study revealed that nizoral acts as corrosion inhibitor for aluminium in the acidic medium. In general, at constant acid concentration, the inhibition efficiency increases with increase in the inhibitor concentration. The addition of KI to the inhibitor enhanced the inhibition efficiency to a considerable extent. The adsorption of nizoral onto the aluminium surface was found to obey the Fruendlich adsorption isotherm. The value of the free energy for the adsorption process shows that the process is spontaneous.

  5. The Effects of Bottom Ash from MSWI Used as Mineral Additions in Concrete

    Directory of Open Access Journals (Sweden)

    Che Amat Roshazita


    Full Text Available Municipal solid waste incinerators (MSWI produce by products which can be classified as bottom and fly ashes. The bottom ash accounts for 85–90 % of the solid product resulting from MSW combustion. The aimed of the present work is to study the effect of replacing partial of bottom ash were manufactured. Fresh and hardened properties of the concrete were compared in order to study the suitable cement-bottom ash replacement. Bottom ash was found to have some reactivity, but without greatly affecting the hydration process of OPC at 10 % replacement. However at more than 10 % replacement, the addition of bottom ash greatly affected strength.

  6. Effect of transition-metal additives on hydrogen desorption kinetics of MgH2 (United States)

    Roy, Anindya; Janotti, Anderson; Van de Walle, Chris G.


    Using first-principles calculations, we study the effect of transition-metal additives (Ti, Fe, Co, and Ni) on the rate of hydrogen desorption in MgH2. The presence of large concentrations of transition-metal impurities causes the Fermi level to shift according to the position of the transition-metal acceptor/donor levels in the band gap. This shift can lower the formation energy of native defects and increase their concentration. The resulting higher rates of hydrogen desorption enhance the prospect of MgH2 as a solid-state hydrogen-storage material.

  7. Reaction rate theory of radiation exposure: Effects of the dose rate on mutation frequencies

    CERN Document Server

    Manabe, Yuichiro; Nakamura, Issei


    We develop a kinetic reaction model for the cells having the irradiated DNA molecules due to the ionizing radiation exposure. Our theory simultaneously accounts for the time-dependent reactions of the DNA damage, the DNA mutation, the DNA repair, and the proliferation and apoptosis of cells in a tissue with a minimal set of model parameters. In contrast to the existing theories for the radiation exposition, we do not assume the relationships between the total dose and the induced mutation frequency. We show good agreement between theory and experiment. Importantly, our result shows a new perspective that the key ingredient in the study of the irradiated cells is the rate constants depending on the dose rate. Moreover, we discuss the universal scaling function for mutation frequencies due to the irradiation at low dose rates.

  8. DNA duplex membrane effect for the electrochemical detection of single-base DNA mutations

    Institute of Scientific and Technical Information of China (English)

    Luo Chunxiong; Mao Yongdong; Ouyang Qi


    Here we report a new method to detect DNA point mutations.The method is based on the formation and deformation of double-stranded DNA(dsDNA)membranes on a gold surface.It can encage reporter molecules between the gold surface and the double-stranded DNA or keep them away from the gold surface.In these systems,Fe(CN)63- was used as the reporter.As the temperature increases,a sharp electrochemical signal change in the melting curve of wild-type dsDNA appears.At a special temperature,the and single base mutation target.Thus,the system provides a simple and sensitive method to detect DNA point mutations without labeling targets.

  9. Effect of mutators on adaptability in time-varying fitness landscapes (United States)

    Gorodetsky, Pavel; Tannenbaum, Emmanuel


    This Brief Report studies the quasispecies dynamics of a population capable of genetic repair evolving on a time-dependent fitness landscape. We develop a model that considers an asexual population of single-stranded, conservatively replicating genomes, whose only source of genetic variation is due to copying errors during replication. We consider a time-dependent, single-fitness-peak landscape where the master sequence changes by a single point mutation at every time τ . We are able to analytically solve for the evolutionary dynamics of the population in the point-mutation limit. In particular, our model provides an analytical expression for the fraction of mutators in the dynamic fitness landscape that agrees well with results from stochastic simulations.

  10. Functional effects of spinocerebellar ataxia type 13 mutations are conserved in zebrafish Kv3.3 channels

    Directory of Open Access Journals (Sweden)

    Mock Allan F


    zebrafish Kv3.3 channels are consistent with a role in facilitating fast, repetitive firing of action potentials in neurons. The functional effects of SCA13 mutations are well conserved between human and zebrafish Kv3.3 channels. The high degree of homology between human and zebrafish Kv3.3 channels suggests that the zebrafish will be a useful model system for studying pathogenic mechanisms in SCA13.

  11. Functional and Structural Consequences of Nine CYP21A2 Mutations Ranging from Very Mild to Severe Effects (United States)

    Silva, Camila D'Almeida Mgnani; Östberg, Linus Joakim; Persson, Bengt; Guerra-Júnior, Gil; Barbaro, Michela


    We present the functional and structural effects of seven novel (p.Leu12Met, p.Arg16Cys, p.Ser101Asn, p.Ser202Gly, p.Pro267Leu, p.Gln389_Ala391del, and p.Thr450Met) and two previously reported but not studied (p.Ser113Phe and p.Thr450Pro) CYP21A2 mutations. Functional analyses were complemented with in silico prediction of mutation pathogenicity based on the recently crystallized human CYP21A2 structure. Mutated proteins were transiently expressed in COS-1 cells and enzyme activities towards 17-hydroxyprogesterone and progesterone were determined. Residual enzyme activities between 43% and 97% were obtained for p.Arg16Cys, p.Ser101Asn, p.Ser202Gly, p.Pro267Leu, and p.Thr450Met, similar to the activities of the well-known nonclassic mutations p.Pro453Ser and p.Pro482Ser, whereas the p.Leu12Met variant showed an activity of 100%. Conversely, the novel p.Ser113Phe, p.Gln389_Ala391del, and p.Thr450Pro mutations drastically reduced the enzyme function below 4%. The Km values for all novel variants were in the same order of magnitude as for the wild-type protein except for p.The450Met. The maximum velocity was decreased for all mutants except for p.Leu12Met. We conclude that p.Leu12Met is a normal variant; the mutations p.Arg16Cys, p.Ser101Asn, p.Ser202Gly, p.Pro267Leu, and p.Thr450Met could be associated with very mild nonclassic CAH, and the mutations p.Ser113Phe, p.Gln389_Ala391del, and p.Thr450Pro are associated with classic CAH. The obtained residual activities indicated a good genotype-phenotype correlation. PMID:27721825

  12. Effect of the Addition of Schisandra chinensis Powder on the Physico-chemical Characteristics of Sausage. (United States)

    Jin, S K; Park, J H


    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 (psausage 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 (psausage significantly (psausage meat resulted in a significant deterioration in quality characteristics of flavor, springiness, juiciness and overall acceptability (psausages, depended on the rate of addition of nitrite (psausages, but may beneficially affect TBARS, nitrite scavenging activity, fatty acid and amino acid content in pork sausages.

  13. Effect of commercial mineral-based additives on composting and compost quality. (United States)

    Himanen, M; Hänninen, K


    The effectiveness of two commercial additives meant to improve the composting process was studied in a laboratory-scale experiment. Improver A (sulphates and oxides of iron, magnesium, manganese, and zinc mixed with clay) and B (mixture of calcium hydroxide, peroxide, and oxide) were added to source-separated biowaste:peat mixture (1:1, v/v) in proportions recommended by the producers. The composting process (T, emissions of CO(2), NH(3), and CH(4)) and the quality of the compost (pH, conductivity, C/N ratio, water-soluble NH(4)-N and NO(3)-N, water- and NaOH-soluble low-weight carboxylic acids, nutrients, heavy metals and phytotoxicity to Lepidium sarivum) were monitored during one year. Compared with the control, the addition of improver B increased pH by two units, led to an earlier elimination of water-soluble ammonia, an increase in nitrates, a 10-fold increase in concentrations of acetic acid, and shortened phytotoxicity period by half; as negative aspect it led to volatilization of ammonia. The addition of improver A led to a longer thermophilic stage by one week and lower concentrations of low-weight carboxylic acids (both water- and NaOH-extractable) with formic and acetic of similar amounts, however, most of the aspects claimed by the improver's producer were not confirmed in this trial.

  14. Monitoring Residual Solvent Additives and Their Effects in Solution Processed Solar Cells (United States)

    Fogel, Derek M.; Basham, James I.; Engmann, Sebastian; Pookpanratana, Sujitra J.; Bittle, Emily G.; Jurchescu, Oana D.; Gundlach, David J.


    High boiling point solvent additives are a widely adopted approach for increasing bulk heterojunction (BHJ) solar cell efficiency. However, experiments show residual solvent can persist for hours after film deposition, and certain common additives are unstable or reactive. We report here on the effects of residual 1,8-diiodooctane on the electrical performance of poly(3-hexylthiophene-2,5-diyl) (P3HT): phenyl-C71-butyric acid methyl ester (PC[71]BM) BHJ photovoltaic cells. We optimized our fabrication process for efficiency at an active layer thickness of 220 nm, and all devices were processed in parallel to minimize unintentional variations between test structures. The one variable in this study is the active layer post spin drying time. Immediately following the cathode deposition, we measured the current-voltage characteristics at one sun equivalent illumination intensity, and performed impedance spectroscopy to quantify charge density, lifetime, and recombination process. Spectroscopic ellipsometry, FTIR, and XPS are also used to monitor residual solvent and correlated with electrical performance. We find that residual additive degrades performance by increasing the series resistance and lowering efficiency, fill factor, and free carrier lifetime.

  15. Effects of La and Ce Addition on the Modification of Al-Si Based Alloys

    Directory of Open Access Journals (Sweden)

    Emad M. Elgallad


    Full Text Available This study focuses on the effects of the addition of rare earth metals (mainly lanthanum and cerium on the eutectic Si characteristics in Al-Si based alloys. Based on the solidification curves and microstructural examination of the corresponding alloys, it was found that addition of La or Ce increases the alloy melting temperature and the Al-Si eutectic temperature, with an Al-Si recalescence of 2-3°C, and the appearance of post-α-Al peaks attributed to precipitation of rare earth intermetallics. Addition of La or Ce to Al-(7–13% Si causes only partial modification of the eutectic Si particles. Lanthanum has a high affinity to react with Sr, which weakens the modification efficiency of the latter. Cerium, however, has a high affinity for Ti, forming a large amount of sludge. Due to the large difference in the length of the eutectic Si particles in the same sample, the normal use of standard deviation in this case is meaningless.

  16. Effect of carbon nanotube addition on the wear behavior of basalt/epoxy woven composites. (United States)

    Kim, M T; Rhee, K Y; Lee, B H; Kim, C J


    The effect of acid-treated carbon nanotube (CNT) addition on the wear and dynamic mechanical thermal properties of basalt/epoxy woven composites was investigated in this study. Basalt/CNT/epoxy composites were fabricated by impregnating woven basalt fibers into epoxy resin mixed with 1 wt% CNTs which were acid-treated. Wear and DMA (dynamic mechanical analyzer) tests were performed on basalt/epoxy composites and basalt/CNT/epoxy composites. The results showed that the addition of the acid-treated CNTs improved the wear properties of basalt/epoxy woven composites. Specifically, the friction coefficient of the basalt/epoxy composite was stabilized in the range of 0.5-0.6 while it fell in the range of 0.3-0.4 for basalt/CNT/epoxy composites. The wear volume loss of the basalt/CNT/epoxy composites was approximately 68% lower than that of the basalt/epoxy composites. The results also showed that the glass transition temperature of basalt/CNT/epoxy composites was higher than that of basalt/epoxy composites. The improvement of wear properties of basalt/epoxy composites by the addition of acid-treated CNTs was caused by the homogeneous load transfer between basalt fibers and epoxy matrix due to the reinforcement of CNTs.

