Sample records for genotype 5a failure

  1. Highly Efficient JFH1-Based Cell-Culture System for Hepatitis C Virus Genotype 5a: Failure of Homologous Neutralizing-Antibody Treatment to Control Infection

    DEFF Research Database (Denmark)

    Jensen, Tanja B; Gottwein, Judith Margarete; Scheel, Troels Kasper Høyer


    of recovered genomes and reverse-genetic studies. Receptor blockage was performed with anti-CD81 and anti-SR-BI. For neutralization experiments, SA13/JFH1 or JFH1-based viruses of other genotypes were incubated with patient sera. Results. @nbsp; SA13/JFH1 with NS2 and NS3 mutations yielded infectivity titers......Background. @nbsp; Recently, a hepatitis C virus (HCV) cell-culture system was developed that employed strain JFH1 (genotype 2a), and JFH1-based intra- and intergenotypic recombinants now permit functional studies of the structural genes (Core, E1, and E2), p7, and NS2 of genotypes 1-4. The goal...... was to adapt the system to employ genotype 5. Methods. @nbsp; Huh7.5 cells infected with SA13/JFH1, containing Core-NS2 of strain SA13 (genotype 5a), were monitored for Core expression and for supernatant infectivity and HCV-RNA titers. Adaptive mutations of SA13/JFH1 were identified by sequence analysis...

  2. NS5A resistance leading to failure of 24-week therapy with sofosbuvir/ledipasvir and ribavirin for the treatment of hepatitis C genotype 1a infection in a HIV-1 co-infected patient. (United States)

    Sevastianova, Ksenia; Dean, Jonathan; Bannan, Ciaran; Coghlan, Miriam; Farrell, Gillian; Murray, Catherine; De Gascun, Cillian F; Bergin, Colm


    Herein we report a previously undescribed case of treatment-emergent non-structural protein 5A (NS5A) resistance mutations, Q30H and Y93C, leading to a failure of 24-week course of sofosbuvir/ledipasvir+ribavirin therapy for the treatment of hepatitis C virus (HCV) genotype 1a in interferon-experienced, human immunodeficiency virus type 1 (HIV-1) co-infected patient with cirrhosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. An autochthonous case of hepatitis C virus genotype 5a in Brazil: phylogenetic analysis

    DEFF Research Database (Denmark)

    Ribeiro, L.C.; Souto, F.J.D.; do Espirito-Santo, M.P.


    Genotype 5 of hepatitis C virus (HCV) has been rarely identified in South America. A female of African descent who never left Brazil was found to be infected by this genotype in Mato Grosso state, Central Brazil. The patient denied drug injections and revealed that she had received blood...... transfusions several years before. One of her blood donors was identified and tested negative for anti-HCV and HCV RNA, as were her husband and offspring. Phylogenetic analysis of the E1 and NS5B regions confirmed that this HCV strain belonged to genotype 5a. However, the E1 region analysis indicates that our...

  4. Efficient hepatitis c virus genotype 1b core-NS5A recombinants permit efficacy testing of protease and NS5A inhibitors

    DEFF Research Database (Denmark)

    Pham, Long V.; Ramirez Almeida, Santseharay; Carlsen, Thomas H R


    Hepatitis C virus (HCV) strains belong to seven genotypes with numerous subtypes that respond differently to antiviral therapies. Genotype 1, and primarily subtype 1b, is the most prevalent genotype worldwide. The development of recombinant HCV infectious cell culture systems for different variants......, permitted by the high replication capacity of strain JFH1 (genotype 2a), has advanced efficacy and resistance testing of antivirals. However, efficient infectious JFH1-based cell cultures of subtype 1b are limited and comprise only the 5= untranslated region (5=UTR)-NS2, NS4A, or NS5A regions. Importantly...

  5. NS5A Sequence Heterogeneity and Mechanisms of Daclatasvir Resistance in Hepatitis C Virus Genotype 4 Infection. (United States)

    Zhou, Nannan; Hernandez, Dennis; Ueland, Joseph; Yang, Xiaoyan; Yu, Fei; Sims, Karen; Yin, Philip D; McPhee, Fiona


    Daclatasvir is an NS5A inhibitor approved for treatment of infection due to hepatitis C virus (HCV) genotypes (GTs) 1-4. To support daclatasvir use in HCV genotype 4 infection, we examined a diverse genotype 4-infected population for HCV genotype 4 subtype prevalence, NS5A polymorphisms at residues associated with daclatasvir resistance (positions 28, 30, 31, or 93), and their effects on daclatasvir activity in vitro and clinically. We performed phylogenetic analysis of genotype 4 NS5A sequences from 186 clinical trial patients and 43 sequences from the European HCV database, and susceptibility analyses of NS5A polymorphisms and patient-derived NS5A sequences by using genotype 4 NS5A hybrid genotype 2a replicons. The clinical trial patients represented 14 genotype 4 subtypes; most prevalent were genotype 4a (55%) and genotype 4d (27%). Daclatasvir 50% effective concentrations for 10 patient-derived NS5A sequences representing diverse phylogenetic clusters were ≤0.080 nM. Most baseline sequences had ≥1 NS5A polymorphism at residues associated with daclatasvir resistance; however, only 3 patients (1.6%) had polymorphisms conferring ≥1000-fold daclatasvir resistance in vitro. Among 46 patients enrolled in daclatasvir trials, all 20 with baseline resistance polymorphisms achieved a sustained virologic response. Circulating genotype 4 subtypes are genetically diverse. Polymorphisms conferring high-level daclatasvir resistance in vitro are uncommon before therapy, and clinical data suggest that genotype 4 subtype and baseline polymorphisms have minimal impact on responses to daclatasvir-containing regimens. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  6. An NS5A single optimized method to determine genotype, subtype and resistance profiles of Hepatitis C strains.

    Directory of Open Access Journals (Sweden)

    Elisabeth Andre-Garnier

    Full Text Available The objective was to develop a method of HCV genome sequencing that allowed simultaneous genotyping and NS5A inhibitor resistance profiling. In order to validate the use of a unique RT-PCR for genotypes 1-5, 142 plasma samples from patients infected with HCV were analysed. The NS4B-NS5A partial region was successfully amplified and sequenced in all samples. In parallel, partial NS3 sequences were analyzed obtained for genotyping. Phylogenetic analysis showed concordance of genotypes and subtypes with a bootstrap >95% for each type cluster. NS5A resistance mutations were analyzed using the Geno2pheno [hcv] v0.92 tool and compared to the list of known Resistant Associated Substitutions recently published. In conclusion, this tool allows determination of HCV genotypes, subtypes and identification of NS5A resistance mutations. This single method can be used to detect pre-existing resistance mutations in NS5A before treatment and to check the emergence of resistant viruses while undergoing treatment in major HCV genotypes (G1-5 in the EU and the US.

  7. Efficacy of NS5A Inhibitors Against Hepatitis C Virus Genotypes 1–7 and Escape Variants

    DEFF Research Database (Denmark)

    Gottwein, Judith M.; Pham, Long V.; Mikkelsen, Lotte S.


    , or that contained RAS previously reported from patients. Results: NS5A inhibitors had varying levels of efficacy against original and resistant viruses. Only velpatasvir and pibrentasvir had uniform high activity against all HCV genotypes tested. RAS hotspots in NS5A were found at amino acids 28, 30, 31, and 93...

  8. Hereditary hemochromatosis (HFE) genotypes in heart failure: relation to etiology and prognosis

    DEFF Research Database (Denmark)

    Møller, Daniel Vega; Pecini, Redi; Gustafsson, Finn


    It is believed that hereditary hemochromatosis (HH) might play a role in cardiac disease (heart failure (HF) and ischemia). Mutations within several genes are HH-associated, the most common being the HFE gene. In a large cohort of HF patients, we sought to determine the etiological role...... and the prognostic significance of HFE genotypes....

  9. Differential sensitivity of 5'UTR-NS5A recombinants of hepatitis C virus genotypes 1-6 to protease and NS5A inhibitors

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Humes, Daryl


    BACKGROUND & AIMS: Hepatitis C virus (HCV) therapy will benefit from the preclinical evaluation of direct-acting antiviral (DAA) agents in infectious culture systems that test the effects on different virus genotypes. We developed HCV recombinants comprising the 5' untranslated region-NS5A (5-5A...... daclatasvir. The 1a(TN) 5-5A and JFH1-independent full-length viruses had similar levels of sensitivity to the DAA agents, validating the 5-5A recombinants as surrogates for full-length viruses in DAA testing. Compared with the 1a(TN) full-length virus, the 3a(S52) 5-5A recombinant was highly resistant to all...... protease inhibitors, and the 4a(ED43) recombinant was highly resistant to telaprevir and boceprevir, but most sensitive to other protease inhibitors. Compared with other protease inhibitors, MK-5172 had exceptional potency against all HCV genotypes. The NS5A inhibitor daclatasvir had the highest potency...

  10. Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa. (United States)

    Prabdial-Sing, N; Blackard, J T; Puren, A J; Mahomed, A; Abuelhassan, W; Mahlangu, J; Vermeulen, M; Bowyer, S M


    Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including ∼ 90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a(N = 10) 1b(N = 12), 3a(N = 5), 4a(N = 3) and 5a(N = 61). Two mutations, associated with interferon resistance-R70Q and T110N-were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of <300 IC50nM to HLA alleles frequently observed in the South African population. No known CD8+ and CD4+ T-cell epitopes were mapped in the NS5B region. The analysis begs the question whether those infected with genotype 5a will benefit better on interferon-free combination therapies. This study provides new insight into one of the lesser studied HCV genotypes and compares the diversity seen in a large pre-treatment cohort with other subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Hereditary Hemochromatosis (HFE genotypes in heart failure: Relation to etiology and prognosis

    Directory of Open Access Journals (Sweden)

    Torp-Pedersen Christian


    Full Text Available Abstract Background It is believed that hereditary hemochromatosis (HH might play a role in cardiac disease (heart failure (HF and ischemia. Mutations within several genes are HH-associated, the most common being the HFE gene. In a large cohort of HF patients, we sought to determine the etiological role and the prognostic significance of HFE genotypes. Methods We studied 667 HF patients (72.7% men with depressed systolic function, enrolled in a multicentre trial with a follow-up period of up to 5 years. All were genotyped for the known HFE variants C282Y, H63D and S65C. Results The genotype and allele frequencies in the HF group were similar to the frequencies determined in the general Danish population. In multivariable analysis mortality was not predicted by C282Y-carrier status (HR 1.2, 95% CI: 0.8-1.7; H63D-carrier status (HR 1.0, 95% CI: 0.7-1.3; nor S65C-carrier status (HR 1.2, 95% CI: 0.7-2.0. We identified 27 (4.1% homozygous or compound heterozygous carriers of HFE variants. None of these carriers had a clinical presentation suggesting hemochromatosis, but hemoglobin and ferritin levels were higher than in the rest of the cohort. Furthermore, a trend towards reduced mortality was seen in this group in univariate analyses (HR 0.4, 95% CI: 0.2-0.9, p = 0.03, but not in multivariate (HR 0.5, 95% CI: 0.2-1.2. Conclusion HFE genotypes do not seem to be a significant contributor to the etiology of heart failure in Denmark. HFE variants do not affect mortality in HF.

  12. New hepatitis C virus genotype 1 subtype naturally harbouring resistance-associated mutations to NS5A inhibitors. (United States)

    Ordeig, Laura; Garcia-Cehic, Damir; Gregori, Josep; Soria, Maria Eugenia; Nieto-Aponte, Leonardo; Perales, Celia; Llorens, Meritxell; Chen, Qian; Riveiro-Barciela, Mar; Buti, Maria; Esteban, Rafael; Esteban, Juan Ignacio; Rodriguez-Frias, Francisco; Quer, Josep


    Hepatitis C virus (HCV) is a highly divergent virus currently classified into seven major genotypes and 86 subtypes (ICTV, June 2017), which can have differing responses to therapy. Accurate genotyping/subtyping using high-resolution HCV subtyping enables confident subtype identification, identifies mixed infections and allows detection of new subtypes. During routine genotyping/subtyping, one sample from an Equatorial Guinea patient could not be classified into any of the subtypes. The complete genomic sequence was compared to reference sequences by phylogenetic and sliding window analysis. Resistance-associated substitutions (RASs) were assessed by deep sequencing. The unclassified HCV genome did not belong to any of the existing genotype 1 (G1) subtypes. Sliding window analysis along the complete genome ruled out recombination phenomena suggesting that it belongs to a new HCV G1 subtype. Two NS5A RASs (L31V+Y93H) were found to be naturally combined in the genome which could limit treatment possibilities in patients infected with this subtype.

  13. Design, synthesis and identification of silicon-containing HCV NS5A inhibitors with pan-genotype activity. (United States)

    Liu, Baomin; Gai, Kuo; Qin, Hui; Liu, Xushi; Cao, Yuan; Lu, Qin; Lu, Dandan; Chen, Deyang; Shen, Hengqiao; Song, Wei; Zhang, Yang; Wang, Xiaojin; Xu, Hongjiang; Zhang, Yinsheng


    Modification of a HCV NS5A inhibitor, ombitasvir, led to the identification of 10d with improved pan-genotype NS5A inhibition and better pharmacokinetic properties. The key structural changes to ombitasvir include bioisosteric replacement of carbon with silicon atom. Compared with ombitasvir, the activity of anti-HCV genotypes (GT 1 to 6) of 10d is increased to some extent, especially the inhibitory activity against genotype 3a and 6a is increased by more than seven times, and the dog's in vivo pharmacokinetics properties were also superior to ombitasvir. Further drug evaluation showed that 10d was similar to ombitasvir on plasma protein binding and liver distribution profiles, with no cytotoxicity and no inhibitory effect on both CYP 450 and hERG ligand binding. However, permeability assay results indicated that 10d was not the substrate of P-gp or BCRP transporter, which is different from that of ombitasvir. The results of a 14-day repeat-dose toxicity study identified no toxicity with 10d. Our findings in preclinical tests suggest that the silicon-containing compound 10d could be worthy of continued study as a potential drug candidate. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. Acute liver failure caused by hepatitis E virus genotype 3 and 4: A systematic review and pooled analysis. (United States)

    Haffar, Samir; Shalimar; Kaur, Ravinder J; Wang, Zhen; Prokop, Larry J; Murad, Mohammad H; Bazerbachi, Fateh


    Acute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4. Two reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus-RNA positive vs negative, and to discern important mortality risk factors. We identified 65 patients, with median age 58 years (range: 3-79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus-RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA. Acute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle-aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Analysis of hepatitis C virus core/NS5A protein co-localization using novel cell culture systems expressing core-NS2 and NS5A of genotypes 1-7

    DEFF Research Database (Denmark)

    Galli, Andrea; Scheel, Troels K H; Prentoe, Jannick C


    Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (c......LDs) or on the endoplasmic reticulum (ER) at different stages of particle assembly. Current knowledge on assembly and release is primarily based on studies in genotype 2a cell culture systems; however, given the high genetic heterogeneity of HCV, variations might exist among genotypes. Here, we developed novel HCV strain...... JFH1-based recombinants expressing core-NS2 and NS5A from genotypes 1-7, and analysed core and NS5A co-localization in infected cells. Huh7.5 cells were transfected with RNA of core-NS2/NS5A recombinants and putative adaptive mutations were analysed by reverse genetics. Adapted core-NS2/NS5A...

  16. Natural prevalence of resistance-associated variants in hepatitis C virus NS5A in genotype 3a-infected people who inject drugs in Germany. (United States)

    Walker, Andreas; Siemann, Holger; Groten, Svenja; Ross, R Stefan; Scherbaum, Norbert; Timm, Jörg


    People who inject drugs (PWID) are the most important risk group for incident Hepatitis C virus (HCV) infection. In PWID in Europe HCV genotype 3a is highly prevalent. Unfortunately, many of the recently developed directly acting antiviral drugs against HCV (DAAs) are suboptimal for treatment of this genotype. Detection of resistance-associated variants (RAV) in genotype 3a may help to optimize treatment decisions, however, robust protocols for amplification and sequencing of HCV NS5A as an important target for treatment of genotype 3a are currently lacking. The aim of this study was to establish a protocol for sequencing of HCV NS5A in genotype 3a and to determine the frequency of RAVs in treatment-naïve PWID living in Germany. The full NS5A region was amplified and sequenced from 110 HCV genotype 3a infected PWID using an in-house PCR protocol. With the established protocol the complete NS5A region was successfully amplified and sequenced from 110 out of 112 (98.2%) genotype 3a infected PWID. Phylogenetic analysis of sequences from PWID together with unrelated genotype 3a sequences from a public database showed a scattered distribution without geographic clustering. Viral polymorphisms A30K and Y93H known to confer resistance in a GT3a replication model were present in 8 subjects (7.2%). A protocol for amplification of nearly all GT3a samples was successfully established. Substitutions conferring resistance to NS5A inhibitors were detected in a few treatment-naive PWID. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Cell culture-adaptive mutations of NS5A affect replication of hepatitis C virus differentially depending on the viral genotypes. (United States)

    Chung, Aeri; Jin, Bora; Han, Kwang-Hyub; Ahn, Sang Hoon; Kim, Seungtaek


    Most of HCV RNAs require cell culture-adaptive mutations for efficient replication in cell culture and a number of such mutations have been described including a well-known S2204I substitution mutation in NS5A protein. In contrast, the replication of genotype 2a JFH1 RNA in cell culture does not require any cell culture-adaptive mutation. Rather, the presence of S2204I mutation impaired the JFH1 RNA replication. In this study, we examined the effect of reversions and substitutions of NS5A cell culture-adaptive mutations on virus replication in different genotypic backgrounds after either placing genotype 1a NS5A in the genotype 2a JFH1 or vice versa. The results from this investigation suggest that the S2204I mutation affects HCV RNA replication differentially depending on the viral genotypes but that the effect was not simply explained by the genotypic background. Perhaps, the effect of the S2204I mutation on HCV replication reflects both intra- and intergenic interactions of NS5A protein. J. Med. Virol. 89:146-152, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. NS5A resistance-associated substitutions in patients with genotype 1 hepatitis C virus: Prevalence and effect on treatment outcome. (United States)

    Zeuzem, Stefan; Mizokami, Masashi; Pianko, Stephen; Mangia, Alessandra; Han, Kwang-Hyub; Martin, Ross; Svarovskaia, Evguenia; Dvory-Sobol, Hadas; Doehle, Brian; Hedskog, Charlotte; Yun, Chohee; Brainard, Diana M; Knox, Steven; McHutchison, John G; Miller, Michael D; Mo, Hongmei; Chuang, Wan-Long; Jacobson, Ira; Dore, Gregory J; Sulkowski, Mark


    The efficacy of NS5A inhibitors for the treatment of patients chronically infected with hepatitis C virus (HCV) can be affected by the presence of NS5A resistance-associated substitutions (RASs). We analyzed data from 35 phase I, II, and III studies in 22 countries to determine the pretreatment prevalence of various NS5A RASs, and their effect on outcomes of treatment with ledipasvir-sofosbuvir in patients with genotype 1 HCV. NS5A gene deep sequencing analysis was performed on samples from 5397 patients in Gilead clinical trials. The effect of baseline RASs on sustained virologic response (SVR) rates was assessed in the 1765 patients treated with regimens containing ledipasvir-sofosbuvir. Using a 15% cut-off, pretreatment NS5A and ledipasvir-specific RASs were detected in 13% and 8% of genotype 1a patients, respectively, and in 18% and 16% of patients with genotype 1b. Among genotype 1a treatment-naïve patients, SVR rates were 91% (42/46) vs. 99% (539/546) for those with and without ledipasvir-specific RASs, respectively. Among treatment-experienced genotype 1a patients, SVR rates were 76% (22/29) vs. 97% (409/420) for those with and without ledipasvir-specific RASs, respectively. Among treatment-naïve genotype 1b patients, SVR rates were 99% for both those with and without ledipasvir-specific RASs (71/72 vs. 331/334), and among treatment-experienced genotype 1b patients, SVR rates were 89% (41/46) vs. 98% (267/272) for those with and without ledipasvir-specific RASs, respectively. Pretreatment ledipasvir-specific RASs that were present in 8-16% of patients have an impact on treatment outcome in some patient groups, particularly treatment-experienced patients with genotype 1a HCV. The efficacy of treatments using NS5A inhibitors for patients with chronic hepatitis C virus (HCV) infection can be affected by the presence of NS5A resistance-associated substitutions (RASs). We reviewed results from 35 clinical trials where patients with genotype 1 HCV infection

  19. Successful retreatment with grazoprevir and elbasvir for patients infected with hepatitis C virus genotype 1b, who discontinued prior treatment with NS5A inhibitor-including regimens due to adverse events. (United States)

    Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Nakamoto, Shingo; Takahashi, Koji; Wu, Shuang; Sasaki, Reina; Haga, Yuki; Ogasawara, Sadahisa; Saito, Tomoko; Kobayashi, Kazufumi; Kiyono, Soichiro; Ooka, Yoshihiko; Suzuki, Eiichiro; Chiba, Tetsuhiro; Maruyama, Hitoshi; Moriyama, Mitsuhiko; Kato, Naoya


    Sustained virologic response (SVR) by interferon and interferon-free treatment can results in the reduction of advanced liver fibrosis and the occurrence of hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). Recent interferon-free treatment for HCV shortens the duration of treatment and leads to higher SVR rates, without any serious adverse events. However, it is important to retreat patients who have had treatment-failure with HCV non-structural protein 5A (NS5A) inhibitor-including regimens. Combination of sofosbuvir and ledipasvir only leads to approximately 100% SVR rates in HCV genotype (GT1b), NS5A inhibitor-naïve patients in Japan. This combination is not an indication for severe renal disease or heart disease, and these patients should be treated or retreated with a different regimen. Retreatment with HCV non-structural protein 3/4A inhibitor, grazoprevir, and HCV NS5A inhibitor, elbasvir, successfully eradicated HCV RNA in three patients with HCV genotype 1b infection who discontinued prior interferon-free treatments including HCV NS5A inhibitors due to adverse events within 2 weeks. Retreatment with the 12-week combination regimen of grazoprevir and elbasvir is effective for HCV GT1b patients who discontinue the HCV NS5A inhibitor-including regimens within 2 weeks. The treatment response may be related to the short duration of initial treatment, which did not produce treatment-emergent RASs.

  20. Recombinant HCV variants with NS5A from genotypes 1-7 have different sensitivities to an NS5A inhibitor but not interferon-a

    DEFF Research Database (Denmark)

    Scheel, Troels K H; Gottwein, Judith M; Mikkelsen, Lotte S


    Heterogeneity in the hepatitis C virus (HCV) protein NS5A influences its sensitivity to interferon-based therapy. Furthermore, NS5A is an important target for development of HCV-specific inhibitors. We aimed to develop recombinant infectious cell culture systems that express NS5A from isolates...

  1. Prevalence of polymorphisms with significant resistance to NS5A inhibitors in treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden. (United States)

    Lindström, Ida; Kjellin, Midori; Palanisamy, Navaneethan; Bondeson, Kåre; Wesslén, Lars; Lannergard, Anders; Lennerstrand, Johan


    The future treatment of hepatitis C virus (HCV) infection will be combinations of direct-acting antivirals (DAAs) that not only target multiple viral targets, but are also effective against different HCV genotypes. Of the many drug targets in HCV, one promising target is the non-structural 5A protein (NS5A), against which inhibitors, namely daclatasvir, ledipasvir and ombitasvir, have shown potent efficacy. However, since HCV is known to have very high sequence diversity, development of resistance is a problem against but not limited to NS5A inhibitors (i.e. resistance also found against NS3-protease and NS5B non-nucleoside inhibitors), when used in suboptimal combinations. Furthermore, it has been shown that natural resistance against DAAs is present in treatment-naïve patients and such baseline resistance will potentially complicate future treatment strategies. A pan-genotypic population-sequencing method with degenerated primers targeting the NS5A region was developed. We have investigated the prevalence of baseline resistant variants in 127 treatment-naïve patients of HCV genotypes 1a, 1b, 2b and 3a. The method could successfully sequence more than 95% of genotype 1a, 1b and 3a samples. Interpretation of fold resistance data against the NS5A inhibitors was done with the help of earlier published phenotypic data. Baseline resistance variants associated with high resistance (1000-50,000-fold) was found in three patients: Q30H or Y93N in genotype 1a patients and further Y93H in a genotype 3a patient. Using this method, baseline resistance can be examined and the data could have a potential role in selecting the optimal and cost-efficient treatment for the patient.

  2. Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer. (United States)

    Vanderlaan, Paul A; Yamaguchi, Norihiro; Folch, Erik; Boucher, David H; Kent, Michael S; Gangadharan, Sidharta P; Majid, Adnan; Goldstein, Michael A; Huberman, Mark S; Kocher, Olivier N; Costa, Daniel B


    Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype. Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples. From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR, KRAS, and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs. 0%, p=0.024 for EGFR) and for decalcified compared to non-decalcified samples (60% vs. 5.5%, p=0.021 for EGFR). Tumor genotype techniques are feasible in most samples, outside small image-guided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special

  3. Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive. (United States)

    Baertling, Fabian; Al-Murshedi, Fathiya; Sánchez-Caballero, Laura; Al-Senaidi, Khalfan; Joshi, Niranjan P; Venselaar, Hanka; van den Brand, Mariël Am; Nijtmans, Leo Gj; Rodenburg, Richard Jt


    COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia, failure to thrive, and isolated complex IV deficiency are presented. We show that the variant lies within the evolutionarily conserved COX5A/COX4 interface domain, suggesting that it alters the interaction between these two subunits during complex IV biogenesis. In patient skin fibroblasts, the enzymatic activity and protein levels of complex IV and several of its subunits are reduced. Lentiviral complementation rescues complex IV deficiency. The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts. © 2017 Wiley Periodicals, Inc.

  4. Prevalence of pre-treatment hepatitis C virus NS5A resistance associated amino-acid substitutions in genotype 1A infected patients in Scotland. (United States)

    Bradley-Stewart, Amanda; Goldstein, Emily; MacLean, Alasdair; Gunson, Rory


    Hepatitis C (HCV) NS5A resistance associated amino-acid substitutions (RAS) can exist at baseline in treatment naïve individuals and have been shown to be associated with lower rates of sustained virological response (SVR) for patients infected with HCV genotype 1A (G1A) following treatment with NS5A inhibitors. The aim of this study was to measure the prevalence of baseline NS5A resistance in Scotland. The study population consisted of 531 treatment naïve, G1A infected patients. The patient samples were collected between March and September 2017. The NS5A region was amplified and sequenced. Baseline NS5A resistance in Scotland is high (16.8%) and is comparable to rates reported by a number of previously published studies. The high rate of baseline RAS, together with the high cost of direct-acting antivirals (DAAs), supports resistance testing to guide current patient treatment. However, given the rate at which new DAAs are currently being licensed with ever broader genotype efficacy and higher SVR rates, baseline resistance testing may not be required in the near future. Baseline NS5A inhibitor resistance is high. The results of the present study support performing resistance testing at baseline for current regimens. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  5. Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Jørgensen, LB; Kronborg, G


    OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients...... range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus ... in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk...

  6. Combination treatment with hepatitis C virus protease and NS5A inhibitors is effective against recombinant genotype 1a, 2a, and 3a viruses

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Jensen, Sanne B; Li, Yi-Ping


    With the development of directly acting antivirals, hepatitis C virus (HCV) therapy entered a new era. However, rapid selection of resistance mutations necessitates combination therapy. To study combination therapy in infectious culture systems, we aimed at developing HCV semi-full-length (semi...... to single-drug treatment, combination treatment with relatively low concentrations of asunaprevir and daclatasvir suppressed infection with all five recombinants. Escaped viruses primarily had substitutions at amino acids in the NS3 protease and NS5A domain I reported to be genotype 1 resistance mutations...

  7. Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b. (United States)

    Kanda, Tatsuo; Nirei, Kazushige; Matsumoto, Naoki; Higuchi, Teruhisa; Nakamura, Hitomi; Yamagami, Hiroaki; Matsuoka, Shunichi; Moriyama, Mitsuhiko


    The recent development of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection could lead to higher sustained virological response (SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions (RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1b (GT1b) is founded in 70% of HCV-infected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1b-infected patients with treatment failure.

  8. Elevated Lipoprotein(a) Levels, LPA Risk Genotypes, and Increased Risk of Heart Failure in the General Population

    DEFF Research Database (Denmark)

    Kamstrup, Pia R; Nordestgaard, Børge G


    OBJECTIVES: This study sough to test whether elevated lipoprotein(a) levels and corresponding LPA risk genotypes (low number of kringle IV type 2 repeats, rs3798220 and rs10455872, minor allele carriers) are associated with an increased risk of heart failure (HF). BACKGROUND: Elevated lipoprotein...

  9. Effect of specific ADRB1/ADRB2/AGT genotype combinations on the association between survival and carvedilol treatment in chronic heart failure

    DEFF Research Database (Denmark)

    Petersen, Morten; Andersen, Jon; Jimenez-Solem, Espen


    OBJECTIVES: The aim of the present study was to determine whether carvedilol-treated chronic heart failure patients have a different prognosis when stratified for a specific combination of a gain-of-function genotype of the adrenergic β-1 receptor gene (ADRB1) (Arg389-homozygous), two gain-of-fun...

  10. Computational models can predict response to HIV therapy without a genotype and may reduce treatment failure in different resource-limited settings. (United States)

    Revell, A D; Wang, D; Wood, R; Morrow, C; Tempelman, H; Hamers, R L; Alvarez-Uria, G; Streinu-Cercel, A; Ene, L; Wensing, A M J; DeWolf, F; Nelson, M; Montaner, J S; Lane, H C; Larder, B A


    Genotypic HIV drug-resistance testing is typically 60%-65% predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs. Random forest models were trained to predict the probability of response to ART (≤400 copies HIV RNA/mL) using the following data from 14 891 treatment change episodes (TCEs) after virological failure, from well-resourced countries: viral load and CD4 count prior to treatment change, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. Models were assessed by cross-validation during development, with an independent set of 800 cases from well-resourced countries, plus 231 cases from Southern Africa, 206 from India and 375 from Romania. The area under the receiver operating characteristic curve (AUC) was the main outcome measure. The models achieved an AUC of 0.74-0.81 during cross-validation and 0.76-0.77 with the 800 test TCEs. They achieved AUCs of 0.58-0.65 (Southern Africa), 0.63 (India) and 0.70 (Romania). Models were more accurate for data from the well-resourced countries than for cases from Southern Africa and India (P < 0.001), but not Romania. The models identified alternative, available drug regimens predicted to result in virological response for 94% of virological failures in Southern Africa, 99% of those in India and 93% of those in Romania. We developed computational models that predict virological response to ART without a genotype with comparable accuracy to genotyping with rule-based interpretation. These models have the potential to help optimize antiretroviral therapy for patients in RLSs where genotyping is not generally available.

  11. Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive

    NARCIS (Netherlands)

    Baertling, F.; Al-Murshedi, F.; Sanchez Caballero, L.M.; Al-Senaidi, K.; Joshi, N.P.; Venselaar, H.; Brand, M.A.M. van den; Nijtmans, L.G.J.; Rodenburg, R.J.T.


    COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia,

  12. Nucleotide mismatches between the VP7 gene and the primer are associated with genotyping failure of a specific lineage from G1 rotavirus strains

    Directory of Open Access Journals (Sweden)

    Espinola Emilio E


    Full Text Available Abstract In recent years it was reported that the accumulation of point mutations in VP4 and VP7 genes of rotavirus strains was the main cause of the failure of the G or P-typing. Failures in the correct genotyping of G1, G2, G8, G9 and G10 rotavirus strains were reported in the most commonly used reverse transcription (RT-PCR strategies. Collecting VP7 gene sequences of G1 rotavirus strains from databases we found that 74 (61.2 % out of 121 G1 strains from lineage I showed the four specific mismatches at the 5' end of the 9T1-1 primer, previously associated with the failure of G1-typing. Thus, a great percentage of the G1 strains from lineage I worldwide reported could not have been typed if the Das's RT-PCR strategy were used. This analysis shows that the failure on the detection of the G1 strains could be due to the diversification of rotavirus strains in phylogenetic lineages. Therefore, the use of different RT-PCR strategies with different primer binding locations on the VP7 gene or new typing methodologies -like microarrays procedures- could be a better option to avoid the failure of the G-typing of rotavirus strains detected during surveillance programs.

  13. Brucellosis seroprevalence in Bali cattle with reproductive failure in South Sulawesi and Brucella abortus biovar 1 genotypes in the Eastern Indonesian archipelago. (United States)

    Muflihanah, Hanah; Hatta, Mochammad; Rood, Ente; Scheelbeek, Pauline; Abdoel, Theresia H; Smits, Henk L


    Brucellosis is a major cause of infertility and reproductive failure in livestock. While cattle in the Eastern Indonesian archipelago suffers from reproductive problems information on bovine brucellosis in the region is fragmentary. The control of brucellosis requires a major and prolonged effort and confirmation of the infection by isolation with detailed knowledge of the spread of the infection is essential when planning a control program. Serological investigation of Brucella infection in beef cattle tended under extensive farming conditions revealed a high seroprevalence (19.3%; 95% CI, 17-22) in the compliment fixation tests. The results of a rapid and simple field test correlated well with the Rose Bengal test (kappa, 0.917) and indicated an acceptable sensitivity (87.5%) and specificity (98.1%) compared with the complement fixation test. Reproductive failure was reported for 39.0% of the cows with a loss of calves due to abortion or early death amounting to 19.3%. Past reproductive failure did not, however, correlate with seropositivity in the complement fixation test (RP = 1.21; P = 0.847). B. abortus biovar 1 was freshly isolated from the hygromas of two cows and together with thirty banked isolates collected since 1990 from different parts of Sulawesi and Timor eight related genotypes could be distinguished with one genotype being identical to that of an isolate (BfR91) from Switzerland. The Indonesian genotypes formed together with BfR91 and one African and one North American isolate a distinct branch on the B. abortus biovar 1 dendogram. Bovine brucellosis appears to be widespread in the Eastern Indonesian archipelago and calls for urgent intervention. The fresh isolation of the pathogen together with the observed high seroprevalence demonstrates the presence and frequent exposure of cattle in the area to the pathogen. The application of a rapid and simple field test for brucellosis could be very useful for the quick screening of cattle at the pen side.

  14. Context-Dependent Effects of Genome-Wide Association Study Genotypes and Macro-Environmental Factors on Time to Biochemical (PSA) Failure after Prostatectomy (United States)

    Rebbeck, Timothy R.; Weber, Anita L.; Walker, Amy H.; Stefflova, Klara; Tran, Teo V.; Spangler, Elaine; Chang, Bao-Li; Zeigler-Johnson, Charnita M.


    Background Disparities in cancer defined by race, age, or gender are well established. However, demographic metrics are surrogates for the complex contributions of genotypes, exposures, health care, socioeconomic and sociocultural environment, and many other factors. Macro-environmental factors represent novel surrogates for exposures, lifestyle and other factors that are difficult to measure but may influence cancer outcomes. Methods We applied a “multilevel molecular epidemiology” approach using a prospective cohort of 444 White prostate cancer cases who underwent prostatectomy and were followed until biochemical failure (BF) or censoring without BF. We applied Cox regression models to test for joint effects of 86 genome-wide association study-identified genotypes and macro-environmental contextual effects after geocoding all cases to their residential census tracts. All analyses were adjusted for age at diagnosis and tumor aggressiveness. Results Residents living in macroenvironments with a high proportion of older single heads of household, high rates of vacant housing, or high unemployment had shorter time until BF post-surgery after adjustment for patient age and tumor aggressiveness. After correction for multiple testing, genotypes alone did not predict time to BF, but interactions predicting time to BF were observed for MSMB (rs10993994) and percent of older single head of households (p=0.0004), and for HNF1B/TCF2 (rs4430796) and macroenvironment per capita income (p=0.0002). Conclusions Context-specific macro-environmental effects of genotype may improve the ability to identify groups that may experience poor prostate cancer outcomes. Impact Risk estimation and clinical translation of genotype information may require an understanding of both individual-level and macroenvironmental context. PMID:20826827

  15. Context-dependent effects of genome-wide association study genotypes and macroenvironment on time to biochemical (prostate specific antigen) failure after prostatectomy. (United States)

    Rebbeck, Timothy R; Weber, Anita L; Walker, Amy H; Stefflova, Klara; Tran, Teo V; Spangler, Elaine; Chang, Bao-Li; Zeigler-Johnson, Charnita M


    Disparities in cancer defined by race, age, or gender are well established. However, demographic metrics are surrogates for the complex contributions of genotypes, exposures, health care, socioeconomic and sociocultural environment, and many other factors. Macroenvironmental factors represent novel surrogates for exposures, lifestyle, and other factors that are difficult to measure but might influence cancer outcomes. We applied a "multilevel molecular epidemiology" approach using a prospective cohort of 444 White prostate cancer cases who underwent prostatectomy and were followed until biochemical failure (BF) or censoring without BF. We applied Cox regression models to test for joint effects of 86 genome-wide association study-identified genotypes and macroenvironment contextual effects after geocoding all cases to their residential census tracts. All analyses were adjusted for age at diagnosis and tumor aggressiveness. Residents living in census tracts with a high proportion of older single heads of household, high rates of vacant housing, or high unemployment had shorter time until BF postsurgery after adjustment for patient age and tumor aggressiveness. After correction for multiple testing, genotypes alone did not predict time to BF, but interactions predicting time to BF were observed for MSMB (rs10993994) and percentage of older single heads of households (P = 0.0004), and for HNF1B/TCF2 (rs4430796) and census tract per capita income (P = 0.0002). The context-specific macroenvironmental effects of genotype might improve the ability to identify groups that might experience poor prostate cancer outcomes. Risk estimation and clinical translation of genotype information might require an understanding of both individual- and macroenvironment-level context. (c) 2010 AACR.

  16. Highly efficient infectious cell culture of three hepatitis C virus genotype 2b strains and sensitivity to lead protease, nonstructural protein 5A, and polymerase inhibitors

    DEFF Research Database (Denmark)

    Ramirez, Santseharay; Li, Yi-Ping; Jensen, Sanne B


    UNLABELLED: Hepatitis C virus (HCV) is a genetically diverse virus with multiple genotypes exhibiting remarkable differences, particularly in drug susceptibility. Drug and vaccine development will benefit from high-titer HCV cultures mimicking the complete viral life cycle, but such systems only ...

  17. HIV-1 drug resistance genotyping from antiretroviral therapy (ART naïve and first-line treatment failures in Djiboutian patients

    Directory of Open Access Journals (Sweden)

    Elmi Abar Aden


    Full Text Available Abstract In this study we report the prevalence of antiretroviral drug resistant HIV-1 genotypes of virus isolated from Djiboutian patients who failed first-line antiretroviral therapy (ART and from ART naïve patients. Patients and methods A total of 35 blood samples from 16 patients who showed first-line ART failure (>1000 viral genome copies/ml and 19 ART-naïve patients were collected in Djibouti from October 2009 to December 2009. Both the protease (PR and reverse transcriptase (RT genes were amplified and sequenced using National Agency for AIDS Research (ANRS protocols. The Stanford HIV database algorithm was used for interpretation of resistance data and genotyping. Results Among the 16 patients with first-line ART failure, nine (56.2% showed reverse transcriptase inhibitor-resistant HIV-1 strains: two (12.5% were resistant to nucleoside (NRTI, one (6.25% to non-nucleoside (NNRTI reverse transcriptase inhibitors, and six (37.5% to both. Analysis of the DNA sequencing data indicated that the most common mutations conferring drug resistance were M184V (38% for NRTI and K103N (25% for NNRTI. Only NRTI primary mutations K101Q, K103N and the PI minor mutation L10V were found in ART naïve individuals. No protease inhibitor resistant strains were detected. In our study, we found no detectable resistance in ∼ 44% of all patients who experienced therapeutic failure which was explained by low compliance, co-infection with tuberculosis and malnutrition. Genotyping revealed that 65.7% of samples were infected with subtype C, 20% with CRF02_AG, 8.5% with B, 2.9% with CRF02_AG/C and 2.9% with K/C. Conclusion The results of this first study about drug resistance mutations in first-line ART failures show the importance of performing drug resistance mutation test which guides the choice of a second-line regimen. This will improve the management of HIV-infected Djiboutian patients. Virtual slides The virtual slide(s for this article can be found

  18. Analysis of functional differences between hepatitis C virus NS5A of genotypes 1-7 in infectious cell culture systems

    DEFF Research Database (Denmark)

    Scheel, Troels K H; Prentoe, Jannick; Carlsen, Thomas H R


    , but ED43(4a) and SA13(5a) also displayed impaired particle assembly. Compared to the original H77C(1a) NS5A recombinant, the changes in LCSII and domain III reduced the amounts of NS5A present. For H77C(1a) and TN(1a) NS5A recombinants, we observed a genetic linkage between NS5A and p7, since introduced...

  19. Identification of nucleotides in the 5'UTR and amino acids substitutions that are essential for the infectivity of 5'UTR-NS5A recombinant of hepatitis C virus genotype 1b (strain Con1). (United States)

    Li, Jinqian; Feng, Shengjun; Liu, Xi; Guo, Mingzhe; Chen, Mingxiao; Chen, Yiyi; Rong, Liang; Xia, Jinyu; Zhou, Yuanping; Zhong, Jin; Li, Yi-Ping


    Genotype 1b strain Con1 represents an important reference in the study of hepatitis C virus (HCV). Here, we aimed to develop an advanced infectious Con1 recombinant. We found that previously identified mutations A1226G/F1464L/A1672S/Q1773H permitted culture adaption of Con1 Core-NS5A (C-5A) recombinant containing 5'UTR and NS5B-3'UTR from JFH1 (genotype 2a), thus acquired additional mutations L725H/F886L/D2415G. C-5A containing all seven mutations (C-5A_7m) replicated efficiently in Huh7.5 and Huh7.5.1 cells and had an increased infectivity in SEC14L2-expressing Huh7.5.1 cells. Incorporation of Con1 NS5B was deleterious to C-5A_7m, however Con1 5'UTR was permissive but attenuated the virus. Nucleotides G1, A4, and G35 primarily accounted for the viral attenuation without affecting RNA translation. C-5A_7m was inhibited dose-dependently by simeprevir and daclatasvir, and substitutions at A4, A29, A34, and G35 conferred resistance to miR-122 antagonism. The novel Con1 5'UTR-NS5A recombinant, adaptive mutations, and critical nucleotides described here will facilitate future studies of HCV culture systems and virus-host interaction. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Prevalence of relevant NS5A resistance-associated substitutions to elbasvir in genotype 1a hepatitis C virus patients in Spain. (United States)

    Palladino, Claudia; Esteban-Cartelle, Beatriz; Mate-Cano, Irene; Sánchez-Carrillo, Marta; Resino, Salvador; Briz, Verónica


    Resistance-associated substitutions (RASs) to the new HCV NS5A inhibitor elbasvir may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are no data outside clinical trials evaluating their prevalence and impact in grazoprevir/elbasvir in GT1a-infected patients in Spain. A multicentre cross-sectional study of 632 initial patients was conducted. In 13 of these patients, the sample could not be amplified or a consensus sequence by Sanger sequencing could not be performed. Ultimately, 617 HCV-G1a-infected individuals treated at 84 Spanish hospitals from the 17 autonomous communities plus the 2 autonomous cities of Spain were analysed. HCV population sequencing was used to identify RAS to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-G1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%, respectively). Only 3.4% of the identified RASs to elbasvir conferred reduced susceptibility to elbasvir by geno2pheno[HCV], which exclusively identified the positions Q30H/R (n=7) and Y93C/H/N (n=8) as single mutations and Q30H+Y93H (n=4) and Q30R+Y93H (n=2) as double mutations as the major RASs to elbasvir. A lower prevalence of RASs to elbasvir was observed in our HCV-G1a Spanish cohort than reported previously in clinical trials evaluating patients from the USA. This information may be essential to guide the implementation of grazoprevir/elbasvir in Spain and to manage G1a-infected patients. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  1. Adaptive mutations enhance assembly and cell-to-cell transmission of a high-titer hepatitis C virus genotype 5a Core-NS2 JFH1-based recombinant

    DEFF Research Database (Denmark)

    Mathiesen, Christian K; Prentoe, Jannick; Meredith, Luke W


    UNLABELLED: Recombinant hepatitis C virus (HCV) clones propagated in human hepatoma cell cultures yield relatively low infectivity titers. Here, we adapted the JFH1-based Core-NS2 recombinant SA13/JFH1C3405G,A3696G (termed SA13/JFH1orig), of the poorly characterized genotype 5a, to Huh7.5 cells......-titer production of diverse HCV strains would be advantageous. Our study offers important functional data on how cell culture-adaptive mutations identified in genotype 5a JFH1-based HCVcc permit high-titer culture by affecting HCV genesis through increasing virus assembly and HCV fitness by enhancing the virus...... specific infectivity and cell-to-cell transmission ability, without influencing the biophysical particle properties. High-titer HCVcc like the one described in this study may be pivotal in future vaccine-related studies where large quantities of infectious HCV particles are necessary....