  17. Effect of Nd2O3 addition on structure and characterization of lead bismuth borate glass

    Directory of Open Access Journals (Sweden)

    I. Kashif


    Full Text Available The effect of different contents of Nd2O3 on the thermal transition temperature, density and structure of 25 Bi2O3 – 25 PbO – 50 B2O3 has been investigated using X-ray diffraction (XRD, differential thermal analysis (DTA, infrared spectrophotometer (FTIR and optical absorption. The amorphous phase has been identified based on X-ray diffraction analysis. The neodymium oxide plays the role as a glass-modifier and influences on BO3 ↔ BO4 conversion. The observed increase in Tg with Nd2O3 reflects an increase in bond strength. The decrease of the density and the increase of the molar volume with the addition of Nd2O3 contents attributed to an increase in the number of Non-bridging oxygen (NBOS. The optical absorption results are indicating the higher covalency of the Nd–O bond for glass containing 2 mol% of Nd2O3. In addition, a lowest covalency is observed in glass with 1 mol% Nd2O3. In addition, it is considered necessary in the construction of compact and efficient laser source.

  18. Compensation and additivity of anthropogenic mortality: life-history effects and review of methods. (United States)

    Péron, Guillaume


    Demographic compensation, the increase in average individual performance following a perturbation that reduces population size, and, its opposite, demographic overadditivity (or superadditivity) are central processes in both population ecology and wildlife management. A continuum of population responses to changes in cause-specific mortality exists, of which additivity and complete compensation constitute particular points. The position of a population on that continuum influences its ability to sustain exploitation and predation. Here I describe a method for quantifying where a population is on the continuum. Based on variance-covariance formulae, I describe a simple metric for the rate of compensation-additivity. I synthesize the results from 10 wildlife capture-recapture monitoring programmes from the literature and online databases, reviewing current statistical methods and the treatment of common sources of bias. These results are used to test hypotheses regarding the effects of life-history strategy, population density, average cause-specific mortality and age class on the rate of compensation-additivity. This comparative analysis highlights that long-lived species compensate less than short-lived species and that populations below their carrying capacity compensate less than those above.

  19. Effect of addition of (different types of) free radical initiators on petroleum pitch formation

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Shalini [Bharat Petroleum Corporation Limited, G' Noida (India). Corporate R and D Center; Srivastava, Manoj [Indian Institute of Petroleum, Dehradun (India); Singh, Himmat [Petroleum and Natural Gas, Dehradun (India)


    Petroleum Pitch is a complex mixture of poly-nuclear aromatic hydrocarbons and is an excellent precursor for a number of advanced carbon materials. Conventionally, pitches are prepared by thermal treatment of aromatic rich feed stocks. The types of reactions taking place during thermal soaking can be described adequately by the free radical mechanism. The properties of pitches can be tailor-made for specific applications by varying thermal soaking temperature and residence time. Different types of free radical initiators can be used to promote the polymerization and condensation reactions viz; organic peroxide, azobisisobutyronitrile (AIBN), polythene etc. Keeping the above details in view, four pitches were prepared using different additives/initiators to study their effect on process parameters leading to polymerization and condensation reactions. The influence of the addition of initiator on pitch composition and properties was monitored by elemental analysis, thermo gravimetric analysis, FTIR and by NMR techniques. The pitches thus prepared, compare well in properties with Ashland Petroleum Company's A-240 pitch (a reference pitch), usedworldwide in graphite electrodes plants. The petroleum pitch formation study described below presents investigations carried out using pyrolysis tar as the feed stock. It is observed that the addition of initiators results in significant reduction in heat treatment time, which can lead to increase in yield of pitches during commercial production within a given time.

  20. Effect of additives on the properties of polyaniline nanofibers prepared by high gravity chemical oxidative polymerization. (United States)

    Zhao, Yibo; Arowo, Moses; Wu, Wei; Chen, Jianfeng


    Polyaniline (PANI) nanofibers with improved properties were prepared by high gravity chemical oxidative polymerization in a rotating packed bed with the assistance of p-aminodiphenylamine (AD) and p-phenylenediamine (AP). The effects of reactor type, additive dosage, reaction temperature, and high-gravity level on the properties of products were investigated in detail. Three conclusions were made: (1) a small amount of additive can significantly improve some properties of the nanofibers such as uniformity, specific surface area, and specific capacitance; (2) in order to obtain high-quality nanofibers, the high-gravity level should coordinate with the reaction rate; (3) the molecular weight and conductivity of PANI decrease with the increase of additive dosage. The products have larger specific surface areas of up to 73.9 and 68.4 m(2)/g and consequently improved specific capacitance of up to 527.5 and 552 F/g for the PANI nanofibers prepared with AD and AP, respectively. However, the specific surface area and specific capacitance of pure PANI are only 49.1 m(2)/g and 333.3 F/g, respectively. This research provides a simple, reliable, and scalable method to produce PANI nanofibers of high performances.

  1. Effect of reinforcement nanoparticles addition on mechanical properties of SBS/curaua fiber composites

    Energy Technology Data Exchange (ETDEWEB)

    Borba, Patricia M. [Servico Nacional de Aprendizagem Industrial (CETEPO/SENAI/RS), Sao Leopoldo, RS (Brazil). Centro Tecnologico de Polimeros; Tedesco, Adriana [Braskem S. A., III Polo Petroquimico, Triunfo, RS (Brazil); Lenz, Denise M., E-mail: [Universidade Luterana do Brasil (ULBRA), Canoas, RS (Brazil). Programa de Pos-graduacao em Engenharia de Materiais e Processos Sustentaveis


    Composites of styrene-butadiene-styrene triblock copolymer (SBS) matrix with curauá fiber and/or a nanoparticulated mineral (montmorillonite clay - MMT) used as reinforcing agents were prepared by melt-mixing. The influence of clay addition on properties like tensile and tear strength, rebound resilience, flex fatigue life, abrasion loss, hardness and water absorption of composites with 5, 10 and 20 wt% of curauá fiber was evaluated in presence of maleic anhydride grafted styrene-(ethylene-co-butylene)-styrene triblock copolymer (MA-g-SEBS) coupling agent. Furthermore, the effect of mineral plasticizer loading on tensile strength of selected composites was investigated. The hybrid SBS composite that showed the best overall mechanical performance was composed by 2 wt% of MMT and 5 wt% of curauá fiber. Increasing fiber content up to 20 wt% resulted in a general decrease in all mechanical properties as well as incorporation of 5 wt% MMT caused a decrease in the tensile strength in all fiber contents. The hybrid composites showed clay agglomerates (tactoids) poorly dispersed that could explain the poor mechanical performance of composites at higher concentrations of curauá fiber and MMT nanoparticles. The addition of plasticizer further decreased the tensile strength while the addition of MMT nanoparticles decreased water absorption for all SBS composites. (author)

  2. Synergistic Effect of Selenium Addition and Water Stress on Melilotus officinalis L. Mineral Content

    Directory of Open Access Journals (Sweden)

    Panagiota KOSTOPOULOU


    Full Text Available The objective of this study was to examine the combined effects of selenium (Se enrichment and water stress on the accumulation of available macro- and micronutrients in Melilotus officinalis L. aerial parts. Plants of M. officinalis were subjected to three levels of Se addition (0, 1 and 3 mg Se L-1 water and to two water treatments: a full irrigation and b limited irrigation (water stress. The above ground biomass (stems and leaves was analyzed for Se, potassium (K, sodium (Na, magnesium (Mg, iron (Fe, copper (Cu, calcium (Ca, manganese (Mn and zinc (Zn. Se addition differentially affected the K, Mg and Ca content of M. officinalis aerial parts, while it led to the reduction of the micronutrients Cu, Fe and Mn. Water stress resulted in the increase of K, Na, Mg, Ca and Cu, and to the decrease of the Fe, Zn and Mn content. An interaction between selenium addition and water treatment was more notable for Ca and Mg, which decreased under water stress at low Se level and for Zn and Cu, which increased under water stress at high Se level. According to our findings, Se-induced increased accumulation of some inorganic ions in the aerial parts of this species under water stress conditions could serve as a means to alleviate the adverse impact of water deficit on important metabolic processes, enhancing M. officinalis tolerance to water stress.

  3. Effect of Meltable Triazine-DOPO Additive on Rheological, Mechanical, and Flammability Properties of PA6

    Directory of Open Access Journals (Sweden)

    Irina Butnaru


    Full Text Available Through a straightforward approach, a new meltable, halogen-free, nitrogen-phosphorus-based flame retardant (FR, 6-(2-(4,6-diamino-1,3,5-triazin-2-ylethyl dibenzo[c,e][1,2]oxaphosphinine 6-oxide (DTE-DOPO was synthesized and incorporated in polyamide 6 (PA6. It was proved that a very low phosphorus content of 1.46 wt% for DTE-DOPO additive improved the flame retardancy of PA6, leading to a non-flammable material. The performance of the new additive was compared to that of the commercially-available Exolit® OP 1230. The PA6 formulations were evaluated by measuring the rheological, mechanical, and flammability behavior. Using compounding by melt extrusion, 17 wt% additives was introduced into PA6 matrix and the corresponding formulations were characterized. The results evidenced a higher homogeneity of DTE-DOPO with PA6, a high thermal stability with a catalyzing decomposition effect on PA6 caused by the presence of the new developed FR, enhanced elasticity for the PA6/DTE-DOPO formulation and a V0 rating for both formulations. Thermal and fire analysis indicated a primary gas-phase activity, combined with a complete suppression of the self-sustained burning for the PA6/DTE-DOPO formulation.

  4. Effect of KRAS exon 2 mutations on antitumor activity of afatinib and gefitinib. (United States)

    Gamba, Sebastian; Camaj, Peter; Heinemann, Volker; Laubender, Rüdiger P; Wang, Yan; Zhao, Yue; Stintzing, Sebastian; Giessen, Clemens; Boeck, Stefan; Haertl, Christoph; Bruns, Christiane J; Modest, Dominik P


    The aim of this study was to investigate the impact of different KRAS mutations on the inhibitory potential of afatinib and gefitinib in SW48 colorectal cancer cells. The influence of afatinib/gefitinib on cell viability and cell cycle was evaluated in isogenic SW48 KRAS wild-type/mutant cells. Protein levels of phosphorylated/total EGFR, HER-2, HER-3, ERK, and AKT were compared between treated/untreated samples using western blotting. The activity of both afatinib and gefitinib was the lowest in KRAS G12C/G12S/G12D and the highest in G13D/G12A mutant subtypes. A 50% decrease in cell viability was achieved at concentrations of 3.0-7.7 μmol/l for afatinib and 5.4-19.5 μmol/l for gefitinib. The effect of both drugs on apoptosis appeared to be stronger than their influence on proliferation and was generally less pronounced in mutant cells than in wild-type cells. The average number of apoptotic cells after treatment with afatinib was 2.6 times as high as the corresponding value following treatment with gefitinib (Pafatinib than by gefitinib (Pafatinib and gefitinib whereas others seem to increase sensitivity to treatment (G13D/G12A) compared with the parental clone (KRAS wild-type). In SW48 colorectal cancer cells, afatinib seems to be more potent than gefitinib because of its superior efficacy in inhibiting both EGFR and HER-2, suppressing signaling along both MEK/ERK and PI3K/AKT pathways to a greater extent.

  5. Effects of Rice Straw and Its Biochar Addition on Soil Labile Carbon and Soil Organic Carbon

    Institute of Scientific and Technical Information of China (English)

    YIN Yun-feng; HE Xin-hua; GAO Ren; MA Hong-liang; YANG Yu-sheng


    Whether the biochar amendment could affect soil organic matter (SOM) turnover and hence soil carbon (C) stock remains poorly understood. Effects of the addition of 13C-labelled rice straw or its pyrolysed biochar at 250 or 350°C to a sugarcane soil (Ferrosol) on soil labile C (dissolved organic C, DOC;microbial biomass C, MBC;and mineralizable C, MC) and soil organic C (SOC) were investigated after 112 d of laboratory incubation at 25°C. Four treatments were examined as (1) the control soil without amendment (Soil);(2) soil plus 13C-labelled rice straw (Soil+Straw);(3) soil plus 250°C biochar (Soil+B250) and (4) soil plus 350°C biochar (Soil+B350). Compared to un-pyrolysed straw, biochars generally had an increased aryl C, carboxyl C, C and nitrogen concentrations, a decreased O-alkyl C and C:N ratio, but similar alkyl C and d13C (1 742-1 877‰). Among treatments, signiifcant higher DOC, MBC and MC derived from the new C (straw or biochar) ranked as Soil+Straw>Soil+B250>Soil+B350, whilst signiifcant higher SOC from the new C as Soil+B250>Soil+Straw≈Soil+B350. Compared to Soil, DOC and MBC derived from the native soil were decreased under straw or biochar addition, whilst MC from the native soil was increased under straw addition but decreased under biochar addition. Meanwhile, native SOC was similar among the treatments, irrespective of the straw or biochar addition. Compared to Soil, signiifcant higher total DOC and total MBC were under Soil+Straw, but not under Soil+B250 and Soil+B350, whilst signiifcant higher total MC and total SOC were under straw or biochar addition, except for MC under Soil+B350. Our results demonstrated that the application of biochar to soil may be an appropriate management practice for increasing soil C storage.

  6. Morphology tuning of CoMo catalysts: Effect of La and Fe as an additive

    Directory of Open Access Journals (Sweden)

    Yu Pei


    Full Text Available Three catalysts CoMo/γ-Al2O3, CoMo-La/γ-Al2O3, CoMo-Fe/γ-Al2O3 with different morphologies were prepared for study the effect of introduction of La and Fe on morphology properties and hydrodesulfurization (HDS activity. The morphology properties of catalysts were characterized by BET, XPS and HRTEM. In addition, the catalytic performances of catalysts were investigated. The results indicated that the introduction of La and Fe promoted the sulfidation of Mo species and made the average length and stacking layer numbers of MoS2 slabs longer and higher. These effects could improve the activity of catalysts for HDS. The present results indicated that the catalyst modified by Fe had the best HDS activity with the optimal morphology among three catalysts

  7. Impact of Zn, Mg, Ni and Co elements on glass alteration: Additive effects (United States)

    Aréna, H.; Godon, N.; Rébiscoul, D.; Podor, R.; Garcès, E.; Cabie, M.; Mestre, J.-P.


    The minor elements present in the nuclear glass composition or coming from the groundwater of the future repository may impact glass alteration. In this study, the effects of Zn, Mg, Ni and Co on the International Simple Glass (ISG) alteration were studied throughout 511 days of aqueous leaching experiments. The aim was to determine their additive or competitive effect on glass alteration and the nature of the alteration products. The four elements were introduced separately or altogether in solution as XCl2 chloride salts (X = Zn, Mg, Ni or Co) with monthly additions to compensate for their consumption. The alteration kinetics were determined by leachate analyses (ICP-AES) and alteration products were characterized in terms of composition, morphology and microstructure (SEM, TEM-EDX, ToF-SIMS and XRD). Results indicate that when they are introduced separately, Zn, Mg, Ni and Co have the same qualitative and quantitative effect on glass alteration kinetics and on pH: they form secondary phases leading to a pH decrease and a significant increase in glass alteration. The secondary phases were identified as silicates of the added X element: trioctahedral smectites with a stoichiometry of[(Si(4-a) Ala) (X(3-b) Alb) O10 (OH)2](a+b)- [Xc Nad Cae] (2c+d+2e)+ with a = 0.11 to 0.45, b = 0.00 to 0.29, c = 0, d = 0.19 to 0.74 and e = 0.10 to 0.14. . It was shown that as pH stabilizes at a minimum value, X-silicates no longer precipitate, thus leading to a significant drop in the glass alteration rate. This pH value depends on X and it has been identified as being 8 for Mg-silicates, probably around 7.3 for Ni and Co-silicates and less than 6.2 for Zn-silicates. When tested together, the effects of these four elements on glass alteration are additive and lead to the formation of a mix of X-silicates that precipitate as long as their constitutive elements are available and the pH is above their respective minimum value. This study brings new quantitative information about the

  8. Effect of methylene methanedisulfonate as an additive on the cycling performance of spinel lithium titanate electrode

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Renheng; Li, Xinhai; Zhang, Bao, E-mail:; Wang, Zhixing; Guo, Huajun


    In order to overcome the poor cyclability of lithium-ion batteries with spinel lithium titanate (Li{sub 4}Ti{sub 5}O{sub 12}), methylene methanedisulfonate (MMDS) is evaluated as electrolyte additive. The linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS) indicate that MMDS participates in the formation process of the solid electrolyte interface (SEI) film above 1 V, which is due to the interfacial reaction between the electrode and electrolyte: Li{sub 4}Ti{sub 5}O{sub 12} anodes are previously considered free from SEI films when cycled between 1 and 3 V. The stable SEI film around Li{sub 4}Ti{sub 5}O{sub 12} is seen most effective as a barrier layer in suppressing the interfacial reaction and resulting gassing from the Li{sub 4}Ti{sub 5}O{sub 12} surface. In addition, the results of electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and transmission electron microscopy (TEM) demonstrate that a thin and good conductive film can be formed on the Li{sub 4}Ti{sub 5}O{sub 12} surface ascribed to MMDS additive, which resulting the improvement of conductivity and a good ability of Li{sup +} migration. - Highlights: • MMDS used as additive to improve cycling performance of the Li{sub 4}Ti{sub 5}O{sub 12}/Li cells. • A SEI film can be formed using MMDS in the electrolyte above 1 V. • Sulfur-containing species is the main component of the SEI formed by MMDS.

  9. Effect of jenny milk addition on the inhibition of late blowing in semihard cheese. (United States)

    Cosentino, C; Paolino, R; Valentini, V; Musto, M; Ricciardi, A; Adduci, F; D'Adamo, C; Pecora, G; Freschi, P


    The occurrence of late blowing defects in cheese produces negative effects on the quality and commercial value of the product. In this work, we verified whether the addition of raw jenny milk to bulk cow milk reduced the late blowing defects in semihard cheeses. During cheesemaking, different aliquots of jenny milk were poured into 2 groups of 4 vats, each containing a fixed amount of cow milk. A group of cheeses was created by deliberately contaminating the 4 vats with approximately 3 log10 cfu/mL milk of Clostridium tyrobutyricum CLST01. The other 4 vats, which were not contaminated, were used for a second group of cheeses. After 120 d of ripening, some physical, chemical, and microbiological parameters were evaluated on the obtained semihard cheeses. Differences in sensory properties among cheeses belonging to the uncontaminated group were evaluated by 80 regular consumers of cheese. Our results showed that the increasing addition of jenny milk to cow milk led to a reduction of pH and total bacterial count in both cheese groups, as well as C. tyrobutyricum spores that either grew naturally or artificially inoculated. We observed a progressive reduction of the occurrence of late blowing defects in cheese as consequence of the increasing addition of jenny milk during cheese making. Moreover, the addition of jenny milk did not affect the acceptability of the product, as consumers found no difference among cheeses concerning sensorial aspects. In conclusion, the important antimicrobial activity of lysozyme contained in jenny milk has been confirmed in the current research. It is recommend for use as a possible and viable alternative to egg lysozyme for controlling late blowing defects in cheese.

  10. Effects of minor yttrium addition on hot deformability of lamellar Ti-45Al-5Nb alloy

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-yong; LI Bao-hui; KONG Fan-tao


    The effects of 0.3%(molar fraction, the same below) yttrium addition on hot deformability of lamellar Ti-45Al-5Nb alloy were investigated by simulated isothermal forging tests. The ingots with the nominal compositions of Ti-45Al-5Nb and Ti-45Al-5Nb-0.3Y were prepared by induction skull melting. Simulated isothermal forging tests were conducted on Gleeble 1500D thermo-simulation machine using a 6 mm in diameter and 10 mm in length compressive specimen at the deformation temperatures of 1 100, 1 150, 1 200 ℃ and strain rates of 1.0, 0.1, 0.01 s-1. The results show that yttrium addition remarkably improves hot deformability of Ti-45Al-5Nb alloy. An appropriate hot deformation processing parameter of Ti-45Al-5Nb-0.3Y alloy is determined as 1 200 ℃, 0.01 s-1. The flow stresses are decreased by yttrium addition under the same compressive conditions. The activation energies of deformation Q are calculated as 448.6 and 399.5 kJ/mol for Y-free and Y-containing alloys, respectively. The deformed microstructure observation under 1 200 ℃, 0.01 s-1 condition indicates that Ti-45Al-5Nb-0.3Y alloy shows more dynamic recrystallization. The improvement of hot deformability of Ti-45Al-5Nb-0.3Y alloy induced by yttrium addition should be attributed to that the smaller the original lamellar colonies, the lower the deformation resistance and activation energy of deformation are, and the more the dynamic recrystallization is.

  11. Radiation processing of thermoplastic starch by blending aromatic additives: Effect of blend composition and radiation parameters (United States)

    Khandal, Dhriti; Mikus, Pierre-Yves; Dole, Patrice; Coqueret, Xavier


    This paper reports on the effects of electron beam (EB) irradiation on poly α-1,4-glucose oligomers (maltodextrins) in the presence of water and of various aromatic additives, as model blends for gaining a better understanding at a molecular level the modifications occurring in amorphous starch-lignin blends submitted to ionizing irradiation for improving the properties of this type of bio-based thermoplastic material. A series of aromatic compounds, namely p-methoxy benzyl alcohol, benzene dimethanol, cinnamyl alcohol and some related carboxylic acids namely cinnamic acid, coumaric acid, and ferulic acid, was thus studied for assessing the ability of each additive to counteract chain scission of the polysaccharide and induce interchain covalent linkages. Gel formation in EB-irradiated blends comprising of maltodextrin was shown to be dependent on three main factors: the type of aromatic additive, presence of glycerol, and irradiation dose. The chain scission versus grafting phenomenon as a function of blend composition and dose were studied using Size Exclusion Chromatography by determining the changes in molecular weight distribution (MWD) from Refractive Index (RI) chromatograms and the presence of aromatic grafts onto the maltodextrin chains from UV chromatograms. The occurrence of crosslinking was quantified by gel fraction measurements allowing for ranking the cross-linking efficiency of the additives. When applying the method to destructurized starch blends, gel formation was also shown to be strongly affected by the moisture content of the sample submitted to irradiation. The results demonstrate the possibility to tune the reactivity of tailored blend for minimizing chain degradation and control the degree of cross-linking.

  12. Effect of Additive Agent on the Electrochemical Capacitance of Activated Carbon

    Institute of Scientific and Technical Information of China (English)

    Wang Gui-Xin; Qu Mei-Zhen; Chen Li; Wang Guo-Ping; Zhang Qing-Tang; Yu Zuo-Long


    In order to compare the effect of additive agent on the electrochemical capacitance of activated carbon, three additive agents like carbon nanotubes (CNTs), activated carbon fibre (ACF)and acetylene black (AB) were added to activated carbon by ultrasonic dispersion. Two electrodes including 95wt.% activated carbon, 2wt.% additive agent and 3wt.% PTFE binder were prepared.Ecs were assembled in an argon-filled glove box by sandwiching a microporous separator (Celgard 2400) between two electrodes. 1.0 M LiClO4/ethylene carbonate (EC)-diethyl carbonate (DEC) (1:1in vol.) was used as the electrolyte. The performance of the Ecs was tested with constant current charge-discharge model between 0.0 and 3.0V at 298K using a battery-testing instrument under the same conditions.From the Fig. 1, we can know that the specific capacitance decreases with the current density increasing. As far as the three carbon materials, CNTs show better performance than others. At low current density, the specific capacitance of CNTs is adjacent to that of ACF, while higher than that of AB; At high current density, the specific capacitance of CNTs is higher than that of both ACF and AB. What's more, capacity fading of CNTs is smaller than those of both ACF and AB. At 10 mA/cm2 current density, the specific capacitance of CNTs is 1.33 times of that ACF and 1.58 times of that AB, respectively. From the CVs (Fig. 2), the capacitance of three materials is contributed mainly by double-layer, nonfaradically. The performance difference is ascribed to the structure and electrolyte reservoir: CNTs used have a wide diameter range between 20 and 100nm and hollow tube structure, ACF has a narrow diameter range and many micropores, AB are dots and cannot form good conductive net. All the above reasons lead the different electrochemical properties of three additive agents.