  2. Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwide Isolates of Viral Genotypes 1 to 6. (United States)

    Patiño-Galindo, Juan Ángel; Salvatierra, Karina; González-Candelas, Fernando; López-Labrador, F Xavier


    There is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. In addition, we found a low genetic barrier for the generation of new RAVs, irrespective of the viral genotype. Furthermore, in 1,126 HCV genomes, including sequences spanning the three genes, haplotype analysis revealed a remarkably high frequency of viruses carrying more than one natural RAV to DAAs (53% of HCV-1a, 28.5% of HCV-1b, 67.1% of HCV-6, and 100% of genotype 2, 3, 4, and 5 haplotypes). With the exception of HCV-1a, the most prevalent haplotypes showed RAVs in at least two different viral genes. Finally, evolutionary analyses revealed that, while most natural RAVs appeared recently, others have been efficiently transmitted over time and cluster in well-supported clades. In summary, and despite the observed high efficacy of DAA-based regimens, we show that naturally occurring RAVs are common in all HCV genotypes and that there is an overall low genetic barrier for the selection of resistance mutations. There is a need for natural DAA resistance profiling specific for each HCV genotype. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Homozygosity for HLA group 2 alleles predicts treatment failure with interferon-α and ribavirin in chronic hepatitis C virus genotype 1 infection. (United States)

    Collison, Meadhbh; Chin, Jun Liong; Abu Shanab, Ahmed; Mac Nicholas, Ross; Segurado, Ricardo; Coughlan, Suzie; Connell, Jeff; Carr, Michael J; Merriman, Raphael B; McCormick, P Aiden; Hall, William W


    Host genetic factors influence treatment responses to antiviral therapy in chronic hepatitis C virus (HCV) infection. We retrospectively investigated associations between host genetic markers and treatment-induced virologic responses to dual therapy with interferon-α and ribavirin in chronically infected HCV genotype 1 (g1)- and genotype 3 (g3)-infected individuals. A total of 171 patients (89 HCV g1 and 82 HCV g3 infected) were investigated for genetic markers influencing treatment-induced sustained virologic response (SVR). Overall, SVR was observed for 46/89 (52%) HCV g1- and 57/82 (70%) HCV g3-infected patients. Of the 4 interleukin 28B (IL28B) single-nucleotide polymorphisms (SNPs), rs12979860 was the host genetic marker most significantly associated with failure to achieve an SVR in HCV g1-infected individuals [P=3.83×10(-4); odds ratio (OR)=5.61; confidence interval (CI)=2.07-15.18] and gave a positive predictive value for treatment failure of 81.3% for minor homozygotes (TT). Using additive (P=3.54×10(-4)) and dominant models (P=3.83×10(-4)), a dosage effect of the T allele was observed, with the dominance term not significant for this SNP. Logistic regression showed an association between HLA-C1/C1 and rapid virologic response in HCV g1 infections with an OR relative to the heterozygote of 10.0 (95% CI: 1.6-62.5, P=0.014). HLA-C2 homozygosity was a significant predictor of nonresponse to treatment in HCV g1-infected individuals (P=0.023).

  4. Real-life prevalence of resistance-associated variants against non-structural protein 5A inhibitors and efficiency of Daclatasvir + Asunaprevir therapy in Korean patients with genotype 1b hepatitis C. (United States)

    Yu, Jung Hwan; Lee, Jung Il; Lee, Kwan Sik; Kim, Ja Kyung


    Direct-acting antivirals (DAAs) for chronic hepatitis C (CHC) treatment are tolerable and highly effective in a shorter period of time than before. However, resistance-associated variants (RAVs) can affect the efficacy of DAAs. The aim of this study was to investigate the real-life prevalence of RAVs against non-structural protein 5A (NS5A) inhibitors in Korean patients with genotype 1b chronic hepatitis C. All consecutive patients with CHC genotype 1b who underwent a RAV test at a single referral hospital were enrolled. A total of 142 patients (male 53, female 89) were tested for RAVs. The average age of the patients was 58 years. Liver cirrhosis was found in 34.5% (49/142) of patients, and 19.0% (29/142) of patients had previously undergone interferon-based treatment. Twenty-nine patients (20.4%) had RAVs (Y93 or L31). Y93H, L31, or Y93H with L31 were detected in 22 (15.5%), 8 (5.6%), and 1 (0.7%) patients, respectively. The presence of RAV was not affected by previous interferon-based treatment or by the existence of liver cirrhosis. Among 113 patients without baseline NS5A RAVs, 72 patients started daclatasvir (DCV) + asunaprevir (ASV) treatment and 95% (68/72) patients achieved virologic response at week 4. Virologic response at end of treatment and sustained virologic response at 12 weeks after treatment were achieved by 94% (68/72) and 94% (68/72), respectively. In Korean patients with genotype 1b CHC, 20.4% (29 of 142) of patients showed RAVs against NS5A inhibitors. Patient without RAVs who received treatment with DCV + ASV showed high virologic response rates in Korea.

  5. Genetic markers associated with dihydroartemisinin–piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study (United States)

    Amato, Roberto; Lim, Pharath; Miotto, Olivo; Amaratunga, Chanaki; Dek, Dalin; Pearson, Richard D.; Almagro-Garcia, Jacob; Neal, Aaron T.; Sreng, Sokunthea; Suon, Seila; Drury, Eleanor; Jyothi, Dushyanth; Stalker, Jim; Kwiatkowski, Dominic P.; Fairhurst, Rick M.


    Summary Background As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong Subregion (GMS), emerging resistance to partner drugs in artemisinin combination therapies (ACTs) seriously threatens global efforts to treat and eliminate this disease. Molecular markers for ACT failure are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in Southeast Asia and beyond. Methods We performed a genome-wide association study (GWAS) of 297 P. falciparum isolates from Cambodia to investigate the relationship of 11,630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50s), and tested whether these genetic variants are markers of dihydroartemisinin-piperaquine failures. We then performed a survival analysis of 133 patients to determine whether candidate molecular markers predicted parasite recrudescence following dihydroartemisinin-piperaquine treatment. Findings Piperaquine IC50s increased significantly from 2011 to 2013 in 3 Cambodian provinces. Genome-wide analysis of SNPs identified a chromosome 13 region that associates with elevated piperaquine IC50s. A nonsynonymous SNP (encoding a Glu415Gly substitution) in this region, within a gene encoding an exonuclease, associates with parasite recrudescence following dihydroartemisinin-piperaquine treatment. Genome-wide analysis of CNVs revealed that a single copy of the mdr1 gene on chromosome 5 and a novel amplification of the plasmepsin II and plasmepsin III genes on chromosome 14 also associate with elevated piperaquine IC50s. After adjusting for covariates, both exo-E415G and plasmepsin II-III markers significantly associate with decreased treatment efficacy (0.38 and 0.41 survival rates, respectively). Interpretation The exo-E415G SNP and plasmepsin II-III amplification are markers of piperaquine resistance and dihydroartemisinin

  6. Stratification by Smoking Status Reveals an Association of CHRNA5-A3-B4 Genotype with Body Mass Index in Never Smokers

    NARCIS (Netherlands)

    Taylor, A.E.; Morris, R.W.; Fluharty, M.E.; Bjorngaard, J.H.; Asvold, B.O.; Gabrielsen, M.E.; Campbell, A.; Marioni, R.; Kumari, M.; Hällfors, J.; Männistö, S.; Marques-Vidal, P.; Kaakinen, M.; Cavadino, A.; Postmus, I.; Husemoen, L.L.N.; Skaaby, T.; Ahluwalia, T.S.; Treur, J.L.; Willemsen, G.; Dale, C.; Wannamethee, S.G.; Lahti, J.; Palotie, A.; Räikkönen, K.; Kisialiou, A.; McConnachie, A.; Padmanabhan, S.; Wong, A.; Dalgard, C.; Paternoster, L.; Ben-Shlomo, Y.; Tyrrell, J.; Horwood, L.J.; Fergusson, D.; Kennedy, M.A.; Frayling, T.M.; Nohr, E.A.; Christiansen, L.; Ohm Kyvik, K.; Kuh, D; Watt, G.; Eriksson, J.; Whincup, P.H.; Vink, J.M.; Boomsma, D.I.; Davey Smith, G.; Lawlor, D.; Linneberg, A.; Ford, I.; Jukema, J.W.; Power, C.; Hyppönen, E.; Järvelin, M.R.; Preisig, M.; Borodulin, K.; Kaprio, J.; Kivimaki, M.; Smith, B.H.; Hayward, C.; Romundstad, P.R.; Sørensen, T.I.A.; Munafo, M.R.; Sattar, N.


    We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a

  7. Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers

    NARCIS (Netherlands)

    Taylor, A.E.; Morris, R.W.; Fluharty, M.E.; Björngaard, J.H.; Asvold, B.A.; Gabrielsen, M.E.; Campbell, A.; Marioni, R.E.; Kumari, M.; Hallfors, J.; Mannisto, S.; Marques-Vidal, P.; Kaakinen, M.; Cavadino, A.; Postmus, I.; Husemoen, L.L.N.; Skaaby, T.; Ahluwalia, T.V.S.; Treur, J.L.; Willemsen, G.; Dale, C.E.; Wannamethee, S.G.; Lahti, J.; Palotie, A.; Raikkonen, K.; Kisialiou, A.; McConnachie, A.; Padmanabhan, S.; Wong, A.; Dalgard, C.; Paternoster, L.; Ben-Shlomo, Y.; Tyrrell, J.; Horwood, J.; Fergusson, D.M.; Kennedy, M.A.; Frayling, T.; Nohr, E.A.; Christiansen, L.; Kyvik, K.O.; Kuh, D.; Watt, G.; Eriksson, J.; Whincup, P.H.; Vink, J.M.; Boomsma, D.I.; Smith, G.D.; Lawlor, D.A.; Linneberg, A.; Ford, I.; Jukema, J.W.; Power, C.; Hypponen, E.; Jarvelin, M.R.; Preisig, M.; Borodulin, K.; Kaprio, J.; Kivimaki, M.; Smith, B.H.; Hayward, C.; Romundstad, P.R.; Sorensen, T.I.A.; Munafò, M.R.; Sattar, N.


    We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a

  8. Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers

    DEFF Research Database (Denmark)

    Taylor, Amy E; Morris, Richard W; Fluharty, Meg E


    in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10...... in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes......We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings...

  9. Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

    Directory of Open Access Journals (Sweden)

    Amy E Taylor


    Full Text Available We previously used a single nucleotide polymorphism (SNP in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10, but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5. An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13. This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

  10. Computational models can predict response to HIV therapy without a genotype and may reduce treatment failure in different resource-limited settings

    NARCIS (Netherlands)

    Revell, A. D.; Wang, D.; Wood, R.; Morrow, C.; Tempelman, H.; Hamers, R. L.; Alvarez-Uria, G.; Streinu-Cercel, A.; Ene, L.; Wensing, A. M. J.; DeWolf, F.; Nelson, M.; Montaner, J. S.; Lane, H. C.; Larder, B. A.


    Genotypic HIV drug-resistance testing is typically 6065 predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART

  11. Frequency of Natural Resistance within NS5a Replication Complex Domain in Hepatitis C Genotypes 1a, 1b: Possible Implication of Subtype-Specific Resistance Selection in Multiple Direct Acting Antivirals Drugs Combination Treatment

    Directory of Open Access Journals (Sweden)

    Sabrina Bagaglio


    Full Text Available Different HCV subtypes may naturally harbor different resistance selection to anti-NS5a inhibitors. 2761 sequences retrieved from the Los Alamos HCV database were analyzed in the NS5a domain 1, the target of NS5a inhibitors. The NS5a resistance-associated polymorphisms (RAPs were more frequently detected in HCV G1b compared to G1a. The prevalence of polymorphisms associated with cross-resistance to compounds in clinical use (daclatasvir, DCV, ledipasvir, LDV, ombitasvir, and OMV or scheduled to come into clinical use in the near future (IDX719, elbasvir, and ELV was higher in G1b compared to G1a (37/1552 (2.4% in 1b sequences and 15/1209 (1.2% in 1a isolates, p = 0.040. Interestingly, on the basis of the genotype-specific resistance pattern, 95 (6.1% G1b sequences had L31M RAP to DCV/IDX719, while 6 sequences of G1a (0.5% harbored L31M RAP, conferring resistance to DCV/LDV/IDX719/ELV (p < 0.0001. Finally, 28 (2.3% G1a and none of G1b isolates harbored M28V RAP to OMV (p < 0.0001. In conclusion, the pattern of subtype-specific resistance selection in the naturally occurring strains may guide the treatment option in association with direct acting antivirals (DAAs targeting different regions, particularly in patients that are difficult to cure, such as those with advanced liver disease or individuals who have failed previous DAAs.

  12. Brucellosis seroprevalence in Bali cattle with reproductive failure in South Sulawesi and Brucella abortus biovar 1 genotypes in the Eastern Indonesian archipelago

    NARCIS (Netherlands)

    Muflihanah, Hanah; Hatta, Mochammad; Rood, Ente; Scheelbeek, Pauline; Abdoel, Theresia H.; Smits, Henk L.


    Brucellosis is a major cause of infertility and reproductive failure in livestock. While cattle in the Eastern Indonesian archipelago suffers from reproductive problems information on bovine brucellosis in the region is fragmentary. The control of brucellosis requires a major and prolonged effort

  13. Infectious genotype 1a, 1b, 2a, 2b, 3a, 5a, 6a and 7a hepatitis C virus lacking the hypervariable region 1 (HVR1)

    DEFF Research Database (Denmark)


    .sub.1389c,A1590G (6a/2a) constructs for the deletion of Hypervariable Region 1 (HVR1) to construct viable, JFH 1 (genotype 2a) based, genomes. The present inventors serially passaged the viruses in cell culture obtaining relatively high HCV RNA titers and infectivity titers. Sequence analysis...... of the viruses identified mutations adapting H77/JFH 1.sub.T27OOC,A4O8OT,.DELTA.HVR1 (1a/2a), J8/JFH .sub.1.DELTA.HVR1 (2b/2a), S52/JFH 1.sub.T2718G,T716OC,.DELTA.HVR1 (3a/2a) and J4/JFH 1.sub.T2996C,A4827T,.DELTA.HVR1 (1b/2a) to the HVR1 deletion....

  14. Development and application of hepatitis C reporter viruses with genotype 1 to 7 core-nonstructural protein 2 (NS2) expressing fluorescent proteins or luciferase in modified JFH1 NS5A

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Jensen, Tanja B; Mathiesen, Christian K


    to 2a(J6) tagged with EGFP, DsRed-Express2, mCherry, or Renilla luciferase (RLuc), yielding peak supernatant infectivity titers of 4 to 5 log(10) focus-forming units (FFU)/ml. 2a(J6) with ¿40 or ¿25 was fully viable in Huh7.5 cells. In human liver chimeric mice, 2a(J6)-EGFP¿40 acquired various...... deletions in EGFP, while 2a(J6)¿40 did not show an impaired viability. We further developed panels of JFH1-based genotype 1 to 7 core-NS2 recombinants expressing EGFP- or RLuc-NS5A¿40 fusion proteins. In cell culture, the different EGFP recombinants showed growth characteristics comparable to those...

  15. Desmanthus GENOTYPES

    Directory of Open Access Journals (Sweden)



    Full Text Available Desmanthus is a genus of forage legumes with potential to improve pastures and livestock produc-tion on clay soils of dry tropical and subtropical regions such as the existing in Brazil and Australia. Despite this patterns of natural or enforced after-ripening of Desmanthus seeds have not been well established. Four year old seed banks of nine Desmanthus genotypes at James Cook University were accessed for their patterns of seed softe-ning in response to a range of temperatures. Persistent seed banks were found to exist under all of the studied ge-notypes. The largest seeds banks were found in the genotypes CPI 78373 and CPI 78382 and the smallest in the genotypes CPI’s 37143, 67643, and 83563. An increase in the percentage of softened seeds was correlated with higher temperatures, in two patterns of response: in some accessions seeds were not significantly affected by tempe-ratures below 80º C; and in others, seeds become soft when temperature rose to as little as 60 ºC. At 80 °C the heat started to depress germination. High seed production of Desmanthus associated with dependence of seeds on eleva-ted temperatures to softening can be a very important strategy for plants to survive in dry tropical regions.

  16. The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy. (United States)

    Backx, M; Lewszuk, A; White, J R; Cole, J; Sreedharan, A; van Sanden, S; Diels, J; Lawson, A; Neal, K R; Wiselka, M J; Ito, T; Irving, W L


    Chronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost-effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium-term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS 'Payment by Results' database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non-SVR) with mean follow-up of 3.5 (SVR) and 4.9 (non-SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non-SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5-year post-treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13-fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56-fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real-life data for future cost-effectiveness analyses related to the treatment for chronic HCV infection. © 2013 John Wiley & Sons Ltd.

  17. Hepatitis C Virus: Viral Quasispecies and Genotypes

    Directory of Open Access Journals (Sweden)

    Kyoko Tsukiyama-Kohara


    Full Text Available Hepatitis C virus (HCV mainly replicates in the cytoplasm, where it easily establishes persistent infection, resulting in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Due to its high rate of mutation, HCV forms viral quasispecies, categorized based on the highly variable regions in the envelope protein and nonstructural 5A protein. HCV possesses seven major genotypes, among which genotype 1 is the most prevalent globally. The distribution of HCV genotypes varies based on geography, and each genotype has a different sensitivity to interferon treatment. Recently-developed direct-acting antivirals (DAAs, which target viral proteases or polymerases, mediate drastically better antiviral effects than previous therapeutics. Although treatment with DAAs has led to the development of drug-resistant HCV mutants, the most recently approved DAAs show improved pan-genomic activity, with a higher barrier to viral resistance.

  18. Hepatitis C Virus: Viral Quasispecies and Genotypes. (United States)

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori


    Hepatitis C virus (HCV) mainly replicates in the cytoplasm, where it easily establishes persistent infection, resulting in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Due to its high rate of mutation, HCV forms viral quasispecies, categorized based on the highly variable regions in the envelope protein and nonstructural 5A protein. HCV possesses seven major genotypes, among which genotype 1 is the most prevalent globally. The distribution of HCV genotypes varies based on geography, and each genotype has a different sensitivity to interferon treatment. Recently-developed direct-acting antivirals (DAAs), which target viral proteases or polymerases, mediate drastically better antiviral effects than previous therapeutics. Although treatment with DAAs has led to the development of drug-resistant HCV mutants, the most recently approved DAAs show improved pan-genomic activity, with a higher barrier to viral resistance.

  19. Respiratory Failure (United States)

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can' ...

  20. Heart Failure (United States)

    Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. Heart failure does not mean that your heart has stopped ... and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and ...

  1. APOE Genotyping, Cardiovascular Disease (United States)

    ... Resources For Health Professionals Subscribe Search APOE Genotyping, Cardiovascular Disease Send Us Your Feedback Choose Topic At a ... help understand the role of genetic factors in cardiovascular disease . However, the testing is sometimes used in clinical ...

  2. Radiosensitivity of fingermillet genotypes

    Energy Technology Data Exchange (ETDEWEB)

    Raveendran, T S; Nagarajan, C; Appadurai, R; Prasad, M N; Sundaresan, N [Tamil Nadu Agricultural Univ., Coimbatore (India)


    Varietal differences in radiosensitivity were observed in a study involving 4 genotypes of fingermillet (Eleusine coracana (Linn.) Gaertn.) subjected to gamma-irradiation. Harder seeds were found to tolerate a higher dose of the mutagen.

  3. Hepatitis C virus expressing reporter tagged NS5A protein

    DEFF Research Database (Denmark)


    Hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A were developed. A deletion upstream of the inserted reporter gene sequence conferred favorable...... growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. JFH1-based intergenotypic recombinants with genotype specific homotypic 5'UTR, or heterotypic 5'UTR (either of genotype 1a (strain H...

  4. Contraceptive failure

    DEFF Research Database (Denmark)

    Rasch, Vibeke


    Most studies focusing on contraceptive failure in relation to pregnancy have focused on contraceptive failure among women having induced abortions, thereby neglecting those women who, despite contraceptive failure, accept the pregnancy and intend to carry the fetus to term. To get a more complete...... picture of the problem of contraceptive failure, this study focuses on contraceptive failure among women with diverse pregnancy outcomes. In all, 3520 pregnant women attending Odense University Hospital were included: 373 had induced abortions, 435 had spontaneous abortions, 97 had ectopic pregnancies......, and 2614 received antenatal care. The variables studied comprise age, partner relationship, number of births, occupational and economical situation, and contraceptive use.Contraceptive failure, defined as contraceptive use (condom, diaphragm, IUD, oral contraception, or another modern method...

  5. Heart Failure


    McMurray, John; Ponikowski, Piotr


    Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure.

  6. Heart Failure (United States)

    ... Other diseases. Chronic diseases — such as diabetes, HIV, hyperthyroidism, hypothyroidism, or a buildup of iron (hemochromatosis) or ... transplantation or support with a ventricular assist device. Prevention The key to preventing heart failure is to ...

  7. Failure Modes

    DEFF Research Database (Denmark)

    Jakobsen, K. P.; Burcharth, H. F.; Ibsen, Lars Bo


    The present appendix contains the derivation of ten different limit state equations divided on three different failure modes. Five of the limit state equations can be used independently of the characteristics of the subsoil, whereas the remaining five can be used for either drained or undrained s...

  8. Baseline NS5A resistance associated substitutions may impair DAA response in real-world hepatitis C patients. (United States)

    Carrasco, Itzíar; Arias, Ana; Benítez-Gutiérrez, Laura; Lledó, Gemma; Requena, Silvia; Cuesta, Miriam; Cuervas-Mons, Valentín; de Mendoza, Carmen


    Oral DAA have demonstrated high efficacy as treatment of hepatitis C. However, the presence of resistance-associated substitutions (RAS) at baseline has occasionally been associated with impaired treatment response. Herein, we examined the impact of baseline RAS at the HCV NS5A gene region on treatment response in a real-life setting. All hepatitis C patients treated with DAA including NS5A inhibitors at our institution were retrospectively examined. The virus NS5A gene was analyzed using population sequencing at baseline and after 24 weeks of completing therapy in all patients that failed. All changes recorded at positions 28, 29, 30, 31, 32, 58, 62, 92, and 93 were considered. A total of 166 patients were analyzed. HCV genotypes were as follows: G1a (31.9%), G1b (48.2%), G3 (10.2%), and G4 (9.6%). Overall, 69 (41.6%) patients were coinfected with HIV and 46.7% had advanced liver fibrosis (Metavir F3-F4). Sixty (36.1%) patients had at least one RAS at baseline, including M28A/G/T (5), Q30X (12), L31I/F/M/V (6), T58P/S (25), Q/E62D (1), A92 K (7), and Y93C/H (15). Overall, 4.8% had two or more RAS, being more frequent in G4 (12.5%) followed by G1b (6.3%) and G1a (1.9%). Of 10 (6%) patients that failed DAA therapy, five had baseline NS5A RAS. No association was found for specific baseline RAS, although changes at position 30 were more frequent in failures than cures (22.2% vs 6.4%, P = 0.074). Moreover, the presence of two or more RAS at baseline was more frequent in failures (HR: 7.2; P = 0.029). Upon failure, six patients showed emerging RAS, including Q30C/H/R (3), L31M (1), and Y93C/H (2). Baseline NS5A RAS are frequently seen in DAA-naïve HCV patients. Two or more baseline NS5A RAS were found in nearly 5% and were significantly associated to DAA failure. Therefore, baseline NS5A testing should be considered when HCV treatment is planned with NS5A inhibitors. © 2017 Wiley Periodicals, Inc.

  9. Types of Heart Failure (United States)

    ... Introduction Types of Heart Failure Classes of Heart Failure Heart Failure in Children Advanced Heart Failure • Causes and ... and procedures related to heart disease and stroke. Heart Failure Questions to Ask Your Doctor Use these questions ...

  10. Classes of Heart Failure (United States)

    ... Introduction Types of Heart Failure Classes of Heart Failure Heart Failure in Children Advanced Heart Failure • Causes and ... and Advanced HF • Tools and Resources • Personal Stories Heart Failure Questions to Ask Your Doctor Use these questions ...

  11. Analysis of Hepatitis C Virus Genotype 1b Resistance Variants in Japanese Patients Treated with Paritaprevir-Ritonavir and Ombitasvir. (United States)

    Krishnan, Preethi; Schnell, Gretja; Tripathi, Rakesh; Beyer, Jill; Reisch, Thomas; Zhang, Xinyan; Setze, Carolyn; Rodrigues, Lino; Burroughs, Margaret; Redman, Rebecca; Chayama, Kazuaki; Kumada, Hiromitsu; Collins, Christine; Pilot-Matias, Tami


    Treatment of HCV genotype 1b (GT1b)-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) in studies M12-536 and GIFT-I demonstrated high sustained virologic response (SVR) rates. The virologic failure rate was 3% (13/436) across the two studies. Analyses were conducted to evaluate the impact of baseline resistance-associated variants (RAVs) on treatment outcome and the emergence and persistence of RAVs in patients experiencing virologic failure. Baseline paritaprevir resistance-conferring variants in NS3 were infrequent, while Y93H in NS5A was the most prevalent ombitasvir resistance-conferring variant at baseline. A comparison of baseline prevalence of polymorphisms in Japanese and western patients showed that Q80L and S122G in NS3 and L28M, R30Q, and Y93H in NS5A were significantly more prevalent in Japanese patients. In the GIFT-I study, the prevalence of Y93H in NS5A varied between 13% and 21% depending on the deep-sequencing detection threshold. Among patients with Y93H comprising 40% of their preexisting viral population, the 24-week SVR (SVR24) rates were >99% (276/277), 93% (38/41), and 76% (25/33), respectively, indicating that the prevalence of Y93H within a patient's viral population is a good predictor of treatment response. The predominant RAVs at the time of virologic failure were D168A/V in NS3 and Y93H alone or in combination with other variants in NS5A. While levels of NS3 RAVs declined over time, NS5A RAVs persisted through posttreatment week 48. Results from these analyses are informative in understanding the resistance profile of an ombitasvir- plus paritaprevir/ritonavir-based regimen in Japanese GT1b-infected patients. Copyright © 2016 Krishnan et al.

  12. Failure Analysis

    International Nuclear Information System (INIS)

    Iorio, A.F.; Crespi, J.C.


    After ten years of operation at the Atucha I Nuclear Power Station a gear belonging to a pressurized heavy water reactor refuelling machine, failed. The gear box was used to operate the inlet-outlet heavy-water valve of the machine. Visual examination of the gear device showed an absence of lubricant and that several gear teeth were broken at the root. Motion was transmitted with a speed-reducing device with controlled adjustable times in order to produce a proper fitness of the valve closure. The aim of this paper is to discuss the results of the gear failure analysis in order to recommend the proper solution to prevent further failures. (Author)

  13. Genotyping panel for assessing response to cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Hampel Heather


    Full Text Available Abstract Background Variants in numerous genes are thought to affect the success or failure of cancer chemotherapy. Interindividual variability can result from genes involved in drug metabolism and transport, drug targets (receptors, enzymes, etc, and proteins relevant to cell survival (e.g., cell cycle, DNA repair, and apoptosis. The purpose of the current study is to establish a flexible, cost-effective, high-throughput genotyping platform for candidate genes involved in chemoresistance and -sensitivity, and treatment outcomes. Methods We have adopted SNPlex for genotyping 432 single nucleotide polymorphisms (SNPs in 160 candidate genes implicated in response to anticancer chemotherapy. Results The genotyping panels were applied to 39 patients with chronic lymphocytic leukemia undergoing flavopiridol chemotherapy, and 90 patients with colorectal cancer. 408 SNPs (94% produced successful genotyping results. Additional genotyping methods were established for polymorphisms undetectable by SNPlex, including multiplexed SNaPshot for CYP2D6 SNPs, and PCR amplification with fluorescently labeled primers for the UGT1A1 promoter (TAnTAA repeat polymorphism. Conclusion This genotyping panel is useful for supporting clinical anticancer drug trials to identify polymorphisms that contribute to interindividual variability in drug response. Availability of population genetic data across multiple studies has the potential to yield genetic biomarkers for optimizing anticancer therapy.

  14. Common genotypes of hepatitis B virus

    International Nuclear Information System (INIS)

    Idrees, M.; Khan, S.; Riazuddin, S.


    Objective: To find out the frequency of common genotypes of hepatitis-B virus (HBV). Subjects and Methods: HBV genotypes were determined in 112 HBV DNA positive sera by a simple and precise molecular genotyping system base on PCR using type-specific primers for the determination of genotypes of HBV A through H. Results: Four genotypes (A,B,C and D) out of total eight reported genotypes so far were identified. Genotypes A, B and C were predominant. HBV genotype C was the most predominant in this collection, appearing in 46 samples (41.7%). However, the genotypes of a total of 5 (4.46%) samples could not be determined with the present genotyping system. Mixed genotypes were seen in 8(7.14% HBV) isolates. Five of these were infected with genotypes A/D whereas two were with genotypes C/D. One patient was infected with 4 genotypes (A/B/C/D). Genotype A (68%) was predominant in Sindh genotype C was most predominant in North West Frontier Province (NWFP) (68.96) whereas genotype C and B were dominant in Punjab (39.65% and 25.86% respectively). Conclusion: All the four common genotypes of HBV found worldwide (A,B,C and D) were isolated. Genotype C is the predominant Genotypes B and C are predominant in Punjab and N.W.F.P. whereas genotype A is predominant in Sindh. (author)

  15. Heart failure - tests (United States)

    CHF - tests; Congestive heart failure - tests; Cardiomyopathy - tests; HF - tests ... the best test to: Identify which type of heart failure (systolic, diastolic, valvular) Monitor your heart failure and ...

  16. In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir. (United States)

    Ng, Teresa I; Krishnan, Preethi; Pilot-Matias, Tami; Kati, Warren; Schnell, Gretja; Beyer, Jill; Reisch, Thomas; Lu, Liangjun; Dekhtyar, Tatyana; Irvin, Michelle; Tripathi, Rakesh; Maring, Clarence; Randolph, John T; Wagner, Rolf; Collins, Christine


    Pibrentasvir (ABT-530) is a novel and pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with 50% effective concentration (EC 50 ) values ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6. Pibrentasvir demonstrated similar activity against a panel of chimeric replicons containing HCV NS5A of genotypes 1 to 6 from clinical samples. Resistance selection studies were conducted using HCV replicon cells with NS5A from genotype 1a, 1b, 2a, 2b, 3a, 4a, 5a, or 6a at a concentration of pibrentasvir that was 10- or 100-fold over its EC 50 for the respective replicon. With pibrentasvir at 10-fold over the respective EC 50 , only a small number of colonies (0.00015 to 0.0065% of input cells) with resistance-associated amino acid substitutions were selected in replicons containing genotype 1a, 2a, or 3a NS5A, and no viable colonies were selected in replicons containing NS5A from other genotypes. With pibrentasvir at 100-fold over the respective EC 50 , very few colonies (0.0002% of input cells) were selected by pibrentasvir in genotype 1a replicon cells while no colonies were selected in other replicons. Pibrentasvir is active against common resistance-conferring substitutions in HCV genotypes 1 to 6 that were identified for other NS5A inhibitors, including those at key amino acid positions 28, 30, 31, or 93. The combination of pibrentasvir with HCV inhibitors of other classes produced synergistic inhibition of HCV replication. In summary, pibrentasvir is a next-generation HCV NS5A inhibitor with potent and pan-genotypic activity, and it maintains activity against common amino acid substitutions of HCV genotypes 1 to 6 that are known to confer resistance to currently approved NS5A inhibitors. Copyright © 2017 Ng et al.

  17. HBV genotypic variability in Cuba.

    Directory of Open Access Journals (Sweden)

    Carmen L Loureiro

    Full Text Available The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed. The most frequent genotype was A (167/250, 67%, mainly A2 (149, 60% but also A1 and one A4. A total of 77 isolates were classified as genotype D (31%, with co-circulation of several subgenotypes (56 D4, 2 D1, 5 D2, 7 D3/6 and 7 D7. Three isolates belonged to genotype E, two to H and one to B3. Complete genome sequence analysis of selected isolates confirmed the phylogenetic analysis performed with the S region. Mutations or polymorphisms in precore region were more common among genotype D compared to genotype A isolates. The HBV genotypic distribution in this Caribbean island correlates with the Y lineage genetic background of the population, where a European and African origin prevails. HBV genotypes E, B3 and H isolates might represent more recent introductions.

  18. HBV Genotypic Variability in Cuba (United States)

    Loureiro, Carmen L.; Aguilar, Julio C.; Aguiar, Jorge; Muzio, Verena; Pentón, Eduardo; Garcia, Daymir; Guillen, Gerardo; Pujol, Flor H.


    The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed. The most frequent genotype was A (167/250, 67%), mainly A2 (149, 60%) but also A1 and one A4. A total of 77 isolates were classified as genotype D (31%), with co-circulation of several subgenotypes (56 D4, 2 D1, 5 D2, 7 D3/6 and 7 D7). Three isolates belonged to genotype E, two to H and one to B3. Complete genome sequence analysis of selected isolates confirmed the phylogenetic analysis performed with the S region. Mutations or polymorphisms in precore region were more common among genotype D compared to genotype A isolates. The HBV genotypic distribution in this Caribbean island correlates with the Y lineage genetic background of the population, where a European and African origin prevails. HBV genotypes E, B3 and H isolates might represent more recent introductions. PMID:25742179

  19. Gel versus capillary electrophoresis genotyping for categorizing treatment outcomes in two anti-malarial trials in Uganda


    Hubbard Alan E; Dorsey Grant; Gupta Vinay; Rosenthal Philip J; Greenhouse Bryan


    Abstract Background Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure) or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Methods Samples were genotyped using both gel and capillary elec...

  20. Heart failure - home monitoring (United States)

    ... this page: // Heart failure - home monitoring To use the sharing features on ... your high blood pressure Fast food tips Heart failure - discharge Heart failure - fluids and diuretics Heart failure - what to ...

  1. A comparison of computational models with and without genotyping for prediction of response to second-line HIV therapy

    NARCIS (Netherlands)

    Revell, A. D.; Boyd, M. A.; Wang, D.; Emery, S.; Gazzard, B.; Reiss, P.; van Sighem, A. I.; Montaner, J. S.; Lane, H. C.; Larder, B. A.


    We compared the use of computational models developed with and without HIV genotype vs. genotyping itself to predict effective regimens for patients experiencing first-line virological failure. Two sets of models predicted virological response for 99 three-drug regimens for patients on a failing

  2. Echinococcus granulosus genotypes in Iran (United States)

    Sharafi, Seyedeh Maryam; Rostami-Nejad, Mohammad; Moazeni, Mohammad; Yousefi, Morteza; Saneie, Behnam; Hosseini-Safa, Ahmad


    Hydatidosis, caused by Echinococcus granulosus is one of the most important zoonotic diseases, throughout most parts of the world. Hydatidosis is endemic in Iran and responsible for approximately 1% of admission to surgical wards. There are extensive genetic variations within E. granulosus and 10 different genotypes (G1–G10) within this parasite have been reported. Identification of strains is important for improvement of control and prevention of the disease. No new review article presented the situation of Echinococcus granulosus genotypes in Iran in the recent years; therefore in this paper we reviewed the different studies regarding Echinococcus granulosus genotypes in Iran. PMID:24834298

  3. Hepatitis C genotype distribution in patient and blood donor samples in South Africa for the period 2008-2012. (United States)

    Prabdial-Sing, N; Chirwa, T; Thaver, J; Smuts, H; Vermeulen, M; Suchard, M; Puren, A J


    There are limited molecular epidemiological studies of hepatitis C at a national level in South Africa. The introduction of newer treatment modalities for hepatitis C requires knowledge of the genotypes as these may have different prognostic and therapeutic implications. This retrospective study describes genotype distributions of patients attending specialist clinics and a blood donor group studied during the period 2008-2012 in South Africa. Residual samples from diagnostic viral load testing from specialist clinics in South Africa (n=941) and from the South African National Blood Service (n=294) were analysed quantitatively by real-time PCR and genotyped using the Versant line probe assay or sequencing. Genotype 1 was predominant in blood donors (34%), whilst genotype 5a was prevalent in patients (36%). In the blood donor group, genotype 4 was detected for the first time. Genotype 2 was rare in the patient group and not detected in blood donors. Genotype 1 was the predominant genotype in the younger age groups (less than 30 years), whereas genotype 5a was found at higher proportions in the older age groups for both the patient and blood donor groups, comprising more than 60% of genotypes in those older than 50 years. Genotypes 1 and 5 were at highest proportions across all provinces compared to other genotypes. In blood donors, genotype 1 was predominant among Caucasians (43%) and genotype 5a among Blacks (54%). Such information is required for planning the impact on the health sector with regard to newly emerging therapies for hepatitis C and burden of disease. © 2016 John Wiley & Sons Ltd.

  4. Transforming microbial genotyping: a robotic pipeline for genotyping bacterial strains.

    Directory of Open Access Journals (Sweden)

    Brian O'Farrell

    Full Text Available Microbial genotyping increasingly deals with large numbers of samples, and data are commonly evaluated by unstructured approaches, such as spread-sheets. The efficiency, reliability and throughput of genotyping would benefit from the automation of manual manipulations within the context of sophisticated data storage. We developed a medium- throughput genotyping pipeline for MultiLocus Sequence Typing (MLST of bacterial pathogens. This pipeline was implemented through a combination of four automated liquid handling systems, a Laboratory Information Management System (LIMS consisting of a variety of dedicated commercial operating systems and programs, including a Sample Management System, plus numerous Python scripts. All tubes and microwell racks were bar-coded and their locations and status were recorded in the LIMS. We also created a hierarchical set of items that could be used to represent bacterial species, their products and experiments. The LIMS allowed reliable, semi-automated, traceable bacterial genotyping from initial single colony isolation and sub-cultivation through DNA extraction and normalization to PCRs, sequencing and MLST sequence trace evaluation. We also describe robotic sequencing to facilitate cherrypicking of sequence dropouts. This pipeline is user-friendly, with a throughput of 96 strains within 10 working days at a total cost of 200,000 items were processed by two to three people. Our sophisticated automated pipeline can be implemented by a small microbiology group without extensive external support, and provides a general framework for semi-automated bacterial genotyping of large numbers of samples at low cost.

  5. Efficient cell culture system for hepatitis C virus genotype 5A

    DEFF Research Database (Denmark)


    of in vitro transcripts in Huh7.5 cells, production of infectious viruses was delayed. However, in subsequent viral passages efficient spread of infection and HCV RNA titers as high as for J6/JFH were obtained. Infectivity titers were at all time points analyzed comparable to J6/JFH control virus. Sequence...

  6. Heart failure - medicines (United States)

    CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... You will need to take most of your heart failure medicines every day. Some medicines are taken ...

  7. Audioprofiles and antioxidant enzyme genotypes in presbycusis. (United States)

    Angeli, Simon I; Bared, Anthony; Ouyang, Xiaomei; Du, Li Lin; Yan, Denise; Zhong Liu, Xue


    Audiometric patterns have been shown to indirectly provide information regarding the pathophysiology of presbycusis and be useful in the phenotyping of hereditary deafness. Hospital-based cohort study of adults with presbycusis, comparing the association of audiometric patterns and polymorphisms of antioxidant enzymes that have been linked to presbycusis: GSTT1, GSTM1 and NAT2. All subjects underwent a clinical evaluation and completed questionnaires regarding ototoxicity and noise exposure. Pure-tone threshold audiometry was obtained and subjects' audiograms were classified into specific patterns. DNA was extracted from blood and the polymorphisms of GSTT1, GSTM1, and the NAT2 variants (NAT2* 5A; NAT2* 6A,B) were analyzed by PCR. The audiometric patterns that were more prevalent in our cohort were "High-Frequency Steeply Sloping" or HFSS (33%), "High-Frequency Gently Sloping" or HFGS (31%), and "Flat" (27%), with other patterns being rare. We did not find a statistical significant effect of gender, age, hearing level, and ear side on the audiometric pattern. Subjects with mutant alleles for GSTT1 were more likely to have a HFSS audiogram than subjects with the wild type genotype. In this cohort, there was a similar prevalence for the three audiometric configurations HFSS, HFGS, and Flat, with other configurations being rare. Subjects with mutant alleles for GSTT1 were more likely to have a HFSS audiogram than subjects with the wild type genotype, suggesting that the basal turn of the cochlea is susceptible to GSTT1 regulated oxidative stress. However, further studies of audioprofiles with larger sample sizes may be needed to establish phenotype-genotype correlations in presbycusis. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  8. HIV genotype resistance testing in antiretroviral (ART) exposed Indian children--a need of the hour. (United States)

    Shah, Ira; Parikh, Shefali


    Development of drug resistance in HIV infected children with treatment failure is a major impediment to selection of appropriate therapy. HIV genotype resistance assays predict drug resistance on the basis of mutations in the viral genome. However, their clinical utility, especially in a resource limited setting is still a subject of debate. The authors report two cases in which both the children suffered from treatment failure of various antiretroviral therapy regimes. In both the cases, Genotype Resistance Testing (GRT) prompted a radical change from proposed failure therapy as per existing guidelines. GRT was specifically important for the selection of a new dual Nucleoside reverse transcriptase inhibitors (NRTI) component of failure regimen by identifying TAMS and M184V mutations in the HIV genome. These case reports highlight the importance of GRT in children failing multiple antiretroviral regimes; and emphasizes the need to recognize situations where GRT is absolutely essential to guide appropriate therapy, even in a resource limited setting.

  9. Advanced Heart Failure (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Advanced Heart Failure Updated:May 9,2017 When heart failure (HF) ... Making This content was last reviewed May 2017. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  10. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D


    : Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after...

  11. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D


    OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURC...

  12. Immune mediated liver failure


    Wang, Xiaojing; Ning, Qin


    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capac...

  13. Chronic heart failure


    Hopper, Ingrid; Easton, Kellie


    1. The common symptoms and signs of chronic heart failure are dyspnoea, ankle swelling, raised jugular venous pressure and basal crepitations. Other conditions may be confused with chronic heart failure, including dependent oedema or oedema due to renal or hepatic disease. Shortness of breath may be due to respiratory disease or severe anaemia. Heart failure secondary to lung disease (cor pulmonale) should be distinguished from congestive cardiac failure. Heart failure may also present with l...

  14. Hepatitis C Virus: Virology and Genotypes

    KAUST Repository

    Abdelaziz, Ahmed


    Hepatitis C virus (HCV) is a major causative agent of chronic liver disease worldwide. HCV is characterized by genetic heterogeneity, with at least six genotypes identified. The geographic distribution of genotypes has shown variations in different

  15. Heart failure - surgeries and devices (United States)

    ... surgery; HF - surgery; Intra-aortic balloon pumps - heart failure; IABP - heart failure; Catheter based assist devices - heart failure ... problem may cause heart failure or make heart failure worse. Heart valve surgery may be needed to repair or ...

  16. Genotype x environment interaction and optimum resource ...

    African Journals Online (AJOL)

    ... x E) interaction and to determine the optimum resource allocation for cassava yield trials. The effects of environment, genotype and G x E interaction were highly significant for all yield traits. Variations due to G x E interaction were greater than those due to genotypic differences for all yield traits. Genotype x location x year ...