  13. Toxic effects of some synthetic food colorants and/or flavor additives on male rats. (United States)

    El-Wahab, Hanan Mohamed Fathy Abd; Moram, Gehan Salah El-Deen


    The objective of the present work was to evaluate the broadest toxic effect of some synthetic additives of colorants and/or flavors on different body organs and metabolic aspects in rats. A number of chemical food color and flavor additives are routinely added during processing to improve the aesthetic appearance of the dietary items. However, many of them are toxic after prolonged use. In this experiment, a total of 100 male albino rats of Spargue Dawley strain were divided into 10 groups: G(1) was fed basal diet and served as control, G(2): basal diet + Brilliant blue (blue dye, No. 2, 124 mg/kg diet), G(3): basal diet + carmoisine (red dye, No. 3, 70 mg/kg diet), G(4): basal diet + tartrazine (yellow dye, FD & C yellow No. 5, 75 mg/kg diet), G(5): basal diet + trans-anethole (4.5 g/kg diet) G(6): basal diet + propylene glycol (0.25 g/kg diet), G(7): basal diet + vanillin(1.25 g/kg diet), G(8): basal diet + Brilliant blue + propylene glycol, G(9): basal diet + carmoisine + trans-anethole, G(10): basal diet + tartrazine + vanillin for 42 successive days. All food colorants mixed with or without flavor additives induced a significant decrease in body weight, hemoglobin concentration and red blood cell count. Also there was a significant decrease in reduced glutathione content; glutathione-S-transferase and superoxide dismutase activities in both blood and liver compared to control group. On the other hand, a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activities, bilirubin, urea, creatinine, total protein and albumin were observed in all test groups when compared to control group. Finally, it is advisable to limit the uses of these food colorants and/or food flavor additives especially those used by children.

  14. Additive and non-additive effects of simulated leaf and inflorescence damage on survival, growth and reproduction of the perennial herb Arabidopsis lyrata. (United States)

    Puentes, Adriana; Ågren, Jon


    Herbivores may damage both leaves and reproductive structures, and although such combined damage may affect plant fitness non-additively, this has received little attention. We conducted a 2-year field experiment with a factorial design to examine the effects of simulated leaf (0, 12.5, 25, or 50% of leaf area removed) and inflorescence damage (0 vs. 50% of inflorescences removed) on survival, growth and reproduction in the perennial herb Arabidopsis lyrata. Leaf and inflorescence damage negatively and independently reduced flower, fruit and seed production in the year of damage; leaf damage also reduced rosette size by the end of the first season and flower production in the second year. Leaf damage alone reduced the proportion of flowers forming a fruit and fruit production per plant the second year, but when combined with inflorescence damage no such effect was observed (significant leaf × inflorescence damage interaction). Damage to leaves (sources) caused a greater reduction in future reproduction than did simultaneous damage to leaves and inflorescences (sinks). This demonstrates that a full understanding of the effects of herbivore damage on plant fitness requires that consequences of damage to vegetative and reproductive structures are evaluated over more than 1 year and that non-additive effects are considered.

  15. Effects of Aluminum Addition on Tensile and Cup Forming Properties of Three Twinning Induced Plasticity Steels (United States)

    Hong, Seokmin; Shin, Sang Yong; Kim, Hyoung Seop; Lee, Sunghak; Kim, Sung-Kyu; Chin, Kwang-Geun; Kim, Nack J.


    In the present study, a high Mn twinning induced plasticity (TWIP) steel and two Al-added TWIP steels were fabricated, and their microstructures, tensile properties, and cup formability were analyzed to investigate the effects of Al addition on deformation mechanisms in tensile and cup forming tests. In the high Mn steel, the twin formation was activated to increase the strain hardening rate and ultimate tensile strength, which needed the high punch load during the cup forming test. In the Al-added TWIP steels, the twin formation was reduced, while the slip activation increased, thereby leading to the decrease in strain hardening rate and ultimate tensile strength. As twins and slips were homogeneously formed during the tensile or cup forming test, the punch load required for the cup forming and residual stresses were relatively low, and the tensile ductility was sufficiently high even after the cup forming test. This indicated that making use of twins and slips simultaneously in TWIP steels by the Al addition was an effective way to improve overall properties including cup formability.

  16. Effect of Co addition on crystallization and magnetic properties of FeSiBPCu alloy

    Directory of Open Access Journals (Sweden)

    Rui Xiang


    Full Text Available The effects of Co addition on the microstructure, crystallization processes and soft magnetic properties of (Fe1−xCox83Si4B8P4Cu1 (x=0.35, 0.5, 0.65 alloys were investigated. The experimental results demonstrated that the addition of Co decreased the thermal stability against crystallization of the amorphous phase, and thus improved the heat treatment temperature of this alloy. FeCoSiBPCu nanocrystalline alloys with a dispersed α′-FeCo phase were obtained by appropriately annealing the as-quenched ribbons at 763 K for 10 min. The α′-FeCo with grains size ranging from 9 to 28 nm was identified in primary crystallization. The coercivity (Hc markedly increased with increasing x and exhibited a minimum value at x=0.35, while the saturation magnetic flux density (Bs shows a slight decrease. The (Fe0.65Co0.3583Si4B8P4Cu1 nanocrystalline alloy exhibited a high saturation magnetic flux density Bs of 1.68 T, a low coercivity, Hc of 5.4 A/m and a high effective permeability µe of 29,000 at 1 kHz.

  17. The influence of additional electrons on memory effect in nitrogen at low pressures

    Energy Technology Data Exchange (ETDEWEB)

    Nesic, Nikola T; Pejovic, Momcilo M; Pejovic, Milic M; Zivanovic, Emilija N, E-mail: [University of Nis, Faculty of Electronic Engineering, Aleksandra Medvedeva 14, 18000 Nis (Serbia)


    Memory effect in nitrogen based on experimental data of electrical breakdown time delay as a function of afterglow period in the presence of additional electrons has been investigated. The additional electrons were supplied as a result of extraction from the auxiliary electrode pair or nitrogen irradiation with the radioactive source {sub 88}{sup 226}Ra of low activity. The results show that these electrons have an important role in the recombination of positive ions formed in mutual metastable molecules' collisions and collisions between metastable and highly vibrationally excited molecules in the early afterglow. As a consequence of the ion-electron recombination N({sup 4}S) atoms are formed which, as well as N({sup 4}S) atoms formed in previous discharge, have a significant influence on the memory effect in late afterglow. The presence of N({sup 4}S) atoms in the late afterglow is tracked by monitoring the secondary emission which they induce via catalytic recombination on the cathode of a nitrogen-filled tube. Also, it has been shown that the contribution of secondary electrons which originate from N({sup 4}S) atoms and Compton electrons when the radioactive source is and isn't present can be distinguished.

  18. Effect of Hydrogen Addition on Low Temperature Metallurgical Property of Sinter

    Institute of Scientific and Technical Information of China (English)

    MU Lin; JIANG Xin; GAO Qiang-jian; WEI Guo; SHEN Feng-man


    Hydrogen-enrich iron making process is certainly to be an effective method to reduce greenhouse gases emission.However,the effect of hydrogen addition on the low temperature metallurgical property of sinter is still unclear.A detailed investigation was performed on the above topic.The results are as follows.When CO is partially replaced by H2,the RDI〈3.15(RDI〈2.8) of sinter decreases with the increase of the H2 content;when the content of H2 increases,the CO,CO2 and N2 decrease proportionally,in this case,RDI〈3.15(RDI〈2.8) of sinter increases with the increase of H2 content;the value of RDI〈3.15(RDI〈2.8) basically depends on the reduction index(Ri).The experimental data of RDI〈2.8 based on Japanese industrial standard(JIS) are a little higher than the data of RDI〈3.15 based on Chinese industrial standard(CIS) in the same condition.In addition,for part of CO is replaced by H2:RDI〈2.8=3.38394+1.1585 RDI〈3.15;for other gases,except H2,are decreased proportionally:RDI〈2.8=17.39678+0.42922 RDI〈3.15

  19. A critical review on the spray drying of fruit extract: effect of additives on physicochemical properties. (United States)

    Krishnaiah, Duduku; Nithyanandam, Rajesh; Sarbatly, Rosalam


    Spray drying accomplishes drying while particles are suspended in the air and is one method in the family of suspended particle processing systems, along with fluid-bed drying, flash drying, spray granulation, spray agglomeration, spray reaction, spray cooling, and spray absorption. This drying process is unique because it involves both particle formation and drying. The present paper reviews spray drying of fruit extracts, such as acai, acerola pomace, gac, mango, orange, cactus pear, opuntia stricta fruit, watermelon, and durian, and the effects of additives on physicochemical properties such as antioxidant activity, total carotenoid content, lycopene and β-carotene content, hygroscopy, moisture content, volatile retention, stickiness, color, solubility, glass transition temperature, bulk density, rehydration, caking, appearance under electron microscopy, and X-ray powder diffraction. The literature clearly demonstrates that the effect of additives and encapsulation play a vital role in determining the physicochemical properties of fruit extract powder. The technical difficulties in spray drying of fruit extracts can be overcome by modifying the spray dryer design. It also reveals that spray drying is a novel technology for converting fruit extract into powder form.

  20. Essential Structural Requirements and Additive Effects for Flavonoids to Scavenge Methylglyoxal. (United States)

    Shao, Xi; Chen, Huadong; Zhu, Yingdong; Sedighi, Rashin; Ho, Chi-Tang; Sang, Shengmin


    Reactive dicarbonyl species, such as methylglyoxal (MGO), are considered as the major precursors of advanced glycation end products (AGEs), which are believed to be one of the physiological causes of diabetes and its complications. Scavenging of reactive dicarbonyl species using naturally occurring flavonoids has been proposed as an effective way to prevent diabetic complications. To elucidate the structural requirements of flavonoids in scavenging MGO, seven flavonoids (quercetin, luteolin, epicatechin, genistein, daidzein, apigenin, and phloretin) and five sub-components of the flavonoids (gallic acid, phloroglucinol, pyrogallol, pyrocatechol, and resorcinol) were examined in this study. Our results showed the following: (1) 1,2,3-trihydroxybenzene (pyrogallol) has higher MGO scavenging activity than 1,3,5-trihydroxybenzene and 1,2- and 1,3-dihydroxybenzene, and substitution at position 5 of pyrogallol diminished the scavenging activity, indicating that position 5 is the active site of pyrogallol; (2) the A ring is the active site of flavonoids in contributing the MGO-trapping efficacy, and the hydroxyl group at C-5 on the A ring enhances the trapping efficacy; (3) the double bond between C-2 and C-3 on the C ring could facilitate the trapping efficacy; and (4) the number of hydroxyl groups on the B ring does not significantly influence the trapping efficacy. In addition, we found there is an additive effect in MGO trapping by two common flavonoids, quercetin and phloretin, indicating that flavonoid-enriched foods and beverages hold great promise to prevent the development of diabetic complications.


    Directory of Open Access Journals (Sweden)

    Henrieta Arpášová


    Full Text Available Essentialoils areintensivefragrant, oilyliquidsubstances containedindifferent parts of theplant. Their function is based on organoleptic effect and stimulation of organism to the production of digestive juices. Result is ahigherdigestibilityandabsorption of nutirents. Besides antibacterial properties, essential oils or their components have been shown to exhibit antiviral,antimycotic, antitoxigenic, antiparasitic, and insecticidal properties. In this experiment the effects of supplementation of the diet for laying hens with thyme essential oils on physical and microbiological egg parameters were studied.Hens of laying hybrid Hy-Line Brown (n=30 were randomly divided into 3 groups (n=10 and fed for 23 weeks on diets with thyme essential oil supplemented. In the first experimental group the feed mixture was supplemented with thyme essential oil addition in a dose 0.5 g/kg, in the second one some essential oil in a dose 1g/kg. The results suggest that all of qualitative parameters of egg internal content (yolk weight (g, yolk index, percentage portion egg yolk (%, yolk index, yolk colour (°HLR, albumen weight (g, percentage portion of albumen (%, Haugh Units (HU, albumen index were with thyme essential oil addition insignificantly influenced (P>0.05. The number of coliforms, enterococci, fungi and yeasts decreased with increasing dose of oil. The number of lactobacilli was zero in all groups.

  2. Effects of insoles and additional shock absorption foam on the cushioning properties of sport shoes. (United States)

    Chiu, Hung-Ta; Shiang, Tzyy-Yuang


    The purpose of this study was to investigate the effects of insoles and additional shock absorption foam on the cushioning properties of various sport shoes with an impact testing method. Three commercial sport shoes were used in this study, and shock absorption foam (TPE5020; Vers Tech Science Co. Ltd., Taiwan) with 2-mm thickness was placed below the insole in the heel region for each shoe. Eight total impacts with potential energy ranged from 1.82 to 6.08 J were performed onto the heel region of the shoe. The order of testing conditions was first without insole, then with insole, and finally interposing the shock absorption foam for each shoe. Peak deceleration of the striker was measured with an accelerometer attached to the striker during impact. The results of this study seemed to show that the insole or additional shock absorption foam could perform its shock absorption effect well for the shoes with limited midsole cushioning. Further, our findings showed that insoles absorbed more, even up to 24-32% of impact energy under low impact energy. It seemed to indicate that insoles play a more important role in cushioning properties of sport shoes under a low impact energy condition.