  17. Hepatitis C virus Genotypes in Patients with End-Stage Renal Disease in East Azerbaijan, Iran

    Directory of Open Access Journals (Sweden)

    Somi Mohammad


    Full Text Available Information about the genotypes and associated risk factors in hepatitis C virus (HCV infected patients in Iran is limited. The aim of this study was to identify the HCV genotypes and associated risk factors in a group of HCV infected patients on dialysis therapy in Iran. The sera of 753 patients with chronic renal failure from fifteen dialysis units in East Azerbaijan Province were screened for anti-HCV antibodies as well as HCV RNA; viral RNA was extracted for the genotype specific primer approach. Patients were questioned concerning documented risk factors. Genotyping analysis was performed in 55 patients with positive anti-HCV and HCV-RNA. Genotypes 1 and 3 were found in 46 (83.7% and three (5.5% patients, respectively. The most frequent HCV subtype was 1a (76.4%, followed by 3a and 1b and 1b (5.5% each while one patient was infected with both 1a and 1b. There was no statistically significant difference between the risk factors analyzed and the acqui-sition of HCV infection. This study gives added evidence of the predominant HCV genotypes in Iran, which is different than reports from other Arab countries and similar with the pattern of genotype in both Europe and United States.

  18. Genetic Divergence in Sugarcane Genotypes


    Tahir, Mohammad; Rahman, Hidayatur; Gul, Rahmani; Ali, Amjad; Khalid, Muhammad


    To assess genetic divergence of sugarcane germplasm, an experiment comprising 25 sugarcane genotypes was conducted at Sugar Crops Research Institute (SCRI), Mardan, Khyber Pakhtunkhwa, Pakistan, in quadruple lattice design during 2008-09. Among the 14 parameters evaluated, majority exhibited significant differences while some showed nonsignificant mean squares. The initial correlation matrix revealed medium to high correlations. Principal Component Analysis (PCA) showed that there were two pr...

  19. Robust HCV Genotype 3a Infectious Cell Culture System Permits Identification of Escape Variants With Resistance to Sofosbuvir

    DEFF Research Database (Denmark)

    Ramirez Almeida, Santseharay; Mikkelsen, Lotte S.; Gottwein, Judith M.


    Background & Aims Direct-acting antivirals (DAAs) effectively eradicate chronic hepatitis C virus (HCV) infection, although HCV genotype 3a is less responsive to these drugs. We aimed to develop genotype 3a infectious cultures and study the effects of inhibitors of NS5A and NS5B and resistance to...

  20. Acute liver failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Bjerring, Peter Nissen


    Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these.......Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these....

  1. Study of correlation between polymorphism of angiotensin II-1 receptor gene A1166 genotype and complications in atrial fibrillation

    International Nuclear Information System (INIS)

    Wang Yueping; Gong Wuxing; Shi Li


    Objective: To investigate the effect of genetic polymorphism on atrial fibrillation. Methods: Polymerase chain reaction-restrictive fragment length polymorphism(PCR-RFLP) was used to identify and compare the genotype of the location of AT1R gene 1166, and color echo-ultrasound was performed with logistic regression used to analyse the independent risk of various genotypes for atrial fibrillation in 121 patients with atrial fibrillation and 100 controls. Results: (1) Frequency of genotype AC + CC, iso-gene C in atrial fibrillation group was higher than that in control group (P=0.017, 0.013), the risk ratio in patients with genotype AC + CC to develop atrial fibrillation was 3.657 compared with genotype AA (95% CI:1.181∼11.322), and genotype difference as well as systolic pressure were involved in occurrence of overall atrial fibrillation. The OR to develop atrial fibrillation in patients with genotype AC + CC was 4.132 compared with genotype AA (95% CI:1.263∼13.513). (2) There were no significant differences of clinical manifestation (heart failure, cerebral embolism) or ultrasonic parameters among patients with different genotypes (AA vs AC + CC)(P>0.05). Conclusion: People carrying iso-gene C in AT1R gene 1166 were more liable to develop atrial fibrillation, but there were no correlationship with development of complications. (authors)

  2. In Support of Failure (United States)

    Carr, Allison


    In this essay, I propose a concerted effort to begin devising a theory and pedagogy of failure. I review the discourse of failure in Western culture as well as in composition pedagogy, ultimately suggesting that failure is not simply a judgement or indication of rank but is a relational, affect-bearing concept with tremendous relevance to…

  3. The failure of earthquake failure models (United States)

    Gomberg, J.


    In this study I show that simple heuristic models and numerical calculations suggest that an entire class of commonly invoked models of earthquake failure processes cannot explain triggering of seismicity by transient or "dynamic" stress changes, such as stress changes associated with passing seismic waves. The models of this class have the common feature that the physical property characterizing failure increases at an accelerating rate when a fault is loaded (stressed) at a constant rate. Examples include models that invoke rate state friction or subcritical crack growth, in which the properties characterizing failure are slip or crack length, respectively. Failure occurs when the rate at which these grow accelerates to values exceeding some critical threshold. These accelerating failure models do not predict the finite durations of dynamically triggered earthquake sequences (e.g., at aftershock or remote distances). Some of the failure models belonging to this class have been used to explain static stress triggering of aftershocks. This may imply that the physical processes underlying dynamic triggering differs or that currently applied models of static triggering require modification. If the former is the case, we might appeal to physical mechanisms relying on oscillatory deformations such as compaction of saturated fault gouge leading to pore pressure increase, or cyclic fatigue. However, if dynamic and static triggering mechanisms differ, one still needs to ask why static triggering models that neglect these dynamic mechanisms appear to explain many observations. If the static and dynamic triggering mechanisms are the same, perhaps assumptions about accelerating failure and/or that triggering advances the failure times of a population of inevitable earthquakes are incorrect.

  4. Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection. (United States)

    Derache, Anne; Wallis, Carole L; Vardhanabhuti, Saran; Bartlett, John; Kumarasamy, Nagalingeswaran; Katzenstein, David


    Virologic failure in subtype C is characterized by high resistance to first-line antiretroviral (ARV) drugs, including efavirenz, nevirapine, and lamivudine, with nucleoside resistance including type 2 thymidine analog mutations, K65R, a T69del, and M184V. However, genotypic algorithms predicting resistance are mainly based on subtype B viruses and may under- or overestimate drug resistance in non-B subtypes. To explore potential treatment strategies after first-line failure, we compared genotypic and phenotypic susceptibility of subtype C human immunodeficiency virus 1 (HIV-1) following first-line ARV failure. AIDS Clinical Trials Group 5230 evaluated patients failing an initial nonnucleoside reverse-transcriptase inhibitor (NNRTI) regimen in Africa and Asia, comparing the genotypic drug resistance and phenotypic profile from the PhenoSense (Monogram). Site-directed mutagenesis studies of K65R and T69del assessed the phenotypic impact of these mutations. Genotypic algorithms overestimated resistance to etravirine and rilpivirine, misclassifying 28% and 32%, respectively. Despite K65R with the T69del in 9 samples, tenofovir retained activity in >60%. Reversion of the K65R increased susceptibility to tenofovir and other nucleosides, while reversion of the T69del showed increased resistance to zidovudine, with little impact on other NRTI. Although genotype and phenotype were largely concordant for first-line drugs, estimates of genotypic resistance to etravirine and rilpivirine may misclassify subtype C isolates compared to phenotype. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail

  5. Decoding noises in HIV computational genotyping. (United States)

    Jia, MingRui; Shaw, Timothy; Zhang, Xing; Liu, Dong; Shen, Ye; Ezeamama, Amara E; Yang, Chunfu; Zhang, Ming


    Lack of a consistent and reliable genotyping system can critically impede HIV genomic research on pathogenesis, fitness, virulence, drug resistance, and genomic-based healthcare and treatment. At present, mis-genotyping, i.e., background noises in molecular genotyping, and its impact on epidemic surveillance is unknown. For the first time, we present a comprehensive assessment of HIV genotyping quality. HIV sequence data were retrieved from worldwide published records, and subjected to a systematic genotyping assessment pipeline. Results showed that mis-genotyped cases occurred at 4.6% globally, with some regional and high-risk population heterogeneities. Results also revealed a consistent mis-genotyping pattern in gp120 in all studied populations except the group of men who have sex with men. Our study also suggests novel virus diversities in the mis-genotyped cases. Finally, this study reemphasizes the importance of implementing a standardized genotyping pipeline to avoid genotyping disparity and to advance our understanding of virus evolution in various epidemiological settings. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Applications of blood group genotyping

    Directory of Open Access Journals (Sweden)

    Mariza A. Mota


    Full Text Available Introduction: The determination of blood group polymorphism atthe genomic level facilitates the resolution of clinical problemsthat cannot be addressed by hemagglutination. They are useful to(a determine antigen types for which currently available antibodiesare weakly reactive; (b type patients who have been recentlytransfused; (c identify fetuses at risk for hemolytic disease of thenewborn; and (d to increase the reliability of repositories of antigennegative RBCs for transfusion. Objectives: This review assessedthe current applications of blood group genotyping in transfusionmedicine and hemolytic disease of the newborn. Search strategy:Blood group genotyping studies and reviews were searched ingeneral database (MEDLINE and references were reviewed.Selection criteria: All published data and reviews were eligible forinclusion provided they reported results for molecular basis ofblood group antigens, DNA analysis for blood group polymorphisms,determination of fetal group status and applications of blood groupgenotyping in blood transfusion. Data collection: All data werecollected based on studies and reviews of blood grouppolymorphisms and their clinical applications.

  7. Managing Feelings about Heart Failure (United States)

    ... About Heart Failure Module 6: Managing Feelings About Heart Failure Download Module Order Hardcopy Heart failure can cause ... professional help for emotional problems. Common Feelings About Heart Failure It is common for people to feel depressed ...

  8. Grain yield stability of early maize genotypes

    Directory of Open Access Journals (Sweden)

    Chitra Bahadur Kunwar


    Full Text Available The objective of this study was to estimate grain yield stability of early maize genotypes. Five early maize genotypes namely Pool-17, Arun1EV, Arun-4, Arun-2 and Farmer’s variety were evaluated using Randomized Complete Block Design along with three replications at four different locations namely Rampur, Rajahar, Pakhribas and Kabre districts of Nepal during summer seasons of three consecutive years from 2010 to 2012 under farmer’s fields. Genotype and genotype × environment (GGE biplot was used to identify superior genotype for grain yield and stability pattern. The genotypes Arun-1 EV and Arun-4 were better adapted for Kabre and Pakhribas where as pool-17 for Rajahar environments. The overall findings showed that Arun-1EV was more stable followed by Arun-2 therefore these two varieties can be recommended to farmers for cultivation in both environments.

  9. Heterogeneous recombination among Hepatitis B virus genotypes. (United States)

    Castelhano, Nadine; Araujo, Natalia M; Arenas, Miguel


    The rapid evolution of Hepatitis B virus (HBV) through both evolutionary forces, mutation and recombination, allows this virus to generate a large variety of adapted variants at both intra and inter-host levels. It can, for instance, generate drug resistance or the diverse viral genotypes that currently exist in the HBV epidemics. Concerning the latter, it is known that recombination played a major role in the emergence and genetic diversification of novel genotypes. In this regard, the quantification of viral recombination in each genotype can provide relevant information to devise expectations about the evolutionary trends of the epidemic. Here we measured the amount of this evolutionary force by estimating global and local recombination rates in >4700 HBV complete genome sequences corresponding to nine (A to I) HBV genotypes. Counterintuitively, we found that genotype E presents extremely high levels of recombination, followed by genotypes B and C. On the other hand, genotype G presents the lowest level, where recombination is almost negligible. We discuss these findings in the light of known characteristics of these genotypes. Additionally, we present a phylogenetic network to depict the evolutionary history of the studied HBV genotypes. This network clearly classified all genotypes into specific groups and indicated that diverse pairs of genotypes are derived from a common ancestor (i.e., C-I, D-E and, F-H) although still the origin of this virus presented large uncertainty. Altogether we conclude that the amount of observed recombination is heterogeneous among HBV genotypes and that this heterogeneity can influence on the future expansion of the epidemic. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Automated multiple failure FMEA

    International Nuclear Information System (INIS)

    Price, C.J.; Taylor, N.S.


    Failure mode and effects analysis (FMEA) is typically performed by a team of engineers working together. In general, they will only consider single point failures in a system. Consideration of all possible combinations of failures is impractical for all but the simplest example systems. Even if the task of producing the FMEA report for the full multiple failure scenario were automated, it would still be impractical for the engineers to read, understand and act on all of the results. This paper shows how approximate failure rates for components can be used to select the most likely combinations of failures for automated investigation using simulation. The important information can be automatically identified from the resulting report, making it practical for engineers to study and act on the results. The strategy described in the paper has been applied to a range of electrical subsystems, and the results have confirmed that the strategy described here works well for realistically complex systems

  11. Heart Failure in Women (United States)

    Bozkurt, Biykem; Khalaf, Shaden


    Heart failure is an important cause of morbidity and mortality in women, and they tend to develop it at an older age compared to men. Heart failure with preserved ejection fraction is more common in women than in men and accounts for at least half the cases of heart failure in women. When comparing men and women who have heart failure and a low left ventricular ejection fraction, the women are more symptomatic and have a similarly poor outcome. Overall recommendations for guideline-directed medical therapies show no differences in treatment approaches between men and women. Overall, women are generally underrepresented in clinical trials for heart failure. Further studies are needed to shed light into different mechanisms, causes, and targeted therapies of heart failure in women. PMID:29744014

  12. Definition of containment failure

    International Nuclear Information System (INIS)

    Cybulskis, P.


    Core meltdown accidents of the types considered in probabilistic risk assessments (PRA's) have been predicted to lead to pressures that will challenge the integrity of containment structures. Review of a number of PRA's indicates considerable variation in the predicted probability of containment failure as a function of pressure. Since the results of PRA's are sensitive to the prediction of the occurrence and the timing of containment failure, better understanding of realistic containment capabilities and a more consistent approach to the definition of containment failure pressures are required. Additionally, since the size and location of the failure can also significantly influence the prediction of reactor accident risk, further understanding of likely failure modes is required. The thresholds and modes of containment failure may not be independent

  13. Hepatitis C virus genotypes in Myanmar. (United States)

    Win, Nan Nwe; Kanda, Tatsuo; Nakamoto, Shingo; Yokosuka, Osamu; Shirasawa, Hiroshi


    Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis C virus (HCV) infection is 2%, and HCV infection accounts for 25% of hepatocellular carcinoma. In this study, we reviewed the prevalence of HCV genotypes in Myanmar. HCV genotypes 1, 3 and 6 were observed in volunteer blood donors in and around the Myanmar city of Yangon. Although there are several reports of HCV genotype 6 and its variants in Myanmar, the distribution of the HCV genotypes has not been well documented in areas other than Yangon. Previous studies showed that treatment with peginterferon and a weight-based dose of ribavirin for 24 or 48 wk could lead to an 80%-100% sustained virological response (SVR) rates in Myanmar. Current interferon-free treatments could lead to higher SVR rates (90%-95%) in patients infected with almost all HCV genotypes other than HCV genotype 3. In an era of heavy reliance on direct-acting antivirals against HCV, there is an increasing need to measure HCV genotypes, and this need will also increase specifically in Myanmar. Current available information of HCV genotypes were mostly from Yangon and other countries than Myanmar. The prevalence of HCV genotypes in Myanmar should be determined.

  14. Hepatitis C Virus: Virology and Genotypes

    KAUST Repository

    Abdelaziz, Ahmed


    Hepatitis C virus (HCV) is a major causative agent of chronic liver disease worldwide. HCV is characterized by genetic heterogeneity, with at least six genotypes identified. The geographic distribution of genotypes has shown variations in different parts of the world over the past decade because of variations in population structure, immigration, and routes of transmission. Genotype differences are of epidemiologic interest and help the study of viral transmission dynamics to trace the source of HCV infection in a given population. HCV genotypes are also of considerable clinical importance because they affect response to antiviral therapy and represent a challenging obstacle for vaccine development.

  15. Evaluation of the Abbott Real Time HCV genotype II assay for Hepatitis C virus genotyping. (United States)

    Sariguzel, Fatma Mutlu; Berk, Elife; Gokahmetoglu, Selma; Ercal, Baris Derya; Celik, Ilhami


    The determination of HCV genotypes and subtypes is very important for the selection of antiviral therapy and epidemiological studies. The aim of this study was to evaluate the performance of Abbott Real Time HCV Genotype II assay in HCV genotyping of HCV infected patients in Kayseri, Turkey. One hundred patients with chronic hepatitis C admitted to our hospital were evaluated between June 2012 and December 2012, HCV RNA levels were determined by the COBAS® AmpliPrep/COBAS® TaqMan® 48 HCV test. HCV genotyping was investigated by the Abbott Real Time HCV Genotype II assay. With the exception of genotype 1, subtypes of HCV genotypes could not be determined by Abbott assay. Sequencing analysis was used as the reference method. Genotypes 1, 2, 3 and 4 were observed in 70, 4, 2 and 24 of the 100 patients, respectively, by two methods. The concordance between the two systems to determine HCV major genotypes was 100%. Of 70 patients with genotype 1, 66 showed infection with subtype 1b and 4 with subtype 1a by Abbott Real Time HCV Genotype II assay. Using sequence analysis, 61 showed infection with subtype 1b and 9 with subtype 1a. In determining of HCV genotype 1 subtypes, the difference between the two methods was not statistically significant (P>0.05). HCV genotype 4 and 3 samples were found to be subtype 4d and 3a, respectively, by sequence analysis. There were four patients with genotype 2. Sequence analysis revealed that two of these patients had type 2a and the other two had type 2b. The Abbott Real Time HCV Genotype II assay yielded results consistent with sequence analysis. However, further optimization of the Abbott Real Time HCV Genotype II assay for subtype identification of HCV is required.

  16. Managing first-line failure. (United States)

    Cooper, David A


    WHO standard of care for failure of a first regimen, usually 2N(t)RTI's and an NNRTI, consists of a ritonavir-boosted protease inhibitor with a change in N(t)RTI's. Until recently, there was no evidence to support these recommendations which were based on expert opinion. Two large randomized clinical trials, SECOND LINE and EARNEST both showed excellent response rates (>80%) for the WHO standard of care and indicated that a novel regimen of a boosted protease inhibitor with an integrase inhibitor had equal efficacy with no difference in toxicity. In EARNEST, a third arm consisting of induction with the combined protease and integrase inhibitor followed by protease inhibitor monotherapy maintenance was inferior and led to substantial (20%) protease inhibitor resistance. These studies confirm the validity of the current recommendations of WHO and point to a novel public health approach of using two new classes for second line when standard first-line therapy has failed, which avoids resistance genotyping. Notwithstanding, adherence must be stressed in those failing first-line treatments. Protease inhibitor monotherapy is not suitable for a public health approach in low- and middle-income countries.

  17. Are Sema5a mutant mice a good model of autism? A behavioral analysis of sensory systems, emotionality and cognition (United States)

    Gunn, Rhian K.; Huentelman, Matthew J.; Brown, Richard E.


    Semaphorin 5A (Sema5A) expression is reduced in the brain of individuals with autism, thus mice with reduced Sema5A levels may serve as a model of this neurodevelopmental disorder. We tested male and female Sema5a knockout mice (B6.129P2SEMA5A/J) and C57BL/6J controls for emotionality, visual ability, prepulse inhibition, motor learning and cognition. Overall, there were only two genotype differences in emotionality: Sema5a mutant mice had more stretch-attend postures in the elevated plus-maze and more defecations in the open field. All mice could see, but Sema5a mice had better visual ability than C57BL/6J mice. There were no genotype differences in sensory-motor gating. Sema5a mice showed higher levels of activity in the elevated plus-maze and light/dark transition box, and there were sex by genotype differences in the Rotarod, suggesting a sex difference in balance and coordination differentially affected by Sema5a. There were no genotype effects on cognition: Sema5a mice did not differ from C57BL/6J in the Morris water maze, set-shifting or cued and contextual fear conditioning. In the social recognition test, all mice preferred social stimuli, but there was no preference for social novelty, thus the Sema5A mice do not have a deficit in social behavior. Overall, there were a number of sex differences, with females showing greater activity and males performing better in tests of spatial learning and memory, but no deficits in the behavior of Sema5A mice. We conclude that the Sema5a mice do not meet the behavioral criteria for a mouse model of autism. PMID:21777623

  18. Per3 VNTR polymorphism and chronic heart failure. (United States)

    Lipkova, Jolana; Bienertova-Vasku, Julie Anna; Spinarova, Lenka; Bienert, Petr; Hlavna, Marian; Pavkova Goldbergova, Monika; Parenica, Jiri; Spinar, Jindrich; Vasku, Anna


    The aim of this study was to investigate the relationship between gene Period3 (Per3) variable number tandem repeat (VNTR) polymorphism and chronic heart failure (CHF). The study subjects (372 patients of Caucasian origin with CHF and 332 healthy controls) were genotyped for Per3 VNTR polymorphism using an allele-specific PCR. No significant differences in genotype or Per3 VNTR allele frequencies were found between CHF cases and controls (Pg=0.30, Pa=0.52). No significant differences were uncovered either between CHF cases according to etiology (DCMP vs. IHD; Pg=0.87, Pa=0.91). In the multivariate regression modeling, no predictive function of VNTR Per3 polymorphism on ejection fraction or NYHA class, hyperlipidaemia or type II diabetes risk was found. Per3 VNTR polymorphism is not a major risk factor for chronic heart failure or a factor modulating the severity of the CHF in this population.

  19. Immune mediated liver failure. (United States)

    Wang, Xiaojing; Ning, Qin


    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  20. The Reconstruction of Failure (United States)

    Turner, Ralph H.


    Seeks to explain the use of ideologies concerning the failure or non-failure in American education in terms of the struggle of sponsoring and professional groups to establish or maintain position on the social scene and, correspondingly, to gain control over those clienteles which are relevant to drives for social or professional mobility. (RJ)

  1. Success by Failure (United States)

    Andrews, Benjamin D.


    By taking the step to talk openly about his failure, the author stumbled upon one of several important lessons that he learned from this experience. The author recognized that he did not have to pretend anymore. In this article, the author shares his story of developing a "growth mindset" to overcome his own failure and support his…

  2. Central oxygen pipeline failure

    African Journals Online (AJOL)

    surgical intensive care unit (ICU), with two patients on full ventilation and ... uncertainty around the cause of the failure and the restoration, .... soon as its level also falls below three tons. Should ... (properly checked and closed prior to each anaesthetic). ... in use at the time of the central oxygen pipeline failure at Tygerberg.

  3. Genotyping isolates of the entomopathogenic fungus Beauveria ...

    African Journals Online (AJOL)

    Multi-locus denaturing gradient gel electrophoresis (DGGE) analysis was developed to investigate the genotypes of Beauveria bassiana sensu lato. ... These results demonstrated that multi-locus DGGE is a potentially useful molecular marker for genotyping, identifying and tracking the fates of experimentally released ...

  4. Genetic relationship among Musa genotypes revealed by ...

    African Journals Online (AJOL)



    Mar 29, 2012 ... A banana germplasm was established containing 44 Musa genotypes collected from various locations in Malaysia. To detect their genetic variation and to rule out duplicates among cultivar, microsatellite markers were used in their analysis. The microsatellite profiles of 44 Musa genotypes of various origins.

  5. Radiology of renal failure

    International Nuclear Information System (INIS)

    Griffiths, H.J.


    This book covers most aspects of imaging studies in patients with renal failure. The initial chapter provides basic information on contrast agents, intravenous urography, and imaging findings in the urinary tract disorders responsible for renal failure and in patients who have undergone transplantation. It illustrates common gastro-intestinal abnormalities seen on barium studies in patients with renal failure. It illustrates the cardiopulmonary complications of renal failure and offers advice for radiologic differentiation. It details different aspects of skeletal changes in renal failure, including a basic description of the pathophysiology of the changes; many excellent illustrations of classic bone changes, arthritis, avascular necrosis, and soft-tissue calcifications; and details of bone mineral analysis

  6. SOR-ring failure

    International Nuclear Information System (INIS)

    Kitamura, Hideo


    It was in the autumn of 1976 that the SOR-ring (synchrotron radiation storage ring) has commenced the regular operation. Since then, the period when the operation was interrupted due to the failures of SOR-ring itself is in total about 8 weeks. Failures and accidents have occurred most in the vacuum system. Those failure experiences are described on the vacuum, electromagnet, radio-frequency acceleration and beam transport systems with their interrupted periods. The eleven failures in the vacuum system have been reported, such as bellows breakage in a heating-evacuating period, leakage from the bellows of straight-through valves (made in U.S.A. and Japan), and leakage from the joint flange of the vacuum system. The longest interruption was 5 weeks due to the failure of a domestically manufactured straight-through valve. The failures of the electromagnet system involve the breakage in a cooling water system, short circuit of a winding in the Q magnet power transformer, blow of a fuse protecting the deflection magnet power source by the current less than the rating, and others. The failures of the RF acceleration system include the breakage of an output electronic tube the breakage of a cavity ceramic, RF voltage fluctuation due to the contact deterioration at a cavity electrode, and the failure of grid bias power source. It is necessary to select the highly reliable components for the vacuum system because the vacuum system failures require longer time for recovery, and very likely to induce secondary and tertiary failures. (Wakatsuki, Y.)

  7. Toward fully automated genotyping: Genotyping microsatellite markers by deconvolution

    Energy Technology Data Exchange (ETDEWEB)

    Perlin, M.W.; Lancia, G.; See-Kiong, Ng [Carnegie Mellon Univ., Pittsburgh, PA (United States)


    Dense genetic linkage maps have been constructed for the human and mouse genomes, with average densities of 2.9 cM and 0.35 cM, respectively. These genetic maps are crucial for mapping both Mendelian and complex traits and are useful in clinical genetic diagnosis. Current maps are largely comprised of abundant, easily assayed, and highly polymorphic PCR-based microsatellite markers, primarily dinucleotide (CA){sub n} repeats. One key limitation of these length polymorphisms is the PCR stutter (or slippage) artifact that introduces additional stutter bands. With two (or more) closely spaced alleles, the stutter bands overlap, and it is difficult to accurately determine the correct alleles; this stutter phenomenon has all but precluded full automation, since a human must visually inspect the allele data. We describe here novel deconvolution methods for accurate genotyping that mathematically remove PCR stutter artifact from microsatellite markers. These methods overcome the manual interpretation bottleneck and thereby enable full automation of genetic map construction and use. New functionalities, including the pooling of DNAs and the pooling of markers, are described that may greatly reduce the associated experimentation requirements. 32 refs., 5 figs., 3 tabs.

  8. Genomic evaluations with many more genotypes

    Directory of Open Access Journals (Sweden)

    Wiggans George R


    Full Text Available Abstract Background Genomic evaluations in Holstein dairy cattle have quickly become more reliable over the last two years in many countries as more animals have been genotyped for 50,000 markers. Evaluations can also include animals genotyped with more or fewer markers using new tools such as the 777,000 or 2,900 marker chips recently introduced for cattle. Gains from more markers can be predicted using simulation, whereas strategies to use fewer markers have been compared using subsets of actual genotypes. The overall cost of selection is reduced by genotyping most animals at less than the highest density and imputing their missing genotypes using haplotypes. Algorithms to combine different densities need to be efficient because numbers of genotyped animals and markers may continue to grow quickly. Methods Genotypes for 500,000 markers were simulated for the 33,414 Holsteins that had 50,000 marker genotypes in the North American database. Another 86,465 non-genotyped ancestors were included in the pedigree file, and linkage disequilibrium was generated directly in the base population. Mixed density datasets were created by keeping 50,000 (every tenth of the markers for most animals. Missing genotypes were imputed using a combination of population haplotyping and pedigree haplotyping. Reliabilities of genomic evaluations using linear and nonlinear methods were compared. Results Differing marker sets for a large population were combined with just a few hours of computation. About 95% of paternal alleles were determined correctly, and > 95% of missing genotypes were called correctly. Reliability of breeding values was already high (84.4% with 50,000 simulated markers. The gain in reliability from increasing the number of markers to 500,000 was only 1.6%, but more than half of that gain resulted from genotyping just 1,406 young bulls at higher density. Linear genomic evaluations had reliabilities 1.5% lower than the nonlinear evaluations with 50

  9. Magnet failure workshop

    Energy Technology Data Exchange (ETDEWEB)

    Marston, P G [Massachusetts Institute of Technology, Cambridge (U.S.A.); Desportes, H [C.E.N.-Saclay, 91 - Gif-sur-Yvette (France); Morpurgo, M [C.E.R.N., Geneva (Switzerland); Komarek, P [Kernforschungszentrum, Karlsruhe (Germany, FR); Van Hulst, K [University of Nijmegen (The Netherlands); Hackley, D [General Dynamics Convair, San Diego, CA (U.S.A.); Young, J L [Westinghouse Electric Corporation, East Pittsburgh, PE (U.S.A.); Kibbe, K [Oak Ridge National Laboratory (U.S.A.)


    The dictionary defines failure as nonperformance or an unacceptable want of success. (The definition implies that the results should have been avoided). In an emerging technology such as ours, the boundaries of expectations and ''unacceptable success'' are often ill defined. Failures are often touted as hugh successes (occasionally rightfully so) and exceptional technological achievement can become dismal failure (if expectations are too high). We all, however, have experienced problems of one sort or another and the basic purpose of the workshop was simply to communicate these so that new or future workers don't make the same mistakes.

  10. Failure Diameter Resolution Study

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    Previously the SURFplus reactive burn model was calibrated for the TATB based explosive PBX 9502. The calibration was based on fitting Pop plot data, the failure diameter and the limiting detonation speed, and curvature effect data for small curvature. The model failure diameter is determined utilizing 2-D simulations of an unconfined rate stick to find the minimum diameter for which a detonation wave propagates. Here we examine the effect of mesh resolution on an unconfined rate stick with a diameter (10mm) slightly greater than the measured failure diameter (8 to 9 mm).

  11. Magnet failure workshop

    International Nuclear Information System (INIS)

    Marston, P.G.; Desportes, H.; Morpurgo, M.; Komarek, P.; Van Hulst, K.; Hackley, D.; Young, J.L.; Kibbe, K.


    The dictionary defines failure as nonperformance or an unacceptable want of success. (The definition implies that the results should have been avoided). In an emerging technology such as ours, the boundaries of expectations and ''unacceptable success'' are often ill defined. Failures are often touted as hugh successes (occasionally rightfully so) and exceptional technological achievement can become dismal failure (if expectations are too high). We all, however, have experienced problems of one sort or another and the basic purpose of the workshop was simply to communicate these so that new or future workers don't make the same mistakes

  12. Nutrition in Heart Failure


    Reci Meseri


    Heart failure is defined as decreased ability of heart due to various reasons. It%u2019s seen 2-3% but the prevalence increases sharply after the age of seventy. The objectives of nutrition therapy in heart failure are to prevent from water retention and edema, to avoid from hard digestion and to offer a balanced diet. In order to avoid fluid retention and edema, daily sodium and fluid intake must be monitored carefully. Main dilemma of the heart failure patients is the obesity-cachexia dilem...

  13. Neurological Respiratory Failure

    Directory of Open Access Journals (Sweden)

    Mohan Rudrappa


    Full Text Available West Nile virus infection in humans is mostly asymptomatic. Less than 1% of neuro-invasive cases show a fatality rate of around 10%. Acute flaccid paralysis of respiratory muscles leading to respiratory failure is the most common cause of death. Although the peripheral nervous system can be involved, isolated phrenic nerve palsy leading to respiratory failure is rare and described in only two cases in the English literature. We present another case of neurological respiratory failure due to West Nile virus-induced phrenic nerve palsy. Our case reiterates the rare, but lethal, consequences of West Nile virus infection, and the increase of its awareness among physicians.

  14. Developmental plasticity: re-conceiving the genotype. (United States)

    Sultan, Sonia E


    In recent decades, the phenotype of an organism (i.e. its traits and behaviour) has been studied as the outcome of a developmental 'programme' coded in its genotype. This deterministic view is implicit in the Modern Synthesis approach to adaptive evolution as a sorting process among genetic variants. Studies of developmental pathways have revealed that genotypes are in fact differently expressed depending on environmental conditions. Accordingly, the genotype can be understood as a repertoire of potential developmental outcomes or norm of reaction. Reconceiving the genotype as an environmental response repertoire rather than a fixed developmental programme leads to three critical evolutionary insights. First, plastic responses to specific conditions often comprise functionally appropriate trait adjustments, resulting in an individual-level, developmental mode of adaptive variation. Second, because genotypes are differently expressed depending on the environment, the genetic diversity available to natural selection is itself environmentally contingent. Finally, environmental influences on development can extend across multiple generations via cytoplasmic and epigenetic factors transmitted to progeny individuals, altering their responses to their own, immediate environmental conditions and, in some cases, leading to inherited but non-genetic adaptations. Together, these insights suggest a more nuanced understanding of the genotype and its evolutionary role, as well as a shift in research focus to investigating the complex developmental interactions among genotypes, environments and previous environments.

  15. Genotype X/C recombinant (putative genotype I) of hepatitis B virus is rare in Hanoi, Vietnam--genotypes B4 and C1 predominate. (United States)

    Phung, Thi Bich Thuy; Alestig, Erik; Nguyen, Thanh Liem; Hannoun, Charles; Lindh, Magnus


    There are eight known genotypes of hepatitis B virus, A-H, and several subgenotypes, with rather well-defined geographic distributions. HBV genotypes were evaluated in 153 serum samples from Hanoi, Vietnam. Of the 87 samples that could be genotyped, genotype B was found in 67 (77%) and genotype C in 19 (22%). All genotype C strains were of subgenotype C1, and the majority of genotype B strains were B4, while a few were B2. The genotype X/C recombinant strain, identified previously in Swedish patients of indigenous Vietnamese origin, was found in one sample. This variant, proposed to be classified as genotype I, has been found recently also by others in Vietnam and Laos. The current study indicates that the genotype X/C recombinant may represent approximately 1% of the HBV strains circulating in Vietnam. (c) 2010 Wiley-Liss, Inc.

  16. Acute heart failure syndrome

    African Journals Online (AJOL)

    and the classical syndrome of chronic persistent heart failure develops. The vast ... Flash pulmonary oedema: This is a severely elevated blood pressure with an .... (CPAP or bilevelNPPV) for cardiogenic pulmonary edema (review). Cochrane.

  17. Acute Liver Failure (United States)

    ... can cause acute liver failure. It is an industrial chemical found in refrigerants and solvents for waxes, varnishes ... measures when spraying insecticides, fungicides, paint and other toxic chemicals. Follow product instructions carefully. Watch what gets on ...

  18. Failure to Fail

    Directory of Open Access Journals (Sweden)

    Samuel Vriezen


    Full Text Available Between pessimism and optimism, Samuel Vriezen attempts to intuit a third way through an assessment of failure and negativity in the consonances and tensions between the prosody of Irish playwright Samuel Becekett and American poet Gertrude Stein.

  19. Inverter ratio failure detector (United States)

    Wagner, A. P.; Ebersole, T. J.; Andrews, R. E. (Inventor)


    A failure detector which detects the failure of a dc to ac inverter is disclosed. The inverter under failureless conditions is characterized by a known linear relationship of its input and output voltages and by a known linear relationship of its input and output currents. The detector includes circuitry which is responsive to the detector's input and output voltages and which provides a failure-indicating signal only when the monitored output voltage is less by a selected factor, than the expected output voltage for the monitored input voltage, based on the known voltages' relationship. Similarly, the detector includes circuitry which is responsive to the input and output currents and provides a failure-indicating signal only when the input current exceeds by a selected factor the expected input current for the monitored output current based on the known currents' relationship.

  20. Acute kidney failure (United States)

    ... Renal failure - acute; ARF; Kidney injury - acute Images Kidney anatomy References Devarajan P. Biomarkers for assessment of renal function during acute kidney injury. In: Alpern RJ, Moe OW, Caplan M, ...

  1. Acute heart failure


    Sénior Sánchez, Juan Manuel; Gándara Ricardo, Jairo Alfonso


    We describe the clinical case of a 26 year-old woman who came to Hospital Universitario San Vicente Fundación (Medellín, Colombia) with symptoms and signs of acute heart failure. She had been previously diagnosed with chronic heart failure with reduced ejection fraction without clear origin, pulmonary thromboembolism and ischemic stroke, without optimal neurohormonal modulation. She was admitted with clinical findings of fluid overload and low tissue perfusion, with inotropic support requirem...

  2. ITER safety task NID-5a: ITER tritium environmental source terms - safety analysis basis

    International Nuclear Information System (INIS)

    Natalizio, A.; Kalyanam, K.M.


    The Canadian Fusion Fuels Technology Project's (CFFTP) is part of the contribution to ITER task NID-5a, Initial Tritium Source Term. This safety analysis basis constitutes the first part of the work for establishing tritium source terms and is intended to solicit comments and obtain agreement. The analysis objective is to provide an early estimate of tritium environmental source terms for the events to be analyzed. Events that would result in the loss of tritium are: a Loss of Coolant Accident (LOCA), a vacuum vessel boundary breach. a torus exhaust line failure, a fuelling machine process boundary failure, a fuel processing system process boundary failure, a water detritiation system process boundary failure and an isotope separation system process boundary failure. 9 figs

  3. A Failure Locus for Hydrogen Assisted Failure

    DEFF Research Database (Denmark)

    Fuentes-Alonso, Sandra; Harris, Zach D.; Burns, James T.


    of a hydrogen-dependent traction separation law. A special control algorithm is employed to overcome numerical instabilities intrinsically associated with cohesive zone formulations. The fracture energy is degraded by means of an experimentally-motivated hydrogen degradation relation. Numerical results provide...... important insight into the failure process, enabling to identify critical values of hydrogen concentration and remote stresses that trigger cracking. The work builds upon previous works by the authors and brings important insight into the technologically important problem of hydrogen assisted cracking....

  4. Hepatitis B virus genotypes circulating in Brazil: molecular characterization of genotype F isolates

    Directory of Open Access Journals (Sweden)

    Virgolino Helaine A


    Full Text Available Abstract Background Hepatitis B virus (HBV isolates have been classified in eight genotypes, A to H, which exhibit distinct geographical distributions. Genotypes A, D and F are predominant in Brazil, a country formed by a miscegenated population, where the proportion of individuals from Caucasian, Amerindian and African origins varies by region. Genotype F, which is the most divergent, is considered indigenous to the Americas. A systematic molecular characterization of HBV isolates from different parts of the world would be invaluable in establishing HBV evolutionary origins and dispersion patterns. A large-scale study is needed to map the region-by-region distribution of the HBV genotypes in Brazil. Results Genotyping by PCR-RFLP of 303 HBV isolates from HBsAg-positive blood donors showed that at least two of the three genotypes, A, D, and F, co-circulate in each of the five geographic regions of Brazil. No other genotypes were identified. Overall, genotype A was most prevalent (48.5%, and most of these isolates were classified as subgenotype A1 (138/153; 90.2%. Genotype D was the most common genotype in the South (84.2% and Central (47.6% regions. The prevalence of genotype F was low (13% countrywide. Nucleotide sequencing of the S gene and a phylogenetic analysis of 32 HBV genotype F isolates showed that a great majority (28/32; 87.5% belonged to subgenotype F2, cluster II. The deduced serotype of 31 of 32 F isolates was adw4. The remaining isolate showed a leucine-to-isoleucine substitution at position 127. Conclusion The presence of genotypes A, D and F, and the absence of other genotypes in a large cohort of HBV infected individuals may reflect the ethnic origins of the Brazilian population. The high prevalence of isolates from subgenotype A1 (of African origin indicates that the African influx during the colonial slavery period had a major impact on the circulation of HBV genotype A currently found in Brazil. Although most genotype F

  5. Forensic SNP genotyping with SNaPshot

    DEFF Research Database (Denmark)

    Fondevila, M; Børsting, C; Phillips, C


    to routine STR profiling, use of SNaPshot is an important part of the development of SNP sets for a wide range of forensic applications with these markers, from genotyping highly degraded DNA with very short amplicons to the introduction of SNPs to ascertain the ancestry and physical characteristics......This review explores the key factors that influence the optimization, routine use, and profile interpretation of the SNaPshot single-base extension (SBE) system applied to forensic single-nucleotide polymorphism (SNP) genotyping. Despite being a mainly complimentary DNA genotyping technique...... of an unidentified contact trace donor. However, this technology, as resourceful as it is, displays several features that depart from the usual STR genotyping far enough to demand a certain degree of expertise from the forensic analyst before tackling the complex casework on which SNaPshot application provides...

  6. HMSRP Hawaiian Monk Seal Microsatellite Genotypes (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Currently ~2,400 Hawaiian monk seal specimens have been analyzed genetically, providing genotypes at 18 microsatellite loci. These data are organized by individual,...

  7. Global distribution of novel rhinovirus genotype

    DEFF Research Database (Denmark)

    Briese, Thomas; Renwick, Neil; Venter, Marietjie


    Global surveillance for a novel rhinovirus genotype indicated its association with community outbreaks and pediatric respiratory disease in Africa, Asia, Australia, Europe, and North America. Molecular dating indicates that these viruses have been circulating for at least 250 years Udgivelsesdato...

  8. Assessment of antibiotic susceptibilities, genotypic characteristics ...

    African Journals Online (AJOL)



    Sep 28, 2011 ... Staphylococcus aureus and Salmonella Typhimurium ... This study was designed to evaluate the antibiotic susceptibilities, genotypic characteristics and ..... Distribution of reference and virulence genes among antibiotic-sensitive S. aureus (SAS), .... environmental factors such as temperature, water activity,.

  9. Early seedling development of Medicago truncatula genotypes ...

    African Journals Online (AJOL)



    Jan 8, 2014 ... heat shock proteins; ABA, abscisic acid. Page 2. Amar et al. 323. Figure 1. Seed vigor of M. truncatula genotypes under different salt stress conditions. Results are means ..... (HSPs) that accumulate during seed late maturation.

  10. Hearing impairment in genotyped Wolfram syndrome patients.

    NARCIS (Netherlands)

    Plantinga, R.F.; Pennings, R.J.E.; Huygen, P.L.M.; Bruno, R.; Eller, P.; Barrett, T.G.; Vialettes, B.; Paquis-Fluklinger, V.; Lombardo, F.; Cremers, C.W.R.J.


    OBJECTIVES: Wolfram syndrome is a progressive neurodegenerative syndrome characterized by the features "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). We sought to study the audiometric data of genotyped Wolfram syndrome patients with sensorineural hearing impairment.

  11. Existence of various human parvovirus B19 genotypes in Chinese plasma pools: genotype 1, genotype 3, putative intergenotypic recombinant variants and new genotypes. (United States)

    Jia, Junting; Ma, Yuyuan; Zhao, Xiong; Huangfu, Chaoji; Zhong, Yadi; Fang, Chi; Fan, Rui; Lv, Maomin; Zhang, Jingang


    Human parvovirus B19 (B19V) is a frequent contaminant of blood and plasma-derived medicinal products. Three distinct genotypes of B19V have been identified. The distribution of the three B19V genotypes has been investigated in various regions or countries. However, in China, data on the existence of different B19V genotypes are limited. One hundred and eighteen B19V-DNA positive source plasma pool samples collected from three Chinese blood products manufacturers were analyzed. The subgenomic NS1/VP1u region junction of B19V was amplified by nested PCR. These amplified products were then cloned and subsequently sequenced. For genotyping, their phylogenetic inferences were constructed based on the NS1/VP1-unique region. Then putative recombination events were analyzed and identified. Phylogenetic analysis of 118 B19V sequences attributed 61.86 % to genotype 1a, 10.17 % to genotype 1b, and 17.80 % to genotype 3b. All the genotype 3b sequences obtained in this study grouped as a specific, closely related cluster with B19V strain D91.1. Four 1a/3b recombinants and 5 new atypical B19V variants with no recombination events were identified. There were at least 3 subtypes (1a, 1b and 3b) of B19V circulating in China. Furthermore, putative B19V 1a/3b recombinants and unclassified strains were identified as well. Such recombinant and unclassified strains may contribute to the genetic diversity of B19V and consequently complicate the B19V infection diagnosis and NAT screening. Further studies will be required to elucidate the biological significance of the recombinant and unclassified strains.

  12. Lower head failure analysis

    International Nuclear Information System (INIS)

    Rempe, J.L.; Thinnes, G.L.; Allison, C.M.; Cronenberg, A.W.