  3. The effect of Tricresyl-Phosphate (TCP) as an additive on wear of Iron (Fe) (United States)

    Ghose, Hiren M.; Ferrante, John; Honecy, Frank C.


    The effect of tricresyl phosphate (TCP) as an antiwear additive in lubricant trimethyol propane triheptanoate (TMPTH) was investigated. The objective was to examine step loading wear by use of surface analysis, wetting, and chemical bonding changes in the lubricant. The investigation consisted of steploading wear studies by a pin or disk tribometer, the effects on wear related to wetting by contact angle and surface tension measurements of various liquid systems, the chemical bonding changes between lubricant and TCP chromatographic analysis, and by determining the reaction between the TCP and metal surfaces through wear scar analysis by Auger emission spectroscopy (AES). The steploading curve for the base fluid alone shows rapid increase of wear rate with load. The steploading curve for the base fluid in presence of 4.25 percent by volume TCP under dry air purge has shown a great reduction of wear rate with all loads studied. It has also been found that the addition of 4.25 percent by volume TCP plus 0.33 percent by volume water to the base lubricant under N2 purge also greatly reduces the wear rate with all loads studied. AES surface analysis reveals a phosphate type wear resistant film, which greatly increases load-bearing capacity, formed on the iron disk. Preliminary chromatographic studies suggest that this film forms either because of ester oxidation or TCP degradation. Wetting studies show direct correlation between the spreading coefficient and the wear rate.

  4. The additive effect on suicidality of family history of suicidal behavior and early traumatic experiences. (United States)

    Lopez-Castroman, J; Guillaume, S; Olié, E; Jaussent, I; Baca-García, E; Courtet, P


    Family history of suicidal behavior and personal history of childhood abuse are reported risk factors for suicide attempts and suicide completion. We aim to quantify the additive effect of family history of suicidal behavior and different subtypes of childhood abuse on suicidal behavior. We examined a sample of 496 suicide attempters, comparing individuals with family history of suicidal behavior and personal history of childhood (physical or sexual) abuse, individuals with family history of suicidal behavior only, individuals with history of early traumatic experiences only, and individuals with none of these two risk factors with regards to suicidal features. An additive effect was found for the age at the first attempt in suicide attempters with both family history of suicidal behavior and either physical or sexual abuse. No significant interactions were found between family history of suicidal behavior and childhood trauma in relation to any characteristics of suicidal behavior. Subjects presenting family history of suicidal behavior and childhood abuse attempt suicide earlier in life than subjects with just one or none of them, particularly if they were sexually abused. Other suicidality indexes were only partially or not associated with this combination of risk factors. A careful assessment of patients with both family history of suicidal behavior and childhood abuse could help to prevent future suicide attempts, particularly in young people.

  5. Effect of highly dispersed yttria addition on thermal stability of hydroxyapatite

    Energy Technology Data Exchange (ETDEWEB)

    Parente, P., E-mail: [Instituto de Ceramica y Vidrio, CSIC, C/Kelsen 5, Madrid 28049 (Spain); Savoini, B. [Departamento de Fisica, Universidad Carlos III de Madrid, Avda. Universidad 30, Leganes 28911 (Spain); Ferrari, B. [Instituto de Ceramica y Vidrio, CSIC, C/Kelsen 5, Madrid 28049 (Spain); Monge, M.A.; Pareja, R. [Departamento de Fisica, Universidad Carlos III de Madrid, Avda. Universidad 30, Leganes 28911 (Spain); Sanchez-Herencia, A.J. [Instituto de Ceramica y Vidrio, CSIC, C/Kelsen 5, Madrid 28049 (Spain)


    The capability of the colloidal method to produce yttria (Y{sub 2}O{sub 3}) dispersed hydroxyapatite (HA) has been investigated as an alternative method to the conventional method of mechanical mixing and sintering for developing HA-based materials that could exhibit controllable and enhanced functional properties. A water based colloidal route to produce HA materials with highly dispersed Y{sub 2}O{sub 3} has been applied, and the effect of 10 wt.% Y{sub 2}O{sub 3} addition to HA investigated by thermal analysis, X-ray diffraction and Fourier transform infrared spectroscopy. These measurements evidence a remarkable effect of this Y{sub 2}O{sub 3} addition on decomposition mechanisms of synthetic HA. Results show that incorporation of Y{sub 2}O{sub 3} as dispersed second phase is beneficial because it hinders the decomposition mechanisms of HA into calcium phosphates. This retardation will allow the control of the sintering conditions for developing HA implants with improved properties. Besides, substitution of Ca{sup 2+} with Y{sup 3+} ions appears to promote the formation of OH{sup -} vacancies, which could improve the conductive properties of HA favorable to osseointegration. - Highlights: Black-Right-Pointing-Pointer We reveal the influence of Y{sub 2}O{sub 3} on thermal stability of hydroxyapatite. Black-Right-Pointing-Pointer Incorporation of Y{sub 2}O{sub 3} delays decomposition of hydroxyapatite to calcium phosphates. Black-Right-Pointing-Pointer Addition of Y{sub 2}O{sub 3} enables sintering conditions more favorable to the densification.

  6. Effect of dietary feed additives on haematological and serum biochemical parameters of broiler chickens.

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    Alonge EO


    Full Text Available The effect of dietary feed additives on haematological and serum biochemical parameters of broiler chickens was evaluated. 180 day-old Arbor acre broiler chicks were weighed and randomly allotted to five dietary treatments with 3 replicates of 12 birds each. Broiler starter diet (2855.7 kcal/kg ME; 23.01% and finisher diet (2911 kcal/kg; 20.71% CP were formulated. Dietary treatments were control diet (basal diet without additives, OXYT diet (basal diet with oxytetracycline at 600 ppm as antibiotic, GRO-UP diet (basal diet with probiotic at 500 ppm, MOS-500 diet (basal diet with mannan oligosaccharide at 500 ppm and MOS-1000 diet (basal diet with mannan oligosaccharide at 1000 ppm. Feed and water were supplied ad libitum. At the end of weeks 4 and 8, blood samples were collected and analyzed. The haematological and serum biochemical parameters of broiler chickens fed diets containing feed additives at the starter phase were not statistically significant (P> 0.05. At the finisher phase, there were no significant (P> 0.05 differences in all the parameters measured except in the heterophils and eosinophils where birds fed the control diets had the lowest value among all treatments. Serum globulin values were significantly (P< 0.05 different as birds fed diets containing OXYT (antibiotics recorded the lowest value among all treatments. The inclusion of prebiotics and probiotics in the diets of broiler chickens elicited no adverse effect on haematological and serum biochemical parameters, thus, they can be used as replacement for antibiotics.

  7. Self-Assembly of Lyotropic Chromonic Liquid Crystal Sunset Yellow and Effects of Ionic Additives

    Energy Technology Data Exchange (ETDEWEB)

    Park, Heung-Shik; Kang, Shin-Woong; Tortora, Luana; Nastishin, Yuriy; Finotello, Daniele; Kumar, Satyendra; Lavrentovich, Oleg D. (NSF); (Institute of Physical Optics, Ukraine); (Kent)


    Lyotropic chromonic liquid crystals (LCLCs) are formed by molecules with ionic groups at the periphery that associate into stacks through noncovalent self-assembly while in water. The very existence of the nematic (N) phase in the typical LCLC, the dye Sunset Yellow (SSY) is a puzzle, as the correlation length associated with the stacking, as measured in the X-ray experiments, is too short to explain the orientational order by the Onsager model. We propose that the aggregates can be more complex than simple rods and contain 'stacking faults' such as junctions with a shift of neighboring molecules, 3-fold junctions, etc. We study how ionic additives, such as salts of different valency and pH-altering agents, alter the N phase of SSY purified by recrystallization. The additives induce two general trends: (a) stabilization of the N phase, caused by the mono and divalent salts (such as NaCl), and evidenced by the increase of the N-to-I transition temperature and the correlation length; (b) suppression of the N phase manifested in the decrease of the N-to-I transition temperature and in separation of the N phase into a more densely packed N phase or the columnar (C) phase, coexisting with a less condensed I phase. The scenario (b) can be triggered by simply increasing pH (adding NaOH). The effects produced by tetravalent spermine fall mostly into the category (b), but the detail depends on whether this additive is in its salt form or a free base form. The base form causes changes through changes in pH and possible excluded volume effects whereas the salt form might disrupt the structure of SSY aggregates.

  8. Effects of Cutting Time, Ensiling Duration and Microbial Additives on Chemical Composition of Alfalfa Silage

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    M.H. Delavar


    Full Text Available This experiment was conducted to assess the effects of daytime cutting management (p.m. vs. a.m. cut, ensiling duration and adding microbial inoculants on chemical composition of alfalfa silage. For this, Second growth Alfalfa harvested at the early bud stage of development after a sunny day at sundown (about 1900 h; PM alfalfa, whereas the second half was cut next day at sunup (about 0800 h; AM alfalfa. After cutting, alfalfa Forage was chopped by using a chopper to a length of 8 to10 cm, and then ensiled without or with microbial additive as factorial experiment (2×2 with repeated measurement design. Silages were provided in laboratory silos (6 repeats in every treatment lined with two layers of plastic, after air exclusion. Silos were opened at 3, 10 and 30 day for determination of pH and other chemical analysis. The numerically lower pH of PM vs. AM silages indicates that the former forage was more extensively fermented possibly because of its increased total non structural carbohydrate (TNC concentration. Shifting alfalfa harvesting from sun up to sundown significantly decreased NDF% and ADF%, because of the dilution effect associated with increased concentrations of TNC in the former forage. The NPN content and N-NH3 concentration of the silages treated in the afternoon was lower compared with AM group. CP content decreased, but NDF, ADF, NPN and N-NH3 concentration increased during ensiling time. Silage pH decreased by using of microbial additive and ensiling time. Dry matter and nitrogen losses were lower in silages treated by microbial inoculants, and, increased with increasing fermentation time. It can be concluded that microbial additives and time of cutting can be used as proper way to improve fermentation situation and silage quality.

  9. Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice.

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    Lu Zhao

    Full Text Available Alzheimer's disease (AD and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aβ not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.

  10. The effect of water plant extracts addition on the oxidative stability of meat products

    Directory of Open Access Journals (Sweden)

    Karolina M. Wójciak


    Full Text Available Background. Natural antioxidants extracted from plants have a lot of antioxidants catechins, epigallocatechins (green tea rosmariquinone, rosmaridiphenol (rosemary, capsaicinoids (red pepper. They can be used as alternatives to the synthetic antioxidants because of their equivalence or greater effect on inhibition of lipid oxidation and haem pigment (nitrosohemachrome protection. The aim of the study was to compare the effect of addition of green tea extract, red pepper extract and rosemary extract while curing process on colour and lipid stability during refrigerated storage of meat products. Material and methods. The pork meat was ground (10 mm plate and divided into four equal parts. To the first part (control sample – C was added curring mixture in amount of 2.2% in a ratio of meat dissolved in water. To the rests of parts were added the same curring mixtures in the same proportion dissolved in 0.5% water plant extracts: green tea (GT, red pepper (P, rosemary (R respectively. All samples were left at 4°C for 24 hours. After curing, samples were stuffed in casings and then heated in water until a final internal temperature of 70°C was reached. All samples were stored up to 30 days at 4°C. Analysis of acidity, oxidation – reduction potential, thiobarbituric acid reactive substances (TBARS, surface colour (Hunter L*, a* and b* values were measured directly after production and after 10, 20 and 30 days of chilling storage. Results. The addition of the plant extracts (pepper, green tea, rosemary to the pork meat samples does not change significantly acidity of the samples during chilling storage. All plants extracts effectively reduce lipid oxidation in cooked pork meat compared to the control. Pepper extract was effective in maintaining redness because of its reduction activity (low potential redox value in sample and low TBARS values in sample during chilling storage. Conclusions. Addition of pepper extract and green tea extract in

  11. Effect of amino acid mutation at position 127 in 3A of a rabbitattenuated foot-and-mouth disease virus serotype Asia1 on viral replication and infection

    Institute of Scientific and Technical Information of China (English)

    Aiguo; Xin; Mingwang; Zhu; Qi; Hu; Haisheng; Miao; Zhenqi; Peng; Yuwen; He; Lin; Gao; Huachun; Li


    An amino acid mutation(R127→I) in the 3A non-structural protein of an FMDV serotype Asia1 rabbit-attenuated ZB strain was previously found after attenuation of the virus. To explore the effects of this mutation on viral replication and infection, the amino acid residue isoleucine(I) was changed to arginine(R) in the infectious cDNA clone of the rabbit-attenuated ZB strain by sitedirected mutagenesis, and the R127-mutated virus was rescued. BHK monolayer cells and suckling mice were inoculated with the R127-mutated virus to test its growth property and pathogenicity, respectively. The effects of the R127 mutation on viral replication and virulence were analyzed. The data showed that there was a slight difference in plaque morphology between the R127-mutated and wild-type viruses. The growth rate of the mutated virus was lower in BHK-21 cells and its virulence in suckling mice was also attenuated. This study indicates that the R127 mutation in 3A may play an important role in FMDV replication in vitro and in pathogenicity in suckling mice.