    The US Nuclear Regulatory Commission is sponsoring a lower vessel head research program to investigate plausible modes of reactor vessel failure in order to determine (a) which modes have the greatest likelihood of occurrence during a severe accident and (b) the range of core debris and accident conditions that lead to these failures. This paper presents the methodology and preliminary results of an investigation of reactor designs and thermodynamic conditions using analytic closed-form approximations to assess the important governing parameters in non-dimensional form. Preliminary results illustrate the importance of vessel and tube geometrical parameters, material properties, and external boundary conditions on predicting vessel failure. Thermal analyses indicate that steady-state temperature distributions will occur in the vessel within several hours, although the exact time is dependent upon vessel thickness. In-vessel tube failure is governed by the tube-to-debris mass ratio within the lower head, where most penetrations are predicted to fail if surrounded by molten debris. Melt penetration distance is dependent upon the effective flow diameter of the tube. Molten debris is predicted to penetrate through tubes with a larger effective flow diameter, such as a boiling water reactor (BWR) drain nozzle. Ex-vessel tube failure for depressurized reactor vessels is predicted to be more likely for a BWR drain nozzle penetration because of its larger effective diameter. At high pressures (between ∼0.1 MPa and ∼12 MPa) ex-vessel tube rupture becomes a dominant failure mechanism, although tube ejection dominates control rod guide tube failure at lower temperatures. However, tube ejection and tube rupture predictions are sensitive to the vessel and tube radial gap size and material coefficients of thermal expansion

  13. Popcorn genotypes resistance to fall armyworm

    Directory of Open Access Journals (Sweden)

    Nádia Cristina de Oliveira


    Full Text Available ABSTRACT: The aim of this study was to evaluate popcorn genotypes for resistance to the fall armyworm, Spodoptera frugiperda. The experiment used a completely randomized design with 30 replicates. The popcorn genotypes Aelton, Arzm 05 083, Beija-Flor, Colombiana, Composto Chico, Composto Gaúcha, Márcia, Mateus, Ufvm Barão Viçosa, Vanin, and Viviane were evaluated,along with the common maize variety Zapalote Chico. Newly hatched fall armyworm larvae were individually assessed with regard to biological development and consumption of food. The data were subjected to multivariate analyses of variance and genetic divergence among genotypes was evaluated through the clustering methods of Tocher based on generalized Mahalanobis distances and canonical variable analyses. Seven popcorn genotypes, namely, Aelton, Arzm 05 083, Composto Chico, Composto Gaúcha, Márcia, Mateus, and Viviane,were shown to form a cluster (cluster I that had antibiosis as the mechanism of resistance to the pest. Cluster I genotypes and the Zapalote Chico genotype could be used for stacking genes for antibiosis and non-preference resistance.

  14. Dependent failures of diesel generators

    International Nuclear Information System (INIS)

    Mankamo, T.; Pulkkinen, U.


    This survey of dependent failures (common-cause failures) is based on the data of diesel generator failures in U. S. nuclear power plants as reported in Licensee Event Reports. Failures were classified into random and potentially dependent failures. All failures due to design errors, manufacturing or installation errors, maintenance errors, or deviations in the operational environment were classified as potentially dependent failures.The statistical dependence between failures was estimated from the relative portion of multiple failures. Results confirm the earlier view of the significance of statistical dependence, a strong dependence on the age of the diesel generator was found in each failure class excluding random failures and maintenance errors, which had a nearly constant frequency independent of diesel generator age

  15. Molecular Analysis of the SRD5A1 and SRD5A2 Genes in Patients with Benign Prostatic Hyperplasia with Regard to Metabolic Parameters and Selected Hormone Levels

    Directory of Open Access Journals (Sweden)

    Aleksandra Rył


    Full Text Available Introduction: The etiology of benign prostatic hyperplasia (BPH has not so far been fully explicated. However, it is assumed that changes in the levels of hormones associated with aging can contribute to the development of prostatic hyperplasia. Dihydrotestosterone combines with the androgen receptor (AR proteins of the prostate gland. Enzyme activity is based on two isoenzymes: type 1 and type 2. 5α-reductase type 1 is encoded by the SRD5A1 gene, and type 2 is encoded by the SRD5A2 gene. The aim of our study was to determine the frequency of the SRD5A1 (rs6884552, rs3797177 and SRD5A2 (rs523349, rs12470143 genes’ polymorphisms, and to assess the relationships between the genotypes of the tested mutations, and the levels of biochemical and hormonal parameters in patients with BPH. Material and Methods: The study involved 299 men with benign prostatic hyperplasia. We determined the serum levels of particular biochemical parameters—fasting plasma glucose (FPG, total cholesterol (TC, low-density lipoprotein (LDL, high-density lipoprotein (HDL and triglycerides (TG—by the spectrophotometric method, using ready reagent kits. The ELISA method was used to determine the levels of the following hormonal parameters and proteins: total testosterone (TT, free testosterone (FT, insulin (I, luteinizing hormone (LH, and sex hormone binding protein (SHBG. Metabolic syndrome was diagnosed. Genotyping was performed by real-time PCR. Results: We analyzed the relationships between the incidence of particular diseases and the genotypes of the SRD5A1 and SRD5A2 polymorphisms among patients with BPH. The BPH patients with the CC genotype of the SRD5A2 rs523349 and rs12470143 polymorphisms were considerably less frequently diagnosed with metabolic syndrome (MetS (p = 0.022 and p = 0.023 respectively. Our analysis revealed that homozygotes with the CC of the SDR5A2 rs12470143 polymorphism had visibly higher HDL levels than those with the TT and CT genotypes (p

  16. Wnt5a Signaling in Cancer

    Directory of Open Access Journals (Sweden)

    Marwa S. Asem


    Full Text Available Wnt5a is involved in activating several non-canonical WNT signaling pathways, through binding to different members of the Frizzled- and Ror-family receptors. Wnt5a signaling is critical for regulating normal developmental processes, including proliferation, differentiation, migration, adhesion and polarity. However, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a in regulating cancer cell invasion, metastasis, metabolism and inflammation. In this article, we review findings regarding the molecular mechanisms and roles of Wnt5a signaling in various cancer types, and highlight Wnt5a in ovarian cancer.

  17. Nutrition in Heart Failure

    Directory of Open Access Journals (Sweden)

    Reci Meseri


    Full Text Available Heart failure is defined as decreased ability of heart due to various reasons. It%u2019s seen 2-3% but the prevalence increases sharply after the age of seventy. The objectives of nutrition therapy in heart failure are to prevent from water retention and edema, to avoid from hard digestion and to offer a balanced diet. In order to avoid fluid retention and edema, daily sodium and fluid intake must be monitored carefully. Main dilemma of the heart failure patients is the obesity-cachexia dilemma. Since one of the main reasons of heart failure is cardiovascular diseases, in first phase, the patient may be obese. In the later phases, cachexia may show up. It was shown that cachexia is associated with mortality. Within this period, patients should not be over-fed and the patient should pass from catabolic state to anabolic state slowly. If the gastrointestinal track is functional oral/enteral feeding must be preferred. Multi vitamin and mineral supportsmay be beneficial, which may replace the increased loss, increase anti-inflammatory response and be anti-oxidants. Large, controlled and well-designed studies must be conducted in order to evaluate the benefits of nutritional practices such as nutritional assessment, enteral feeding and nutrient supports in heart failure patients.

  18. Ductile failure modeling

    DEFF Research Database (Denmark)

    Benzerga, Ahmed Amine; Leblond, Jean Baptiste; Needleman, Alan


    Ductile fracture of structural metals occurs mainly by the nucleation, growth and coalescence of voids. Here an overview of continuum models for this type of failure is given. The most widely used current framework is described and its limitations discussed. Much work has focused on extending void...... growth models to account for non-spherical initial void shapes and for shape changes during growth. This includes cases of very low stress triaxiality, where the voids can close up to micro-cracks during the failure process. The void growth models have also been extended to consider the effect of plastic...... anisotropy, or the influence of nonlocal effects that bring a material size scale into the models. Often the voids are not present in the material from the beginning, and realistic nucleation models are important. The final failure process by coalescence of neighboring voids is an issue that has been given...

  19. Modeling Epidemic Network Failures

    DEFF Research Database (Denmark)

    Ruepp, Sarah Renée; Fagertun, Anna Manolova


    This paper presents the implementation of a failure propagation model for transport networks when multiple failures occur resulting in an epidemic. We model the Susceptible Infected Disabled (SID) epidemic model and validate it by comparing it to analytical solutions. Furthermore, we evaluate...... the SID model’s behavior and impact on the network performance, as well as the severity of the infection spreading. The simulations are carried out in OPNET Modeler. The model provides an important input to epidemic connection recovery mechanisms, and can due to its flexibility and versatility be used...... to evaluate multiple epidemic scenarios in various network types....

  20. Echo and heart failure

    DEFF Research Database (Denmark)

    Modin, Daniel; Andersen, Ditte Madsen; Biering-Sørensen, Tor


    Heart failure (HF) is a threat to public health. Heterogeneities in aetiology and phenotype complicate the diagnosis and management of HF. This is especially true when considering HF with preserved ejection fraction (HFpEF), which makes up 50% of HF cases. Natriuretic peptides may aid in establis......Heart failure (HF) is a threat to public health. Heterogeneities in aetiology and phenotype complicate the diagnosis and management of HF. This is especially true when considering HF with preserved ejection fraction (HFpEF), which makes up 50% of HF cases. Natriuretic peptides may aid...

  1. Generalized Block Failure

    DEFF Research Database (Denmark)

    Jönsson, Jeppe


    Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...... shows that no readily available tests with a well-defined substantial eccentricity have been performed. This paper presents theoretical and experimental work leading towards generalized block failure capacity methods. Simple combination of normal force, shear force and moment stress distributions along...... yield lines around the block leads to simple interaction formulas similar to other interaction formulas in the codes....

  2. Mumps vaccine failure investigation in Novosibirsk, Russia, 2002-2004. (United States)

    Atrasheuskaya, A V; Kulak, M V; Rubin, S; Ignatyev, G M


    The aims of this study were to estimate the importance of vaccine failure (VF) in cases of mumps during 2002-2004 in the city of Novosibirsk, Western Siberia, Russia, and to genotype the responsible virus strain. Mumps virus-specific RT-PCR testing of saliva was performed for 18 cases of mumps. Sera were tested for IgM and IgG, IgG avidity, and the ability to neutralise a panel of mumps viruses, including the Leningrad-3 mumps vaccine virus. Of the 12 patients for whom vaccination status was positively determined, 11 showed serological evidence of primary VF. Sequence analysis of virus RNA amplified from saliva revealed a genotype C2 virus in 2002, a genotype H2 virus in 2003, and both genotypes in 2004. Although several vaccinated patients were positive for mumps virus IgG at the time of first sampling, only nominal levels of neutralising antibody were detected, and these were effective in neutralising the vaccine strain, but not genotype C and H mumps virus strains. These results suggest that the majority of cases of mumps in vaccinees are caused by primary VF, defined as either a lack of seroconversion or a lack of IgG maturity, as based on avidity testing. The results also support the hypothesis that sera of low neutralising antibody titre have a limited ability to neutralise heterologous mumps virus strains, suggesting that antigenic differences between circulating and mumps vaccine virus strains may play a role in cases of breakthrough infection. Consistent with previous reports, mumps virus genotypes C and H continue to circulate in Novosibirsk.

  3. Cotton genotypes selection through artificial neural networks. (United States)

    Júnior, E G Silva; Cardoso, D B O; Reis, M C; Nascimento, A F O; Bortolin, D I; Martins, M R; Sousa, L B


    Breeding programs currently use statistical analysis to assist in the identification of superior genotypes at various stages of a cultivar's development. Differently from these analyses, the computational intelligence approach has been little explored in genetic improvement of cotton. Thus, this study was carried out with the objective of presenting the use of artificial neural networks as auxiliary tools in the improvement of the cotton to improve fiber quality. To demonstrate the applicability of this approach, this research was carried out using the evaluation data of 40 genotypes. In order to classify the genotypes for fiber quality, the artificial neural networks were trained with replicate data of 20 genotypes of cotton evaluated in the harvests of 2013/14 and 2014/15, regarding fiber length, uniformity of length, fiber strength, micronaire index, elongation, short fiber index, maturity index, reflectance degree, and fiber quality index. This quality index was estimated by means of a weighted average on the determined score (1 to 5) of each characteristic of the HVI evaluated, according to its industry standards. The artificial neural networks presented a high capacity of correct classification of the 20 selected genotypes based on the fiber quality index, so that when using fiber length associated with the short fiber index, fiber maturation, and micronaire index, the artificial neural networks presented better results than using only fiber length and previous associations. It was also observed that to submit data of means of new genotypes to the neural networks trained with data of repetition, provides better results of classification of the genotypes. When observing the results obtained in the present study, it was verified that the artificial neural networks present great potential to be used in the different stages of a genetic improvement program of the cotton, aiming at the improvement of the fiber quality of the future cultivars.

  4. Hepatitis C virus genotypes in Bahawalpur

    International Nuclear Information System (INIS)

    Qazi, M.A.; Fayyaz, M.; Chaudhry, G.M.D.; Jamil, A.


    This study was conducted at Medical Unit-II Bahawal Victoria Hospital / Quaid-e-Azam Medical College Bahawalpur from May 1st , 2005 to December 31st 2005. The objective of this study was to determine hepatitis C virus (HCV) genotypes in Bahawalpur, Pakistan. In consecutive 105 anti-HCV (ELISA-3) positive patients, complete history and physical examination was performed. Liver function tests, complete blood counts and platelet count, blood sugar fasting and 2 hours after breakfast, prothrombin time, serum albumin, serum globulin and abdominal ultrasound were carried out in all the patients. Tru cut biopsy was performed on 17 patients. We studied HCV RNA in all these patients by Nested PCR method. HCV RNA was detected in 98 patients and geno typing assay was done by genotype specific PCR. Among total of 105 anti-HCV positive patients, HCV-RNA was detected in 98 patients. Out of these 98 patients there were 57 (58.2%) males and 41 (42.8%) females. Their age range was 18-75 years. The age 18-29 years 26 (26.5%), 30-39 years 35 (35.7%) and 40-75 37 (37.8%), while 10 (10.2%) patients were diabetics and 34 (34.7%) patients were obese. Liver cirrhosis was present in 10 (10.2%) patients. Forty two (43.9%) patients were symptomatic while 56 (57.1%) were asymptomatic. Out of 98 patients 11 (11.2%) were un type-able and 87 (88.8%) were type able. 70/98 (71.4%) were genotype 3; 10/98 (10.2%) were genotype 1; 03/98 (3.1%) were genotype 2; 03/98 (3.1%) were mixed genotype 2 and 3; 01/98 (1%) were mixed genotype 3a and 3b. Genotype 3 is the most common HCV virus in our area which shows that both virological and biochemical response will be better. Because HCV genotype 3 is more frequent among the drug users which points towards unsafe injection practices in our area. (author)

  5. Successful retreatment with sofosbuvir plus ledipasvir for cirrhotic patients with hepatitis C virus genotype 1b, who discontinued the prior treatment with asunaprevir plus daclatasvir: A case series and review of the literature (United States)

    Haga, Yuki; Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Ooka, Yoshihiko; Takahashi, Koji; Wu, Shuang; Nakamoto, Shingo; Arai, Makoto; Chiba, Tetsuhiro; Maruyama, Hitoshi; Yokosuka, Osamu; Takada, Nobuo; Moriyama, Mitsuhiko; Imazeki, Fumio; Kato, Naoya


    Background Interferon-free treatment results in higher sustained virologic response (SVR) rates, with no serious adverse events in hepatitis C virus (HCV)-infected patients. However, in some patients with treatment-failure in HCV NS5A inhibitor-including interferon-free regimens, the treatment-emergent HCV NS5A resistance-associated variants (RAVs), which are resistant to interferon-free retreatment including HCV NS5A inhibitors, are observed. In HCV-infected Japanese patients with daclatasvir and asunaprevir treatment failure, retreatment with sofosbuvir and ledipasvir could lead to only ∼70% SVR rates. Case summary Three HCV genotype (GT)-1b-infected cirrhotic patients who discontinued the combination of daclatasvir and asunaprevir due to adverse drug reactions within 4 weeks; retreatment with sofosbuvir and ledipasvir combination could result in SVR in these patients without RAVs. One HCV GT-1b-infected cirrhotic patient who discontinued the combination of daclatasvir and asunaprevir due to viral breakthrough at week 10; retreatment with sofosbuvir and ledipasvir combination for this patient with the treatment-emergent HCV NS5A RAV-Y93H resulted in viral relapse at week 4 after the end of the treatment. Conclusion Retreatment with sofosbuvir and ledipasvir is effective for HCV GT-1b patients who discontinue the combination of daclatasvir and asunaprevir within 4 weeks. The treatment response should be related to the existence of treatment-emergent HCV NS5A RAVs, but may not be related to the short duration of treatment. PMID:29435197

  6. Isogeometric failure analysis

    NARCIS (Netherlands)

    Verhoosel, C.V.; Scott, M.A.; Borden, M.J.; Borst, de R.; Hughes, T.J.R.; Mueller-Hoeppe, D.; Loehnert, S.; Reese, S.


    Isogeometric analysis is a versatile tool for failure analysis. On the one hand, the excellent control over the inter-element continuity conditions enables a natural incorporation of continuum constitutive relations that incorporate higher-order strain gradients, as in gradient plasticity or damage.

  7. Beyond Success and Failure

    NARCIS (Netherlands)

    Etalle, Sandro; Jaffar, Joxan; van Raamsdonk, Femke

    We study a new programming framework based on logic programming where success and failure are replaced by predicates for adequacy and inadequacy. Adequacy allows to extract a result from a partial computation, and inadequacy allows to flexibly constrain the search space. In this parameterized

  8. Poverty and Aspirations Failure

    NARCIS (Netherlands)

    Dalton, P.S.; Ghosal, S.; Mani, A.


    We develop a theoretical framework to study the psychology of poverty and 'aspirations failure'. In our framework, the rich and the poor share the same preferences - and also a behavioral bias in setting aspirations. Greater downside risks imposed by poverty exacerbates the effects of this

  9. Poverty and aspirations failure

    NARCIS (Netherlands)

    Dalton, P.S.; Ghosal, S.; Mani, A.

    We develop a theoretical framework to study the psychology of poverty and ‘aspirations failure’, defined as the failure to aspire to one’s own potential. In our framework, rich and the poor persons share the same preferences and same behavioral bias in setting aspirations. We show that poverty can

  10. Copeptin in Heart Failure

    DEFF Research Database (Denmark)

    Balling, Louise; Gustafsson, Finn


    Heart failure (HF) is one of the most common causes of hospitalization and mortality in the modern Western world and an increasing proportion of the population will be affected by HF in the future. Although HF management has improved quality of life and prognosis, mortality remains very high...

  11. Acute liver failure

    DEFF Research Database (Denmark)

    Bernal, William; Lee, William M; Wendon, Julia


    Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver...

  12. Premature ovarian failure


    Pacheco, José


    Premature ovarian failure is characterized by secondary amenorrhea affecting a woman before the age of 40, leading to hypoestrogenism, infertility, and consequences of premature menopause, such as osteoporosis, cardiovascular disease, neurovegetative alterations, and others. Follicular exhaustion is due to either follicles shortage or oocytes accelerated destruction. Main causes are genetic, autoimmune and iatrogenic. Among genetic causes Xq and Xp deletions, translocations, numeric aberratio...

  13. CMR in Heart Failure.


    Sado, D. M.; Hasleton, J. M.; Herrey, A. S.; Moon, J. C.


    Heart Failure (HF) is a common syndrome with multiple causes. Cardiovascular magnetic resonance (CMR) is a medical imaging technique with significant advantages, allowing the understanding of aetiology and pathophysiology of HF in the individual patient, permitting specific therapy to be administered and predicting prognosis. This paper discusses the diverse role of CMR in HF.

  14. Perioperative acute renal failure.

    LENUS (Irish Health Repository)

    Mahon, Padraig


    PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

  15. Phenotypic and genotypic variation in Iranian Pistachios

    Directory of Open Access Journals (Sweden)

    Somayeh Tayefeh Aliakbarkhani


    Full Text Available As Iran is one of the richest pistachio germplasms a few studies have been conducted on different sexes of pistachio trees, in areas where this crop emerged. To this end, 40 male and female Iranian pistachio genotypes from Feizabad region, Khorasan, Iran; were evaluated using morphological characters and randomly amplified polymorphic DNA (RAPD markers. For morphological assessments, 54 variables were considered to investigate similarities between and among the studied genotypes. Morphological data indicated relative superiority in some female genotypes (such as Sefid 1, Sefid Sabuni 2, Garmesiah, and Ghermezdorosht Z regarding characters such as halfcrackedness, the percentages of protein and fat content. 115 polymorphic bands were recorded with 92.83% average polymorphism among all primers. The total resolving power (Rp of the primers was 74.54. The range of genetic similarity varied from about 0.31 to about 0.70. Genotypes were segregated into eight groups at the similarity limit of 0.41. Results of present investigation could be helpful for strategic decisions for maintaining Iranian pistachio genotypes.

  16. Precise genotyping and recombination detection of Enterovirus (United States)


    Enteroviruses (EV) with different genotypes cause diverse infectious diseases in humans and mammals. A correct EV typing result is crucial for effective medical treatment and disease control; however, the emergence of novel viral strains has impaired the performance of available diagnostic tools. Here, we present a web-based tool, named EVIDENCE (EnteroVirus In DEep conception,, for EV genotyping and recombination detection. We introduce the idea of using mixed-ranking scores to evaluate the fitness of prototypes based on relatedness and on the genome regions of interest. Using phylogenetic methods, the most possible genotype is determined based on the closest neighbor among the selected references. To detect possible recombination events, EVIDENCE calculates the sequence distance and phylogenetic relationship among sequences of all sliding windows scanning over the whole genome. Detected recombination events are plotted in an interactive figure for viewing of fine details. In addition, all EV sequences available in GenBank were collected and revised using the latest classification and nomenclature of EV in EVIDENCE. These sequences are built into the database and are retrieved in an indexed catalog, or can be searched for by keywords or by sequence similarity. EVIDENCE is the first web-based tool containing pipelines for genotyping and recombination detection, with updated, built-in, and complete reference sequences to improve sensitivity and specificity. The use of EVIDENCE can accelerate genotype identification, aiding clinical diagnosis and enhancing our understanding of EV evolution. PMID:26678286

  17. 5A/6A Polymorphism of the Stromelysin-1 Gene and Angiographic Restenosis After Coronary Artery Stenting

    Directory of Open Access Journals (Sweden)

    Kuan-Rau Chiou


    Conclusion: There is a low frequency of the stromelysin-1 promoter 5A allele in the Chinese population in Taiwan. How stromelysin-1 5A/6A polymorphism affects ISR appears to be linked to angina status. These results merit further study to identify patients carrying genotypes which put them at increased risk of ISR, and which matrix metalloproteinase inhibitors or drug-eluting stents are more effective for those at risk.

  18. Diuretics for heart failure. (United States)

    Faris, Rajaa F; Flather, Marcus; Purcell, Henry; Poole-Wilson, Philip A; Coats, Andrew J S


    Chronic heart failure is a major cause of morbidity and mortality worldwide. Diuretics are regarded as the first-line treatment for patients with congestive heart failure since they provide symptomatic relief. The effects of diuretics on disease progression and survival remain unclear. To assess the harms and benefits of diuretics for chronic heart failure Updated searches were run in the Cochrane Central Register of Controlled Trials in The Cochrane Library (CENTRAL Issue 1 of 4, 2011), MEDLINE (1966 to 22 February 2011), EMBASE (1980 to 2011 Week 07) and HERDIN database (1990 to February 2011). We hand searched pertinent journals and reference lists of papers were inspected. We also contacted manufacturers and researchers in the field. No language restrictions were applied. Double-blinded randomised controlled trials of diuretic therapy comparing one diuretic with placebo, or one diuretic with another active agent (e.g. ACE inhibitors, digoxin) in patients with chronic heart failure. Two authors independently abstracted the data and assessed the eligibility and methodological quality of each trial. Extracted data were analysed by determining the odds ratio for dichotomous data, and difference in means for continuous data, of the treated group compared with controls. The likelihood of heterogeneity of the study population was assessed by the Chi-square test. If there was no evidence of statistical heterogeneity and pooling of results was clinically appropriate, a combined estimate was obtained using the fixed-effects model. This update has not identified any new studies for inclusion. The review includes 14 trials (525 participants), 7 were placebo-controlled, and 7 compared diuretics against other agents such as ACE inhibitors or digoxin. We analysed the data for mortality and for worsening heart failure. Mortality data were available in 3 of the placebo-controlled trials (202 participants). Mortality was lower for participants treated with diuretics than for

  19. Highly efficient full-length hepatitis C virus genotype 1 (strain TN) infectious culture system

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Jensen, Sanne B


    Chronic infection with hepatitis C virus (HCV) is an important cause of end stage liver disease worldwide. In the United States, most HCV-related disease is associated with genotype 1 infection, which remains difficult to treat. Drug and vaccine development was hampered by inability to culture...... full-length TN infection dose-dependently. Given the unique importance of genotype 1 for pathogenesis, this infectious 1a culture system represents an important advance in HCV research. The approach used and the mutations identified might permit culture development for other HCV isolates, thus......) culture systems in Huh7.5 cells. Here, we developed a highly efficient genotype 1a (strain TN) full-length culture system. We initially found that the LSG substitutions conferred viability to an intergenotypic recombinant composed of TN 5' untranslated region (5'UTR)-NS5A and JFH1 NS5B-3'UTR; recovered...

  20. Resistance Patterns Associated with HCV NS5A Inhibitors Provide Limited Insight into Drug Binding

    Directory of Open Access Journals (Sweden)

    Moheshwarnath Issur


    Full Text Available Direct-acting antivirals (DAAs have significantly improved the treatment of infection with the hepatitis C virus. A promising class of novel antiviral agents targets the HCV NS5A protein. The high potency and broad genotypic coverage are favorable properties. NS5A inhibitors are currently assessed in advanced clinical trials in combination with viral polymerase inhibitors and/or viral protease inhibitors. However, the clinical use of NS5A inhibitors is also associated with new challenges. HCV variants with decreased susceptibility to these drugs can emerge and compromise therapy. In this review, we discuss resistance patterns in NS5A with focus prevalence and implications for inhibitor binding.

  1. Saponin profile of green asparagus genotypes. (United States)

    Vázquez-Castilla, Sara; Jaramillo-Carmona, Sara; Fuentes-Alventosa, Jose María; Jiménez-Araujo, Ana; Rodríguez-Arcos, Rocío; Cermeño-Sacristán, Pedro; Espejo-Calvo, Juan Antonio; Guillén-Bejarano, Rafael


    The main goal of this study was to determine the saponin profiles of different "triguero" asparagus genotypes and to compare them to green asparagus commercial hybrids. The samples consisted of 31 commercial hybrids and 58 genotypes from the Huétor-Tájar (HT) population variety ("triguero"). The saponin analysis by high-performance liquid chromatography-mass spectrometry allowed for the determination of 12 saponins derived from a furostan-type steroidal genin, 4 of which had never been described in the edible part of asparagus. The saponin profile of "triguero" asparagus was a combination of these new saponins and protodioscin. Although protodioscin was the major saponin found in commercial hybrids, some of these 12 saponins were detected as major components in some of the commercial hybrids. The total contents of saponins described in some of these HT genotypes reach values as high as 10-100 times higher than those found in commercial hybrids.

  2. Carcass traits of four rabbit genotypes

    Directory of Open Access Journals (Sweden)

    Ajda Kermauner


    Full Text Available Seventy-three rabbits of four genotypes (A - SIKA maternal line; C - SIKA sire line; AxC - hybrids between line A and C; AxCal - crossbreds between line A and the Californian breed were used to evaluate the effect of genotype on carcass traits. Rabbits were weaned at 35 days and slaughtered at 93 days of age. Rabbits were fed standard feed mixture ad libitum. The highest live weight at slaughter and dressing percentage was achieved by line C, and the lowest in line A. Hybrids between line A and C exhibited slightly worse carcass traits than rabbits in line C, but the differences were not statistically significant. The Californian breed gave worse results than crossbreeding with line C, though in most cases the differences between AxC and AxCal were not significant. The differences between genotypes in hind leg tissue composition, pH and meat colour were not statistically significant.

  3. Genotype x environment interaction for grain yield of wheat genotypes tested under water stress conditions

    International Nuclear Information System (INIS)

    Sail, M.A.; Dahot, M.U.; Mangrio, S.M.; Memon, S.


    Effect of water stress on grain yield in different wheat genotypes was studied under field conditions at various locations. Grain yield is a complex polygenic trait influenced by genotype, environment and genotype x environment (GxE) interaction. To understand the stability among genotypes for grain yield, twenty-one wheat genotypes developed Through hybridization and radiation-induced mutations at Nuclear Institute of Agriculture (NIA) TandoJam were evaluated with four local check varieties (Sarsabz, Thori, Margalla-99 and Chakwal-86) in multi-environmental trails (MET/sub s/). The experiments were conducted over 5 different water stress environments in Sindh. Data on grain yield were recorded from each site and statistically analyzed. Combined analysis of variance for all the environments indicated that the genotype, environment and genotype x environment (GxE) interaction were highly significant (P greater then 0.01) for grain yield. Genotypes differed in their response to various locations. The overall highest site mean yield (4031 kg/ha) recorded at Moro and the lowest (2326 kg/ha) at Thatta. Six genotypes produced significantly (P=0.01) the highest grain yield overall the environments. Stability analysis was applied to estimate stability parameters viz., regression coefficient (b), standard error of regression coefficient and variance due to deviation from regression (S/sub 2/d) genotypes 10/8, BWS-78 produced the highest mean yield over all the environments with low regression coefficient (b=0.68, 0.67 and 0.63 respectively and higher S/sup 2/ d value, showing specific adaptation to poor (un favorable) environments. Genotype 8/7 produced overall higher grain yield (3647 kg/ha) and ranked as third high yielding genotype had regression value close to unity (b=0.9) and low S/sup d/ value, indicating more stability and wide adaptation over the all environments. The knowledge of the presence and magnitude of genotype x environment (GE) interaction is important to

  4. Use of Sequenom sample ID Plus® SNP genotyping in identification of FFPE tumor samples.

    Directory of Open Access Journals (Sweden)

    Jessica K Miller

    Full Text Available Short tandem repeat (STR analysis, such as the AmpFlSTR® Identifiler® Plus kit, is a standard, PCR-based human genotyping method used in the field of forensics. Misidentification of cell line and tissue DNA can be costly if not detected early; therefore it is necessary to have quality control measures such as STR profiling in place. A major issue in large-scale research studies involving archival formalin-fixed paraffin embedded (FFPE tissues is that varying levels of DNA degradation can result in failure to correctly identify samples using STR genotyping. PCR amplification of STRs of several hundred base pairs is not always possible when DNA is degraded. The Sample ID Plus® panel from Sequenom allows for human DNA identification and authentication using SNP genotyping. In comparison to lengthy STR amplicons, this multiplexing PCR assay requires amplification of only 76-139 base pairs, and utilizes 47 SNPs to discriminate between individual samples. In this study, we evaluated both STR and SNP genotyping methods of sample identification, with a focus on paired FFPE tumor/normal DNA samples intended for next-generation sequencing (NGS. The ability to successfully validate the identity of FFPE samples can enable cost savings by reducing rework.

  5. Mapping the functional landscape of frequent phenylalanine hydroxylase (PAH) genotypes promotes personalised medicine in phenylketonuria. (United States)

    Danecka, Marta K; Woidy, Mathias; Zschocke, Johannes; Feillet, François; Muntau, Ania C; Gersting, Søren W


    In phenylketonuria, genetic heterogeneity, frequent compound heterozygosity, and the lack of functional data for phenylalanine hydroxylase genotypes hamper reliable phenotype prediction and individualised treatment. A literature search revealed 690 different phenylalanine hydroxylase genotypes in 3066 phenylketonuria patients from Europe and the Middle East. We determined phenylalanine hydroxylase function of 30 frequent homozygous and compound heterozygous genotypes covering 55% of the study population, generated activity landscapes, and assessed the phenylalanine hydroxylase working range in the metabolic (phenylalanine) and therapeutic (tetrahydrobiopterin) space. Shared patterns in genotype-specific functional landscapes were linked to biochemical and pharmacological phenotypes, where (1) residual activity below 3.5% was associated with classical phenylketonuria unresponsive to pharmacological treatment; (2) lack of defined peak activity induced loss of response to tetrahydrobiopterin; (3) a higher cofactor need was linked to inconsistent clinical phenotypes and low rates of tetrahydrobiopterin response; and (4) residual activity above 5%, a defined peak of activity, and a normal cofactor need were associated with pharmacologically treatable mild phenotypes. In addition, we provide a web application for retrieving country-specific information on genotypes and genotype-specific phenylalanine hydroxylase function that warrants continuous extension, updates, and research on demand. The combination of genotype-specific functional analyses with biochemical, clinical, and therapeutic data of individual patients may serve as a powerful tool to enable phenotype prediction and to establish personalised medicine strategies for dietary regimens and pharmacological treatment in phenylketonuria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  6. Oilseed rape genotypes response to boron toxicity

    Directory of Open Access Journals (Sweden)

    Savić Jasna


    Full Text Available Response of 16 oilseed rape genotypes to B (boron toxicity was analyzed by comparing the results of two experiments conducted in a glasshouse. In Experiment 1 plants were grown in standard nutrient solutions with 10 µMB (control and 1000 µM B. Relative root and shoot growth varied from 20-120% and 31-117%, respectively. Variation in B concentration in shoots was also wide (206.5-441.7 µg B g-1 DW as well as total B uptake by plant (62.3-281.2 µg B g1. Four selected genotypes were grown in Experiment 2 in pots filled with high B soil (8 kg ha-1 B; B8. Shoot growth was not affected by B8 treatment, while root and shoot B concentration was significantly increased compared to control. Genotypes Panther and Pronto which performed low relative root and shoot growth and high B accumulation in plants in Experiment 1, had good growth in B8 treatment. In Experiment 2 genotype NS-L-7 had significantly lower B concentration in shots under treatment B8, but also very high B accumulation in Experiment 1. In addition, cluster analyses classified genotypes in three groups according to traits contrasting in their significance for analyzing response to B toxicity. The first group included four varieties based on their shared characteristics that have small value for the relative growth of roots and shoots and large values of B concentration in shoot. In the second largest group were connected ten genotypes that are heterogeneous in traits and do not stand out on any characteristic. Genotypes NS-L-7 and Navajo were separated in the third group because they had big relative growth of root and shoot, but also a high concentration of B in the shoot, and high total B uptake. Results showed that none of tested genotypes could not be recommended for breeding process to tolerance for B toxicity. [Projekat Ministarstva nauke Republike Srbije, br. OI 173028


    Directory of Open Access Journals (Sweden)



    Full Text Available Renal failure in obstetrics is rare but important complication, associated with significant mortality and long term morbidity.1,2 It includes acute renal failure due to obstetrical complications or due to deterioration of existing renal disease. AIMS AND OBJECTIVES: To evaluate the etiology and outcome of renal failure in obstetric patients. METHODS: We prospectively analyzed 30 pregnant and puerperal women with acute renal failure or pre-existing renal disease developing renal failure during pregnancy between November 2007 to sep-2009. Patients who presented/developed ARF during the hospital stay were included in this study. RESULTS: Among 30 patients, mean age was 23 years and 33 years age group. 12 cases (40% patients were primigravidae and 9(30% patients were multigravidae and 9 cases (30% presented in post-partum period. Eighteen cases (60% with ARF were seen in third trimester, followed by in postpartum period 9 cases (30%. Most common contributing factors to ARF were Pre-eclampsia, eclampsia and HELLP syndrome 60%, sepsis 56.6%, post abortal ARF 10%. DIC 40%. Haemorrhage as the aetiology for ARF was present 46%, APH in 20% and PPH in 26.6%. The type of ARF was renal in (63% and prerenal (36%; Oliguric seen in 10 patients (33% and high mortality (30%. Among the 20 pregnant patients with ARF, The average period of gestation was 33±2 weeks (30 -36 weeks, 5 cases (25% presented with intrauterine fetal demise and 18 cases (66% had preterm vaginal delivery and 2 cases (10% had induced abortion. And the average birth weight was 2±0.5 kg (1.5 kg. Eight cases (26% required dialysis. 80% of patients recovered completely of renal functions. 63% patients recovered without renal replacement therapy whereas 17% required dialysis. the maternal mortality was 20%, the main reason for mortality was septic shock and multi organ dysfunction (66%. CONCLUSION: ARF related pregnancy was seen commonly in the primigravidae and in the third trimester, the most

  8. Genetic associations of body composition, flexibility and injury risk with ACE, ACTN3 and COL5A1 polymorphisms in Korean ballerinas (United States)

    Kim, Jun Ho; Jung, Eun Sun; Kim, Chul-Hyun; Youn, Hyeon; Kim, Hwa Rye


    [Purpose] The purpose of this study was to exam the association of body composition, flexibility, and injury risk to genetic polymorphisms including ACE ID, ACTN3 RX, and COL5A1 polymorphisms in ballet dancers in Korea. [Methods] For the purpose of this study, elite ballerinas (n = 97) and normal female adults (n = 203) aged 18 to 39 were recruited and these participants were tested for body weight, height, body fat, fat free mass, flexibility, injury risks on the joints and gene polymorphisms (ACE, ACTN3, COL5A1 polymorphism). [Results] As results, the ACE DD genotype in ballerinas was associated with higher body fat and percentage of body fat than the ACE II and ID genotypes (p sports injuries, the ankle injury of the XX-genotyped ballerinas was in significantly more prevalence than the RR and XX-genotyped ballerinas (p < 0.05). According to the odd ratio analysis, XX-genotyped ballerinas have the injury risk on the ankle about 4.7 (95% CI: 1.6~13.4, p < 0.05) times more than the RR and RX-genotyped ballerinas. Meanwhile, the COL5A1 polymorphism in ballerinas has no association with any factors including flexibility and injury risks. [Conclusion] In conclusion, ACE polymorphism and ACTN3 polymorphism were associated with ballerinas' performance capacity; COL5A1 was not associated with any factors of performance of Ballerinas. The results suggested that the ACE DD genotype is associated with high body fat, the ACTN3 XX genotype is associated with low fat-free mass, low flexibility, and higher risk of ankle-joint injury. PMID:25566457

  9. Efficient cell culture system for hepatitis C virus genotype 1a and 1b

    DEFF Research Database (Denmark)


    isolate in generating efficient cell culture systems for other isolates by transfer of mutations across isolates, subtypes or major genotypes. Furthermore neutralization studies showed that viruses of e.g. genotype 1 were efficiently neutralized by genotype Ia, 4a and 5a serum, an effect that could......The present inventors developed hepatitis C virus 1a/2a and 1b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and NS2 were replaced by the corresponding genes of the genotype Ia reference strain H77C or TN or the corresponding genes of the genotype Ib...... reference strain J4. Sequence analysis of recovered 1a/2a and 1b/2a recombinants from 2 serial passages and subsequent reverse genetic studies revealed adaptive mutations in e.g. p7, NS2 and/or NS3. In addition, the inventors demonstrate the possibility of using adaptive mutations identified for one HCV...

  10. GenoType HelicoDR test in the determination of antimicrobial resistance of Helicobacter pylori in Korea. (United States)

    Lee, Jung Won; Kim, Nayoung; Nam, Ryoung Hee; Park, Ji Hyun; Choi, Yoon Jin; Kim, Jung Mogg; Kim, Joo Sung; Jung, Hyun Chae


    Antimicrobial resistance of Helicobacter pylori is most important factor in eradication success. GenoType HelicoDR test has been developed for rapid detection of antimicrobial resistance. The present study evaluated the clinical usefulness of GenoType HelicoDR test in Korea. To detect 23S rRNA for clarithromycin resistance and gyrA mutations for fluoroquinolone resistance, both DNA sequencing after minimal inhibitory test (MIC) and GenoType HelicoDR test were performed in H. pylori isolates from the gastric mucosa of 101 patients. The eradication results of clarithromycin and moxifloxacin-containing triple therapy were evaluated by the 23S rRNA and gyrA mutations. For 42 isolates with A2143G mutation by GenoType HelicoDR, 83.3% (35/42) of concordance rate was estimated with DNA sequencing method and 85.7% (36/42) for MIC test. For 43 isolates with N87K mutation by GenoType HelicoDR, 71.1% (31/43) of concordance rate was estimated with DNA sequencing and 88.4% (38/43) for MIC test. The sensitivity and specificity of GenoType HelicoDR test in determination of 23S rRNA mutation were 94.9% and 87.1%, and those of gyrA 98.2% and 80.0%. The sensitivity and specificity of GenoType HelicoDR test in determination of clarithromycin resistance based on MIC test were 55.0% and 80.0%, for fluoroquinolone 74.4% and 70.0%. GenoType HelicoDR test is useful to determine mutations responsible for clarithromycin or fluoroquinolone-containing eradication failure but has a limitation for the clinical applicability in determination of resistance.

  11. Autoimmune premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Beata Komorowska


    Full Text Available Premature ovarian failure (POF, also termed as primary ovarian insufficiency (POI, is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.

  12. Scarred by Failure?

    DEFF Research Database (Denmark)

    Mahieu, Jeroen; Melillo, Francesca; Reichstein, Toke

    Are failed entrepreneurs penalized in the labour market? The answer is yes under certain conditions. Using a novel dataset of matched entrepreneurs and employees in Belgium, we show that: on average, entrepreneurs returning to the labour market after a business failure are penalized, but this eff......Are failed entrepreneurs penalized in the labour market? The answer is yes under certain conditions. Using a novel dataset of matched entrepreneurs and employees in Belgium, we show that: on average, entrepreneurs returning to the labour market after a business failure are penalized...... years do not get penalized. Entrepreneurs who fail fast and move to a new employer limit the wage penalty by changing industry compared to the industry they were venturing in. These results are consistent with theories of adverse selection in the labour market....

  13. Satellite failures revisited (United States)

    Balcerak, Ernie


    In January 1994, the two geostationary satellites known as Anik-E1 and Anik-E2, operated by Telesat Canada, failed one after the other within 9 hours, leaving many northern Canadian communities without television and data services. The outage, which shut down much of the country's broadcast television for hours and cost Telesat Canada more than $15 million, generated significant media attention. Lam et al. used publicly available records to revisit the event; they looked at failure details, media coverage, recovery effort, and cost. They also used satellite and ground data to determine the precise causes of those satellite failures. The researchers traced the entire space weather event from conditions on the Sun through the interplanetary medium to the particle environment in geostationary orbit.

  14. Rate based failure detection (United States)

    Johnson, Brett Emery Trabun; Gamage, Thoshitha Thanushka; Bakken, David Edward


    This disclosure describes, in part, a system management component and failure detection component for use in a power grid data network to identify anomalies within the network and systematically adjust the quality of service of data published by publishers and subscribed to by subscribers within the network. In one implementation, subscribers may identify a desired data rate, a minimum acceptable data rate, desired latency, minimum acceptable latency and a priority for each subscription. The failure detection component may identify an anomaly within the network and a source of the anomaly. Based on the identified anomaly, data rates and or data paths may be adjusted in real-time to ensure that the power grid data network does not become overloaded and/or fail.

  15. LHC Magnet test failure

    CERN Multimedia


    "On Tueday, March 22, a Fermilab-built quadrupole magnet, one of an "inner triplet" of three focusing magnets, failed a high-pressure test at Point 5 in the tunnel of the LHC accelerator at CERN. Since Tuesday, teams at CERN and Fermilab have worked closely together to address the problem and have identified the cause of the failure. Now they are at work on a solution.:" (1 page)

  16. Failures of chain systems

    CSIR Research Space (South Africa)

    James, A


    Full Text Available ?C and intermittent exposure at 400--450 ?C. Unlike structural steels, which become softer and more ductile when reheated in service, manga- nese steels become brittle when reheated sufficiently to induce carbide... to form a roughly oval shaped crack until the link section could no longer withstand the applied loading experienced during normal dragline operations, and this resulted in final fast brittle failure. The general...

  17. Rethinking Heart Failure


    F?rstenwerth, Hauke


    An increasing body of clinical observations and experimental evidence suggests that cardiac dysfunction results from autonomic dysregulation of the contractile output of the heart. Excessive activation of the sympathetic nervous system and a decrease in parasympathetic tone are associated with increased mortality. Elevated levels of circulating catecholamines closely correlate with the severity and poor prognosis in heart failure. Sympathetic over-stimulation causes increased levels of catech...