  12. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. (United States)

    Rumi, Elisa; Pietra, Daniela; Pascutto, Cristiana; Guglielmelli, Paola; Martínez-Trillos, Alejandra; Casetti, Ilaria; Colomer, Dolors; Pieri, Lisa; Pratcorona, Marta; Rotunno, Giada; Sant'Antonio, Emanuela; Bellini, Marta; Cavalloni, Chiara; Mannarelli, Carmela; Milanesi, Chiara; Boveri, Emanuela; Ferretti, Virginia; Astori, Cesare; Rosti, Vittorio; Cervantes, Francisco; Barosi, Giovanni; Vannucchi, Alessandro M; Cazzola, Mario


    We studied the impact of driver mutations of JAK2, CALR, (calreticulin gene) or MPL on clinical course, leukemic transformation, and survival of patients with primary myelofibrosis (PMF). Of the 617 subjects studied, 399 (64.7%) carried JAK2 (V617F), 140 (22.7%) had a CALR exon 9 indel, 25 (4.0%) carried an MPL (W515) mutation, and 53 (8.6%) had nonmutated JAK2, CALR, and MPL (so-called triple-negative PMF). Patients with CALR mutation had a lower risk of developing anemia, thrombocytopenia, and marked leukocytosis compared with other subtypes. They also had a lower risk of thrombosis compared with patients carrying JAK2 (V617F). At the opposite, triple-negative patients had higher incidence of leukemic transformation compared with either CALR-mutant or JAK2-mutant patients. Median overall survival was 17.7 years in CALR-mutant, 9.2 years in JAK2-mutant, 9.1 years in MPL-mutant, and 3.2 years in triple-negative patients. In multivariate analysis corrected for age, CALR-mutant patients had better overall survival than either JAK2-mutant or triple-negative patients. The impact of genetic lesions on survival was independent of current prognostic scoring systems. These observations indicate that driver mutations define distinct disease entities within PMF. Accounting for them is not only relevant to clinical decision-making, but should also be considered in designing clinical trials.

  13. The butterfly effect in cancer: a single base mutation can remodel the cell. (United States)

    Hart, Jonathan R; Zhang, Yaoyang; Liao, Lujian; Ueno, Lynn; Du, Lisa; Jonkers, Marloes; Yates, John R; Vogt, Peter K


    We have compared the proteome, transcriptome, and metabolome of two cell lines: the human breast epithelial line MCF-10A and its mutant descendant MCF-10A-H1047R. These cell lines are derived from the same parental stock and differ by a single amino acid substitution (H1047R) caused by a single nucleotide change in one allele of the PIK3CA gene, which encodes the catalytic subunit p110α of PI3K (phosphatidylinositol 3-kinase). They are considered isogenic. The H1047R mutation of PIK3CA is one of the most frequently encountered somatic cancer-specific mutations. In MCF-10A, this mutation induces an extensive cellular reorganization that far exceeds the known signaling activities of PI3K. The changes are highly diverse, with examples in structural protein levels, the DNA repair machinery, and sterol synthesis. Gene set enrichment analysis reveals a highly significant concordance of the genes differentially expressed in MCF-10A-H1047R cells and the established protein and RNA signatures of basal breast cancer. No such concordance was found with the specific gene signatures of other histological types of breast cancer. Our data document the power of a single base mutation, inducing an extensive remodeling of the cell toward the phenotype of a specific cancer.

  14. Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia (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...

  15. Effects of Coating Materials and Mineral Additives on Nitrate Reduction by Zerovalent Iron (United States)

    Kim, K. H.; Jeong, H. Y.; Lee, S.; Kang, N.; Choi, H. J.; Park, M.


    In efforts to facilitate nitrate removal, a variety of coating materials and mineral additives were assessed for their effects on the nitrate reduction by zerovalent iron (ZVI). Coated ZVIs were prepared by reacting Fe particles with Cr(III), Co(II), Ni(II), Cu(II), and S(-II) solutions under anoxic conditions, with the resultant materials named Cr/Fe, Co/Fe, Ni/Fe, Cu/Fe, and FeS/Fe, respectively. The mineral additives used, synthesized or purchased, included goethite, magnetite, and hydrous ferric oxide (HFO). Kinetic experiments were performed using air-tight serum vials containing 1.0 g Fe (uncoated or coated forms) in 15 mL of 100 mg NO3×N/L solutions with pH buffered at 7.0. To monitor the reaction progress, the solution phase was analyzed for NO3-, NO2-, and NH4+ on an ion chromatography, while the headspace was analyzed for H2, N2, and O2 on a gas chromatography. By uncoated Fe, ca. 60% of nitrate was reductively transformed for 3.6 h, with NH4+ being the predominant product. Compared with uncoated one, Cr/Fe, Co/Fe, and Cu/Fe showed faster removal rates of nitrate. The observed reactivity enhancement was thought to result from additional reduction of nitrate by H atoms adsorbed on the surface of Cr, Co, or Cu metal. In contrast, both Ni/Fe and FeS/Fe showed slower removal of nitrate than uncoated Fe. In both cases, the coating, which highly disfavors the adsorption of nitrate, would form on the Fe surface. When goethite, HFO, and magnetite were amended, the nitrate reduction by Fe was significantly increased, with the effect being most evident with HFO. Although not capable of reducing nitrate, the mineral additives would serve as crystal nuclei for the corrosion products of Fe, thus making the development of passivation layers on the Fe surface less. In the future, we will perform a kinetic modeling of the experimental data to assess the relative contribution of multiple reaction paths in the nitrate reduction by Fe.


    Directory of Open Access Journals (Sweden)

    Saptadi Darmawan


    Full Text Available The manufacturing of medium density fiberboard (MDF using dry forming process for interior purpose requires extensive amount of thermo-setting urea formaldehyde (UF adhesive. Unfortunately, this adhesive brings about formaldehyde emission from the resulting MDF, which was potentially harmful to human beings. The use of activated charcoal can be effective to reduce such emission. As the relevance, this research aimed to investigate the effect of activated charcoal addition to the MDF pulp on formaldehyde emission from the MDF. The fibers for the MDF-mat forming were the pulp procured from the MDF factory, resulting from the thermo-mechanical pulping (TMP conducted on the mixed mangium wood (Acacia mangium and rubber wood (Hevea brasiliensis in 3:1 (w/w proportion, respectively.  Such mixed TMP pulping was also done in the factor y.  The bonding between TMP pulp fiber during mat forming was assisted by the use of UF adhesive.  Prior to the MDF mat forming , was added to the resulting TMP pulp-fibers activated charcoal in  various amount, 2%, 4% and 6% based on fiber mass as well as based on UF adhesive mass. The activated charcoal was prepared by carbonizing candle nut shell into charcoal followed by activation process using phosphate solution.  Meanwhile the forming of MDF mat employed air-dr y process. As the control, MDF forming with UF adhesive was performed without addition of activated charcoal. It turned out that the activated charcoal-added MDF exhibited effective reduction in formaldehyde emission and significant improvement in physical and mechanical properties, i.e. lower thickness swelling , and greater MOR , MOE and internal bond, compared to the control MDF. The use of activated charcoal at 4% based on the adhesive mass seemed to be the optimum amount.  Physical and mechanical properties of the activated charcoal added MDF could mostly meet the JIS specification.

  17. Seasonal variation exceeds effects of salmon carcass additions on benthic food webs in the Elwha River (United States)

    Morley, S.A.; Coe, H.J.; Duda, J.J.; Dunphy, L.S.; McHenry, M.L.; Beckman, B.R.; Elofson, M.; Sampson, E. M.; Ward, L.


    Dam removal and other fish barrier removal projects in western North America are assumed to boost freshwater productivity via the transport of marine-derived nutrients from recolonizing Pacific salmon (Oncorhynchus spp.). In anticipation of the removal of two hydroelectric dams on the Elwha River in Washington State, we tested this hypothesis with a salmon carcass addition experiment. Our study was designed to examine how background nutrient dynamics and benthic food webs vary seasonally, and how these features respond to salmon subsidies. We conducted our experiment in six side channels of the Elwha River, each with a spatially paired reference and treatment reach. Each reach was sampled on multiple occasions from October 2007 to August 2008, before and after carcass placement. We evaluated nutrient limitation status; measured water chemistry, periphyton, benthic invertebrates, and juvenile rainbow trout (O. mykiss) response; and traced salmon-derived nutrient uptake using stable isotopes. Outside of winter, algal accrual was limited by both nitrogen and phosphorous and remained so even in the presence of salmon carcasses. One month after salmon addition, dissolved inorganic nitrogen levels doubled in treatment reaches. Two months after addition, benthic algal accrual was significantly elevated. We detected no changes in invertebrate or fish metrics, with the exception of 15N enrichment. Natural seasonal variability was greater than salmon effects for the majority of our response metrics. Yet seasonality and synchronicity of nutrient supply and demand are often overlooked in nutrient enhancement studies. Timing and magnitude of salmon-derived nitrogen utilization suggest that uptake of dissolved nutrients was favored over direct consumption of carcasses. The highest proportion of salmon-derived nitrogen was incorporated by herbivores (18–30%) and peaked 1–2 months after carcass addition. Peak nitrogen enrichment in predators (11–16%) occurred 2–3

  18. A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds. (United States)

    Göttlich, Claudia; Müller, Lena C; Kunz, Meik; Schmitt, Franziska; Walles, Heike; Walles, Thorsten; Dandekar, Thomas; Dandekar, Gudrun; Nietzer, Sarah L


    In the present study, we combined an in vitro 3D lung tumor model with an in silico model to optimize predictions of drug response based on a specific mutational background. The model is generated on a decellularized porcine scaffold that reproduces tissue-specific characteristics regarding extracellular matrix composition and architecture including the basement membrane. We standardized a protocol that allows artificial tumor tissue generation within 14 days including three days of drug treatment. Our article provides several detailed descriptions of 3D read-out screening techniques like the determination of the proliferation index Ki67 staining's, apoptosis from supernatants by M30-ELISA and assessment of epithelial to mesenchymal transition (EMT), which are helpful tools for evaluating the effectiveness of therapeutic compounds. We could show compared to 2D culture a reduction of proliferation in our 3D tumor model that is related to the clinical situation. Despite of this lower proliferation, the model predicted EGFR-targeted drug responses correctly according to the biomarker status as shown by comparison of the lung carcinoma cell lines HCC827 (EGFR -mutated, KRAS wild-type) and A549 (EGFR wild-type, KRAS-mutated) treated with the tyrosine-kinase inhibitor (TKI) gefitinib. To investigate drug responses of more advanced tumor cells, we induced EMT by long-term treatment with TGF-beta-1 as assessed by vimentin/pan-cytokeratin immunofluorescence staining. A flow-bioreactor was employed to adjust culture to physiological conditions, which improved tissue generation. Furthermore, we show the integration of drug responses upon gefitinib treatment or TGF-beta-1 stimulation - apoptosis, proliferation index and EMT - into a Boolean in silico model. Additionally, we explain how drug responses of tumor cells with a specific mutational background and counterstrategies against resistance can be predicted. We are confident that our 3D in vitro approach especially with its

  19. Differentiation-specific effects of LHON mutations introduced into neuronal NT2 cells. (United States)

    Wong, Alice; Cavelier, Lucia; Collins-Schramm, Heather E; Seldin, Michael F; McGrogan, Michael; Savontaus, Marja-Liisa; Cortopassi, Gino A


    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.

  20. Modelling the effects of selection temperature and mutation on the prisoner's dilemma game on a complete oriented star.

    Directory of Open Access Journals (Sweden)

    Jianguo Ren

    Full Text Available This paper models the prisoner's dilemma game based on pairwise comparison in finite populations on a complete oriented star (COS. First, we derive a linear system on a COS for calculating the corresponding fixation probabilities that imply dependence of the selection temperature and mutation. Then we observe and analyze the effects of two parameters on fixation probability under different population sizes. In particular, it is found through the experimental results that (1 high mutation is more sensitive to the fixation probability than the low one when population size is increasing, while the opposite is the case when the number of cooperators is increasing, and (2 selection temperature demotes the fixation probability.

  1. Additive effect of linseed oil supplementation on the lipid profiles of older adults

    Directory of Open Access Journals (Sweden)

    Avelino APA


    Full Text Available Ana Paula A Avelino,1 Gláucia MM Oliveira,1 Célia CD Ferreira,2 Ronir R Luiz,3 Glorimar Rosa1,4 1Post-Graduate Program of Medicine-Cardiology, 2Department of Nutrition and Dietetics, 3Institute of Public Health Studies, 4Department of Nutrition and Dietetics, Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Background: Linseed oil has been investigated as a rich source of n-3 series polyunsaturated fatty acids, which mainly produce a non-atherogenic lipid profile. The objective of this study was to investigate the effect of linseed oil supplementation associated with nutritional guidelines on the lipid profiles of older adults, according to the intake of saturated fatty acids (SFA.Methods: We conducted a double-blind, placebo-controlled clinical trial with 110 older adults randomized in two groups: placebo and linseed oil. The linseed oil group received supplementation with 3 g of linseed oil. Both groups received nutritional guidance and were supplemented for 90 days with monthly blood collection for biochemical analysis. The dietary intake of saturated fat was subdivided into low (<7% SFA/day of the total energy value and high consumption groups (>7% SFA/day of the total energy value.Results: Low SFA (<7% SFA/day of total energy value consumption was associated with lower total cholesterol concentrations. However, we observed that the linseed oil group, including older adults who consumed >7% SFA/day, had a greater reduction in total cholesterol than the placebo group (P=0.020. The same was observed for low-density lipoprotein (LDL cholesterol (P<0.050, suggesting an additive effect of linseed oil and diet. High-density lipoprotein (HDL cholesterol concentrations were increased significantly in only the linseed group, suggesting that the nutritional intervention alone did not improve HDL cholesterol.Conclusion: The results suggest that the nutritional intervention was effective, but linseed

  2. Combined treatment of xenon and hypothermia in newborn rats--additive or synergistic effect?

    Directory of Open Access Journals (Sweden)

    Hemmen Sabir

    Full Text Available Breathing the inert gas Xenon (Xe enhances hypothermic (HT neuroprotection after hypoxia-ischemia (HI in small and large newborn animal models. The underlying mechanism of the enhancement is not yet fully understood, but the combined effect of Xe and HT could either be synergistic (larger than the two effects added or simply additive. A previously published study, using unilateral carotid ligation followed by hypoxia in seven day old (P7 rats, showed that the combination of mild HT (35°C and low Xe concentration (20%, both not being neuroprotective alone, had a synergistic effect and was neuroprotective when both were started with a 4 h delay after a moderate HI insult. To examine whether another laboratory could confirm this finding, we repeated key aspects of the study.After the HI-insult 120 pups were exposed to different post-insult treatments: three temperatures (normothermia (NT NT37°C, HT35°C, HT32°C or Xe concentrations (0%, 20% or 50% starting either immediately or with a 4 h delay. To assess the synergistic potency of Xe-HT, a second set (n = 101 of P7 pups were exposed to either HT35°C+Xe0%, NT+Xe20% or a combination of HT35°C+Xe20% starting with a 4 h delay after the insult. Brain damage was analyzed using relative hemispheric (ligated side/unligated side brain tissue area loss after seven day survival.Immediate HT32°C (p = 0.042, but not HT35°C significantly reduced brain injury compared to NT37°C. As previously shown, adding immediate Xe50% to HT32°C increased protection. Neither 4 h-delayed Xe20%, nor Xe50% at 37°C significantly reduced brain injury (p>0.050. In addition, neither 4 h-delayed HT35°C alone, nor HT35°C+Xe20% reduced brain injury. We found no synergistic effect of the combined treatments in this experimental model.Combining two treatments that individually were ineffective (delayed HT35°C and delayed Xe20% did not exert neuroprotection when combined, and therefore did not show a synergistic

  3. Effect of ascorbic acid on the properties of ammonia caramel colorant additives and acrylamide formation. (United States)

    Chen, Hongxing; Gu, Zhengbiao


    Ammonia caramels are among the most widely used colorant additives in the food industry. They are commonly prepared through the Maillard reaction and caramelization of mixtures of reducing sugars with ammonia or ammonium salts. Antioxidants are known to inhibit acrylamide formation during the Maillard reaction, and they may affect the properties of the ammonia caramel products. Thus, the objective of this study was to investigate the effect of the antioxidant ascorbic acid on the properties of ammonia caramel. A mixture of glucose and ammonia was allowed to react at 120 °C for 60 min in the presence of ascorbic acid at final concentrations of 0 to 0.08 M. The ammonia caramels obtained from these reactions were all positively charged. As the concentration of ascorbic acid increased, the color intensity of the ammonia caramel showed a decreasing trend, while the intensity of the fluorescence and total amount of pyrazines in the volatiles showed a tendency to increase. The addition of ascorbic acid did not result in obvious changes in the UV-visible spectra of the ammonia caramels and the types of pyrazines in the volatiles were also unchanged. It is noteworthy that the addition of 0.02 to 0.08 M ascorbic acid did reduce the formation of the by-product acrylamide, a harmful substance in food. When the concentration of ascorbic acid added reached 0.04 M, the content of acrylamide in the ammonia caramel was 20.53 μg/L, which was approximately 44% lower than that without ascorbic acid. As a result, ascorbic acid can be considered to improve the quality and safety of ammonia caramels.

  4. Addition of Urban Waste to Semiarid Degraded Soil: Long-term Effect

    Institute of Scientific and Technical Information of China (English)


    The addition of municipal solid wastes (MSW) is considered as a possible strategy for soil rehabilitation in southeast Spain. The objective of this study was to evaluate the long-term (17 years) effect of five doses of MSW addition on the microbiological, biochemical, and physical properties of semiarid soil. Increased values of several parameters that serve as indicators of general microbiological activity, such as, basal respiration, adenosine triphosphate (ATP) or dehydrogenase activity; microbial population size (microbial biomass C), and extracellular hydrolase activity related to macronutrient cycles, such as, urease, β-glucosidase, and N-α-benzoyl-L-argininamide protease, were observed in the amended soils. The highest MSW doses showed the highest values in these hydrolase activities. The incorporation of municipal waste resulted in a more dense development of the plant cover, 50% greater in higher doses than in the control treatment, which generated a substantial increase in several C fractions. Total organic carbon reached 12 g kg-1 soil with the highest MSW doses,compared to 4.30 g kg-1 soil in the control treatment. The physical properties of the soil were also improved, showing greater percentage of stable aggregates and water holding capacity. Positive correlation coefficients between C fractions and parameters related to microbial activity and aggregate stability were observed. Although these improvements were greater in the soils receiving the highest doses of organic amendment, the increases were not proportional to the amount added, demonstrating the existence of a threshold, above which an increase in the amount of organic matter added is not reflected in an increase in the soil's physical, biochemical, and microbiological properties. However, the addition of municipal solid wastes proved its suitability for improving soil quality, thereby indicating the potential of such an amendment, to prevent desertification in Mediterranean areas such as

  5. Effect of Additives on Liner Properties of Case-bonded Composite Propellants

    Directory of Open Access Journals (Sweden)

    S. B. Navale


    Full Text Available A thin layer of liner is applied to ensure a good bond between the insulator and the propellant in case-bonded rocket motors. It also acts as a protective shield for the insulatorby providing a limited fire protection effect. Liner compositions should preferably be based on the same binder system used in the propellant formulations. As the liner has to hold the propellant and the insulator without debond under all the environmental conditions, it plays a key role in predicted performance of a rocket motor. Hence, studies were carried out to improve the liner properties using various hydroxyl compounds, such as butanediol, cardanol, trimethylol propane, pyrogallol, etc as additives. Butanediol and phloroglucinol combination gave the best results in terms of mechanical properties and interface properties for the liner compositions. The effect of filler content on the liner properties was also studied. The results showed that higher filler content does not affect interface properties. Considering the fire retardancy effect and reinforcement of antimony trioxide (S£203, the formulation containing higher Sb2O3 was selected. The studies on pot life/castable life of liner showed that propellant could be cast up to 6 days after liner coating, without adversely affecting the bonding and the bond strength.

  6. Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival

    DEFF Research Database (Denmark)

    Benn, Christine S; Fisker, Ane B; Whittle, Hilton C


    BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesi......BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore....... In a quasi-experimental study two doses before and after 9months compared with one dose of MV after 9months of age reduced mortality by 59% (25-81%). BCG-revaccination significantly enhanced BCG's effect against overall child mortality in two RCTs. In a natural experiment study of OPV campaigns over a 13......-year-period in Guinea-Bissau, each additional dose of OPV was associated with a 13% (4-21%) reduction in mortality rate. The beneficial NSEs of smallpox vaccination for survival increased significantly with the number of smallpox vaccination scars. INTERPRETATION: Revaccination with live vaccines led...

  7. Cryptic biodiversity effects: importance of functional redundancy revealed through addition of food web complexity. (United States)

    Philpott, Stacy M; Pardee, Gabriella L; Gonthier, David J


    Interactions between predators and the degree of functional redundancy among multiple predator species may determine whether herbivores experience increased or decreased predation risk. Specialist parasites can modify predator behavior, yet rarely have cascading effects on multiple predator species and prey been evaluated. We examined influences of specialist phorid parasites (Pseudacteon spp.) on three predatory ant species and herbivores in a coffee agroecosystem. Specifically, we examined whether changes in ant richness affected fruit damage by the coffee berry borer (Hypothenemus hampei) and whether phorids altered multi-predator effects. Each ant species reduced borer damage, and without phorids, increasing predator richness did not further decrease borer damage. However, with phorids, activity of one ant species was reduced, indicating that the presence of multiple ant species was necessary to limit borer damage. In addition, phorid presence revealed synergistic effects of multiple ant species, not observed without the presence of this parasite. Thus, a trait-mediated cascade resulting from a parasite-induced predator behavioral change revealed the importance of functional redundancy, predator diversity, and food web complexity for control of this important pest.

  8. Effect of crystals and fibrous network polymer additives on cellular morphology of microcellular foams (United States)

    Miyamoto, Ryoma; Utano, Tatsumi; Yasuhara, Shunya; Ishihara, Shota; Ohshima, Masahiro


    In this study, the core-back foam injection molding was used for preparing microcelluar polypropylene (PP) foam with either a 1,3:2,4 bis-O-(4-methylbenzylidene)-D-sorbitol gelling agent (Gel-all MD) or a fibros network polymer additive (Metablen 3000). Both agent and addiive could effectively control the celluar morphology in foams but somehow different ways. In course of cooling the polymer with Gel-all MD in the mold caity, the agent enhanced the crystal nucleation and resulted in the large number of small crystals. The crystals acted as effective bubble nucleation agent in foaming process. Thus, the agent reduced the cell size and increased the cell density, drastically. Furthermore, the small crystals provided an inhomogenuity to the expanding cell wall and produced the high open cell content with nano-scale fibril structure. Gell-all as well as Metablene 3000 formed a gel-like fibrous network in melt. The network increased the elongational viscosity and tended to prevent the cell wall from breaking up. The foaming temperature window was widened by the presence of the network. Especially, the temperature window where the macro-fibrous structure was formed was expanded to the higher temperature. The effects of crystal nucleating agent and PTFE on crystals' size and number, viscoelsticity, rheological propreties of PP and cellular morphology were compared and thorougly investigated.