  18. Diastolic Heart Failure


    Wake, Ryotaro; Yoshikawa, Junichi; Yoshiyama, Minoru


    Primary diastolic failure is typically seen in patients with hypertensive or valvular heart disease as well as in hypertrophic or restrictive cardiomyopathy but can also occur in a variety of clinical disorders, especially tachycardia and ischemia. Diastolic dysfunction has a particularly high prevalence in elderly patients and is generally associated, with low mortality but high morbidity. The pathophysiology of diastolic dysfunction includes delayed relaxation, impaired LV filling and/or in...

  19. Specificity of the Linear Array HPV Genotyping Test for detecting human papillomavirus genotype 52 (HPV-52)


    Kocjan, Boštjan; Poljak, Mario; Oštrbenk, Anja


    Introduction: HPV-52 is one of the most frequent human papillomavirus (HPV) genotypes causing significant cervical pathology. The most widely used HPV genotyping assay, the Roche Linear Array HPV Genotyping Test (Linear Array), is unable to identify HPV- 52 status in samples containing HPV-33, HPV-35, and/or HPV-58. Methods: Linear Array HPV-52 analytical specificity was established by testing 100 specimens reactive with the Linear Array HPV- 33/35/52/58 cross-reactive probe, but not with the...

  20. Development of JFH1-based cell culture systems for hepatitis C virus genotype 4a and evidence for cross-genotype neutralization

    DEFF Research Database (Denmark)

    Scheel, Troels Kasper Høyer; Gottwein, Judith Margarete; Jensen, Tina Birk


    in serial passages. Sequence analysis of recovered viruses and subsequent reverse genetic studies revealed a vital dependence on one or two NS2 mutations, depending on the 4a/2a junction. Infectivity of ED43/JFH1 viruses was CD81 dependent. The genotype 4 cell culture systems permit functional analyses...... as well as drug and vaccine research on an increasingly important genotype in the Middle East, Africa, and Europe. We also developed genotype 1a intergenotypic recombinants from H77C with vital mutations in NS3. Using H77C/JFH1 and ED43/JFH1 viruses, we demonstrated high homologous neutralizing antibody...... titers in 1a and 4a patient sera, respectively. Furthermore, availability of JFH1 viruses with envelope proteins of the six major HCV genotypes permitted cross-neutralization studies; 1a and 4a serum cross-neutralized 1a, 4a, 5a, and 6a but not 2a and 3a viruses. Thus, the JFH1 intergenotypic...

  1. Dynamic variable selection in SNP genotype autocalling from APEX microarray data

    Directory of Open Access Journals (Sweden)

    Zamar Ruben H


    model-based genotype calling algorithm captures the redundancy in the system considering all the underlying probe features of a particular SNP, automatically down-weighting any 'bad data' corresponding to image artifacts on the microarray slide or failure of a specific chemistry. In this regard, our method is able to automatically select the probes which work well and reduce the effect of other so-called bad performing probes in a sample-specific manner, for any number of SNPs.

  2. Heart Failure Society of America (United States)

    ... MACRA Resource Portal The Heart Failure Society of America, Inc. (HFSA) represents the first organized effort by heart failure experts from the Americas to provide a forum for all those interested ...

  3. Heart Failure in the Elderly

    NARCIS (Netherlands)

    B. Cost (Bernard)


    textabstractHeart failure is a clinical syndrome with various causes for which no universally accepted definition exists. Packer's definition of heart failure "representing a complex clinical syndrome characterised by abnonnalities of left ventricular function and neurohumoral regulation. which are

  4. Heart failure - fluids and diuretics (United States)

    ... this page: // Heart failure - fluids and diuretics To use the sharing features ... to Expect at Home When you have heart failure, your heart does not pump out enough blood. This causes ...

  5. Hepatitis C Virus Resistance Testing in Genotype 1: The Changing Role in Clinical Utility. (United States)

    Molino, Suzanne; Martin, Michelle T


    To review the role and utility of baseline resistance testing with currently available and pipeline genotype 1 hepatitis C virus (HCV) treatment. Authors reviewed liver meeting abstracts for data on currently-available and pipeline genotype 1 retreatment regimens from January 1, 2015, to March 23, 2017. Additional trials were identified from a review of using the pipeline medication names. Authors identified reports of current and pipeline genotype 1 retreatment regimens. Seven references were clinical study results presented at the meetings of the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver, and 2 studies were from . Retreatment trial data of currently available salvage regimens indicate that baseline NS5A resistance-associated substitutions (RASs) may decrease sustained virological response (SVR) rates when retreating with ledipasvir/sofosbuvir but are not affected when using elbasvir/grazoprevir + sofosbuvir + ribavirin, paritaprevir/ritonavir/ombitasvir + dasabuvir + sofosbuvir, or sofosbuvir/velpatasvir + ribavirin. Pipeline data indicate that baseline NS5A RASs do not affect SVR rates when retreating with sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir. Baseline resistance testing was used for decisional support for 3 clinical scenarios in patients with HCV genotype 1 infection at the time of manuscript submission. Pending the approval of 2 new direct-acting antiviral regimens in the third quarter of 2017, the rapidly evolving HCV treatment guidelines will likely reflect a decreased clinical utility for resistance testing.

  6. An Affymetrix Microarray Design for Microbial Genotyping (United States)


    les échantillons qui ne se prêtent pas aux méthodes culturales de la microbiologie classique. La puce à ADN est une technologie qui permet la... area of microbial genotyping there are multiple platforms that can identify one or a few microbial targets in a single assay iteration. For most

  7. Human papillomavirus genotyping by multiplex pyrosequencing in ...

    Indian Academy of Sciences (India)


    malignant cervical samples ... low- and high-risk HPV genotypes without identifying ... Since these samples were not from “healthy .... major capsid protein, any variation in its coding sequence is .... worldwide: a meta-analysis; Br. J. Cancer 88 63–73.

  8. Physicochemical and sensorial quality of banana genotypes

    Directory of Open Access Journals (Sweden)

    Ronielli Cardoso Reis


    Full Text Available Despite the diversity of banana varieties in Brazil, only a few cultivars have the proper agronomic traits and fruit quality for commercial exploitation. This study aimed at evaluating the physicochemical traits and sensorial acceptance of banana genotypes, in order to identify those with potential for commercial growing. Six improved banana genotypes were assessed (BRS Maravilha, PC 0101, FHIA 18, TM 2803, YB 4203 and BRS Caipira, as well as three commercial cultivars (Grand Naine, Pacovan and Prata Anã. Analyses of peel and pulp color, peel thickness, pulp yield, moisture, pH, soluble solids, titratable acidity, total carotenoids and sensorial acceptance were performed. The BRS Maravilha, FHIA 18, YB 4203 and BRS Caipira genotypes presented physicochemical traits similar to the Grand Naine, Pacovan and Prata Anã commercial cultivars. The BRS Maravilha and TM 2803 genotypes had sensorial acceptance similar to the Prata Anã and Grand Naine cultivars, and are therefore promising for commercial growing, with the advantage of being resistant to the black Sigatoka and Panama disease.

  9. Genotyping of human pappilomavirus in cervical precancerous ...

    African Journals Online (AJOL)

    Background: Cervical cancer caused by human papilloma virus (HPV), is the second most common cancer for women. This cancer is distributed worldwide, with ~80% of cases are found in the developing countries. In Indonesia, data of HPV genotypes are still limited and do not represent all regions of the country. Thus ...

  10. Cryptosporidium Pig Genotype II in Immunocompetent Man

    Czech Academy of Sciences Publication Activity Database

    Kváč, Martin; Květoňová, Dana; Sak, Bohumil; Ditrich, Oleg


    Roč. 15, č. 6 (2009), s. 982-983 ISSN 1080-6040 R&D Projects: GA ČR GP523/07/P117 Institutional research plan: CEZ:AV0Z60220518 Keywords : immunocompetent patients * cryptosporidiosis * Cryptosporidium pig genotype II Subject RIV: GJ - Animal Vermins ; Diseases , Veterinary Medicine Impact factor: 6.794, year: 2009

  11. Morphometric characteristics of Lotus corniculatus L. genotypes ...

    African Journals Online (AJOL)

    The aim of this study was to examine the degree of variability in morphological and agronomic characteristics of 20 Lotus corniculatus L. local genotypes, and also to set aside germplasm that will be used as a source of genetic basis for improvement of the studied properties. In poor quality soils, L. corniculatus L. plays an ...

  12. Genotype X Fertility Interactions in Seedling Sweetgum (United States)

    Scott X. Chang; Daniel J. Robison


    Genotype x fertility interactions may affect the suitability of sweetgum (Liquidambar styraciflua L.) for specific sites or the efficiency of nutrient use. To gain a better understanding of these interactions, 2-year-old sweetgum seedlings from two half-sib families were tested for growth response to N (0 and 100 kg/ha equivalent) and P (0 and 50 kg...

  13. (AMMI) and genotype by environment interaction

    African Journals Online (AJOL)



    Apr 30, 2014 ... Background and justification: Lack of stable high yielding cultivars is one ... of advanced finger millet genotypes evaluated in multiple environments, and (ii) identify stable high yielding .... for interaction principal component axis (IPCA) n, γgn ..... Table 2: Analysis of variance for grain yield using AMMI model.

  14. Impact of inter-genotypic recombination and probe cross-reactivity on the performance of the Abbott RealTime HCV Genotype II assay for hepatitis C genotyping. (United States)

    Sridhar, Siddharth; Yip, Cyril C Y; Chan, Jasper F W; To, Kelvin K W; Cheng, Vincent C C; Yuen, Kwok-Yung


    The Abbott RealTime HCV Genotype II assay (Abbott-RT-HCV assay) is a real-time PCR based genotyping method for hepatitis C virus (HCV). This study measured the impact of inter-genotypic recombination and probe cross-reactivity on the performance of the Abbott-RT-HCV assay. 517 samples were genotyped using the Abbott-RT-HCV assay over a one-year period, 34 (6.6%) were identified as HCV genotype 1 without further subtype designation raising the possibility of inaccurate genotyping. These samples were subjected to confirmatory sequencing. 27 of these 34 (79%) samples were genotype 1b while five (15%) were genotype 6. One HCV isolate was an inter-genotypic 1a/4o recombinant. This is a novel natural HCV recombinant that has never been reported. Inter-genotypic recombination and probe cross-reactivity can affect the accuracy of the Abbott-RT-HCV assay, both of which have significant implications on antiviral regimen choice. Confirmatory sequencing of ambiguous results is crucial for accurate genotyping. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Stochastic failure modelling of unidirectional composite ply failure

    International Nuclear Information System (INIS)

    Whiteside, M.B.; Pinho, S.T.; Robinson, P.


    Stochastic failure envelopes are generated through parallelised Monte Carlo Simulation of a physically based failure criteria for unidirectional carbon fibre/epoxy matrix composite plies. Two examples are presented to demonstrate the consequence on failure prediction of both statistical interaction of failure modes and uncertainty in global misalignment. Global variance-based Sobol sensitivity indices are computed to decompose the observed variance within the stochastic failure envelopes into contributions from physical input parameters. The paper highlights a selection of the potential advantages stochastic methodologies offer over the traditional deterministic approach.

  16. In Vitro Conservation of Sweet Potato Genotypes

    Directory of Open Access Journals (Sweden)

    Maria de Fátima Arrigoni-Blank


    Full Text Available The aim of this study was to develop a protocol for the in vitro conservation of sweet potato genotypes using the slow growth technique. The first experiment was conducted in a 4×5×2 factorial scheme, testing four genotypes (IPB-007, IPB-052, IPB-072, and IPB-137, five concentrations of abscisic acid (ABA (0.0, 1.0, 2.0, 4.0, and 8.0 mg·L−1, and two temperatures (18 and 25°C. The second experiment was conducted in a 4×3×3 factorial scheme at 18°C, testing four genotypes (IPB-007, IPB-052, IPB-072, and IPB-137, three variations of MS salts (50, 75, and 100%, and three concentrations of sucrose (10, 20, and 30 g·L−1. Every three months, we evaluated the survival (%, shoot height, and shoot viability. In vitro conservation of the sweet potato genotypes IPB-052 and IPB-007 was obtained over three and six months, respectively, using MS medium plus 2.0 mg·L−1 of ABA at either 18 or 25°C. Genotypes IPB-072 and IPB-137 can be kept for three and six months, respectively, in MS medium without ABA at 18°C. It is possible to store IPB-052 and IPB-072 for six months and IPB-007 and IPB-137 for nine months using 30 g·L−1 of sucrose and 50% MS salts.

  17. Generic component failure data base

    International Nuclear Information System (INIS)

    Eide, S.A.; Calley, M.B.


    This report discusses comprehensive component generic failure data base which has been developed for light water reactor probabilistic risk assessments. The Nuclear Computerized Library for Assessing Reactor Reliability (NUCLARR) was used to generate component failure rates. Using this approach, most of the failure rates are based on actual plant data rather then existing estimates

  18. Your Heart Failure Healthcare Team (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Your Heart Failure Healthcare Team Updated:May 9,2017 Patients with ... to the Terms and Conditions and Privacy Policy Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  19. Planning Ahead: Advanced Heart Failure (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Planning Ahead: Advanced Heart Failure Updated:May 9,2017 An important part of ... Care This content was last reviewed May 2017. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  20. Haplotypes of the TaGS5-A1 gene are associated with thousand-kernel weight in Chinese bread wheat

    Directory of Open Access Journals (Sweden)

    Wang Sha Sha


    Full Text Available In previous work, we cloned TaGS5 gene and found the association of TaGS5-A1 alleles with agronomic traits. In this study, the promoter sequence of the TaGS5-A1 gene was isolated from bread wheat. Sequencing results revealed that a G insertion was found in position -1925 bp of the TaGS5-A1 gene (Reference to ATG, which occurred in the Sp1 domain of the promoter sequence. Combined with previous single nucleotide polymorphism (SNP in the TaGS5-A1 exon sequence, four genotypes were formed at the TaGS5-A1 locus and were designated as TaGS5-A1a-a, TaGS5-A1a-b, TaGS5-A1b-a, and TaGS5-A1b-b, respectively. Analysis of the association of TaGS5-A1 alleles with agronomic traits indicated that cultivars with the TaGS5-A1a-b allele possessed significantly higher thousand-kernel weight (TKW and lower plant height than cultivars with the TaGS5-A1a-a allele, and cultivars with the TaGS5-A1b-b allele showed higher TKW than cultivars with the TaGS5-A1b-a allele. The differences of these traits between the TaGS5-A1a-a and TaGS5-A1a-b alleles were larger than those of the TaGS5-A1b-a and TaGS5-A1b-b alleles, suggesting that the -1925G insertion plays the more important role in TaGS5-A1a genotypes than in TaGS5-A1b genotypes. qRT-PCR indicated that TaGS5-A1b-b possessed the significantly highest expression level among four TaGS5-A1 haplotypes in mature seeds and further showed a significantly higher expression level than TaGS5-A1b-a at five different developmental stages of the seeds, suggesting that high expression of TaGS5-A1 was positively associated with high TKW in bread wheat. This study could provide a relatively superior genotype in view of TKW in wheat breeding programs and could also provide important information for dissection of the regulatory mechanism of the yield-related traits.

  1. The potential of plant viruses to promote genotypic diversity via genotype x environment interactions

    DEFF Research Database (Denmark)

    van Mölken, Tamara; Stuefer, Josef F.


    † Background and Aims Genotype by environment (G × E) interactions are important for the long-term persistence of plant species in heterogeneous environments. It has often been suggested that disease is a key factor for the maintenance of genotypic diversity in plant populations. However, empirical...... and the G × E interactions were examined with respect to genotypespecific plant responses to WClMV infection. Thus, the environment is defined as the presence or absence of the virus. † Key Results WClMV had a negative effect on plant performance as shown by a decrease in biomass and number of ramets...... evidence for this contention is scarce. Here virus infection is proposed as a possible candidate for maintaining genotypic diversity in their host plants. † Methods The effects of White clover mosaic virus (WClMV) on the performance and development of different Trifolium repens genotypes were analysed...

  2. Genotypic Variation of Early Maturing Soybean Genotypes for Phosphorus Utilization Efficiency under Field Grown Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Abaidoo, R. C. [Kwame Nkrumah University of Technology, Kumasi (Ghana); International Institute of Tropical Agriculture, Ibadan (Nigeria); Opoku, A.; Boahen, S. [Kwame Nkrumah University of Technology, Kumasi (Ghana); Dare, M. O. [Federal University of Agriculture, Abeokuta (Nigeria)


    Variability in the utilization of phosphorus (P) by 64 early-maturing soybean (Glycine max L. Merr.) genotypes under low-P soil conditions were evaluated in 2009 and 2010 at Shika, Nigeria. Fifteen phenotypic variables; number of nodules, nodule dry weight, grain yield, plant biomass, total biomass, biomass N and P content, Phosphorus Utilization Index (PUI), shoot P Utilization efficiency (PUIS), grain P Utilization efficiency (PUIG), Harvest Index (HI), Biological N fixed (BNF), total N fixed and N and P uptake were measured. The four clusters revealed by cluster analysis were basically divided along (1) plant biomass and uptake, (2) nutrient acquisition and utilization and (3) nodulation components. Three early maturing genotypes, TGx1842-14E, TGx1912-11F and TGx1913-5F, were identified as having high P utilization index and low P uptake. These genotypes could be a potential source for breeding for P use efficiency in early maturing soybean genotypes. (author)

  3. Zeolite 5A Catalyzed Etherification of Diphenylmethanol (United States)

    Cooke, Jason; Henderson, Eric J.; Lightbody, Owen C.


    An experiment for the synthetic undergraduate laboratory is described in which zeolite 5A catalyzes the room temperature dehydration of diphenylmethanol, (C[subscript 6]H[subscript 5])[subscript 2]CHOH, producing 1,1,1',1'-tetraphenyldimethyl ether, (C[subscript 6]H[subscript 5])[subscript 2]CHOCH(C[subscript 6]H[subscript 5])[subscript 2]. The…

  4. Gel versus capillary electrophoresis genotyping for categorizing treatment outcomes in two anti-malarial trials in Uganda

    Directory of Open Access Journals (Sweden)

    Hubbard Alan E


    Full Text Available Abstract Background Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Methods Samples were genotyped using both gel and capillary electrophoresis from randomized trials of artemether-lumefantrine (AL vs. dihydroartemisinin-piperaquine (DP performed in two areas of Uganda: Kanungu, where transmission is moderate, and Apac, where transmission is very high. Both gel and capillary methods evaluated polymorphic regions of the merozoite surface protein 1 and 2 and glutamine rich protein genes. Results Capillary electrophoresis detected more alleles and provided higher discriminatory power than agarose gel electrophoresis at both study sites. There was only moderate agreement between classification of outcomes with the two methods in Kanungu (kappa = 0.66 and poor agreement in Apac (kappa = 0.24. Overall efficacy results were similar when using gel vs. capillary methods in Kanungu (42-day risk of treatment failure for AL: 6.9% vs. 5.5%, p = 0.4; DP 2.4% vs. 2.9%, p = 0.5. However, the measured risk of recrudescence was significantly higher when using gel vs. capillary electrophoresis in Apac (risk of treatment failure for AL: 17.0% vs. 10.7%, p = 0.02; DP: 8.5% vs. 3.4%, p = 0.03. Risk differences between AL and DP were not significantly different whether gel or capillary methods were used. Conclusions Genotyping with gel electrophoresis overestimates the risk of recrudescence in anti-malarial trials performed in areas of high transmission intensity. Capillary electrophoresis provides more accurate outcomes for such trials and should be performed when possible. In areas of moderate transmission

  5. Gel versus capillary electrophoresis genotyping for categorizing treatment outcomes in two anti-malarial trials in Uganda. (United States)

    Gupta, Vinay; Dorsey, Grant; Hubbard, Alan E; Rosenthal, Philip J; Greenhouse, Bryan


    Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure) or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Samples were genotyped using both gel and capillary electrophoresis from randomized trials of artemether-lumefantrine (AL) vs. dihydroartemisinin-piperaquine (DP) performed in two areas of Uganda: Kanungu, where transmission is moderate, and Apac, where transmission is very high. Both gel and capillary methods evaluated polymorphic regions of the merozoite surface protein 1 and 2 and glutamine rich protein genes. Capillary electrophoresis detected more alleles and provided higher discriminatory power than agarose gel electrophoresis at both study sites. There was only moderate agreement between classification of outcomes with the two methods in Kanungu (kappa = 0.66) and poor agreement in Apac (kappa = 0.24). Overall efficacy results were similar when using gel vs. capillary methods in Kanungu (42-day risk of treatment failure for AL: 6.9% vs. 5.5%, p = 0.4; DP 2.4% vs. 2.9%, p = 0.5). However, the measured risk of recrudescence was significantly higher when using gel vs. capillary electrophoresis in Apac (risk of treatment failure for AL: 17.0% vs. 10.7%, p = 0.02; DP: 8.5% vs. 3.4%, p = 0.03). Risk differences between AL and DP were not significantly different whether gel or capillary methods were used. Genotyping with gel electrophoresis overestimates the risk of recrudescence in anti-malarial trials performed in areas of high transmission intensity. Capillary electrophoresis provides more accurate outcomes for such trials and should be performed when possible. In areas of moderate transmission, gel electrophoresis appears adequate to estimate comparative

  6. Teton Dam failure

    Energy Technology Data Exchange (ETDEWEB)

    Snorteland, N. [United States Dept. of the Interior, Washington, DC (United States). Bureau of Reclamation


    This case summary discussed an internal erosion failure that occurred at the embankment foundation of Teton Dam. The project was designed as a run-of-the-river power generation facility and to provide irrigation, flood protection, and power generation to the lower Teton region of southern Idaho. The dam site was located next to the eastern Snake River plain, a volcanic filled depression. The foundation's cutoff trench was excavated into the bedrock along the length of the dam. The dam was designed as a zoned earthfill with a height of 305 feet. A trench made of low plasticity windblown silt was designed to connect the embankment core to the rock foundation. Seeps were noted in 1976, and a leak was observed near the toe of the dam. A wet spot appeared on the downstream face of the dam at elevation 5200. A sinkhole then developed. The embankment crest collapsed, and the dam breached. Peak outflow was estimated at 1,000,000 cfs. The failure was attributed to a lack of communication between designers, a failure to understand geologic information about the region, and an insufficient review of designs and specifications by designers and field personnel. No monitoring instrumentation was installed in the embankment. Approximately 300 square miles were inundated, and 25,000 people were displaced. Eleven people were killed. A review group noted that the rock surface was not adequately sealed, and that the dam failed as a result of inadequate protection of the impervious core material from internal erosion. 42 figs.

  7. Steam generator tube failures

    International Nuclear Information System (INIS)

    MacDonald, P.E.; Shah, V.N.; Ward, L.W.; Ellison, P.G.


    A review and summary of the available information on steam generator tubing failures and the impact of these failures on plant safety is presented. The following topics are covered: pressurized water reactor (PWR), Canadian deuterium uranium (CANDU) reactor, and Russian water moderated, water cooled energy reactor (VVER) steam generator degradation, PWR steam generator tube ruptures, the thermal-hydraulic response of a PWR plant with a faulted steam generator, the risk significance of steam generator tube rupture accidents, tubing inspection requirements and fitness-for-service criteria in various countries, and defect detection reliability and sizing accuracy. A significant number of steam generator tubes are defective and are removed from service or repaired each year. This wide spread damage has been caused by many diverse degradation mechanisms, some of which are difficult to detect and predict. In addition, spontaneous tube ruptures have occurred at the rate of about one every 2 years over the last 20 years, and incipient tube ruptures (tube failures usually identified with leak detection monitors just before rupture) have been occurring at the rate of about one per year. These ruptures have caused complex plant transients which have not always been easy for the reactor operators to control. Our analysis shows that if more than 15 tubes rupture during a main steam line break, the system response could lead to core melting. Although spontaneous and induced steam generator tube ruptures are small contributors to the total core damage frequency calculated in probabilistic risk assessments, they are risk significant because the radionuclides are likely to bypass the reactor containment building. The frequency of steam generator tube ruptures can be significantly reduced through appropriate and timely inspections and repairs or removal from service

  8. Toxoplasma gondii seroprevalence and genotype diversity in select wildlife species from the southeastern United States

    Directory of Open Access Journals (Sweden)

    Richard W. Gerhold


    Full Text Available Abstract Background Toxoplasma gondii is a widespread protozoan parasite that infects humans and other animals. Previous studies indicate some genotypes of T. gondii are more frequently isolated in wildlife than agricultural animals, suggesting a wild/feral animal diversity model. To determine seroprevalence and genetic diversity of T. gondii in southeastern US wildlife, we collected sera from 471 wild animals, including 453 mammals and 18 birds, between 2011 and 2014. These serum samples were assayed for T. gondii infection using the modified agglutination test (MAT. Heart or tongue tissues from 66 seropositive animals were bioassayed in mice and 19 isolates were obtained. The isolated parasites were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP method employing 10 genetic markers. Results One hundred and ninety-six of 471 samples (41.6% had a titer ≥1:32 and were considered positive for T. gondii infection. Of 453 mammals, 195 (43% were seropositive, whereas only one (5.6% of 18 birds was seropositive. The seroprevalence in mammals was significantly higher than in the birds. Mammalian hosts with adequate samples size (≥ 20 comprised white-tailed deer (n = 241, feral hogs (n = 100, raccoons (n = 34 and coyotes (n = 22, with seroprevalences of 41.0%, 51.0%, 50.0% and 72.7%, respectively. Coyotes had significantly higher seroprevalence than the white-tailed deer. Genotyping revealed five distinct genotypes, including the ToxoDB PCR-RFLP genotype #5 (a.k.a type 12 for 15 isolates, genotype #3 (a.k.a. type II for 1 isolate, and genotypes #154, #167 and #216, each for 1 isolate. The results showed moderate to high infection rates of T. gondii in white-tailed deer, feral hogs, raccoons and coyotes. Genotyping results indicated limited genetic diversity and a dominance of genotype #5, which has been reported as a major type in wildlife in North America. Conclusions We conclude that T. gondii

  9. Distribution of genotype network sizes in sequence-to-structure genotype-phenotype maps. (United States)

    Manrubia, Susanna; Cuesta, José A


    An essential quantity to ensure evolvability of populations is the navigability of the genotype space. Navigability, understood as the ease with which alternative phenotypes are reached, relies on the existence of sufficiently large and mutually attainable genotype networks. The size of genotype networks (e.g. the number of RNA sequences folding into a particular secondary structure or the number of DNA sequences coding for the same protein structure) is astronomically large in all functional molecules investigated: an exhaustive experimental or computational study of all RNA folds or all protein structures becomes impossible even for moderately long sequences. Here, we analytically derive the distribution of genotype network sizes for a hierarchy of models which successively incorporate features of increasingly realistic sequence-to-structure genotype-phenotype maps. The main feature of these models relies on the characterization of each phenotype through a prototypical sequence whose sites admit a variable fraction of letters of the alphabet. Our models interpolate between two limit distributions: a power-law distribution, when the ordering of sites in the prototypical sequence is strongly constrained, and a lognormal distribution, as suggested for RNA, when different orderings of the same set of sites yield different phenotypes. Our main result is the qualitative and quantitative identification of those features of sequence-to-structure maps that lead to different distributions of genotype network sizes. © 2017 The Author(s).

  10. Pollen diversity, viability and floral structure of some Musa genotypes

    African Journals Online (AJOL)

    Pollen diversity, viability and floral structure of some Musa genotypes. ... This experiment was designed to study the floral structure, pollen morphology and the potential pollen viability of five Musa genotypes obtained ... HOW TO USE AJOL.

  11. Behavior of durum wheat genotypes under normal irrigation and ...

    African Journals Online (AJOL)

    Behavior of durum wheat genotypes under normal irrigation and drought stress conditions in the greenhouse. ... African Journal of Biotechnology ... Genotypes were grouped in cluster analysis (using Ward's method) based on Yp, Ys and ...

  12. Genetic variability in cowpea (Vigna unguiculata (L.) Walp.) genotypes

    African Journals Online (AJOL)

    sive protein in human diets with grains containing about. 23–25% protein ... Keywords: heritability, phenotype, principal component analysis, variance. Introduction .... be due to genotype, environment, and the interaction of genotype and ...

  13. magnitude of genotype x environment interaction for bacterial leaf

    African Journals Online (AJOL)


    African Crop Science Journal, Vol. ... effects of treatments into genotype, environment, and genotype x environment (G x E) interactions. Results .... method is economically effective (Niño-Liu et al., ..... This phenomenon indicated differences in.

  14. FRELIB, Failure Reliability Index Calculation

    International Nuclear Information System (INIS)

    Parkinson, D.B.; Oestergaard, C.


    1 - Description of problem or function: Calculation of the reliability index given the failure boundary. A linearization point (design point) is found on the failure boundary for a stationary reliability index (min) and a stationary failure probability density function along the failure boundary, provided that the basic variables are normally distributed. 2 - Method of solution: Iteration along the failure boundary which must be specified - together with its partial derivatives with respect to the basic variables - by the user in a subroutine FSUR. 3 - Restrictions on the complexity of the problem: No distribution information included (first-order-second-moment-method). 20 basic variables (could be extended)

  15. Automotive component failures

    CSIR Research Space (South Africa)

    Heyes, AM


    Full Text Available in service for approximately 19\\999 km[ 1[1[ Visual examination Upon stripping the engine it was found that one of the combustion chambers showed heavy carbonaceous deposits indicative of the burning of oil "Fig[ 2# Circumferential black marks were found... whether failures in other vehicles could be expected[ 2[1[ Visual and stereo microscope examination The section of torsion bar submitted for examination was coated with a black paint coating which had ~aked o} at localised spots\\ where light rusting had...

  16. Triggers of State Failure (United States)


    à 1990) à l’aide de données collatérales additionnelles. Les auteurs du document n’ont pas essayé de suivre les événements qui étaient en cours...défaillance étatique, et les auteurs du document ont reconnu qu’il ne serait pas très utile de reproduire toutes ces informations. Le document s’appuie le...30 Carment, David. Assessing state failure: implications for theory and policy. in Third World Quarterly. Vol 24, no 3. pp 407-427. 30 DRDC

  17. New product failure

    DEFF Research Database (Denmark)

    Dijksterhuis, Garmt Bernard


    When new consumer products are developed and later launched, 50 to 75 percent of them are removed from the market far short of meeting their projected financial targets. In short: they fail. We conclude that this failure is due to institutionalized insufficiencies in the use of the sciences...... that are best geared to understand and predict consumer behaviour, viz. the behavioural sciences. These are not necessarily the same as the marketing science that is performed by marketing departments. A scientific approach to understanding consumer behaviour appears to be lacking in many corporate research...

  18. Premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Persani Luca


    Full Text Available Abstract Premature ovarian failure (POF is a primary ovarian defect characterized by absent menarche (primary amenorrhea or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea. It is a heterogeneous disorder affecting approximately 1% of women e.g. Turner syndrome represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of the cases. Management includes substitution of the hormone defect by estrogen/progestin preparations. The only solution presently available for the fertility defect in women with absent follicular reserve is ovum donation.

  19. Genotype 3 is the predominant hepatitis C genotype in a multi-ethnic Asian population in Malaysia. (United States)

    Ho, Shiaw-Hooi; Ng, Kee-Peng; Kaur, Harvinder; Goh, Khean-Lee


    Genotypes of hepatitis C virus (HCV) are distributed differently across the world. There is a paucity of such data in a multi-ethnic Asian population like Malaysia. The objectives of this study were to determine the distribution of HCV genotypes between major ethnic groups and to ascertain their association with basic demographic variables like age and gender. This was a cross-sectional prospective study conducted from September 2007 to September 2013. Consecutive patients who were detected to have anti-HCV antibodies in the University of Malaya Medical Centre were included and tested for the presence of HCV RNA using Roche Cobas Amplicor Analyzer and HCV genotype using Roche single Linear Array HCV Genotyping strip. Five hundred and ninety-six subjects were found to have positive anti-HCV antibodies during this period of time. However, only 396 (66.4%) were HCV RNA positive and included in the final analysis. Our results showed that HCV genotype 3 was the predominant genotype with overall frequency of 61.9% followed by genotypes 1 (35.9%), 2 (1.8%) and 6 (0.5%). There was a slightly higher prevalence of HCV genotype 3 among the Malays when compared to the Chinese (P=0.043). No other statistical significant differences were observed in the distribution of HCV genotypes among the major ethnic groups. There was also no association between the predominant genotypes and basic demographic variables. In a multi-ethnic Asian society in Malaysia, genotype 3 is the predominant genotype among all the major ethnic groups with genotype 1 as the second commonest genotype. Both genotypes 2 and 6 are uncommon. Neither genotype 4 nor 5 was detected. There is no identification of HCV genotype according to ethnic origin, age and gender.

  20. Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study

    DEFF Research Database (Denmark)

    Røge, B T; Barfod, T S; Kirk, O


    OBJECTIVES: To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens. METHODS: We retrospectively identified 56 verified primary virological failures (viral load >400 HIV-1 RNA...... copies/mL) among 293 patients randomized to two nucleoside reverse transcriptase inhibitors (NRTIs)+ritonavir+saquinavir (RS-arm) (n=115), two NRTIs+nevirapine+nelfinavir (NN-arm) (n=118), or abacavir+stavudine+didanosine (ASD-arm) (n=60) followed up for a median of 90 weeks. Data on adherence were...... collected from patient files, and genotyping was performed on plasma samples collected at time of failure. RESULTS: Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing...

  1. HPV genotypes in invasive cervical cancer in Danish women

    DEFF Research Database (Denmark)

    Kirschner, Benny; Junge, Jette; Holl, Katsiaryna


    Human papillomavirus (HPV) genotype distribution in invasive cervical cancers may differ by geographic region. The primary objective of this study was to estimate HPV-genotype distribution in Danish women with a diagnosis of invasive cervical cancer.......Human papillomavirus (HPV) genotype distribution in invasive cervical cancers may differ by geographic region. The primary objective of this study was to estimate HPV-genotype distribution in Danish women with a diagnosis of invasive cervical cancer....

  2. HCV Genotype 6a Escape From and Resistance to Velpatasvir, Pibrentasvir, and Sofosbuvir in Robust Infectious Cell Culture Models

    DEFF Research Database (Denmark)

    Pham, Long V; Ramirez, Santseharay; Gottwein, Judith M


    V was able to propagate and escape in the presence of pibrentasvir with emergence of NS5A-L28S, conferring a high level of resistance to this inhibitor. CONCLUSIONS: Strains of HCV genotype 6a isolated from patients can be adapted to propagate in cultured cells, permitting studies of the complete...... infectious cell culture models of HCV genotype 6a infection to study the effects of these inhibitors and the development of resistance. METHODS: The consensus sequences of prototype strains HK2 (MG717925) and HK6a (MG717928), originating from serum of patients with chronic HCV infection, were determined...... by Sanger sequencing of genomes amplified by reverse-transcription polymerase chain reaction. In vitro noninfectious full-length clones of these 6a strains were subsequently adapted in Huh7.5 cells, primarily by using substitutions identified in JFH1-based Core-NS5A and Core-NS5B genotype 6a recombinants...

  3. Scaling of structural failure

    Energy Technology Data Exchange (ETDEWEB)

    Bazant, Z.P. [Northwestern Univ., Evanston, IL (United States); Chen, Er-Ping [Sandia National Lab., Albuquerque, NM (United States)


    This article attempts to review the progress achieved in the understanding of scaling and size effect in the failure of structures. Particular emphasis is placed on quasibrittle materials for which the size effect is complicated. Attention is focused on three main types of size effects, namely the statistical size effect due to randomness of strength, the energy release size effect, and the possible size effect due to fractality of fracture or microcracks. Definitive conclusions on the applicability of these theories are drawn. Subsequently, the article discusses the application of the known size effect law for the measurement of material fracture properties, and the modeling of the size effect by the cohesive crack model, nonlocal finite element models and discrete element models. Extensions to compression failure and to the rate-dependent material behavior are also outlined. The damage constitutive law needed for describing a microcracked material in the fracture process zone is discussed. Various applications to quasibrittle materials, including concrete, sea ice, fiber composites, rocks and ceramics are presented.

  4. Delusions as performance failures. (United States)

    Gerrans, P


    Delusions are explanations of anomalous experiences. A theory of delusion requires an explanation of both the anomalous experience and the apparently irrational explanation generated by the delusional subject. Hence, we require a model of rational belief formation against which the belief formation of delusional subjects can be evaluated. I first describe such a model, distinguishing procedural from pragmatic rationality. Procedural rationality is the use of rules or procedures, deductive or inductive, that produce an inferentially coherent set of propositions. Pragmatic rationality is the use of procedural rationality in context. I then apply the distinction to the explanation of the Capgras and the Cotard delusions. I then argue that delusions are failures of pragmatic rationality. I examine the nature of these failures employing the distinction between performance and competence familiar from Chomskian linguistics. This approach to the irrationality of delusions reconciles accounts in which the explanation of the anomalous experience exhausts the explanation of delusion, accounts that appeal to further deficits within the reasoning processes of delusional subjects, and accounts that argue that delusions are not beliefs at all. (Respectively, one-stage, two-stage, and expressive accounts.) In paradigm cases that concern cognitive neuropsychiatry the irrationality of delusional subjects should be thought of as a performance deficit in pragmatic rationality.

  5. Preparing for Failure

    International Nuclear Information System (INIS)

    Murphy, L.T.; Manson, A.W.


    Risk management is one of the most complex project management processes, requiring rigorous management and discipline. Unfortunately, for many organizations, the risk management process has become contaminated by poor management practices, an absence of meaningful risk assessments, meaningless risk event descriptions, incomplete and vague risk impact analyses, poor follow through on risk mitigation activities and a general lack of attention to accuracy, completeness and quality. At this point, the risk register, instead of being a key tool used by the organization to systematically identify and eliminate risk, while exploiting opportunities, has become a list of pre-prepared excuses based on the repeat of failures encountered on past projects. However, organizations are not condemned to repeat past failures. By returning to the basics of risk management, and through the application of some basic management guidelines, the risk register-instead of being an 'Excuse Register' - can become the cornerstone of a comprehensive risk management program to promote a systematic, pro-active approach within an organization that will result in accomplishing mitigation activities, reducing risk and gaining advantage through opportunities. (authors)

  6. Evaluation of promising sweetpotato genotypes for high altitude ...

    African Journals Online (AJOL)

    The trials were set up to identify sweetpotato genotypes with adaptation to highland agroecologies with special reference to resistance to Ahemaria blight ... growth and at harvest, four genotypes and the local check, Magabari, bad high levels of resistance toA/Jemaria blight. Eight genotypes had total storage root yield ...

  7. Hepatitis B virus Genotypes in West Azarbayjan Province, Northwest Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Hasan Khadem Ansari


    CONCLUSIONS: The results reveal that D genotype is the main genotype of HBV in West Azarbayjan province. Presence of this genotype conformed with the low rate of acute liver diseases caused by hepatitis B chronic infection, cirrhosis of the liver and hepatocellular carcinoma.

  8. Genotype-based personalised nutrition for obesity prevention and ...

    African Journals Online (AJOL)

    Typically, genotype-based personalised nutrition involves genotyping for a number of susceptibility SNPs associated with the prevention, or management, of a particular disease. Dietary advice is then personalised to the individual's genotype to ensure optimal prevention or treatment outcomes. To ensure evidence-based ...

  9. Introduction to a special issue on genotype by environment interaction (United States)

    Expression of a phenotype is a function of the genotype, the environment, and the differential sensitivity of certain genotypes to different environments, also known as genotype by environment (G × E) interaction. This special issue of Crop Science includes a collection of manuscripts that reviews t...

  10. Core Gene Expression and Association of Genotypes with Viral ...

    African Journals Online (AJOL)

    Purpose: To determine genotypic distribution, ribonucleic acid (RNA) RNA viral load and express core gene from Hepatitis C Virus (HCV) infected patients in Punjab, Pakistan. Methods: A total of 1690 HCV RNA positive patients were included in the study. HCV genotyping was tested by type-specific genotyping assay, viral ...

  11. Effect of Genotype and Age on Some Morphometric, Body Linear ...

    African Journals Online (AJOL)

    A population of 231 roosters of the Nigerian indigenous chickens of normal feathered frizzle feathered and naked neck genotypes was evaluated for the effect of genotype and age on some morphometric body linear measurements and semen characteristics of three Nigerian chicken genotypes. 20 roosters from each ...

  12. 21 CFR 862.3360 - Drug metabolizing enzyme genotyping system. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Drug metabolizing enzyme genotyping system. 862... Test Systems § 862.3360 Drug metabolizing enzyme genotyping system. (a) Identification. A drug metabolizing enzyme genotyping system is a device intended for use in testing deoxyribonucleic acid (DNA...

  13. Relationship of status of polymorphic rapd bands with genotypic ...

    African Journals Online (AJOL)

    Relationship of status of polymorphic rapd bands with genotypic adaptation in early finger millet genotypes. S Das, RC Misra, GR Rout, MC Pattanaik, S Aparajita. Abstract. Molecular characterisation of the 15 early duration finger millet (Eleusine coracana G) genotypes was done through RAPD markers. Twenty-five ...

  14. Genotype x Environment Interaction for Tuber Yield, Dry Matter ...

    African Journals Online (AJOL)

    A study was conducted to determine stability of tuber yield, dry matter content and specific gravity, and the nature and magnitude of genotype x environment (G x E) interaction in elite tetraploid potato genotypes. Eleven potato genotypes including two standard checks were evaluated in the eastern part of Ethiopia at ...

  15. [Evaluation of hepatitis B virus genotyping EIA kit]. (United States)

    Tanaka, Yasuhito; Sugauchi, Fuminaka; Matsuuraa, Kentaro; Naganuma, Hatsue; Tatematsu, Kanako; Takagi, Kazumi; Hiramatsu, Kumiko; Kani, Satomi; Gotoh, Takaaki; Wakimoto, Yukio; Mizokami, Masashi


    Clinical significance of Hepatitis B virus(HBV) genotyping is increasingly recognized. The aim of this study was to evaluate reproducibility, accuracy, and sensitivity of an enzyme immunoassay (EIA) based HBV genotyping kit, which designed to discriminate between genotypes to A, B, C, or D by detecting genotype-specific epitopes in PreS2 region. Using the four genotypes panels, the EIA demonstrated complete inter and intra-assay genotyping reproducibility. Serum specimens had stable results after 8 days at 4 degrees C, or 10 cycles of freezing-thawing. In 91 samples that have been genotyped by DNA sequencing, 87(95.6%) were in complete accordance with EIA genotyping. Of examined 344 HBsAg-positive serum specimens, genotypes A, B, C and D were determined in 26 (7.6%), 62 (18.0%), 228 (66.3%), and 9 (2.6%) cases, respectively. Of 19 (5.5%) specimens unclassified by the EIA, 13 were found to have low titer of HBsAg concentration (< 3 IU/ml), and the other 5 had amino acid mutations or deletions within targeted PreS2 epitopes. The EIA allowed genotyping even in HBV DNA negative samples (96.2%). In conclusion, HBV genotype EIA is reliable, sensitive and easy assay for HBV genotyping. The assay would be useful for clinical use.

  16. Genotype by environment interactions and yield stability of stem ...

    African Journals Online (AJOL)

    In a maize breeding program, potential genotypes are usually evaluated in different environments before desirable ones are selected. Genotype x environment (G x E) interaction is associated with the differential performance of genotypes tested at different locations and in different years, and influences selection and ...

  17. Genotype x environment interaction and stability analysis for yield ...

    African Journals Online (AJOL)

    Chickpea is the major pulse crop cultivated in Ethiopia. However, its production is constrained due to genotype instability and environmental variability. This research was carried out to examine the magnitude of environmental effect on yield of chickpea genotypes and to investigate the stability and adaptability of genotypes ...

  18. Reactions of some potato genotypes to late blight in Cameroon ...

    African Journals Online (AJOL)

    Reactions of some potato genotypes to late blight in Cameroon. D. K. Njualem, P. Demo, H. A. Mendoza, J. T. Koi, S. F. Nana. Abstract. Field experiments were conducted in Cameroon in 1995 and 1996 to evaluate reactions of different potato genotypes to late blight. There were significant differences among genotypes for ...