  9. Effects of pulverized coal fly-ash addition as a wet-end filler in papermaking

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, A.S.K. [SLIET, Longowal (India). Dept. of Chemical Technology


    This experimental study is based on the innovative idea of using pulverized coal fly ash as a wet-end filler in papermaking. This is the first evaluation of the possible use of fly ash in the paper industry. Coal-based thermal power plants throughout the world are generating fly ash as a solid waste product. The constituents of fly ash can be used effectively in papermaking. Fly ash has a wide variation in particle size, which ranges from a few micrometers to one hundred micrometers. Fly ash acts as an inert material in acidic, neutral, and alkaline papermaking processes. Its physical properties such as bulk density (800-980 kg/m{sup 3}), porosity (45%-57%), and surface area (0.138-2.3076 m{sup 2}/g) make it suitable for use as a paper filler. Fly ash obtained from thermal power plants using pulverized coal was fractionated by a vibratory-sieve stack. The fine fraction with a particle size below 38 micrometers was used to study its effect on the important mechanical-strength and optical properties of paper. The effects of fly-ash addition on these properties were compared with those of kaolin clay. Paper opacity was found to be much higher with fly ash as a filler, whereas brightness decreased as the filler percentage increased Mechanical strength properties of the paper samples with fly ash as filler were superior to those with kaolin clay.

  10. Effect of herbicide resistance endowing Ile-1781-Leu and Asp-2078-Gly ACCase gene mutations on ACCase kinetics and growth traits in Lolium rigidum. (United States)

    Vila-Aiub, Martin M; Yu, Qin; Han, Heping; Powles, Stephen B


    The rate of herbicide resistance evolution in plants depends on fitness traits endowed by alleles in both the presence and absence (resistance cost) of herbicide selection. The effect of two Lolium rigidum spontaneous homozygous target-site resistance-endowing mutations (Ile-1781-Leu, Asp-2078-Gly) on both ACCase activity and various plant growth traits have been investigated here. Relative growth rate (RGR) and components (net assimilation rate, leaf area ratio), resource allocation to different organs, and growth responses in competition with a wheat crop were assessed. Unlike plants carrying the Ile-1781-Leu resistance mutation, plants homozygous for the Asp-2078-Gly mutation exhibited a significantly lower RGR (30%), which translated into lower allocation of biomass to roots, shoots, and leaves, and poor responses to plant competition. Both the negligible and significant growth reductions associated, respectively, with the Ile-1781-Leu and Asp-2078-Gly resistance mutations correlated with their impact on ACCase activity. Whereas the Ile-1781-Leu mutation showed no pleiotropic effects on ACCase kinetics, the Asp-2078-Gly mutation led to a significant reduction in ACCase activity. The impaired growth traits are discussed in the context of resistance costs and the effects of each resistance allele on ACCase activity. Similar effects of these two particular ACCase mutations on the ACCase activity of Alopecurus myosuroides were also confirmed.

  11. Effect of fluoride additives on production and characterization of nano--Al2O3 particles

    Indian Academy of Sciences (India)

    F Mirjalili


    Nano--Al2O3 particles were synthesized by a sol–gel method using aqueous solutions of aluminum isopropoxide and 0.5 Maluminum nitrate. Sodium dodecylbenzenesulfonate (SDBS) was used as surfactant stabilizing agents. The solution was stirred for 48 h at 60 °C. The microstructural observation showed that surfactant with 48 h stirring time nanoscale -Al2O3 powder was produced at 1200 °C in the range of 20–30 nm in the presence of SDBS as a surfactant with 48 h stirring time. Temperature reduction of -Al2O3 formation has been achieved by introducing fluoride in the alumina precursor. 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, scanning electron microscopy and transmission electron microscopy. Results indicated that using zinc fluoride (ZnF2) additive accompanied by milling led to retardation of the transformation temperature and modification of the alumina particle shape. The finest size for nonagglomerated nano-plate-like -Al2O3 particles (15–20 nm) was achieved at 950 °C.

  12. Effects of Additives, Photodegradation, and Water-tree Degradation on the Photoluminescence in Polyethylene and Polypropylene (United States)

    Ito, Toshihide; Fuse, Norikazu; Ohki, Yoshimichi

    Photoluminescence (PL) spectra induced by irradiation of ultraviolet photons are compared among low-density polyethylene (LDPE), crosslinked polyethylene (XLPE), and polypropylene (PP). Three PL bands appear around 4.2, 3.6, and 3.1 eV in LDPE and XLPE, while similar three PL bands are observed at similar energies in PP. The PL spectra and their decay profiles are independent of the presence of additives and are also independent of whether the samples were crosslinked or not. These results indicate that neither the additives nor the crosslinking has any significant effects on the respective three PLs in PE and PP. When the sample was pre-irradiated by the ultraviolet photons under different atmospheres (air, O2, and vacuum), all the PL intensities decrease with the progress of the pre-irradiation regardless of whether the sample is PE or PP. Therefore, all the PLs are considered to result from impurities. In all the pre-irradiated samples, a new PL band appears at 2.9 eV, of which intensity is stronger when the oxygen partial pressure during the pre-irradiation was lower. This PL is considered to be due to photo-induced conjugated double bonds. It has also been confirmed that water-tree degradation in LDPE or in XLPE does not contribute to PL.

  13. Effect of titania addition on hot hardness of UO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Sengupta, A.K. E-mail:; Basak, C.B.; Jarvis, T.; Bhagat, R.K.; Pandey, V.D.; Majumdar, S


    Large grain UO{sub 2} is a potential fuel for LWR's for achieving extended burn up. Large grains are obtained by addition of dopants like Nb{sub 2}O{sub 5}, TiO{sub 2}, Cr{sub 2}O{sub 3}, V{sub 2}O{sub 5} etc. However, presence of such dopants might affect the thermophysical and thermomechanical properties of the fuel. In the present investigation the effect of TiO{sub 2} addition on the hot hardness (H) of sintered UO{sub 2} fuel has been studied from ambient to 1573 K in vacuum. TiO{sub 2} content was varied from 0.01 to 0.15 w/o resulting in a grain size (G) variation of 9 to 94 {mu}m. With increase in grain size (or TiO{sub 2} content) H first decreases, attains a minima and then increases further. The increase is more prominent at lower temperature (<773 K) than that at higher temperatures. H vs. G{sup -1/2} plots indicates the same type of variation like other oxide ceramics with H minima at an intermediate grain size at low temperature. The intrinsic hardness and softening coefficient of UO{sub 2} indicate cubic dependence on TiO{sub 2} content.

  14. Effect of electrolyte addition to rehydration drinks consumed after severe fluid and energy restriction. (United States)

    James, Lewis J; Shirreffs, Susan M


    This study examined the effect of electrolyte addition to drinks ingested after severe fluid and energy restriction (FER). Twelve subjects (6 male and 6 female) completed 3 trials consisting of 24-hour FER (energy intake: 21 kJ·kg body mass; water intake: 5 ml·kg body mass), followed by a 2-hour rehydration period and a 4-hour monitoring period. During rehydration, subjects ingested a volume of drink equal to 125% of the body mass lost during FER in 6 aliquots, once every 20 minutes. Drinks were a sugar-free lemon squash (P) or the P drink with the addition of 50 mmol·L sodium chloride (Na) or 30 mmol·L potassium chloride (K). Total void urine samples were given before and after FER and every hour during rehydration and monitoring. Over all trials, FER produced a 2.1% reduction in body mass and negative sodium (-67 mmol), potassium (-48 mmol), and chloride (-84 mmol) balances. Urine output after drinking was 1627 (540) ml (P), 1391 (388) ml (K), and 1150 (438) ml (Na), with a greater postdrinking urine output during P than Na (p ≤ 0.05). Ingestion of drink Na resulted in a more positive sodium balance compared with P or K (p drink K resulted in a more positive potassium balance compared with P or Na (p drink results in an increased sodium balance that augments greater drink retention compared with a low electrolyte placebo drink.

  15. Effect of Boron Addition on the Thermal, Degradation, and Cytocompatibility Properties of Phosphate-Based Glasses

    Directory of Open Access Journals (Sweden)

    Nusrat Sharmin


    Full Text Available In this study eight different phosphate-based glass compositions were prepared by melt-quenching: four in the (P2O545-(CaO16--(MgO24- system and four in the system (P2O550-(CaO16--(MgO24-, where and 10 mol%. The effect of B2O3 addition on the thermal properties, density, molar volume, dissolution rates, and cytocompatibility were studied for both glass systems. Addition of B2O3 increased the glass transition (, crystallisation (, melting (, Liquidus ( and dilatometric softening ( temperature and molar volume (. The thermal expansion coefficient (α and density ( were seen to decrease. An assessment of the thermal stability of the glasses was made in terms of their processing window (crystallisation onset, minus glass transition temperature, , and an increase in the processing window was observed with increasing B2O3 content. Degradation studies of the glasses revealed that the rates decreased with increasing B2O3 content and a decrease in degradation rates was also observed as the P2O5 content reduced from 50 to 45 mol%. MG63 osteoblast-like cells cultured in direct contact with the glass samples for 14 days revealed comparative data to the positive control for the cell metabolic activity, proliferation, ALP activity, and morphology for glasses containing up to 5 mol% of B2O3.

  16. Effect of Ca and Y additions on oxidation behavior of AZ91 alloy at elevated temperatures

    Institute of Scientific and Technical Information of China (English)

    CHENG Su-ling; YANG Gen-cang; FAN Jian-feng; LI You-jie; ZHOU Yao-he


    In order to develop the ignition-proof magnesium alloy, the effect of alloying elements, Ca and Y, on the oxidation behavior of AZ91 magnesium alloy at elevated temperatures was investigated. The ignition-proof performance, oxide products and oxidation kinetics of Ca- and Y-containing AZ91 alloys were studied. The results indicate that the proper addition of Ca can increase the ignition point of AZ91 alloy greatly. However, the oxide film of Ca-bearing AZ91 alloy formed at elevated temperature is thick and brittle, which is prone to crack in melting and cooling process. In addition, the oxide film of AZ91-xCa alloy is incompact and cannot inhibit the diffusion of reaction particles. The oxide film of AZ91-xCa alloy turns to thin and plastic one after Y is added, and the density of the oxide film increases greatly due to the formation of composite oxide film composed of MgO, CaO and Y2O3.

  17. Effect of fluxing additive on sintering temperature, microstructure and properties of BaTiO3

    Indian Academy of Sciences (India)

    Yaseen Iqbal; Asad Jamal; Riaz Ullah; M Naeem Khan; Rick Ubic


    Various fluxing materials are added to technical ceramics in an attempt to lower their sintering temperatures and make their processing economical. The effect of 0.3wt%Li2CO3 addition on the phase, microstructure, phase transition temperatures and dielectric properties of BaTiO3 was investigated in the present study. The addition of 0.3wt% Li2CO3 was observed to lower the optimum sintering temperature by ∼200°C with no second phase formation and cause a five-fold reduction in grain size. Rhombohedral-to-orthorhombic and tetragonal-to-cubic phase transitions at the expected temperatures were evident from the Raman spectra, but the orthorhombic-totetragonal phase transition was not clearly discernible. The persistence of various phase(s) at higher temperatures in the flux-added materials indicated that the phase transitions occurred relatively slowly. A decrease in dielectric constant of Li2O-added BaTiO3 in comparison to pure BaTiO3 may be due to the diminished dielectric polarizability of Li+ in comparison to Ba2+.

  18. Effect of Ti-V-Nb-Mo addition on microstructure of high chromium cast iron

    Directory of Open Access Journals (Sweden)

    Ma Youping


    Full Text Available The effects of trace additions of multi-alloying elements (Ti, Nb, V, Mo on carbides precipitation and as-cast microstructure of eutectic high chromium cast iron containing 2.85wt.%C and 31.0wt.%Cr were investigated from thermodynamic and kinetic considerations. The thermodynamic calculations show that Ti and Nb exist in the multi-alloying system in the forms of TiC and NbC. The formation of VC during the solidification is not feasible from the thermodynamic consideration. XRD analysis shows that the V exists in alloy compounds (VCr2C2, VCrFe8. The first precipitated high melting point particles (TiC, NbC can act as the heterogeneous substrate of M7C3 carbides, which results in significant refinement of the M7C3 carbides. After the addition of alloying elements, C atom diffusion is hindered due to the strong affinities of the strong carbide forming elements for carbon, which decreases the growth rate of carbides. The combined roles of the increase of nucleation rate and the decrease of carbides growth rate lead to the finer microstructure.

  19. Effect of tert-butyl hydroperoxide