  19. Discovery of novel variants in genotyping arrays improves genotype retention and reduces ascertainment bias

    Directory of Open Access Journals (Sweden)

    Didion John P


    Full Text Available Abstract Background High-density genotyping arrays that measure hybridization of genomic DNA fragments to allele-specific oligonucleotide probes are widely used to genotype single nucleotide polymorphisms (SNPs in genetic studies, including human genome-wide association studies. Hybridization intensities are converted to genotype calls by clustering algorithms that assign each sample to a genotype class at each SNP. Data for SNP probes that do not conform to the expected pattern of clustering are often discarded, contributing to ascertainment bias and resulting in lost information - as much as 50% in a recent genome-wide association study in dogs. Results We identified atypical patterns of hybridization intensities that were highly reproducible and demonstrated that these patterns represent genetic variants that were not accounted for in the design of the array platform. We characterized variable intensity oligonucleotide (VINO probes that display such patterns and are found in all hybridization-based genotyping platforms, including those developed for human, dog, cattle, and mouse. When recognized and properly interpreted, VINOs recovered a substantial fraction of discarded probes and counteracted SNP ascertainment bias. We developed software (MouseDivGeno that identifies VINOs and improves the accuracy of genotype calling. MouseDivGeno produced highly concordant genotype calls when compared with other methods but it uniquely identified more than 786000 VINOs in 351 mouse samples. We used whole-genome sequence from 14 mouse strains to confirm the presence of novel variants explaining 28000 VINOs in those strains. We also identified VINOs in human HapMap 3 samples, many of which were specific to an African population. Incorporating VINOs in phylogenetic analyses substantially improved the accuracy of a Mus species tree and local haplotype assignment in laboratory mouse strains. Conclusion The problems of ascertainment bias and missing

  20. Polyandry in dragon lizards: inbred paternal genotypes sire fewer offspring (United States)

    Frère, Celine H; Chandrasoma, Dani; Whiting, Martin J


    Multiple mating in female animals is something of a paradox because it can either be risky (e.g., higher probability of disease transmission, social costs) or provide substantial fitness benefits (e.g., genetic bet hedging whereby the likelihood of reproductive failure is lowered). The genetic relatedness of parental units, particularly in lizards, has rarely been studied in the wild. Here, we examined levels of multiple paternity in Australia's largest agamid lizard, the eastern water dragon (Intellagama lesueurii), and determined whether male reproductive success is best explained by its heterozygosity coefficient or the extent to which it is related to the mother. Female polyandry was the norm: 2/22 clutches (9.2%) were sired by three or more fathers, 17/22 (77.2%) were sired by two fathers, and only 3/22 (13.6%) clutches were sired by one father. Moreover, we reconstructed the paternal genotypes for 18 known mother–offspring clutches and found no evidence that females were favoring less related males or that less related males had higher fitness. However, males with greater heterozygosity sired more offspring. While the postcopulatory mechanisms underlying this pattern are not understood, female water dragons likely represent another example of reproduction through cryptic means (sperm selection/sperm competition) in a lizard, and through which they may ameliorate the effects of male-driven precopulatory sexual selection. PMID:25937911

  1. COMT genotype, gambling activity, and cognition

    DEFF Research Database (Denmark)

    Grant, Jon E; Leppink, Eric W; Redden, Sarah A


    adjustment and delay aversion) and the Spatial Working Memory task (total errors). This study adds to the growing literature on the role of COMT in impulsive behaviors by showing that the Val/Val genotype was associated with specific clinical and cognitive elements among young adults who gamble......Neuropsychological studies of adults with problem gambling indicate impairments across multiple cognitive domains. Catechol-O-methyltransferase (COMT) plays a unique role in the regulation of dopamine in the prefrontal cortex, and has been implicated in the cognitive dysfunction evident in problem...... gambling. This study examined adults with varying levels of gambling behavior to determine whether COMT genotype was associated with differences in gambling symptoms and cognitive functioning. 260 non-treatment-seeking adults aged 18-29 years with varying degrees of gambling behavior provided saliva...


    Directory of Open Access Journals (Sweden)

    Irina Ancu


    Full Text Available In Romania the blueberry breeding program started in 1982 and till now was conducted by dr. Paulina Mladin. For inducing the variability, different genetic resources of American blueberry cultivars (V. corymbosum, V. angustifolium were involved in a high number of crosses. For identify the genotype with the best fruit quality, some biometric quality indicators (average fruit weight, size index and basically chemical compounds of fruits including ascorbic acid, dry matter, ash, soluble solids, total sugar, titratable acidity, tanoid substances, pectic substances, protein crude, phosphorus and potassium were determined. Of the eleven chemical studied properties who reflected the fruits quality, for five of them were found no statistically significant differences. The purpose of this paper work was to evaluate fruit quality and to identify the valuable genotypes resulted from Romanian blueberry breeding program.

  3. BCL2 genotypes and prostate cancer survival

    Energy Technology Data Exchange (ETDEWEB)

    Renner, Wilfried [Medical University of Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz (Austria); Langsenlehner, Uwe [GKK Outpatient Department, Division of Internal Medicine, Graz (Austria); Krenn-Pilko, Sabine; Langsenlehner, Tanja [Medical University of Graz, Department of Therapeutic Radiology and Oncology, Graz (Austria); Eder, Petra [University Hospital Wuerzburg, Department of Internal Medicine I, Wuerzburg (Germany)


    The antiapoptotic B-cell lymphoma 2 (BCL2) gene is a key player in cancer development and progression. A functional single-nucleotide polymorphism (c.-938C>A, rs2279115) in the inhibitory P2 BCL2 gene promoter has been associated with clinical outcomes in various types of cancer. Aim of the present study was to analyze the role of BCL2-938C>A genotypes in prostate cancer mortality. The association between BCL2-938C>A (rs2279115) genotypes and prostate cancer outcome was studied within the prospective PROCAGENE study comprising 702 prostate cancer patients. During a median follow-up time of 92 months, 120 (17.1%) patients died. A univariate Cox regression model showed a significant association of the CC genotype with reduced cancer-specific survival (CSS; hazard ratio, HR, 2.13, 95% confidence interval, CI, 1.10-4.12; p = 0.024) and overall survival (OS; HR 2.34, 95% CI 1.58-3.47; p < 0.001). In a multivariate Cox regression model including age at diagnosis, risk group, and androgen deprivation therapy, the CC genotype remained a significant predictor of poor CSS (HR 2.05, 95% CI 1.05-3.99; p = 0.034) and OS (HR 2.25, 95% CI 1.51-3.36; p < 0.001). This study provides evidence that the homozygous BCL2-938 CC genotype is associated with OS and C in prostate cancer patients. (orig.) [German] Das antiapoptotische Gen B cell lymphoma 2 (BCL2) spielt eine Schluesselrolle in der Entstehung und Progression von Krebserkrankungen. Ein funktioneller Einzelnukleotid-Polymorphismus (c.-938C>A, rs2279115) im inhibitorischen P2-BCL2-Promotor wurde mit dem klinischen Outcome verschiedener Krebserkrankungen verknuepft. Ziel der vorliegenden Studie war die Untersuchung der Rolle von BCL2-938C>A-Genotypen fuer die Mortalitaet bei Patienten mit Prostatakarzinom. Der Zusammenhang zwischen BCL2-938C>A-Genotypen (rs2279115) und dem Outcome bei Prostatakrebs wurde in der prospektiven PROCAGENE-Studie, die 702 Patienten mit Prostatakarzinom umfasste, untersucht. Waehrend der medianen

  4. Hepatitis C virus NS3 protease genotyping and drug concentration determination during triple therapy with telaprevir or boceprevir for chronic infection with genotype 1 viruses, southeastern France. (United States)

    Aherfi, Sarah; Solas, Caroline; Motte, Anne; Moreau, Jacques; Borentain, Patrick; Mokhtari, Saadia; Botta-Fridlund, Danielle; Dhiver, Catherine; Portal, Isabelle; Ruiz, Jean-Marie; Ravaux, Isabelle; Bregigeon, Sylvie; Poizot-Martin, Isabelle; Stein, Andreas; Gérolami, René; Brouqui, Philippe; Tamalet, Catherine; Colson, Philippe


    Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease inhibitors (PIs), considerably increase rates of sustained virologic response in association with pegylated interferon and ribavirin in chronic HCV genotype 1 infections. The 30 first patients treated by telaprevir or boceprevir including anti-HCV therapies since 2011 in Marseille University hospitals, France, were monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir were determined on sequential blood samples. HCV NS3 protease gene population sequencing was performed at baseline of treatment and in case of treatment failure. Fifteen patients (including 7 co-infected with HIV) received telaprevir and the other 15 patients (including 4 co-infected with HIV) received boceprevir. At baseline, HCV NS3 protease from six patients harbored amino acid substitutions associated with PI-resistance. Treatment failure occurred at week 12 for 7 patients. Amino acid substitutions associated with PI-resistance were observed in six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were found from four patients. Median (interquartile range) plasma concentrations were 3,092 ng/ml (2,320-3,525) for telaprevir and 486 ng/ml (265-619) for boceprevir. For HIV-HCV co-infected patients, median concentrations were 3,162 ng/ml (2,270-4,232) for telaprevir and 374 ng/ml (229-519) for boceprevir. Plasma drug concentration monitoring revealed undetectable concentrations for two patients at week 4, and probable non-adherence to therapy for another patient. These findings indicate that routine HCV NS3 protease sequencing and plasma PI concentration monitoring might be helpful to characterize cases of therapy failure, at a cost dramatically low compared to that of anti-HCV therapy. © 2014 Wiley Periodicals, Inc.

  5. Novel approach for CES1 genotyping

    DEFF Research Database (Denmark)

    Bjerre, Ditte; Berg Rasmussen, Henrik


    AIM: Development of a specific procedure for genotyping of CES1A1 (CES1) and CES1A2, a hybrid of CES1A1 and the pseudogene CES1P1. MATERIALS & METHODS: The number of CES1A1 and CES1A2 copies and that of CES1P1 were determined using real-time PCR. Long range PCRs followed by secondary PCRs allowed...

  6. Failure analysis of buried tanks

    International Nuclear Information System (INIS)

    Watkins, R.K.


    Failure of a buried tank can be hazardous. Failure may be a leak through which product is lost from the tank; but also through which contamination can occur. Failures are epidemic -- because buried tanks are out of sight, but also because designers of buried tanks have adopted analyses developed for pressure tanks. So why do pressure tanks fail when they are buried? Most failures of buried tanks are really soil failures. Soil compresses, or slips, or liquefies. Soil is not only a load, it is a support without which the tank deforms. A high water table adds to the load on the tank. It also reduces the strength of the soil. Based on tests, structural analyses are proposed for empty tanks buried in soils of various quality, with the water table at various levels, and with internal vacuum. Failure may be collapse tank. Such collapse is a sudden, audible inversion of the cylinder when the sidefill soil slips. Failure may be flotation. Failure may be a leak. Most leaks are fractures in the welds in overlap seams at flat spots. Flat spots are caused by a hard bedding or a heavy surface wheel load. Because the tank wall is double thick at the overlap, shearing stress in the weld is increased. Other weld failures occur when an end plate shears down past a cylinder; or when the tank is supported only at its ends like a beam. These, and other, failures can be analyzed with justifiable accuracy using basic principles of mechanics of materials. 10 figs

  7. Screening cotton genotypes for seedling drought tolerance

    Directory of Open Access Journals (Sweden)

    Penna Julio C. Viglioni


    Full Text Available The objectives of this study were to adapt a screening method previously used to assess seedling drought tolerance in cereals for use in cotton (Gossypium hirsutum L. and to identify tolerant accessions among a wide range of genotypes. Ninety genotypes were screened in seven growth chamber experiments. Fifteen-day-old seedlings were subjected to four 4-day drought cycles, and plant survival was evaluated after each cycle. Three cycles are probably the minimum required in cotton work. Significant differences (at the 0.05 level or lower among entries were obtained in four of the seven experiments. A "confirmation test" with entries previously evaluated as "tolerant" (high survival and "susceptible" (low survival was run. A number of entries duplicated their earlier performance, but others did not, which indicates the need to reevaluate selections. Germplasms considered tolerant included: `IAC-13-1', `IAC-RM4-SM5', `Minas Sertaneja', `Acala 1517E-1' and `4521'. In general, the technique is simple, though time-consuming, with practical value for screening a large number of genotypes. Results from the screening tests generally agreed with field information. The screening procedure is suitable to select tolerant accessions from among a large number of entries in germplasm collections as a preliminary step in breeding for drought tolerance. This research also demonstrated the need to characterize the internal lack of uniformity in growth chambers to allow for adequate designs of experiments.

  8. Insomnia Self-Management in Heart Failure (United States)


    Cardiac Failure; Heart Failure; Congestive Heart Failure; Heart Failure, Congestive; Sleep Initiation and Maintenance Disorders; Chronic Insomnia; Disorders of Initiating and Maintaining Sleep; Fatigue; Pain; Depressive Symptoms; Sleep Disorders; Anxiety

  9. Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection

    DEFF Research Database (Denmark)

    Hézode, Christophe; Hirschfield, Gideon M; Ghesquiere, Wayne


    OBJECTIVE: To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. DESIGN: In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30...

  10. An analytical model for interactive failures

    International Nuclear Information System (INIS)

    Sun Yong; Ma Lin; Mathew, Joseph; Zhang Sheng


    In some systems, failures of certain components can interact with each other, and accelerate the failure rates of these components. These failures are defined as interactive failure. Interactive failure is a prevalent cause of failure associated with complex systems, particularly in mechanical systems. The failure risk of an asset will be underestimated if the interactive effect is ignored. When failure risk is assessed, interactive failures of an asset need to be considered. However, the literature is silent on previous research work in this field. This paper introduces the concepts of interactive failure, develops an analytical model to analyse this type of failure quantitatively, and verifies the model using case studies and experiments

  11. Component failure data handbook

    International Nuclear Information System (INIS)

    Gentillon, C.D.


    This report presents generic component failure rates that are used in reliability and risk studies of commercial nuclear power plants. The rates are computed using plant-specific data from published probabilistic risk assessments supplemented by selected other sources. Each data source is described. For rates with four or more separate estimates among the sources, plots show the data that are combined. The method for combining data from different sources is presented. The resulting aggregated rates are listed with upper bounds that reflect the variability observed in each rate across the nuclear power plant industry. Thus, the rates are generic. Both per hour and per demand rates are included. They may be used for screening in risk assessments or for forming distributions to be updated with plant-specific data

  12. Iridium: failures & successes (United States)

    Christensen, CarissaBryce; Beard, Suzette


    This paper will provide an overview of the Iridium business venture in terms of the challenges faced, the successes achieved, and the causes of the ultimate failure of the venture — bankruptcy and system de-orbit. The paper will address technical, business, and policy issues. The intent of the paper is to provide a balanced and accurate overview of the Iridium experience, to aid future decision-making by policy makers, the business community, and technical experts. Key topics will include the history of the program, the objectives and decision-making of Motorola, the market research and analysis conducted, partnering strategies and their impact, consumer equipment availability, and technical issues — target performance, performance achieved, technical accomplishments, and expected and unexpected technical challenges. The paper will use as sources trade media and business articles on the Iridium program, technical papers and conference presentations, Wall Street analyst's reports, and, where possible, interviews with participants and close observers.

  13. Comparative Failure in Science

    Directory of Open Access Journals (Sweden)

    Barney Glaser, PhD, Hon Phd


    Full Text Available A perennial problem for some scientists is their feeling of comparative failure as scientists. This problem becomes clearer if we consider two major sources of this feeling that are inherent in the vary nature of scientific work. (i In science, strong emphasis is placed on the achievement of recognition; (ii the typical basic scientist works in a community filled with “great men” who have made important and decisive discoveries in their respective fields; they are the acknowledge guiding lights. These esteemed scientists, who have attained honors beyond the reach of most of their colleagues, tend to become models for those who have been trained by them or who have worked under them. As Eiduson has put it in her recent psychological study of basic research scientists “Scientists: are idols-oriented.”

  14. Comparative Failure in Science

    Directory of Open Access Journals (Sweden)

    Barney G. Glaser, Ph.D., Hon. Ph.D


    Full Text Available A perennial problem for some scientists is their feeling of comparative failure as scientists. This problem becomes clearer if we consider two major sources of this feeling that are inherent in the vary nature of scientific work. (i In science, strong emphasis is placed on the achievement of recognition; (ii the typical basic scientist works in a community filled with “great men” who have made important and decisive discoveries in their respective fields; they are the acknowledge guiding lights. These esteemed scientists, who have attained honors beyond the reach of most of their colleagues, tend to become models for those who have been trained by them or who have worked under them. As Eiduson has put it in her recent psychological study of basic research scientists “Scientists: are idols-oriented.”

  15. Premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Vujović Svetlana


    Full Text Available Premature ovarian failure (POF is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc. The diagnosis is confirmed by the level of FSH of over 40 IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin, TSH, prolactin, testosterone, karyotype (<30 years of age, ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications. Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc.

  16. Identification of zoonotic genotypes of Giardia duodenalis.

    Directory of Open Access Journals (Sweden)

    Hein Sprong

    Full Text Available Giardia duodenalis, originally regarded as a commensal organism, is the etiologic agent of giardiasis, a gastrointestinal disease of humans and animals. Giardiasis causes major public and veterinary health concerns worldwide. Transmission is either direct, through the faecal-oral route, or indirect, through ingestion of contaminated water or food. Genetic characterization of G. duodenalis isolates has revealed the existence of seven groups (assemblages A to G which differ in their host distribution. Assemblages A and B are found in humans and in many other mammals, but the role of animals in the epidemiology of human infection is still unclear, despite the fact that the zoonotic potential of Giardia was recognised by the WHO some 30 years ago. Here, we performed an extensive genetic characterization of 978 human and 1440 animal isolates, which together comprise 3886 sequences from 4 genetic loci. The data were assembled into a molecular epidemiological database developed by a European network of public and veterinary health Institutions. Genotyping was performed at different levels of resolution (single and multiple loci on the same dataset. The zoonotic potential of both assemblages A and B is evident when studied at the level of assemblages, sub-assemblages, and even at each single locus. However, when genotypes are defined using a multi-locus sequence typing scheme, only 2 multi-locus genotypes (MLG of assemblage A and none of assemblage B appear to have a zoonotic potential. Surprisingly, mixtures of genotypes in individual isolates were repeatedly observed. Possible explanations are the uptake of genetically different Giardia cysts by a host, or subsequent infection of an already infected host, likely without overt symptoms, with a different Giardia species, which may cause disease. Other explanations for mixed genotypes, particularly for assemblage B, are substantial allelic sequence heterogeneity and/or genetic recombination. Although the

  17. Identification of polymorphic inversions from genotypes

    Directory of Open Access Journals (Sweden)

    Cáceres Alejandro


    Full Text Available Abstract Background Polymorphic inversions are a source of genetic variability with a direct impact on recombination frequencies. Given the difficulty of their experimental study, computational methods have been developed to infer their existence in a large number of individuals using genome-wide data of nucleotide variation. Methods based on haplotype tagging of known inversions attempt to classify individuals as having a normal or inverted allele. Other methods that measure differences between linkage disequilibrium attempt to identify regions with inversions but unable to classify subjects accurately, an essential requirement for association studies. Results We present a novel method to both identify polymorphic inversions from genome-wide genotype data and classify individuals as containing a normal or inverted allele. Our method, a generalization of a published method for haplotype data 1, utilizes linkage between groups of SNPs to partition a set of individuals into normal and inverted subpopulations. We employ a sliding window scan to identify regions likely to have an inversion, and accumulation of evidence from neighboring SNPs is used to accurately determine the inversion status of each subject. Further, our approach detects inversions directly from genotype data, thus increasing its usability to current genome-wide association studies (GWAS. Conclusions We demonstrate the accuracy of our method to detect inversions and classify individuals on principled-simulated genotypes, produced by the evolution of an inversion event within a coalescent model 2. We applied our method to real genotype data from HapMap Phase III to characterize the inversion status of two known inversions within the regions 17q21 and 8p23 across 1184 individuals. Finally, we scan the full genomes of the European Origin (CEU and Yoruba (YRI HapMap samples. We find population-based evidence for 9 out of 15 well-established autosomic inversions, and for 52 regions

  18. Vitamin D and Heart Failure. (United States)

    Marshall Brinkley, D; Ali, Omair M; Zalawadiya, Sandip K; Wang, Thomas J


    Vitamin D is principally known for its role in calcium homeostasis, but preclinical studies implicate multiple pathways through which vitamin D may affect cardiovascular function and influence risk for heart failure. Many adults with cardiovascular disease have low vitamin D status, making it a potential therapeutic target. We review the rationale and potential role of vitamin D supplementation in the prevention and treatment of chronic heart failure. Substantial observational evidence has associated low vitamin D status with the risk of heart failure, ventricular remodeling, and clinical outcomes in heart failure, including mortality. However, trials assessing the influence of vitamin D supplementation on surrogate markers and clinical outcomes in heart failure have generally been small and inconclusive. There are insufficient data to recommend routine assessment or supplementation of vitamin D for the prevention or treatment of chronic heart failure. Prospective trials powered for clinical outcomes are warranted.

  19. Genotypic diversity of root and shoot characteristics of

    Directory of Open Access Journals (Sweden)

    ali ganjali


    Full Text Available Root and shoot characteristics of chickpea (Cicer arietinum L. genotypes are believed to be important in drought tolerance. There is a little information about the response of genotypes root growth in hydroponics and greenhouse culture, also the relationships between root size and drought tolerance. This study was conducted to observe whether genotypes differ in root size, and to see that root size is associated with drought tolerance during early vegetative growth. We found significant differences (p0.01 in root dry weight, total root length, tap root length, root area, leaf dry weight, leaf area and shoot biomass per plant among 30 genotypes of chickpea grown in hydroponics culture for three weeks. Each of these parameters correlated with all others, positively. Among 30 genotypes, 10 genotypes with different root sizes were selected and were grown in a greenhouse in sand culture experiment under drought stress (FC %30 for three weeks. There were not linear or non-linear significant correlations between root characters in hydroponics and greenhouse environments. It seems that environmental factors are dominant on genetic factors in seedling stage and so, the expression of genotypics potential for root growth characteristics of genotypes are different in hydroponic and greenhouse conditions. In this study, the selection of genotypes with vigorous roots system in hydroponic condition did not lead to genotypes with the same root characters in greenhouse environment. The genotype×drought interactions for root characters of chickpea seedlings in 30 days were not significant (p

  20. Performance of chickpea genotypes under Swat valley conditions

    International Nuclear Information System (INIS)

    Khan, A.; Rahim, M.; Ahmad, F.; Ali, A.


    Twenty-two genetically diverse chickpeas genotypes were studied for their physiological efficiency to select the most desirable genotype/genotypes for breeding program on chickpea. Genotype 'CM7-1' was found physiologically efficient stain with maximum harvest index (37.33%) followed by genotype 'CM1571-1-A' with harvest index of 35.73%. Genotype '90206' produced maximum biological yield (7463 kg ha/sup -1/) followed by genotypes 'CM31-1' and 'E-2034' with biological yield of 7352 and 7167 kg ha/sup -1/, respectively. Harvest index and economic yield showed significant positive correlation value of (r=+0.595), while negative correlation value of (r = -0.435) was observed between harvest index and biological yield. (author)

  1. Subtype Specific Differences in NS5A Domain II Reveals Involvement of Proline at Position 310 in Cyclosporine Susceptibility of Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Israr-ul H. Ansari


    Full Text Available Hepatitis C virus (HCV is susceptible to cyclosporine (CsA and other cyclophilin (CypA inhibitors, but the genetic basis of susceptibility is controversial. Whether genetic variation in NS5A alters cell culture susceptibility of HCV to CypA inhibition is unclear. We constructed replicons containing NS5A chimeras from genotypes 1a, 2a and 4a to test how variation in carboxy terminal regions of NS5A altered the genotype 1b CsA susceptibility. All chimeric replicons including genotype 1b Con1LN-wt replicon exhibited some cell culture sensitivity to CsA with genotype 4a being most sensitive and 1a the least. The CypA binding pattern of truncated NS5A genotypes correlated with the susceptibility of these replicons to CsA. The Con1LN-wt replicon showed increased susceptibility towards CsA when proline at position 310P was mutated to either threonine or alanine. Furthermore, a 15 amino acid long peptide fused N terminally to GFP coding sequences confirmed involvement of proline at 310 in CypA binding. Our findings are consistent with CypA acting on multiple prolines outside of the previously identified CypA binding sites. These results suggest multiple specific genetic variants between genotype 1a and 1b in the C-terminus of NS5A alter the CsA susceptibility of replicons, and some variants may oppose the effects of others.

  2. A Failure Criterion for Concrete

    DEFF Research Database (Denmark)

    Ottosen, N. S.


    A four-parameter failure criterion containing all the three stress invariants explicitly is proposed for short-time loading of concrete. It corresponds to a smooth convex failure surface with curved meridians, which open in the negative direction of the hydrostatic axis, and the trace in the devi......A four-parameter failure criterion containing all the three stress invariants explicitly is proposed for short-time loading of concrete. It corresponds to a smooth convex failure surface with curved meridians, which open in the negative direction of the hydrostatic axis, and the trace...

  3. Strategies of learning from failure. (United States)

    Edmondson, Amy C


    Many executives believe that all failure is bad (although it usually provides Lessons) and that Learning from it is pretty straightforward. The author, a professor at Harvard Business School, thinks both beliefs are misguided. In organizational life, she says, some failures are inevitable and some are even good. And successful learning from failure is not simple: It requires context-specific strategies. But first leaders must understand how the blame game gets in the way and work to create an organizational culture in which employees feel safe admitting or reporting on failure. Failures fall into three categories: preventable ones in predictable operations, which usually involve deviations from spec; unavoidable ones in complex systems, which may arise from unique combinations of needs, people, and problems; and intelligent ones at the frontier, where "good" failures occur quickly and on a small scale, providing the most valuable information. Strong leadership can build a learning culture-one in which failures large and small are consistently reported and deeply analyzed, and opportunities to experiment are proactively sought. Executives commonly and understandably worry that taking a sympathetic stance toward failure will create an "anything goes" work environment. They should instead recognize that failure is inevitable in today's complex work organizations.

  4. Submersion and acute respiratory failure

    Directory of Open Access Journals (Sweden)

    Yu-Jang Su


    Conclusions: Submersion patients who are hypothermic on arrival of emergency department (ED are risky to respiratory failure and older, more hypothermic, longer hospital stay in suicidal submersion patients.

  5. Public Choice, Market Failure, and Government Failure in Principles Textbooks (United States)

    Fike, Rosemarie; Gwartney, James


    Public choice uses the tools of economics to analyze how the political process allocates resources and impacts economic activity. In this study, the authors examine twenty-three principles texts regarding coverage of public choice, market failure, and government failure. Approximately half the texts provide coverage of public choice and recognize…

  6. Comparing Learning from Productive Failure and Vicarious Failure (United States)

    Kapur, Manu


    A total of 136 eighth-grade math students from 2 Singapore schools learned from either productive failure (PF) or vicarious failure (VF). PF students "generated" solutions to a complex problem targeting the concept of variance that they had not learned yet before receiving instruction on the targeted concept. VF students…

  7. Corrosion failure analysis as related to prevention of corrosion failures

    International Nuclear Information System (INIS)

    Suss, H.


    The factors and conditions which have contributed to many of the corrosion related service failures are discussed based on a review of actual case histories. The anti-corrosion devices which developed as a result of these failure analyses are reviewed, and the method which must be adopted and used to take advantage of the available corrosion prevention techniques is discussed

  8. Laboratory Information Management Software for genotyping workflows: applications in high throughput crop genotyping

    Directory of Open Access Journals (Sweden)

    Prasanth VP


    Full Text Available Abstract Background With the advances in DNA sequencer-based technologies, it has become possible to automate several steps of the genotyping process leading to increased throughput. To efficiently handle the large amounts of genotypic data generated and help with quality control, there is a strong need for a software system that can help with the tracking of samples and capture and management of data at different steps of the process. Such systems, while serving to manage the workflow precisely, also encourage good laboratory practice by standardizing protocols, recording and annotating data from every step of the workflow. Results A laboratory information management system (LIMS has been designed and implemented at the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT that meets the requirements of a moderately high throughput molecular genotyping facility. The application is designed as modules and is simple to learn and use. The application leads the user through each step of the process from starting an experiment to the storing of output data from the genotype detection step with auto-binning of alleles; thus ensuring that every DNA sample is handled in an identical manner and all the necessary data are captured. The application keeps track of DNA samples and generated data. Data entry into the system is through the use of forms for file uploads. The LIMS provides functions to trace back to the electrophoresis gel files or sample source for any genotypic data and for repeating experiments. The LIMS is being presently used for the capture of high throughput SSR (simple-sequence repeat genotyping data from the legume (chickpea, groundnut and pigeonpea and cereal (sorghum and millets crops of importance in the semi-arid tropics. Conclusion A laboratory information management system is available that has been found useful in the management of microsatellite genotype data in a moderately high throughput genotyping

  9. An update to the HIV-TRePS system: the development of new computational models that do not require a genotype to predict HIV treatment outcomes. (United States)

    Revell, Andrew D; Wang, Dechao; Wood, Robin; Morrow, Carl; Tempelman, Hugo; Hamers, Raph; Alvarez-Uria, Gerardo; Streinu-Cercel, Adrian; Ene, Luminita; Wensing, Annemarie; Reiss, Peter; van Sighem, Ard I; Nelson, Mark; Emery, Sean; Montaner, Julio S G; Lane, H Clifford; Larder, Brendan A


    The optimal individualized selection of antiretroviral drugs in resource-limited settings is challenging because of the limited availability of drugs and genotyping. Here we describe the development of the latest computational models to predict the response to combination antiretroviral therapy without a genotype, for potential use in such settings. Random forest models were trained to predict the probability of a virological response to therapy (HIV RNA/mL) following virological failure using the following data from 22,567 treatment-change episodes including 1090 from southern Africa: baseline viral load and CD4 cell count, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. The models were assessed during cross-validation and with an independent global test set of 1000 cases including 100 from southern Africa. The models' accuracy [area under the receiver-operating characteristic curve (AUC)] was evaluated and compared with genotyping using rules-based interpretation systems for those cases with genotypes available. The models achieved AUCs of 0.79-0.84 (mean 0.82) during cross-validation, 0.80 with the global test set and 0.78 with the southern African subset. The AUCs were significantly lower (0.56-0.57) for genotyping. The models predicted virological response to HIV therapy without a genotype as accurately as previous models that included a genotype. They were accurate for cases from southern Africa and significantly more accurate than genotyping. These models will be accessible via the online treatment support tool HIV-TRePS and have the potential to help optimize antiretroviral therapy in resource-limited settings where genotyping is not generally available.

  10. Genotyping of Coxiella burnetii from domestic ruminants in northern Spain

    Directory of Open Access Journals (Sweden)

    Astobiza Ianire


    Full Text Available Abstract Background Information on the genotypic diversity of Coxiella burnetii isolates from infected domestic ruminants in Spain is limited. The aim of this study was to identify the C. burnetii genotypes infecting livestock in Northern Spain and compare them to other European genotypes. A commercial real-time PCR targeting the IS1111a insertion element was used to detect the presence of C. burnetii DNA in domestic ruminants from Spain. Genotypes were determined by a 6-loci Multiple Locus Variable number tandem repeat analysis (MLVA panel and Multispacer Sequence Typing (MST. Results A total of 45 samples from 4 goat herds (placentas, N = 4, 12 dairy cattle herds (vaginal mucus, individual milk, bulk tank milk, aerosols, N = 20 and 5 sheep flocks (placenta, vaginal swabs, faeces, air samples, dust, N = 21 were included in the study. Samples from goats and sheep were obtained from herds which had suffered abortions suspected to be caused by C. burnetii, whereas cattle samples were obtained from animals with reproductive problems compatible with C. burnetii infection, or consisted of bulk tank milk (BTM samples from a Q fever surveillance programme. C. burnetii genotypes identified in ruminants from Spain were compared to those detected in other countries. Three MLVA genotypes were found in 4 goat farms, 7 MLVA genotypes were identified in 12 cattle herds and 4 MLVA genotypes were identified in 5 sheep flocks. Clustering of the MLVA genotypes using the minimum spanning tree method showed a high degree of genetic similarity between most MLVA genotypes. Overall 11 different MLVA genotypes were obtained corresponding to 4 different MST genotypes: MST genotype 13, identified in goat, sheep and cattle from Spain; MST genotype 18, only identified in goats; and, MST genotypes 8 and 20, identified in small ruminants and cattle, respectively. All these genotypes had been previously identified in animal and human clinical samples from several

  11. Heart failure report

    Directory of Open Access Journals (Sweden)

    Pamila Dua


    Full Text Available Despite advancements in diagnosis and pharmacotherapy, heart failure (HF remains as a major health problem. The prevalence in the general population is estimated to range from 0.3% to 2.0%, increases considerably with age, and approximately doubles with every additional decade of life. In the last two decades, hospital admission rates for HF have increased steadily. The prevalence of HF can be estimated at 1–2% in the Western world and the incidence approaches 5–10/1000 persons/year. Estimates of the occurrence of HF in the developing world are largely absent. In a recent US population-based study, the prevalence of HF was 2.2% (95 confidence interval 1.6–2.8%, increasing from 0.7% in persons aged 45 through 54 years to 8.4% for those aged 75 years or older. In this article, we look at the major papers published in HF in the past 1 year.

  12. Failure to recall. (United States)

    Laming, Donald


    Mathematical analysis shows that if the pattern of rehearsal in free-recall experiments (of necessity, the pattern observed when participants rehearse aloud) be continued without any further interruption by stimuli (as happens during recall), it terminates with the retrieval of the same 1 word over and over again. Such a terminal state is commonly reached before some of the words in the list have been retrieved even once; those words are not recalled. The 1 minute frequently allowed for recall in free-recall experiments is ample time for retrieval to seize up in this way. The author proposes a model that represents the essential features of the pattern of rehearsal; validates that model by reference to the overt rehearsal data from B. B. Murdock, Jr., and J. Metcalfe (1978) and the recall data from B. B. Murdock, Jr., and R. Okada (1970); demonstrates the long-term properties of continued sequences of retrievals and, also, a fundamental relation linking recall to the total time of presentation; and, finally, compares failure to recall in free-recall experiments with forgetting in general.

  13. Adult intestinal failure

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, J., E-mail: [Salford Royal Hospital, Salford (United Kingdom); Plumb, A.; Burnett, H. [Salford Royal Hospital, Salford (United Kingdom)


    Intestinal failure (IF) is the inability of the alimentary tract to digest and absorb sufficient nutrition to maintain normal fluid balance, growth, and health. It commonly arises from disease affecting the mesenteric root. Although severe IF is usually managed in specialized units, it lies at the end of a spectrum with degrees of nutritional compromise being widely encountered, but commonly under-recognized. Furthermore, in the majority of cases, the initial enteric insult occurs in non-specialist IF centres. The aim of this article is to review the common causes of IF, general principles of its management, some commoner complications, and the role of radiology in the approach to a patient with severe IF. The radiologist has a crucial role in helping provide access for feeding solutions (both enteral and parenteral) and controlling sepsis (via drainage of collections) in an initial restorative phase of treatment, whilst simultaneously mapping bowel anatomy and quality, and searching for disease complications to assist the clinicians in planning a later, restorative phase of therapy.

  14. Plant genotypic diversity reduces the rate of consumer resource utilization. (United States)

    McArt, Scott H; Thaler, Jennifer S


    While plant species diversity can reduce herbivore densities and herbivory, little is known regarding how plant genotypic diversity alters resource utilization by herbivores. Here, we show that an invasive folivore--the Japanese beetle (Popillia japonica)--increases 28 per cent in abundance, but consumes 24 per cent less foliage in genotypic polycultures compared with monocultures of the common evening primrose (Oenothera biennis). We found strong complementarity for reduced herbivore damage among plant genotypes growing in polycultures and a weak dominance effect of particularly resistant genotypes. Sequential feeding by P. japonica on different genotypes from polycultures resulted in reduced consumption compared with feeding on different plants of the same genotype from monocultures. Thus, diet mixing among plant genotypes reduced herbivore consumption efficiency. Despite positive complementarity driving an increase in fruit production in polycultures, we observed a trade-off between complementarity for increased plant productivity and resistance to herbivory, suggesting costs in the complementary use of resources by plant genotypes may manifest across trophic levels. These results elucidate mechanisms for how plant genotypic diversity simultaneously alters resource utilization by both producers and consumers, and show that population genotypic diversity can increase the resistance of a native plant to an invasive herbivore.

  15. Relationship of some upland rice genotype after gamma irradiation (United States)

    Suliartini, N. W. S.; Wijayanto, T.; Madiki, A.; Boer, D.; Muhidin; Juniawan


    The objective of the research was to group local upland rice genotypes after being treated with gamma irradiation. The research materials were upland rice genotypes resulted from mutation of the second generation and two parents: Pae Loilo (K3D0) and Pae Pongasi (K2D0) Cultivars. The research was conducted at the Indonesian Sweetener and Fiber Crops Research Institute, Malang Regency, and used the augmented design method. Research data were analyzed with R Program. Eight hundred and seventy one genotypes were selected with the selection criteria were based on yields on the average parents added 1.5 standard deviation. Based on the selection, eighty genotypes were analyzed with cluster analyses. Nine observation variables were used to develop cluster dendrogram using average linked method. Genetic distance was measured by euclidean distance. The results of cluster dendrogram showed that tested genotypes were divided into eight groups. Group 1, 2, 7, and 8 each had one genotype, group 3 and 6 each had two genotypes, group 4 had 25 genotypes, and group 5 had 51 genotypes. Check genotypes formed a separate group. Group 6 had the highest yield per plant of 126.11 gram, followed by groups 5 and 4 of 97.63 and 94.08 gram, respectively.

  16. Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in patients with hepatitis C virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection. (United States)

    Foster, Graham R; Pianko, Stephen; Brown, Ashley; Forton, Daniel; Nahass, Ronald G; George, Jacob; Barnes, Eleanor; Brainard, Diana M; Massetto, Benedetta; Lin, Ming; Han, Bin; McHutchison, John G; Subramanian, G Mani; Cooper, Curtis; Agarwal, Kosh


    We conducted an open-label, randomized, phase 3 trial to determine the efficacy and safety of sofosbuvir and ribavirin, with and without peginterferon-alfa, in treatment-experienced patients with cirrhosis and hepatitis C virus (HCV) genotype 2 infection and treatment-naïve or treatment-experienced patients with HCV genotype 3 infection. The study was conducted at 80 sites in Europe, North America, Australia, and New Zealand Patients were randomly assigned (1:1:1) to groups given sofosbuvir and ribavirin for 16 weeks (n = 196); sofosbuvir and ribavirin for 24 weeks (n = 199); or sofosbuvir, peginterferon-alfa, and ribavirin for 12 weeks (n = 197). The primary end point was the percentage of patients with HCV RNA <15 IU/mL 12 weeks after stopping therapy (sustained virologic response [SVR12]). From October 2013 until April 2014, we enrolled and treated 592 patients-48 with genotype 2 HCV and compensated cirrhosis who had not achieved SVR with previous treatments and 544 with genotype 3 HCV (279 treatment-naïve and 265 previously treated). Overall, 219 patients (37%) had compensated cirrhosis. The last post-treatment week 12 patient visit was in January 2015. Rates of SVR12 among patients with genotype 2 HCV were 87% and 100%, for those receiving 16 and 24 weeks of sofosbuvir and ribavirin, respectively, and 94% for those receiving sofosbuvir, peginterferon, and ribavirin for 12 weeks. Rates of SVR12 among patients with genotype 3 HCV were 71% and 84% in those receiving 16 and 24 weeks of sofosbuvir and ribavirin, respectively, and 93% in those receiving sofosbuvir, peginterferon, and ribavirin. On-treatment virologic failure occurred in 3 patients with HCV genotype 3a receiving sofosbuvir and ribavirin for 24 weeks. The most common adverse events were fatigue, headache, insomnia, and nausea. Overall, 1% of patients discontinued treatment due to adverse events. Among patients with genotype 3 HCV infection, including a large proportion of treatment

  17. Failure Rates in Introductory Programming

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard


    It is a common conception that CS1 is a very difficult course and that failure rates are high. However, until now there has only been anecdotal evidence for this claim. This article reports on a survey among institutions around the world regarding failure rates in introductory programming courses...

  18. On the Quality of Failure

    Directory of Open Access Journals (Sweden)

    Bengt-Arne Vedin


    Full Text Available No innovation without failed experiments. No acquisition of competency without hard work, efforts to translate mistakes and insufficient – failed – attempts into mastery. The human condition is one defined by trial and error. Success equates with narrow escape from failure, whereas failure may be a success just missed. The purpose of management can be said to achieve success, so the management of failure is a key one, seeking to turn failure into profit. Almost no successful solutions remain eternally, so signals indicating that they have arrived in their twilight zone are important. Success may be too comforting and lulling, creating a dangerous success lock-in. Courting failure by acting against conventional wisdom and routine intuitions may, though risky, generate huge payoffs. A productive failure management should appreciate that failure is a way to uncertainty reduction, to better information and knowledge, new wisdom and new intuitions. Failure can and should be celebrated and harvested. The most successful mineral prospectors are those who drill more holes; while their percentage of dry ones is average, their number of lucky ones makes for success. The same holds for ideas, where there is the additional benefit that a larger number of ideas, diverse as they are, makes for improved idea handling proficiency.

  19. Biomarkers in acute heart failure. (United States)

    Mallick, Aditi; Januzzi, James L


    The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Bisoprolol for congestive heart failure

    DEFF Research Database (Denmark)

    Rosenberg, J.; Gustafsson, F.


    was obtained from the FDA website. Conclusion: Bisoprolol is an effective and well-tolerated first-line beta-blocker for patients with systolic heart failure. The knowledge is primarily based on study patients with moderate-to-severe heart failure from the three CIBIS trials Udgivelsesdato: 2008/2...

  1. Childhood heart failure in Ibadan

    African Journals Online (AJOL)

    Childhood heart failure in Ibadan. I. A. Lagunju and S. I. Omokhodion*. Department of Paediatrics. University College Hospital, Ibadan. Summary. One hundred consecutive admissions of children with a diagnosis of congestive cardiac failure to the paediatric department of the University College Hospital, Ibadan were.

  2. Intelligent Design and Intelligent Failure (United States)

    Jerman, Gregory


    Good Evening, my name is Greg Jerman and for nearly a quarter century I have been performing failure analysis on NASA's aerospace hardware. During that time I had the distinct privilege of keeping the Space Shuttle flying for two thirds of its history. I have analyzed a wide variety of failed hardware from simple electrical cables to cryogenic fuel tanks to high temperature turbine blades. During this time I have found that for all the time we spend intelligently designing things, we need to be equally intelligent about understanding why things fail. The NASA Flight Director for Apollo 13, Gene Kranz, is best known for the expression "Failure is not an option." However, NASA history is filled with failures both large and small, so it might be more accurate to say failure is inevitable. It is how we react and learn from our failures that makes the difference.

  3. Diabetes Mellitus and Heart Failure. (United States)

    Lehrke, Michael; Marx, Nikolaus


    Epidemiologic and clinical data from the last 2 decades have shown that the prevalence of heart failure in diabetes is very high, and the prognosis for patients with heart failure is worse in those with diabetes than in those without diabetes. Experimental data suggest that various mechanisms contribute to the impairment in systolic and diastolic function in patients with diabetes, and there is an increased recognition that these patients develop heart failure independent of the presence of coronary artery disease or its associated risk factors. In addition, current clinical data demonstrated that treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin reduced hospitalization for heart failure in patients with type 2 diabetes mellitus and high cardiovascular risk. This review article summarizes recent data on the prevalence, prognosis, pathophysiology, and therapeutic strategies to treat patients with diabetes and heart failure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Nuclear cardiology and heart failure

    International Nuclear Information System (INIS)

    Giubbini, Raffaele; Bertagna, Francesco; Milan, Elisa; Mut, Fernando; Dondi, Maurizio; Metra, Marco; Rodella, Carlo


    The prevalence of heart failure in the adult population is increasing. It varies between 1% and 2%, although it mainly affects elderly people (6-10% of people over the age of 65 years will develop heart failure). The syndrome of heart failure arises as a consequence of an abnormality in cardiac structure, function, rhythm, or conduction. Coronary artery disease is the leading cause of heart failure and it accounts for this disorder in 60-70% of all patients affected. Nuclear techniques provide unique information on left ventricular function and perfusion by gated-single photon emission tomography (SPECT). Myocardial viability can be assessed by both SPECT and PET imaging. Finally, autonomic dysfunction has been shown to increase the risk of death in patients with heart disease and this may be applicable to all patients with cardiac disease regardless of aetiology. MIBG scanning has a very promising prognostic value in patients with heart failure. (orig.)

  5. No significant fuel failures (NSFF)

    International Nuclear Information System (INIS)

    Domaratzki, Z.


    It has long been recognized that no emergency core cooling system (ECCS) could be absolutely guaranteed to prevent fuel failures. In 1976 the Atomic Energy Control Board decided that the objective for an ECCS should be to prevent fuel failures, but if the objective could not be met it should be shown that the consequences are acceptable for dual failures comprising any LOCA combined with an assumed impairment of containment. Out of the review of the Bruce A plant came the definition of 'no significant fuel failures': for any postulated LOCA combined with any one mode of containment impairment the resultant dose to a person at the edge of the exclusion zone is less than the reference dose limits for dual failures

  6. Bisoprolol for congestive heart failure

    DEFF Research Database (Denmark)

    Rosenberg, J.; Gustafsson, F.


    Background: beta-Blockers are a cornerstone in the treatment of systolic heart failure treatment, but not all beta-blockers are effective or in this setting. Objective: To define the role of bisoprolol, a highly selective beta(1)-antagonist in congestive heart failure due to systolic dysfunction....... Methods: Using the keywords 'bisoprolol' and 'heart failure' PubMed and BIOSIS databases were searched for information regarding pharmacology and relevant randomised clinical trials. Supplementary publications were acquired by scrutinising reference lists of relevant papers. Additional information...... was obtained from the FDA website. Conclusion: Bisoprolol is an effective and well-tolerated first-line beta-blocker for patients with systolic heart failure. The knowledge is primarily based on study patients with moderate-to-severe heart failure from the three CIBIS trials Udgivelsesdato: 2008/2...

  7. Failure Criteria for Reinforced Materials

    DEFF Research Database (Denmark)

    Rathkjen, Arne

    Failure of materials is often characterized as ductile yielding, brittle fracture, creep rupture, etc., and different criteria given in terms of different parameters have been used to describe different types of failure. Only criteria expressing failure in terms of stress are considered in what...... place until the matrix, the continuous component of the composite, fails. When an isotropic matrix is reinforced as described above, the result is an anisotropic composite material. Even if the material is anisotropic, it usually exhibits a rather high degree of symmetry and such symmetries place...... certain restrictions on the form of the failure criteria for anisotropic materials. In section 2, some failure criteria for homogenous materials are reviewed. Both isotropic and anisotropic materials are described, and in particular the constraints imposed on the criteria from the symmetries orthotropy...

  8. Nuclear cardiology and heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Giubbini, Raffaele; Bertagna, Francesco [University of Brescia, Department of Nuclear Medicine, Brescia (Italy); Milan, Elisa [Ospedale Di Castelfranco Veneto, Nuclear Medicine Unit, Castelfranco Veneto (Italy); Mut, Fernando; Dondi, Maurizio [International Atomic Energy Agency, Nuclear Medicine Section, Division of Human Health, Vienna (Austria); Metra, Marco [University of Brescia, Department of Cardiology, Brescia (Italy); Rodella, Carlo [Health Physics Department, Spedali Civili di Brescia, Brescia (Italy)


    The prevalence of heart failure in the adult population is increasing. It varies between 1% and 2%, although it mainly affects elderly people (6-10% of people over the age of 65 years will develop heart failure). The syndrome of heart failure arises as a consequence of an abnormality in cardiac structure, function, rhythm, or conduction. Coronary artery disease is the leading cause of heart failure and it accounts for this disorder in 60-70% of all patients affected. Nuclear techniques provide unique information on left ventricular function and perfusion by gated-single photon emission tomography (SPECT). Myocardial viability can be assessed by both SPECT and PET imaging. Finally, autonomic dysfunction has been shown to increase the risk of death in patients with heart disease and this may be applicable to all patients with cardiac disease regardless of aetiology. MIBG scanning has a very promising prognostic value in patients with heart failure. (orig.)

  9. Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure. (United States)

    Freedman, B I; Julian, B A; Pastan, S O; Israni, A K; Schladt, D; Gautreaux, M D; Hauptfeld, V; Bray, R A; Gebel, H M; Kirk, A D; Gaston, R S; Rogers, J; Farney, A C; Orlando, G; Stratta, R J; Mohan, S; Ma, L; Langefeld, C D; Hicks, P J; Palmer, N D; Adams, P L; Palanisamy, A; Reeves-Daniel, A M; Divers, J


    Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Failure detection system risk reduction assessment (United States)

    Aguilar, Robert B. (Inventor); Huang, Zhaofeng (Inventor)


    A process includes determining a probability of a failure mode of a system being analyzed reaching a failure limit as a function of time to failure limit, determining a probability of a mitigation of the failure mode as a function of a time to failure limit, and quantifying a risk reduction based on the probability of the failure mode reaching the failure limit and the probability of the mitigation.

  11. Failure probabilistic model of CNC lathes

    International Nuclear Information System (INIS)

    Wang Yiqiang; Jia Yazhou; Yu Junyi; Zheng Yuhua; Yi Shangfeng


    A field failure analysis of computerized numerical control (CNC) lathes is described. Field failure data was collected over a period of two years on approximately 80 CNC lathes. A coding system to code failure data was devised and a failure analysis data bank of CNC lathes was established. The failure position and subsystem, failure mode and cause were analyzed to indicate the weak subsystem of a CNC lathe. Also, failure probabilistic model of CNC lathes was analyzed by fuzzy multicriteria comprehensive evaluation

  12. SCN5A mutations and polymorphisms in patients with ventricular fibrillation during acute myocardial infarction. (United States)

    Boehringer, Tim; Bugert, Peter; Borggrefe, Martin; Elmas, Elif


    Mutations in the SCN5A gene encoding the Nav1.5 channel α-subunit are known to be risk factors of arrhythmia, including Brugada Syndrome and Long QT syndrome subtype 3. The present study focused on the role of SCN5A variants in the development of ventricular fibrillation (VF) during acute myocardial infarction (AMI). Since VF during AMI is the major cause of sudden death in the Western world, SCN5A mutations represent genetic risk factors for sudden death. By exon re-sequencing, the entire coding region and flanking intron regions were sequenced in 46 AMI/VF+ patients. In total, nine single nucleotide variants were identified of which four represented common single nucleotide polymorphisms (SNPs; 87G>A, 1673A>G, IVS16‑6C>T and 5457T>A). Only five rare variants were identified, each in only one patient. Only two of the rare variants represented missense mutations (3578G>A and 4786T>A). The common SNPs and the missense mutations were also genotyped using polymerase chain reaction methods in 79 AMI/VF‑ patients and 480 healthy controls. The SNPs did not demonstrate significant differences in allele and genotype frequencies between the study groups. The 3578G>A mutation was identified in one out of the 480 controls, whereas the 4786T>A mutation was not present in AMI/VF- patients and controls. In conclusion, the majority of AMI/VF+ patients demonstrated a wild type sequence or common SNPs in SCN5A. Only two out of 46 (4.3%) AMI/VF+ patients revealed mutations that may be involved in Nav1.5 dysfunction and VF. However, this requires further functional validation.

  13. Linking genotypes database with locus-specific database and genotype-phenotype correlation in phenylketonuria. (United States)

    Wettstein, Sarah; Underhaug, Jarl; Perez, Belen; Marsden, Brian D; Yue, Wyatt W; Martinez, Aurora; Blau, Nenad


    The wide range of metabolic phenotypes in phenylketonuria is due to a large number of variants causing variable impairment in phenylalanine hydroxylase function. A total of 834 phenylalanine hydroxylase gene variants from the locus-specific database PAHvdb and genotypes of 4181 phenylketonuria patients from the BIOPKU database were characterized using FoldX, SIFT Blink, Polyphen-2 and SNPs3D algorithms. Obtained data was correlated with residual enzyme activity, patients' phenotype and tetrahydrobiopterin responsiveness. A descriptive analysis of both databases was compiled and an interactive viewer in PAHvdb database was implemented for structure visualization of missense variants. We found a quantitative relationship between phenylalanine hydroxylase protein stability and enzyme activity (r(s) = 0.479), between protein stability and allelic phenotype (r(s) = -0.458), as well as between enzyme activity and allelic phenotype (r(s) = 0.799). Enzyme stability algorithms (FoldX and SNPs3D), allelic phenotype and enzyme activity were most powerful to predict patients' phenotype and tetrahydrobiopterin response. Phenotype prediction was most accurate in deleterious genotypes (≈ 100%), followed by homozygous (92.9%), hemizygous (94.8%), and compound heterozygous genotypes (77.9%), while tetrahydrobiopterin response was correctly predicted in 71.0% of all cases. To our knowledge this is the largest study using algorithms for the prediction of patients' phenotype and tetrahydrobiopterin responsiveness in phenylketonuria patients, using data from the locus-specific and genotypes database.

  14. Antioxidant capacity of anthocyanins from acerola genotypes

    Directory of Open Access Journals (Sweden)

    Vera Lúcia Arroxelas Galvão De Lima


    Full Text Available Anthocyanins from 12 acerola genotypes cultivated at the Active Germplasm Bank at Federal Rural University of Pernambuco were isolated for antioxidant potential evaluation. The antioxidant activity and radical scavenging capacity of the anthocyanin isolates were measured according to the β-carotene bleaching method and 1,1-diphenyl-2-picrylhydrazyl (DPPH free radical scavenging assay, respectively. The antioxidant activity varied from 25.58 to 47.04% at 0.2 mg.mL-1, and it was measured using the β-carotene bleaching method. The free radical scavenging capacity increased according to the increase in concentration and reaction time by the DPPH assay. At 16.7 μg.mL-1 concentration and after 5 minutes and 2 hours reaction time, the percentage of scavenged radicals varied from 36.97 to 63.92% and 73.27 to 94.54%, respectively. Therefore, the antioxidant capacity of acerola anthocyanins varied amongst acerola genotypes and methods used. The anthocyanins present in this fruit may supply substantial dietary source of antioxidant which may promote health and produce disease prevention effects.

  15. [Mexican phenotype and genotype Vibrio cholerae 01]. (United States)

    Giono, S; Gutiérrez Cogno, L; Rodríguez Angeles, G; del Rio Zolezzi, A; Valdespino González, J L; Sepúlveda Amor, J


    This paper presents the phenotypical and genotypical characterization of 26922 Vibrio cholerae 01 strains isolated in Mexico from 1991 to 1993. All strains isolated were El Tor biovar. Strains were sensitive to antibiotics excluding furazolidone, streptomycin and sulfisoxasole to which we found resistance in 97% and we are using this characteristic as epidemiological markers. We detected a marked change in frequency of Inaba serotype from 1991, when it was dominant, with 99.5%, until 1992 when Ogawa serotype turned to be dominant with 95% of isolates. All Vibrio cholerae 01 strains, except one Ogawa strain, were to igenic, and V. choleraeno 01 were not toxigenic by ELISA, PCR and cell culture tests. Dominant ribotype was 5, but we found some strains with 6a pattern and two with ribotype 12. We are searching for ribotype 2 among hemolytic strains in order to learn if there is any relation to Gulf Coast strains prevalent in the USA, but until now we have not found any V. cholerae ribotype 2 in our isolates. Even if rapid tests are recommended for immediate diagnosis of cholera, it is necessary to continue bacterial isolation in order to have strains for phenotyping and genotyping studies that may support epidemiological analysis.

  16. HFE genotype affects exosome phenotype in cancer. (United States)

    Mrowczynski, Oliver D; Madhankumar, A B; Slagle-Webb, Becky; Lee, Sang Y; Zacharia, Brad E; Connor, James R


    Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. Tumor progression and recurrence is common with little understanding of mechanisms. A major recent focus in cancer biology is the impact of exosomes on metastatic behavior and the tumor microenvironment. Exosomes have been demonstrated to contribute to the oncogenic effect on the surrounding tumor environment and also mediate resistance to therapy. The effect of genotype on exosomal phenotype has not yet been explored. We interrogated exosomes from human neuroblastoma cells that express wild-type or mutant forms of the HFE gene. HFE, one of the most common autosomal recessive polymorphisms in the Caucasian population, originally associated with hemochromatosis, has also been associated with increased tumor burden, therapeutic resistance boost, and negative impact on patient survival. Herein, we demonstrate that changes in genotype cause major differences in the molecular and functional properties of exosomes; specifically, HFE mutant derived exosomes have increased expression of proteins relating to invasion, angiogenesis, and cancer therapeutic resistance. HFE mutant derived exosomes were also shown to transfer this cargo to recipient cells and cause an increased oncogenic functionality in those recipient cells. Copyright © 2017. Published by Elsevier B.V.

  17. Haplotype-Based Genotyping in Polyploids

    Directory of Open Access Journals (Sweden)

    Josh P. Clevenger


    Full Text Available Accurate identification of polymorphisms from sequence data is crucial to unlocking the potential of high throughput sequencing for genomics. Single nucleotide polymorphisms (SNPs are difficult to accurately identify in polyploid crops due to the duplicative nature of polyploid genomes leading to low confidence in the true alignment of short reads. Implementing a haplotype-based method in contrasting subgenome-specific sequences leads to higher accuracy of SNP identification in polyploids. To test this method, a large-scale 48K SNP array (Axiom Arachis2 was developed for Arachis hypogaea (peanut, an allotetraploid, in which 1,674 haplotype-based SNPs were included. Results of the array show that 74% of the haplotype-based SNP markers could be validated, which is considerably higher than previous methods used for peanut. The haplotype method has been implemented in a standalone program, HAPLOSWEEP, which takes as input bam files and a vcf file and identifies haplotype-based markers. Haplotype discovery can be made within single reads or span paired reads, and can leverage long read technology by targeting any length of haplotype. Haplotype-based genotyping is applicable in all allopolyploid genomes and provides confidence in marker identification and in silico-based genotyping for polyploid genomics.

  18. Hearing impairment in genotyped Wolfram syndrome patients. (United States)

    Plantinga, Rutger F; Pennings, Ronald J E; Huygen, Patrick L M; Bruno, Rocco; Eller, Philipp; Barrett, Timothy G; Vialettes, Bernard; Paquis-Fluklinger, Veronique; Lombardo, Fortunato; Cremers, Cor W R J


    Wolfram syndrome is a progressive neurodegenerative syndrome characterized by the features "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). We sought to study the audiometric data of genotyped Wolfram syndrome patients with sensorineural hearing impairment. Pure tone threshold data of 23 Wolfram syndrome patients were used for cross-sectional analysis in subgroups (age less than 16 years or between 19 and 25 years, gender, and origin). All subgroups, with 1 exception, showed a fairly similar type of hearing impairment with, on average, thresholds of about 25 dB (range, 0 to 65 dB) at 0.25 to 1 kHz, gently sloping downward to about 60 dB (range, 25 to 95 dB) at 8 kHz. The subgroup of Dutch women, which was excluded from the calculations of the average hearing thresholds, showed a higher degree of hearing impairment. Only the latter subgroup showed progression; however, contrary to the previous longitudinal analysis, progression was not significant in the present cross-sectional analysis, presumably because of the high degree of cross-subject variability. This unique collection of audiometric data from genotyped Wolfram syndrome patients shows no substantial progression in sensorineural hearing impairment with advancing age, no relation to the types of WFS1 mutations identified, and, with exclusion of the subgroup of Dutch female patients, no significant sex-related differences.

  19. Lessons learned from failure analysis

    International Nuclear Information System (INIS)

    Le May, I.


    Failure analysis can be a very useful tool to designers and operators of plant and equipment. It is not simply something that is done for lawyers and insurance companies, but is a tool from which lessons can be learned and by means of which the 'breed' can be improved. In this presentation, several failure investigations that have contributed to understanding will be presented. Specifically, the following cases will be discussed: 1) A fire at a refinery that occurred in a desulphurization unit. 2) The failure of a pipeline before it was even put into operation. 3) Failures in locomotive axles that took place during winter operation. The refinery fire was initially blamed on defective Type 321 seamless stainless steel tubing, but there were conflicting views between 'experts' involved as to the mechanism of failure and the writer was called upon to make an in-depth study. This showed that there were a variety of failure mechanism involved, including high temperature fracture, environmentally-induced cracking and possible manufacturing defects. The unraveling of the failure sequence is described and illustrated. The failure of an oil transmission was discovered when the line was pressure tested some months after it had been installed and before it was put into service. Repairs were made and failure occurred in another place upon the next pressure test being conducted. After several more repairs had been made the line was abandoned and a lawsuit was commenced on the basis that the steel was defective. An investigation disclosed that the material was sensitive to embrittlement and the causes of this were determined. As a result, changes were made in the microstructural control of the product to avoid similar problems in future. A series of axle failures occurred in diesel electric locomotives during winter. An investigation was made to determine the nature of the failures which were not by classical fatigue, nor did they correspond to published illustrations of Cu

  20. Deep sequencing analysis of HBV genotype shift and correlation with antiviral efficiency during adefovir dipivoxil therapy.

    Directory of Open Access Journals (Sweden)

    Yuwei Wang

    Full Text Available Viral genotype shift in chronic hepatitis B (CHB patients during antiviral therapy has been reported, but the underlying mechanism remains elusive.38 CHB patients treated with ADV for one year were selected for studying genotype shift by both deep sequencing and Sanger sequencing method.Sanger sequencing method found that 7.9% patients showed mixed genotype before ADV therapy. In contrast, all 38 patients showed mixed genotype before ADV treatment by deep sequencing. 95.5% mixed genotype rate was also obtained from additional 200 treatment-naïve CHB patients. Of the 13 patients with genotype shift, the fraction of the minor genotype in 5 patients (38% increased gradually during the course of ADV treatment. Furthermore, responses to ADV and HBeAg seroconversion were associated with the high rate of genotype shift, suggesting drug and immune pressure may be key factors to induce genotype shift. Interestingly, patients with genotype C had a significantly higher rate of genotype shift than genotype B. In genotype shift group, ADV treatment induced a marked enhancement of genotype B ratio accompanied by a reduction of genotype C ratio, suggesting genotype C may be more sensitive to ADV than genotype B. Moreover, patients with dominant genotype C may have a better therapeutic effect. Finally, genotype shifts was correlated with clinical improvement in terms of ALT.Our findings provided a rational explanation for genotype shift among ADV-treated CHB patients. The genotype and genotype shift might be associated with antiviral efficiency.

  1. The genotype-phenotype map of an evolving digital organism


    Fortuna, Miguel A.; Zaman, Luis; Ofria, Charles; Wagner, Andreas


    To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms fr...

  2. Molecular genotyping of HCV infection in seropositive blood donor (United States)

    Zarin, Siti Noraziah Abu; Ibrahim, Nazlina


    This study is to investigate the prevalence of hepatitis C virus infection in seropositive blood donor. RNA was extracted from 32 positive samples in National Blood Centre and Melaka Hospital. The core and NS5B sequences were obtained from 23 samples. Genotype 3a is most prevalent in this study followed by genotype 1a. Evidence of mixed-genotypes (3a and 1b) infections was found in 5 subjects.

  3. New Medications for Heart Failure (United States)

    Gordin, Jonathan S.; Fonarow, Gregg C.


    Heart failure is common and results in substantial morbidity and mortality. Current guideline-based therapies for heart failure with reduced ejection fraction, including beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and aldosterone antagonists aim to interrupt deleterious neurohormonal pathways and have shown significant success in reducing morbidity and mortality associated with heart failure. Continued efforts to further improve outcomes in patients with heart failure with reduced ejection fraction have led to the first new-in-class medications approved for heart failure since 2005, ivabradine and sacubitril/valsartan. Ivabradine targets the If channels in the sinoatrial node of the heart, decreasing heart rate. Sacubitril/valsartan combines a neprilysin inhibitor that increases levels of beneficial vasodilatory peptides with an angiotensin receptor antagonist. On a background of previously approved, guideline-directed medical therapies for heart failure, these medications have shown improved clinical outcomes ranging from decreased hospitalizations in a select group of patients to a reduction in all-cause mortality across all pre-specified subgroups. In this review, we will discuss the previously established guideline-directed medical therapies for heart failure with reduced ejection fraction, the translational research that led to the development of these new therapies, and the results from the major clinical trials of ivabradine and sacubitril/valsartan. PMID:27038558

  4. Periodontitis in Chronic Heart Failure. (United States)

    Fröhlich, Hanna; Herrmann, Kristina; Franke, Jennifer; Karimi, Alamara; Täger, Tobias; Cebola, Rita; Katus, Hugo A; Zugck, Christian; Frankenstein, Lutz


    Periodontal disease has been associated with an increased risk of cardiovascular events. The purpose of our study was to investigate whether a correlation between periodontitis and chronic heart failure exists, as well as the nature of the underlying cause. We enrolled 71 patients (mean age, 54 ± 13 yr; 56 men) who had stable chronic heart failure; all underwent complete cardiologic and dental evaluations. The periodontal screening index was used to quantify the degree of periodontal disease. We compared the findings to those in the general population with use of data from the 4th German Dental Health Survey. Gingivitis, moderate periodontitis, and severe periodontitis were present in 17 (24%), 17 (24%), and 37 (52%) patients, respectively. Severe periodontitis was more prevalent among chronic heart failure patients than in the general population. In contrast, moderate periodontitis was more prevalent in the general population (P periodontal disease was not associated with the cause of chronic heart failure or the severity of heart failure symptoms. Six-minute walking distance was the only independent predictor of severe periodontitis. Periodontal disease is highly prevalent in chronic heart failure patients regardless of the cause of heart failure. Prospective trials are warranted to clarify the causal relationship between both diseases.

  5. Bottom head failure program plan

    International Nuclear Information System (INIS)

    Meyer, R.O.


    Earlier this year the NRC staff presented a Revised Severe Accident Research Program Plan (SECY-89-123) to the Commission and initiated work on that plan. Two of the near-term issues in that plan involve failure of the bottom head of the reactor pressure vessel. These two issues are (1) depressurization and DCH and (2) BWR Mark I Containment Shell Meltthrough. ORNL has developed models for several competing failure mechanisms for BWRs. INEL has performed analytical and experimental work directly related to bottom head failure in connection with several programs. SNL has conducted a number of analyses and experimental activities to examine the failure of LWR vessels. In addition to the government-sponsored work mentioned above, EPRI and FAI performed studies on vessel failure for the Industry Degraded Core Rulemaking Program (IDCOR). EPRI examined the failure of a PWR vessel bottom head without penetrations, as found in some Combustion Engineering reactors. To give more attention to this subject as called for by the revised Severe Accident Research Plan, two things are being done. First, work previously done is being reviewed carefully to develop an overall picture and to determine the reliability of assumptions used in those studies. Second, new work is being planned for FY90 to try to complete a reasonable understanding of the failure process. The review and planning are being done in close cooperation with the ACRS. Results of this exercise will be presented in this paper

  6. Understanding failures in petascale computers

    International Nuclear Information System (INIS)

    Schroeder, Bianca; Gibson, Garth A


    With petascale computers only a year or two away there is a pressing need to anticipate and compensate for a probable increase in failure and application interruption rates. Researchers, designers and integrators have available to them far too little detailed information on the failures and interruptions that even smaller terascale computers experience. The information that is available suggests that application interruptions will become far more common in the coming decade, and the largest applications may surrender large fractions of the computer's resources to taking checkpoints and restarting from a checkpoint after an interruption. This paper reviews sources of failure information for compute clusters and storage systems, projects failure rates and the corresponding decrease in application effectiveness, and discusses coping strategies such as application-level checkpoint compression and system level process-pairs fault-tolerance for supercomputing. The need for a public repository for detailed failure and interruption records is particularly concerning, as projections from one architectural family of machines to another are widely disputed. To this end, this paper introduces the Computer Failure Data Repository and issues a call for failure history data to publish in it

  7. Cardio-facio-cutaneous syndrome: does genotype predict phenotype? (United States)

    Allanson, Judith E; Annerén, Göran; Aoki, Yoki; Armour, Christine M; Bondeson, Marie-Louise; Cave, Helene; Gripp, Karen W; Kerr, Bronwyn; Nystrom, Anna-Maja; Sol-Church, Katia; Verloes, Alain; Zenker, Martin


    Cardio-facio-cutaneous (CFC) syndrome is a sporadic multiple congenital anomalies/mental retardation condition principally caused by mutations in BRAF, MEK1, and MEK2. Mutations in KRAS and SHOC2 lead to a phenotype with overlapping features. In approximately 10–30% of individuals with a clinical diagnosis of CFC, a mutation in one of these causative genes is not found. Cardinal features of CFC include congenital heart defects, a characteristic facial appearance, and ectodermal abnormalities. Additional features include failure to thrive with severe feeding problems, moderate to severe intellectual disability and short stature with relative macrocephaly. First described in 1986, more than 100 affected individuals are reported. Following the discovery of the causative genes, more information has emerged on the breadth of clinical features. Little, however, has been published on genotype–phenotype correlations. This clinical study of 186 children and young adults with mutation-proven CFC syndrome is the largest reported to date. BRAF mutations are documented in 140 individuals (approximately 75%), while 46 (approximately 25%) have a mutation in MEK 1 or MEK 2. The age range is 6 months to 32 years, the oldest individual being a female from the original report [Reynolds et al. (1986); Am J Med Genet 25:413–427]. While some clinical data on 136 are in the literature, 50 are not previously published. We provide new details of the breadth of phenotype and discuss the frequency of particular features in each genotypic group. Pulmonary stenosis is the only anomaly that demonstrates a statistically significant genotype–phenotype correlation, being more common in individuals with a BRAF mutation.

  8. Failure probability under parameter uncertainty. (United States)

    Gerrard, R; Tsanakas, A


    In many problems of risk analysis, failure is equivalent to the event of a random risk factor exceeding a given threshold. Failure probabilities can be controlled if a decisionmaker is able to set the threshold at an appropriate level. This abstract situation applies, for example, to environmental risks with infrastructure controls; to supply chain risks with inventory controls; and to insurance solvency risks with capital controls. However, uncertainty around the distribution of the risk factor implies that parameter error will be present and the measures taken to control failure probabilities may not be effective. We show that parameter uncertainty increases the probability (understood as expected frequency) of failures. For a large class of loss distributions, arising from increasing transformations of location-scale families (including the log-normal, Weibull, and Pareto distributions), the article shows that failure probabilities can be exactly calculated, as they are independent of the true (but unknown) parameters. Hence it is possible to obtain an explicit measure of the effect of parameter uncertainty on failure probability. Failure probability can be controlled in two different ways: (1) by reducing the nominal required failure probability, depending on the size of the available data set, and (2) by modifying of the distribution itself that is used to calculate the risk control. Approach (1) corresponds to a frequentist/regulatory view of probability, while approach (2) is consistent with a Bayesian/personalistic view. We furthermore show that the two approaches are consistent in achieving the required failure probability. Finally, we briefly discuss the effects of data pooling and its systemic risk implications. © 2010 Society for Risk Analysis.

  9. Can Genetics Predict Sports Injury? The Association of the Genes GDF5, AMPD1, COL5A1 and IGF2 on Soccer Player Injury Occurrence

    Directory of Open Access Journals (Sweden)

    Kiah McCabe


    Full Text Available Genetics plays an integral role in athletic performance and is increasingly becoming recognised as an important risk factor for injury. Ankle and knee injuries are the most common injuries sustained by soccer players. Often these injuries result in players missing training and matches, which can incur significant costs to clubs. This study aimed to identify genotypes associated with ankle and knee injuries in soccer players and how these impacted the number of matches played. 289 soccer players, including 46 professional, 98 semi-professional and 145 amateur players, were genetically tested. Ankle and knee injuries and the number of matches played were recorded during the 2014/15 season. Four genes were assessed in relation to injury. Genotypes found to be associated with injury included the TT (nucleobase genotype of the GDF5 gene, TT and CT (nucleobase genotypes of AMPD1 gene, TT genotype of COL5A1 and GG (nucleobase genotype of IGF2 gene. These genes were also associated with a decrease in the number of matches played.

  10. Association of CYP17 and SRD5A2 gene polymorphisms with Prostate cancer risk among Iranian and Indian populations

    Directory of Open Access Journals (Sweden)

    kh onsory


    Full Text Available Aims and objectives: Prostate cancer is a complicated disease that genetics and environmental factors may be playing a promoting role in its progression. Polymorphism of genes such as steroid hormone receptors are having very important role in developing this disease. One such gene, CYP17 is playing role in hydroxylation and SRD5A2 gene, the predominant 5&alpha-reductase isozyme in prostate, catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT, which is required for the normal growth and development of the prostate gland. The purpose of this study was to investigate association of CYP17 and SRD5A2 genes polymorphisms with prostate cancer risk. Materials and methods: PCR-RFLP analysis of CYP17 and SRD5A2 genes were performed on 100 prostate cancer patients admitted to the Department of Urology, Postgraduate Institute of Medical Science and Research (PGIMER, Chandigarh, India, and 150 patients from Imam Khomeini Hospital, Tehran, Iran, compared with equal number of matching controls for each group visiting same centers for other reason. The data was analyzed using the computer software SPSS for windows (version 19, using logistic regression. Results: In this case-control study, there was a significant increase with risk of prostate cancer association for individuals carrying one copy of CYP17 A2 allele in Iranian (OR= 2.10 95% CI, 1.03-4.27 P=0.041 and Indian populations (OR= 2.16 95% CI, 1.08-4.33 P=0.029. While the risk was decreased in individuals having two A2 alleles in both groups. Compared with men having the VV genotype of SRD5A2 gene, there was no significant association between the VL genotype and the risk of prostate cancer among Iranian (OR, 0.87 95% CI, 0.49 -1.56 P=0.661 and Indian (OR, 0.99 95% CI, 0.54 -1.81 P=0.989 patients. Also there was no difference in the occurrence of the genotype LL between prostate cancer patients and control groups in both studied populations therefore, there

  11. Component failure data base of TRIGA reactors

    International Nuclear Information System (INIS)

    Djuricic, M.


    This compilation provides failure data such as first criticality, component type description (reactor component, population, cumulative calendar time, cumulative operating time, demands, failure mode, failures, failure rate, failure probability) and specific information on each type of component of TRIGA Mark-II reactors in Austria, Bangladesh, Germany, Finland, Indonesia, Italy, Indonesia, Slovenia and Romania. (nevyjel)

  12. Genomic Variants Revealed by Invariably Missing Genotypes in Nelore Cattle.

    Directory of Open Access Journals (Sweden)

    Joaquim Manoel da Silva

    Full Text Available High density genotyping panels have been used in a wide range of applications. From population genetics to genome-wide association studies, this technology still offers the lowest cost and the most consistent solution for generating SNP data. However, in spite of the application, part of the generated data is always discarded from final datasets based on quality control criteria used to remove unreliable markers. Some discarded data consists of markers that failed to generate genotypes, labeled as missing genotypes. A subset of missing genotypes that occur in the whole population under study may be caused by technical issues but can also be explained by the presence of genomic variations that are in the vicinity of the assayed SNP and that prevent genotyping probes from annealing. The latter case may contain relevant information because these missing genotypes might be used to identify population-specific genomic variants. In order to assess which case is more prevalent, we used Illumina HD Bovine chip genotypes from 1,709 Nelore (Bos indicus samples. We found 3,200 missing genotypes among the whole population. NGS re-sequencing data from 8 sires were used to verify the presence of genomic variations within their flanking regions in 81.56% of these missing genotypes. Furthermore, we discovered 3,300 novel SNPs/Indels, 31% of which are located in genes that may affect traits of importance for the genetic improvement of cattle production.

  13. Phosphorus use efficiency in pima cotton (Gossypium barbadense L. genotypes

    Directory of Open Access Journals (Sweden)

    Elcio Santos


    Full Text Available In the Brazilian Cerrado, P deficiency restricts cotton production, which requires large amounts of phosphate fertilizer. To improve the yield of cotton crops, genotypes with high P use efficiency must be identified and used. The present study evaluated P uptake and use efficiency of different Gossypium barbadense L. genotypes grown in the Cerrado. The experiment was carried out in a greenhouse with a completely randomized design, 15 x 2 factorial treatment structure (15 genotypes x 2 P levels, and four replicates. The genotypes were MT 69, MT 70, MT 87, MT 91, MT 92, MT 94, MT 101, MT 102, MT 103, MT 105, MT 106, MT 110, MT 112, MT 124, and MT 125; P levels were sufficient (1000 mg pot-1, PS treatment or deficient (PD treatment. Dry matter (DM and P levels were determined in cotton plant parts and used to calculate plant P content and use efficiency. In general, DM and P content were higher in the PS than in the PD treatment, with the exception of root DM and total DM in some genotypes. Genotypes also differed in terms of P uptake and use capacity. In the PS treatment, genotypes MT 92 and MT 102 had the highest response to phosphate fertilization. Genotype MT 69 exhibited the most efficient P uptake in the PD treatment. Genotype MT 124 showed the best shoot physiological efficiency, apparent recovery efficiency, and utilization efficiency, whereas MT 110 exhibited the highest root physiological efficiency.

  14. Management of Postoperative Respiratory Failure. (United States)

    Mulligan, Michael S; Berfield, Kathleen S; Abbaszadeh, Ryan V


    Despite best efforts, postoperative complications such as postoperative respiratory failure may occur and prompt recognition of the process and management is required. Postoperative respiratory failure, such as postoperative pneumonia, postpneumonectomy pulmonary edema, acute respiratory distress-like syndromes, and pulmonary embolism, are associated with high morbidity and mortality. The causes of these complications are multifactorial and depend on preoperative, intraoperative, and postoperative factors, some of which are modifiable. The article identifies some of the risk factors, causes, and treatment strategies for successful management of the patient with postoperative respiratory failure. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Governing of common cause failures

    International Nuclear Information System (INIS)

    Bock, H.W.


    Agreed strategy is to govern common cause failures by the application of diversity, to assure that the overall plant safety objectives are met even in the case that a common cause failure of a system with all redundant trains is assumed. The presented strategy aims on the application of functional diversity without the implementation of equipment diversity. In the focus are the design criteria which have to be met for the design of independent systems in such a way that the time-correlated failure of such independent systems according a common cause can be excluded deterministically. (author)

  16. Secondary Hyperparathyroidism in Heart Failure. (United States)

    Morsy, Mohamed S; Dishmon, Dwight A; Garg, Nadish; Weber, Karl T


    Secondary hyperparathyroidism (SHPT) is a well-known pathophysiologic feature of chronic renal failure. In recent years, SHPT has become recognized as a complication of the aldosteronism associated with congestive heart failure and where excretory Ca 2+ and Mg 2+ wasting results in plasma-ionized hypocalcemia and hypomagnesemia. Elevations in plasma parathyroid hormone have adverse systemic consequences, including intracellular Ca 2+ overloading of myocytes and vascular smooth muscle with the induction of oxidative stress. Herein, we briefly review the presence and adverse outcomes of SHPT in persons with heart failure. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  17. Welcome to the neighbourhood: interspecific genotype by genotype interactions in Solidago influence above- and belowground biomass and associated communities. (United States)

    Genung, Mark A; Bailey, Joseph K; Schweitzer, Jennifer A


    Intra- and interspecific plant-plant interactions are fundamental to patterns of community assembly and to the mixture effects observed in biodiversity studies. Although much research has been conducted at the species level, very little is understood about how genetic variation within and among interacting species may drive these processes. Using clones of both Solidago altissima and Solidago gigantea, we found that genotypic variation in a plant's neighbours affected both above- and belowground plant traits, and that genotype by genotype interactions between neighbouring plants impacted associated pollinator communities. The traits for which focal plant genotypic variation explained the most variation varied by plant species, whereas neighbour genotypic variation explained the most variation in coarse root biomass. Our results provide new insight into genotypic and species diversity effects in plant-neighbour interactions, the extended consequences of diversity effects, and the potential for evolution in response to competitive or to facilitative plant-neighbour interactions. © 2011 Blackwell Publishing Ltd/CNRS.

  18. Effect of the Winter Wheat Cheyenne 5A Substituted Chromosome on Dynamics of Abscisic Acid and Cytokinins in Freezing-Sensitive Chinese Spring Genetic Background (United States)

    Kalapos, Balázs; Novák, Aliz; Dobrev, Petre; Vítámvás, Pavel; Marincs, Ferenc; Galiba, Gábor; Vanková, Radomira


    The effect of short- and long-term cold treatment on the abscisic acid (ABA) and cytokinin (CK) metabolism, and their main biosynthesis- and signaling-related genes were investigated in freezing-sensitive and freezing-tolerant wheat genotypes. Varieties Cheyenne and Chinese Spring substituted with the 5A Cheyenne chromosome, which represented freezing-tolerant genotypes, were compared with the freezing-sensitive Chinese Spring. Hormone levels and gene expression data indicated that the short- and long-term cold treatments are associated with specific regulation of the accumulation of cold-protective proteins and phytohormone levels, as well as the expression profiles of the hormone-related genes. The significant differences were observed between the genotypes, and between their leaf and crown tissues, too. The level of dehydrins, including WCS120 protein, and expression of WCS120 gene were considerably higher in the freezing-tolerant genotypes after 21 days of cold treatment. Expression of Cor14b and CBF14, cold-responsive regulator genes, was increased by cold treatment in all genotypes, to higher extent in freezing-tolerant genotypes. Cluster analysis revealed that the tolerant genotypes had a similar response to cold treatment, regarding expression of the ABA and CK metabolic genes, as well as hormone levels in leaves. As far as hormone levels in crowns are concerned, however, the strongly freezing-tolerant Cheyenne variety clustered separately from the Chinese Spring and the substitution line, which were more similar to each other after both 1 and 21 days of cold treatment than to Cheyenne. Based on these results we concluded that the 5A chromosome of wheat might have both a direct and an indirect impact on the phytohormone-dependent cold-induced freezing tolerance. Based on the gene expression data, novel genetic markers could be developed, which may be used to determine the freezing tolerance level in a wide range of wheat varieties. PMID:29238355

  19. Pregnancy failure and heritable thrombophilia

    NARCIS (Netherlands)

    Middeldorp, Saskia


    Heritable thrombophilia is associated with an increased risk for pregnancy failure, defined as sporadic and recurrent miscarriage, late fetal loss, and other vascular pregnancy complications such as preeclampsia and intrauterine growth retardation. The pathogenesis is likely to include effects on

  20. Warning Signs of Heart Failure (United States)

    ... the two terms are used interchangeably. View an animation of heart failure . If you have been diagnosed ... resources here Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Heart Attack Symptoms ...

  1. Antibiotic managment in renal failure. (United States)

    Winter, R E


    This is a brief compilation of the work of many investigators. It includes facts about toxicity and recommendations about antibiotic management in patients with renal failure. As new data are accrued, changes in these recommendations will be necessary.

  2. Common mode and coupled failure

    International Nuclear Information System (INIS)

    Taylor, J.R.


    Based on examples and data from Abnormal Occurence Reports for nuclear reactors, a classification of common mode or coupled failures is given, and some simple statistical models are investigated. (author)

  3. Health market failures: Colombian case

    Directory of Open Access Journals (Sweden)

    Javier Eduardo Bejarano-Daza


    Conclusion: There are significant failures in the Colombian health market which make the system inefficient and inequitable; this situation demands for reconsideration of an economic model for financing and operation under a new paradigm.

  4. Palliative Care in Heart Failure

    Directory of Open Access Journals (Sweden)

    Hatice Mert


    Full Text Available Heart failure is an important health problem since its incidence and prevalence is increasing year by year. Since symptom burden and mortality are high in heart failure, supportive and palliative care should be provided. However, very few patients are referred to palliative care services. In comparison with cancer patients, it is difficult to identify end of life care for patients with heart failure, because these patients are hospitalized when the signs of acute decompensation appear, and their symptoms decrease and functional status improve before they are discharged. Therefore, palliative care, which is a holistic approach aiming to improve patients’ quality of life, to detect and treat the attacks of the disease before they become severe, and to deal with patients’ physical, psychological, social, and mental health altogether during their care, should be integrated into heart failure patients’ care. [TAF Prev Med Bull 2012; 11(2.000: 217-222

  5. A Theory of Interoperability Failures

    National Research Council Canada - National Science Library

    McBeth, Michael S


    This paper develops a theory of interoperability failures. Interoperability in this paper refers to the exchange of information and the use of information, once exchanged, between two or more systems...

  6. Creep-Fatigue Failure Diagnosis (United States)

    Holdsworth, Stuart


    Failure diagnosis invariably involves consideration of both associated material condition and the results of a mechanical analysis of prior operating history. This Review focuses on these aspects with particular reference to creep-fatigue failure diagnosis. Creep-fatigue cracking can be due to a spectrum of loading conditions ranging from pure cyclic to mainly steady loading with infrequent off-load transients. These require a range of mechanical analysis approaches, a number of which are reviewed. The microstructural information revealing material condition can vary with alloy class. In practice, the detail of the consequent cracking mechanism(s) can be camouflaged by oxidation at high temperatures, although the presence of oxide on fracture surfaces can be used to date events leading to failure. Routine laboratory specimen post-test examination is strongly recommended to characterise the detail of deformation and damage accumulation under known and well-controlled loading conditions to improve the effectiveness and efficiency of failure diagnosis. PMID:28793676

  7. Claudin5a is required for proper inflation of Kupffer's vesicle lumen and organ laterality.

    Directory of Open Access Journals (Sweden)

    Jeong-Gyun Kim

    Full Text Available Left-right asymmetric organ development is critical to establish a proper body plan of vertebrates. In zebrafish, the Kupffer's vesicle (KV is a fluid-filled sac which controls asymmetric organ development, and a properly inflated KV lumen by means of fluid influx is a prerequisite for the asymmetric signal transmission. However, little is known about the components that support the paracellular tightness between the KV luminal epithelial cells to sustain hydrostatic pressure during KV lumen expansion. Here, we identified that the claudin5a (cldn5a is highly expressed at the apical surface of KV epithelial cells and tightly seals the KV lumen. Downregulation of cldn5a in zebrafish showed a failure in organ laterality that resulted from malformed KV. In addition, accelerated fluid influx into KV by combined treatment of forskolin and 3-isobutyl-1-methylxanthine failed to expand the partially-formed KV lumen in cldn5a morphants. However, malformed KV lumen and defective heart laterality in cldn5a morphants were significantly rescued by exogenous cldn5a mRNA, suggesting that the tightness between the luminal epithelial cells is important for KV lumen formation. Taken together, these findings suggest that cldn5a is required for KV lumen inflation and left-right asymmetric organ development.

  8. Claudin5a is required for proper inflation of Kupffer's vesicle lumen and organ laterality. (United States)

    Kim, Jeong-Gyun; Bae, Sung-Jin; Lee, Hye Shin; Park, Ji-Hyeon; Kim, Kyu-Won


    Left-right asymmetric organ development is critical to establish a proper body plan of vertebrates. In zebrafish, the Kupffer's vesicle (KV) is a fluid-filled sac which controls asymmetric organ development, and a properly inflated KV lumen by means of fluid influx is a prerequisite for the asymmetric signal transmission. However, little is known about the components that support the paracellular tightness between the KV luminal epithelial cells to sustain hydrostatic pressure during KV lumen expansion. Here, we identified that the claudin5a (cldn5a) is highly expressed at the apical surface of KV epithelial cells and tightly seals the KV lumen. Downregulation of cldn5a in zebrafish showed a failure in organ laterality that resulted from malformed KV. In addition, accelerated fluid influx into KV by combined treatment of forskolin and 3-isobutyl-1-methylxanthine failed to expand the partially-formed KV lumen in cldn5a morphants. However, malformed KV lumen and defective heart laterality in cldn5a morphants were significantly rescued by exogenous cldn5a mRNA, suggesting that the tightness between the luminal epithelial cells is important for KV lumen formation. Taken together, these findings suggest that cldn5a is required for KV lumen inflation and left-right asymmetric organ development.

  9. Plant genotype, microbial recruitment and nutritional security. (United States)

    Patel, Jai S; Singh, Akanksha; Singh, Harikesh B; Sarma, Birinchi K


    Agricultural food products with high nutritional value should always be preferred over food products with low nutritional value. Efforts are being made to increase nutritional value of food by incorporating dietary supplements to the food products. The same is more desirous if the nutritional value of food is increased under natural environmental conditions especially in agricultural farms. Fragmented researches have demonstrated possibilities in achieving the same. The rhizosphere is vital in this regard for not only health and nutritional status of plants but also for the microorganisms colonizing the rhizosphere. Remarkably robust composition of plant microbiome with respect to other soil environments clearly suggests the role of a plant host in discriminating its colonizers (Zancarini et al., 2012). A large number of biotic and abiotic factors are believed to manipulate the microbial communities in the rhizosphere. However, plant genotype has proven to be the key in giving the final shape of the rhizosphere microbiome (Berendsen et al., 2012; Marques et al., 2014).

  10. Sources of Wilhelm Johannsen's genotype theory. (United States)

    Roll-Hansen, Nils


    This paper describes the historical background and early formation of Wilhelm Johannsen's distinction between genotype and phenotype. It is argued that contrary to a widely accepted interpretation (For instance, W. Provine, 1971. The Origins of Theoretical Population Genetics. Chicago: The University of Chicago Press; Mayr, 1973; F. B. Churchill, 1974. Journal of the History of Biology 7: 5-30; E. Mayr, 1982. The Growth of Biological Thought, Cambridge: Harvard University Press; J. Sapp, 2003. Genesis. The Evolution of Biology. New York: Oxford University Press) his concepts referred primarily to properties of individual organisms and not to statistical averages. Johannsen's concept of genotype was derived from the idea of species in the tradition of biological systematics from Linnaeus to de Vries: An individual belonged to a group - species, subspecies, elementary species - by representing a certain underlying type (S. Müller-Wille and V. Orel, 2007. Annals of Science 64: 171-215). Johannsen sharpened this idea theoretically in the light of recent biological discoveries, not least those of cytology. He tested and confirmed it experimentally combining the methods of biometry, as developed by Francis Galton, with the individual selection method and pedigree analysis, as developed for instance by Louis Vilmorin. The term "genotype" was introduced in W. Johannsen's 1909 (Elemente der Exakten Erblichkeitslehre. Jena: Gustav Fischer) treatise, but the idea of a stable underlying biological "type" distinct from observable properties was the core idea of his classical bean selection experiment published 6 years earlier (W. Johannsen, 1903. Ueber Erblichkeit in Populationen und reinen Linien. Eine Beitrag zur Beleuchtung schwebender Selektionsfragen, Jena: Gustav Fischer, pp. 58-59). The individual ontological foundation of population analysis was a self-evident presupposition in Johannsen's studies of heredity in populations from their start in the early 1890s till his

  11. Identification of Zoonotic Genotypes of Giardia duodenalis

    DEFF Research Database (Denmark)

    Sprong, H.; Cacciò, S.M.; van der Giessen, J.W.B


    Giardia duodenalis, originally regarded as a commensal organism, is the etiologic agent of giardiasis, a gastrointestinal disease of humans and animals. Giardiasis causes major public and veterinary health concerns worldwide. Transmission is either direct, through the faecal-oral route, or indirect......, through ingestion of contaminated water or food. Genetic characterization of G. duodenalis isolates has revealed the existence of seven groups (assemblages A to G) which differ in their host distribution. Assemblages A and B are found in humans and in many other mammals, but the role of animals......, mixtures of genotypes in individual isolates were repeatedly observed. Possible explanations are the uptake of genetically different Giardia cysts by a host, or subsequent infection of an already infected host, likely without overt symptoms, with a different Giardia species, which may cause disease. Other...

  12. Comparing Refinements for Failure and Bisimulation Semantics

    NARCIS (Netherlands)

    Eshuis, H.; Fokkinga, M.M.


    Refinement in bisimulation semantics is defined differently from refinement in failure semantics: in bisimulation semantics refinement is based on simulations between labelled transition systems, whereas in failure semantics refinement is based on inclusions between failure systems. There exist

  13. Heart Failure Questions to Ask Your Doctor (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Heart Failure Questions to Ask Your Doctor Updated:May 9, ... you? This content was last reviewed May 2017. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  14. The failure-tolerant leader. (United States)

    Farson, Richard; Keyes, Ralph


    "The fastest way to succeed," IBM's Thomas Watson, Sr., once said, "is to double your failure rate." In recent years, more and more executives have embraced Watson's point of view, coming to understand what innovators have always known: Failure is a prerequisite to invention. But while companies may grasp the value of making mistakes at the level of corporate practices, they have a harder time accepting the idea at the personal level. People are afraid to fail, and corporate culture reinforces that fear. In this article, psychologist and former Harvard Business School professor Richard Farson and coauthor Ralph Keyes discuss how companies can reduce the fear of miscues. What's crucial is the presence of failure-tolerant leaders--executives who, through their words and actions, help employees overcome their anxieties about making mistakes and, in the process, create a culture of intelligent risk-taking that leads to sustained innovation. Such leaders don't just accept productive failure, they promote it. Drawing from their research in business, politics, sports, and science, the authors identify common practices among failure-tolerant leaders. These leaders break down the social and bureaucratic barriers that separate them from their followers. They engage at a personal level with the people they lead. They avoid giving either praise or criticism, preferring to take a nonjudgmental, analytical posture as they interact with staff. They openly admit their own mistakes rather than trying to cover them up or shifting the blame. And they try to root out the destructive competitiveness built into most organizations. Above all else, failure-tolerant leaders push people to see beyond traditional definitions of success and failure. They know that as long as a person views failure as the opposite of success, rather than its complement, he or she will never be able to take the risks necessary for innovation.

  15. [Failure to thrive in childhood]. (United States)

    Furlano, Raoul I; Sidler, Marc A; Köhler, Henrik


    Failure to thrive is a state of malnutrition in a child due to inadequate caloric intake, inadequate caloric absorption, or excessive caloric expenditure. This all can lead to underweight and retarded growing, but also to a possible impairment of the immune system, as well as an impairment of the psychomotoric and cognitive development of a child. The aim of this article is to offer sound knowledge to the practising physician about definition, prevalence, etiology, diagnostic evaluation and therapy of failure to thrive.

  16. Coordination failure caused by sunspots

    DEFF Research Database (Denmark)

    Beugnot, Julie; Gürgüç, Zeynep; Øvlisen, Frederik Roose


    on the efficient equilibrium, we consider sunspots as a potential reason for coordination failure. We conduct an experiment with a three player 2x2x2 game in which coordination on the efficient equilibrium is easy and should normally occur. In the control session, we find almost perfect coordination on the payoff......-dominant equilibrium, but in the sunspot treatment, dis-coordination is frequent. Sunspots lead to significant inefficiency, and we conclude that sunspots can indeed cause coordination failure....

  17. Heart Failure in North America


    Blair, John E. A; Huffman, Mark; Shah, Sanjiv J


    Heart failure is a major health problem that affects patients and healthcare systems worldwide. Within the continent of North America, differences in economic development, genetic susceptibility, cultural practices, and trends in risk factors and treatment all contribute to both inter-continental and within-continent differences in heart failure. The United States and Canada represent industrialized countries with similar culture, geography, and advanced economies and infrastructure. During t...

  18. Failure Prediction for Autonomous Driving


    Hecker, Simon; Dai, Dengxin; Van Gool, Luc


    The primary focus of autonomous driving research is to improve driving accuracy. While great progress has been made, state-of-the-art algorithms still fail at times. Such failures may have catastrophic consequences. It therefore is important that automated cars foresee problems ahead as early as possible. This is also of paramount importance if the driver will be asked to take over. We conjecture that failures do not occur randomly. For instance, driving models may fail more likely at places ...

  19. Collective Success or Collective Failure?

    DEFF Research Database (Denmark)

    Fayyaz, Anjum

    study of soccer village project to learn how various attempts at facilitating joint CSR action in the Pakistani football manufacturing have consistently failed in addressing international CSR compliance demands. I conclude that this form of collective failure – along with technological changes, lack...... of innovation, and government failure - can partly explain why Sialkot has been marginalized in terms of its overall share of world football manufacturing in the last decade....

  20. Automated genotyping of dinucleotide repeat markers

    Energy Technology Data Exchange (ETDEWEB)

    Perlin, M.W.; Hoffman, E.P. [Carnegie Mellon Univ., Pittsburgh, PA (United States)]|[Univ. of Pittsburgh, PA (United States)


    The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

  1. Reassessing guidelines for heart failure

    Directory of Open Access Journals (Sweden)

    Helmut Drexler


    Full Text Available Significant progress has been made in the last few years in the management of heart failure. In particular several trials have given significant results. It has become apparent that heart failure may be prevented in some patients by treatment of risk factors such as coronary artery disease. Experience with angiotensin-converting enzyme (ACE inhibitors has shown that the survival and symptomatic benefits do last in the long term, and confirm that they are the first-line treatment in heart failure. The results of a number of trials using the angiotensin receptor blockers (ARBs candesartan, valsartan and losartan are presented and discussed. There is also some experience now in the use of candesartan for patients with heart failure and preserved left ventricular systolic function. The COMET trial compared the β-blockers carvedilol and metoprolol tartrate, and suggests that there may be differences in clinical effect between β-blockers. The selective aldosterone receptor blocker eplerenone was evaluated in the EPHESUS trial in post-MI patients with signs of heart failure. Based on these clinical trials, heart failure guidelines are now being updated.

  2. Failure to thrive in childhood. (United States)

    Nützenadel, Walter


    Failure to thrive impairs children's weight gain and growth, their defenses against infection, and their psychomotor and intellectual development. This paper is a review of pertinent articles that were published from 1995 to October 2010 and contained the terms "failure to thrive", "underweight", "malnutrition", "malabsorption", "maldigestion" and "refeeding syndrome". The articles were retrieved by a search in the PubMed and Cochrane Library databases. In developed countries, failure to thrive is usually due to an underlying disease. The degree of malnutrition is assessed with anthropometric techniques. For each patient, the underlying disease must be identified and the mechanism of failure to thrive understood, so that proper medical and nutritional treatment can be provided. Nutritional treatment involves either giving more food, or else raising the caloric density of the patient's food. Liquid formulas can be given as a supplement to normal meals or as balanced or unbalanced tube feeds; they can be given orally, through a nasogastric tube, or through a gastrostomy tube. Severely malnourished children with poor oral intake should be treated with parenteral nutrition. To avoid refeeding syndrome in severely malnourished children, food intake should be increased slowly at first, and phosphate, magnesium, and potassium supplements should be given. The proper treatment of failure to thrive in childhood consists of treatment of the underlying illness, combined with nutritional treatment that addresses the mechanism of the accompanying failure to thrive.

  3. Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer

    International Nuclear Information System (INIS)

    Lizard-Nacol, Sarab; Coudert, Bruno; Colosetti, Pascal; Riedinger, Jean-Marc; Fargeot, Pierre; Brunet-Lecomte, Patrick


    Glutathione S-transferase (GST)M1, a member of the μ class GST gene family, has been shown to be polymorphic because of a partial gene deletion. This results in a failure to express the GSTM1 gene in 50-60% of individuals. Several studies have demonstrated a possible link with the GSTM1-null genotype and susceptibility to cancer. Furthermore, a GSTM1 isoenzyme has been positively associated with protective effect against mutagenic drugs, such as alkylating agents and anthracyclines. To determine whether GSTM1 polymorphisms are associated with tumour characteristics and survival in advanced breast cancer patients, and whether it may constitute a prognostic factor. We genotyped 92 patients receiving primary chemotherapy, which included cyclophosphamide, doxorubicine and 5-fluorouracil. The relationships between allelism at GSTM1 and clinicopathological parameters including age, menopausal status, tumour size, grade hormone receptors, involved nodes and p53 gene mutations were analysed. Of the patients with GSTM1-positive genotype, tissue samples obtained before and after treatment were available from 28 cases, allowing RNA extraction and GSTM1 expression by reverse transcription polymerase chain reaction. Relationships with clinical response to chemotherapy, and disease-free and overall survival were also evaluated. The data obtained was analysed using logistic regression to estimate the odds ratio and 95% confidence interval. Of 92 patients, 57.6% (n = 53) were classified as heritably GSTM1-deficient, and 42.4% (n = 39) were of the GSTM1-positive genotype. There were no statistically significant relationships between GSTM1-null genotype and the clinicopathological parameters analysed. No relationship was observed between GSTM1 RNA expression and objective clinical response to chemotherapy. Objective clinical response to chemotherapy was related only to clinical tumour size (P = 0.0177) and to the absence of intraductal carcinoma (P = 0.0013). GSTM1-null genotype

  4. Improved Ancestry Estimation for both Genotyping and Sequencing Data using Projection Procrustes Analysis and Genotype Imputation (United States)

    Wang, Chaolong; Zhan, Xiaowei; Liang, Liming; Abecasis, Gonçalo R.; Lin, Xihong


    Accurate estimation of individual ancestry is important in genetic association studies, especially when a large number of samples are collected from multiple sources. However, existing approaches developed for genome-wide SNP data do not work well with modest amounts of genetic data, such as in targeted sequencing or exome chip genotyping experiments. We propose a statistical framework to estimate individual ancestry in a principal component ancestry map generated by a reference set of individuals. This framework extends and improves upon our previous method for estimating ancestry using low-coverage sequence reads (LASER 1.0) to analyze either genotyping or sequencing data. In particular, we introduce a projection Procrustes analysis approach that uses high-dimensional principal components to estimate ancestry in a low-dimensional reference space. Using extensive simulations and empirical data examples, we show that our new method (LASER 2.0), combined with genotype imputation on the reference individuals, can substantially outperform LASER 1.0 in estimating fine-scale genetic ancestry. Specifically, LASER 2.0 can accurately estimate fine-scale ancestry within Europe using either exome chip genotypes or targeted sequencing data with off-target coverage as low as 0.05×. Under the framework of LASER 2.0, we can estimate individual ancestry in a shared reference space for samples assayed at different loci or by different techniques. Therefore, our ancestry estimation method will accelerate discovery in disease association studies not only by helping model ancestry within individual studies but also by facilitating combined analysis of genetic data from multiple sources. PMID:26027497

  5. Genotypic and phenotypic characterization of Chikungunya virus of different genotypes from Malaysia.

    Directory of Open Access Journals (Sweden)

    I-Ching Sam

    Full Text Available BACKGROUND: Mosquito-borne Chikungunya virus (CHIKV has recently re-emerged globally. The epidemic East/Central/South African (ECSA strains have spread for the first time to Asia, which previously only had endemic Asian strains. In Malaysia, the ECSA strain caused an extensive nationwide outbreak in 2008, while the Asian strains only caused limited outbreaks prior to this. To gain insight into these observed epidemiological differences, we compared genotypic and phenotypic characteristics of CHIKV of Asian and ECSA genotypes isolated in Malaysia. METHODS AND FINDINGS: CHIKV of Asian and ECSA genotypes were isolated from patients during outbreaks in Bagan Panchor in 2006, and Johor in 2008. Sequencing of the CHIKV strains revealed 96.8% amino acid similarity, including an unusual 7 residue deletion in the nsP3 protein of the Asian strain. CHIKV replication in cells and Aedes mosquitoes was measured by virus titration. There were no differences in mammalian cell lines. The ECSA strain reached significantly higher titres in Ae. albopictus cells (C6/36. Both CHIKV strains infected Ae. albopictus mosquitoes at a higher rate than Ae. aegypti, but when compared to each other, the ECSA strain had much higher midgut infection and replication, and salivary gland dissemination, while the Asian strain infected Ae. aegypti at higher rates. CONCLUSIONS: The greater ability of the ECSA strain to replicate in Ae. albopictus may explain why it spread far more quickly and extensively in humans in Malaysia than the Asian strain ever did, particularly in rural areas where Ae. albopictus predominates. Intergenotypic genetic differences were found at E1, E2, and nsP3 sites previously reported to be determinants of host adaptability in alphaviruses. Transmission of CHIKV in humans is influenced by virus strain and vector species, which has implications for regions with more than one circulating CHIKV genotype and Aedes species.

  6. Methods for discovering and validating relationships among genotyped animals (United States)

    Genomic selection based on single-nucleotide polymorphisms (SNPs) has led to the collection of genotypes for over 2.2 million animals by the Council on Dairy Cattle Breeding in the United States. To assure that a genotype is assigned to the correct animal and that the animal’s pedigree is correct, t...

  7. Variation of meat quality traits among five genotypes of chicken. (United States)

    Tang, H; Gong, Y Z; Wu, C X; Jiang, J; Wang, Y; Li, K


    The main objective of this study was to examine the diversity of meat quality traits among 5 chicken genotypes. The genotypes included 2 Chinese native breeds (Wenchang,WCH, and Xianju), 1 commercial broiler line (Avian, AV), 1 commercial layer line (Hy-Line Brown, HLB), and 1 Chinese commercial broiler line (Lingnanhuang, LNH) synthesized by exotic and native breeds, which were slaughtered at their market ages: 16, 7, 16, and 8 wk, respectively. The effects of genotype, muscle type, and sex on meat quality traits were examined. Birds from slow-growing genotypes (WCH, Xianju, and HLB) exhibited higher shear value, inosine-5'-monophosphate concentration, lower cook loss, and more fat than those from fast-growing genotypes (AV and LNH). Chickens from WCH possessed the lowest expressible moisture, cook loss, and the highest lipid (%) among the 3 slow-growing genotypes. The HLB birds were intermediate in expressible moisture and cook loss and lowest in lipid among all genotypes. The LNH cross birds were similar to AV broilers in most meat quality parameters, although they had a lower shear force value and higher fat content than AV broilers. Breast muscle had higher expressible moisture, shear force, protein (%), inosine-5'-monophosphate content, lower cook loss, and lipid (%) than leg muscle. Muscles from male chickens had higher expressible moisture than those from the females. Variability of meat quality characteristics is mainly related to genotype and muscle type differences.

  8. Screening of Wheat Genotypes for Boron Efficiency in Bangladesh (United States)

    A number of Bangladeshi wheat genotypes (varieties and advanced lines) have been tested for boron efficiency through sand culture experiments over two years (2007-08 & 2008-09) against two Thai check varieties ‘Fang 60’ (boron efficient) and ‘SW41’ (boron inefficient). Performances of the genotypes ...

  9. Crossbreeding of large white and Nsukka local pigs: Genotype and ...

    African Journals Online (AJOL)

    5-Blood samples from 80 pigs of 4 genotypes - the Nsukka local (Lo), the exotic Large White (LW), the one-way F1 (LW x Lo) and the F2 crosses belonging to 5 age groups, were analyzed, to determine the mean values of the haematological parameters in the genotypes and different age groups and to check if and how the ...

  10. Enhanced fodder yield of maize genotypes under saline irrigation is ...

    African Journals Online (AJOL)

    Poor quality irrigation water adversely affects the growth and yield of crops. This study was designed to evaluate the growth, fodder yield and ionic concentration of three promising maize (Zea mays L.) genotypes under the influence of varying quality irrigation water, with different salinity levels. The genotypes, such as ...

  11. Breeding of a Tomato Genotype Readily Accessible to Genetic Manipulation

    NARCIS (Netherlands)

    Koornneef, Maarten; Hanhart, Corrie; Jongsma, Maarten; Toma, Ingrid; Weide, Rob; Zabel, Pim; Hille, Jacques


    A tomato genotype, superior in regenerating plants from cell cultures, was obtained by transferring regeneration capacity from Lycopersicon peruvianum into L. esculentum by classical breeding. This genotype, MsK93, greatly facilitates genetic manipulation of tomato, as was demonstrated by successful

  12. Application of mixed models for the assessment genotype and ...

    African Journals Online (AJOL)

    Application of mixed models for the assessment genotype and environment interactions in cotton ( Gossypium hirsutum ) cultivars in Mozambique. ... The cultivars ISA 205, STAM 42 and REMU 40 showed superior productivity when they were selected by the Harmonic Mean of Genotypic Values (HMGV) criterion in relation ...

  13. The influence of host genotype X environment Interactions on the ...

    African Journals Online (AJOL)

    Mean squares for environments, genotypes and G x E interactions were highly significant (P<0.0001) for anthracnose infection. Significant G x E interactions, accounting for 19% of the treatment sums of squares, indicated that genotypes responded differentially to anthracnose infection across environments. The additive ...

  14. The genotype-phenotype map of an evolving digital organism.

    Directory of Open Access Journals (Sweden)

    Miguel A Fortuna


    Full Text Available To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes (instruction sequences, which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable.

  15. The genotype-phenotype map of an evolving digital organism. (United States)

    Fortuna, Miguel A; Zaman, Luis; Ofria, Charles; Wagner, Andreas


    To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes (instruction sequences), which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable.

  16. The influence of temperature on photosynthesis of different tomato genotypes

    NARCIS (Netherlands)

    Gosiewski, W.; Nilwik, H.J.M.; Bierhuizen, J.F.


    Net photosynthesis and dark respiration from whole plants of various tomato genotypes were measured in a closed system. At low irradiance (27 W m−2) and low external CO2 concentration (550 mg m−3), net photosynthesis of 10 genotypes was found to vary between 0.122 and 0.209 mg CO2 m−2 s−1.

  17. characterisation of common bean genotypes based on storage

    African Journals Online (AJOL)


    of pliers and then ground to fine powder with a ... segregation of genotypes were Rm 23.75, 32.50,. 33.75, 22.50 ... Figure 1. Positions of Phaseolus vulgarisL. genotypes on the first and second correspondence scores based on storage protein.

  18. Integrated analysis for genotypic adaptation in rice | Das | African ...

    African Journals Online (AJOL)

    Integrated analysis for genotypic adaptation in rice. S Das, RC Misra, MC Pattnaik, SK Sinha. Abstract. Development of varieties with high yield potential coupled with wide adaptability is an important plant breeding objective. The presence of genotype by environment (GxE) interaction plays a crucial role in determining the ...

  19. Characteristics of Streptococcus mutans genotypes and dental caries in children (United States)

    Cheon, Kyounga; Moser, Stephen A.; Wiener, Howard W.; Whiddon, Jennifer; Momeni, Stephanie S.; Ruby, John D.; Cutter, Gary R.; Childers, Noel K.


    This longitudinal cohort study evaluated the diversity, commonality, and stability of Streptococcus mutans genotypes associated with dental caries history. Sixty-seven 5 and 6 yr-old children, considered being at high caries risk, had plaque collected from baseline through 36 months for S. mutans isolation and genotyping with repetitive extragenic palindromic-PCR (4,392 total isolates). Decayed, missing, filled surfaces (dmfs/DMFS) for each child were recorded at baseline. At baseline, 18 distinct genotypes were found among 911 S. mutans isolates from 67 children (diversity) and 13 genotypes were shared by at least 2 children (commonality). The number of genotypes per individual was positively associated with the proportion of decayed surfaces (p-ds) at baseline. Twenty-four of the 39 children who were available at follow-up visits maintained a predominant genotype for the follow-up periods (stability) and was negatively associated with p-ds. The observed diversity, commonality, and stability of S. mutans genotypes represent a pattern of dental caries epidemiology in this high caries risk community, which suggest fewer decayed surfaces are significantly associated with lower diversity and stability of S. mutans genotypes. PMID:23659236

  20. Beijing/W genotype Mycobacterium tuberculosis and drug resistance.

    NARCIS (Netherlands)

    Glynn, Judith R; Kremer, Kristin; Borgdorff, Martien W; Rodriguez, Mar Pujades; Soolingen, Dick van


    Beijing/W genotype Mycobacterium tuberculosis is widespread, may be increasing, and may have a predilection for drug resistance. Individual-level data on >29,000 patients from 49 studies in 35 countries were combined to assess the Beijing genotype's prevalence worldwide, trends over time and with

  1. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke

    DEFF Research Database (Denmark)

    Khan, Tauseef A; Shah, Tina; Prieto, David


    At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less c...

  2. Genotype dependent callus induction and shoot regeneration in ...

    African Journals Online (AJOL)

    This study aims to observe the effect of genotype, hormone and culture conditions on sunflower (Helianthus annuus L.) callus induction and indirect plant regeneration. Calli were obtained from hypocotyl and cotyledon explants of five different sunflower genotypes; Trakya 80, Trakya 129, Trakya 259, Trakya 2098 and ...

  3. Efficiency and response of conilon coffee genotypes to nitrogen supply

    African Journals Online (AJOL)

    The objective of the study was to differentiate genotypes with higher efficiency and responsiveness to nitrogen supply, to understand how the nitrogen supply can impact the dry matter allocation and the accumulation of this nutrient in the different plant compartments of genotypes of conilon coffee, cultivated under ...

  4. Haemoglobin genotype of children with severe malaria seen at the ...

    African Journals Online (AJOL)

    Abstract: Introduction: Types of haemoglobin (Hb) genotype have been found to be crucial to the rate of red blood cell parasite invasion, multiplication, and destruction as well as outcome of malaria disease. In a bid to provide more information on the relationship between Hb genotype and level of protection conferred by ...

  5. participatory selection of mungbean genotypes in uganda abstract

    African Journals Online (AJOL)



    May 29, 2017 ... that there were no significant differences in genotype choices based on gender ... However, there were significant genotype preference differences between eastern and northern regions (χ2 = ..... for southern Ethiopia. ... of improved cowpea cultivars in the Guinea and Sudan savanna zones of north east.

  6. Genetic variation of response to water deficit in parental genotypes ...

    African Journals Online (AJOL)


    In this study, we investigated morphological and photosynthetic responses to water deficit in parental genotypes of M. ... for adaptation to water deficit in legumes is a prerequisite for any research aiming to improve legume yields. ...... tolerant genotypes in rainfed lowland rice. Field Crop. Res. 99:48-58. Rouached A, Slama I, ...

  7. Clusters of incompatible genotypes evolve with limited dispersal (United States)

    Erin L. Landguth; Norman A. Johnson; Samuel A. Cushman


    Theoretical and empirical studies have shown heterogeneous selection to be the primary driver for the evolution of reproductively isolated genotypes in the absence of geographic barriers. Here, we ask whether limited dispersal alone can lead to the evolution of reproductively isolated genotypes despite the absence of any geographic barriers or heterogeneous...

  8. Evaluation of sorghum genotypes under drought stress conditions ...

    African Journals Online (AJOL)

    Seven genotypes of sorghum (Sorghum bicolour (L.) Moench) were studied in both drought and normal conditions. In each condition, the genotypes were evaluated using a split plot based randomized complete block design with three replications. Drought tolerance indices including stability tolerance index (STI), mean ...

  9. Genotyping-By-Sequencing for Plant Genetic Diversity Analysis: A Lab Guide for SNP Genotyping

    Directory of Open Access Journals (Sweden)

    Gregory W. Peterson


    Full Text Available Genotyping-by-sequencing (GBS has recently emerged as a promising genomic approach for exploring plant genetic diversity on a genome-wide scale. However, many uncertainties and challenges remain in the application of GBS, particularly in non-model species. Here, we present a GBS protocol we developed and use for plant genetic diversity analysis. It uses two restriction enzymes to reduce genome complexity, applies Illumina multiplexing indexes for barcoding and has a custom bioinformatics pipeline for genotyping. This genetic diversity-focused GBS (gd-GBS protocol can serve as an easy-to-follow lab guide to assist a researcher through every step of a GBS application with five main components: sample preparation, library assembly, sequencing, SNP calling and diversity analysis. Specifically, in this presentation, we provide a brief overview of the GBS approach, describe the gd-GBS procedures, illustrate it with an application to analyze genetic diversity in 20 flax (Linum usitatissimum L. accessions and discuss related issues in GBS application. Following these lab bench procedures and using the custom bioinformatics pipeline, one could generate genome-wide SNP genotype data for a conventional genetic diversity analysis of a non-model plant species.

  10. Genotypic character relationship and phenotypic path coefficient analysis in chili pepper genotypes grown under tropical condition. (United States)

    Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Oladosu, Yusuff; Kashiani, Pedram


    Studies on genotypic and phenotypic correlations among characters of crop plants are useful in planning, evaluating and setting selection criteria for the desired characters in a breeding program. The present study aimed to estimate the phenotypic correlation coefficients among yield and yield attributed characters and to work out the direct and indirect effects of yield-related characters on yield per plant using path coefficient analysis. Twenty-six genotypes of chili pepper were laid out in a randomized complete block design with three replications. Yield per plant showed positive and highly significant (P ≤ 0.01) correlations with most of the characters studied at both the phenotypic and genotypic levels. By contrast, disease incidence and days to flowering showed a significant negative association with yield. Fruit weight and number of fruits exerted positive direct effect on yield and also had a positive and significant (P ≤ 0.01) correlation with yield per plant. However, fruit length showed a low negative direct effect with a strong and positive indirect effect through fruit weight on yield and had a positive and significant association with yield. Longer fruits, heavy fruits and a high number of fruits are variables that are related to higher yields of chili pepper under tropical conditions and hence could be used as a reliable indicator in indirect selection for yield. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  11. Genotypic diversity of european Phytophthora ramorum isolates based on SSR analysis (United States)

    Kris Van Poucke; Annelies Vercauteren; Martine Maes; Sabine Werres; Kurt Heungens


    in Scotland were genotyped using seven microsatellite markers as described by Vercauteren et al. (2010). Thirty multilocus genotypes were identified within the Scottish population, with 51 percent of the isolates belonging to the main European genotype EU1MG1 and 13 unique detected genotypes. Ten of those genotypes were site specific, often represented by...

  12. Impact of the β-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between β adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study. (United States)

    Lee, Hae-Young; Chung, Wook-Jin; Jeon, Hui-Kyung; Seo, Hong-Seog; Choi, Dong-Ju; Jeon, Eun-Seok; Kim, Jae-Joong; Shin, Joon Han; Kang, Seok-Min; Lim, Sung Cil; Baek, Sang-Hong


    We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF). One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from 80.8 ± 14.3 to 70.0 ± 15.0 beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group (5.26 ± 2.62 mg vs. 3.96 ± 2.05 mg, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group. The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring β-blocker therapy according to genotype.

  13. SNPMClust: Bivariate Gaussian Genotype Clustering and Calling for Illumina Microarrays

    Directory of Open Access Journals (Sweden)

    Stephen W. Erickson


    Full Text Available SNPMClust is an R package for genotype clustering and calling with Illumina microarrays. It was originally developed for studies using the GoldenGate custom genotyping platform but can be used with other Illumina platforms, including Infinium BeadChip. The algorithm first rescales the fluorescent signal intensity data, adds empirically derived pseudo-data to minor allele genotype clusters, then uses the package mclust for bivariate Gaussian model fitting. We compared the accuracy and sensitivity of SNPMClust to that of GenCall, Illumina's proprietary algorithm, on a data set of 94 whole-genome amplified buccal (cheek swab DNA samples. These samples were genotyped on a custom panel which included 1064 SNPs for which the true genotype was known with high confidence. SNPMClust produced uniformly lower false call rates over a wide range of overall call rates.

  14. Micropropagation of six Paulownia genotypes through tissue culture

    Directory of Open Access Journals (Sweden)

    Lydia Shtereva


    Full Text Available We investigated the effect of genotype and culture medium on the in vitro germination and development of plantlets from seeds of 6 different Paulownia genotypes (P. tomentosa, hybrid lines P. tomentosa P. fortunei (Mega, Ganter and Caroline, P. elongata and hybrid line P. elongata P. fortunei. Nodal and shoot tip explants were used for micropropagation of Paulownia genotypes by manipulating plant growth regulators. The highest germination percentage for all genotypes was obtained for seeds inoculated on medium supplemented with 50 mg*L GA3 (MSG2. On Thidiazuron containing media, the explants of hybrid line P. elongata P. fortunei exhibited the highest frequency of axillary shoot proliferation following by P. tomentosa P. fortunei. The results are discussed with the perspective of applying an improved protocol for in vitro seed germination and plantlet formation in several economically valuable Paulownia genotypes.

  15. Genetic variants of age at menopause are not related to timing of ovarian failure in breast cancer survivors. (United States)

    Homer, Michael V; Charo, Lindsey M; Natarajan, Loki; Haunschild, Carolyn; Chung, Karine; Mao, Jun J; DeMichele, Angela M; Su, H Irene


    To determine if interindividual genetic variation in single-nucleotide polymorphisms (SNPs) related to age at natural menopause is associated with risk of ovarian failure in breast cancer survivors. A prospective cohort of 169 premenopausal breast cancer survivors recruited at diagnosis with stages 0 to III disease were followed longitudinally for menstrual pattern via self-reported daily menstrual diaries. Participants were genotyped for 13 SNPs previously found to be associated with age at natural menopause: EXO1, TLK1, HELQ, UIMC1, PRIM1, POLG, TMEM224, BRSK1, and MCM8. A risk variable summed the total number of risk alleles in each participant. The association between individual genotypes, and also the risk variable, and time to ovarian failure (>12 months of amenorrhea) was tested using time-to-event methods. Median age at enrollment was 40.5 years (range 20.6-46.1). The majority of participants were white (69%) and underwent chemotherapy (76%). Thirty-eight participants (22%) experienced ovarian failure. None of the candidate SNPs or the summary risk variable was significantly associated with time to ovarian failure. Sensitivity analysis restricted to whites or only to participants receiving chemotherapy yielded similar findings. Older age, chemotherapy exposure, and lower body mass index were related to shorter time to ovarian failure. Thirteen previously identified genetic variants associated with time to natural menopause were not related to timing of ovarian failure in breast cancer survivors.


    Directory of Open Access Journals (Sweden)

    Budeanu Andreea


    Full Text Available Internationally, services represent the most important sector of the economy both in terms of economic performance and labor utilization. Becoming essential part of today society, they are considered the basis of a healthy economy, fact that has increased the importance of services and the research in the field.T hrough this work we intend to address a number of issues that require clarification and are relevant to this sector. Increased competition and customers higher demands lead to difficulties in service delivery, so managers of service organizations must work hard towards developing appropiate strategies that can lead to improved customers satisfaction and to increased efficiency. Because it is inevitably for service providers to face situations in which service failure occurs and their customers are not satisfied, understanding the nature of service failures and the ways in which an organization can recover after a failure are considered key factors for achieving customer satisfaction. Since the data suggests that over 50% of customers who are facing problems are not satisfied with the way they were resolved, we consider appropriate to approach this topic. We intend to draw attention to service providers to the importance of proper management of service failure. They can find ways to recover from these failures and even to turn them into some very pleasant situations that can contribute to customer loyalty. This paper begins by highlighting the various features specific to services which contribute to the increased chances of failure, it continues by presenting the concepts of service failure and service recovery and then it presents some links that exist between service recovery and other aspects of providing services that are demonstrated in the literature. We hope that this paper will significantly contribute to the knowledge and development of the sector under analysis and will highlight some practices that will lead to improved

  17. Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity. (United States)

    Nagasawa, Hideko; Uto, Yoshihiro; Sasaki, Hideyuki; Okamura, Natsuko; Murakami, Aya; Kubo, Shinichi; Kirk, Kenneth L; Hori, Hitoshi


    The Gc protein (human group-specific component (Gc), a vitamin D-binding protein or Gc globulin), has important physiological functions that include involvement in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5a for neutrophils in inflammation and macrophage activation (mediated by a GalNAc-modified Gc protein (GcMAF)). In this review, the structure and function of the Gc protein is focused on especially with regard to Gc genotyping and GcMAF precursor activity. A discussion of the research strategy "GcMAF as a target for drug discovery" is included, based on our own research.

  18. In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir. (United States)

    Cheng, Guofeng; Tian, Yang; Doehle, Brian; Peng, Betty; Corsa, Amoreena; Lee, Yu-Jen; Gong, Ruoyu; Yu, Mei; Han, Bin; Xu, Simin; Dvory-Sobol, Hadas; Perron, Michel; Xu, Yili; Mo, Hongmei; Pagratis, Nikos; Link, John O; Delaney, William


    Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. The future of pharmacogenetics in the treatment of heart failure. (United States)

    Anwar, Mohamed Subhan; Iskandar, Muhammad Zaid; Parry, Helen M; Doney, Alex S; Palmer, Colin N; Lang, Chim C


    Heart failure is a common disease with high levels of morbidity and mortality. Current treatment comprises β-blockers, ACE inhibitors, aldosterone antagonists and diuretics. Variation in clinical response seen in patients begs the question of whether there is a pharmacogenetic component yet to be identified. To date, the genes most studied involve the β-1, β-2, α-2 adrenergic receptors and the renin-angiotensin-aldosterone pathway, mainly focusing on SNPs. However results have been inconsistent. Genome-wide association studies and next-generation sequencing are seen as alternative approaches to discovering genetic variations influencing drug response. Hopefully future research will lay the foundations for genotype-led drug management in these patients with the ultimate aim of improving their clinical outcome.

  20. Failure to thrive: an update. (United States)

    Cole, Sarah Z; Lanham, Jason S


    Failure to thrive in childhood is a state of undernutrition due to inadequate caloric intake, inadequate caloric absorption, or excessive caloric expenditure. In the United States, it is seen in 5 to 10 percent of children in primary care settings. Although failure to thrive is often defined as a weight for age that falls below the 5th percentile on multiple occasions or weight deceleration that crosses two major percentile lines on a growth chart, use of any single indicator has a low positive predictive value. Most cases of failure to thrive involve inadequate caloric intake caused by behavioral or psychosocial issues. The most important part of the outpatient evaluation is obtaining an accurate account of a child's eating habits and caloric intake. Routine laboratory testing rarely identifies a cause and is not generally recommended. Reasons to hospitalize a child for further evaluation include failure of outpatient management, suspicion of abuse or neglect, or severe psychosocial impairment of the caregiver. A multidisciplinary approach to treatment, including home nursing visits and nutritional counseling, has been shown to improve weight gain, parent-child relationships, and cognitive development. The long-term effects of failure to thrive on cognitive development and future academic performance are unclear.

  1. The phenotype, psychotype and genotype of bruxism (United States)

    Cruz-Fierro, Norma; Martínez-Fierro, Margarita; Cerda-Flores, Ricardo M.; Gómez-Govea, Mayra A.; Delgado-Enciso, Iván; Martínez-De-Villarreal, Laura E.; González-Ramírez, Mónica T.; Rodríguez-Sánchez, Irám Pablo


    Bruxism is a jaw muscle activity that involves physio-pathological, psycho-social, hereditary and genetic factors. The purpose of this study was to determine the associations between self-reported bruxism, anxiety, and neuroticism personality trait with the rs6313 polymorphism in the gene HTR2A. A sample of 171 subjects of both sexes (14–53 years of age) was included. The control group (group 1, n=60) exhibited no signs or symptoms of bruxism. The case group had signs and symptoms of bruxism (n=112) and was subdivided into group 2, bruxism during sleep (n=22); group 3, awake bruxism (n=44); and group 4 combined bruxism (n=46). As diagnostic tools, the Self-Reported Bruxism Questionnaire (SBQ), the Beck Anxiety Inventory (BAI) and the Eysenck Personality Questionnaire Revised-Abbreviated (EPQR-A) were used. HTR2A (rs6313) SNPs were determined by qPCR for all the participants. The packages SPSS, maxLik and EPI-INFO were used for data analysis. The combined bruxism group reported higher scores in bruxism symptoms, mean = 32.21; anxiety symptoms, mean = 14.80; and neuroticism, mean = 3.26. Combined bruxism was associated with a higher degree of neuroticism (OR=15.0; CI 1.52–148.32) and anxiety in grade 3-moderate (OR=3.56; CI 1.27–10.03), and grade 4-severe (OR=8.40; CI 1.45–48.61), as determined using EPISODE computer software. Genotypic homogeneity analysis revealed no significant differences in allele frequency (P=0.612) among the four groups. The population was in Hardy-Weinberg equilibrium (maxLik package). In conclusion, the three instruments confirm traits of bruxism, anxiety and neuroticism in individuals with bruxism. These data were ratified when the sample was divided by genotypic homogeneity. On the other hand, there was no significant difference between the groups in the SNPs rs6313 from the HTR2A gene. PMID:29599979

  2. Single Endemic Genotype of Measles Virus Continuously Circulating in China for at Least 16 Years (United States)

    Wang, Huiling; Zhu, Zhen; Ji, Yixin; Liu, Chunyu; Zhang, Xiaojie; Sun, Liwei; Zhou, Jianhui; Lu, Peishan; Hu, Ying; Feng, Daxing; Zhang, Zhenying; Wang, Changyin; Fang, Xueqiang; Zheng, Huanying; Liu, Leng; Sun, Xiaodong; Tang, Wei; Wang, Yan; Liu, Yan; Gao, Hui; Tian, Hong; Ma, Jiangtao; Gu, Suyi; Wang, Shuang; Feng, Yan; Bo, Fang; Liu, Jianfeng; Si, Yuan; Zhou, Shujie; Ma, Yuyan; Wu, Shengwei; Zhou, Shunde; Li, Fangcai; Ding, Zhengrong; Yang, Zhaohui; Rota, Paul A.; Featherstone, David; Jee, Youngmee; Bellini, William J.; Xu, Wenbo


    The incidence of measles in China from 1991 to 2008 was reviewed, and the nucleotide sequences from 1507 measles viruses (MeV) isolated during 1993 to 2008 were phylogenetically analyzed. The results showed that measles epidemics peaked approximately every 3 to 5 years with the range of measles cases detected between 56,850 and 140,048 per year. The Chinese MeV strains represented three genotypes; 1501 H1, 1 H2 and 5 A. Genotype H1 was the predominant genotype throughout China continuously circulating for at least 16 years. Genotype H1 sequences could be divided into two distinct clusters, H1a and H1b. A 4.2% average nucleotide divergence was found between the H1a and H1b clusters, and the nucleotide sequence and predicted amino acid homologies of H1a viruses were 92.3%–100% and 84.7%–100%, H1b were 97.1%–100% and 95.3%–100%, respectively. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Cluster H1a and H1b viruses were co-circulating during 1993 to 2005, while no H1b viruses were detected after 2005 and the transmission of that cluster has presumably been interrupted. Analysis of the nucleotide and predicted amino acid changes in the N proteins of H1a and H1b viruses showed no evidence of selective pressure. This study investigated the genotype and cluster distribution of MeV in China over a 16-year period to establish a genetic baseline before MeV elimination in Western Pacific Region (WPR). Continuous and extensive MeV surveillance and the ability to quickly identify imported cases of measles will become more critical as measles elimination goals are achieved in China in the near future. This is the first report that a single endemic genotype of measles virus has been found to be continuously circulating in one country for at least 16 years. PMID:22532829

  3. Single endemic genotype of measles virus continuously circulating in China for at least 16 years.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available The incidence of measles in China from 1991 to 2008 was reviewed, and the nucleotide sequences from 1507 measles viruses (MeV isolated during 1993 to 2008 were phylogenetically analyzed. The results showed that measles epidemics peaked approximately every 3 to 5 years with the range of measles cases detected between 56,850 and 140,048 per year. The Chinese MeV strains represented three genotypes; 1501 H1, 1 H2 and 5 A. Genotype H1 was the predominant genotype throughout China continuously circulating for at least 16 years. Genotype H1 sequences could be divided into two distinct clusters, H1a and H1b. A 4.2% average nucleotide divergence was found between the H1a and H1b clusters, and the nucleotide sequence and predicted amino acid homologies of H1a viruses were 92.3%-100% and 84.7%-100%, H1b were 97.1%-100% and 95.3%-100%, respectively. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Cluster H1a and H1b viruses were co-circulating during 1993 to 2005, while no H1b viruses were detected after 2005 and the transmission of that cluster has presumably been interrupted. Analysis of the nucleotide and predicted amino acid changes in the N proteins of H1a and H1b viruses showed no evidence of selective pressure. This study investigated the genotype and cluster distribution of MeV in China over a 16-year period to establish a genetic baseline before MeV elimination in Western Pacific Region (WPR. Continuous and extensive MeV surveillance and the ability to quickly identify imported cases of measles will become more critical as measles elimination goals are achieved in China in the near future. This is the first report that a single endemic genotype of measles virus has been found to be continuously circulating in one country for at least 16 years.

  4. The analysis of failure data in the presence of critical and degraded failures

    International Nuclear Information System (INIS)

    Haugen, Knut; Hokstad, Per; Sandtorv, Helge


    Reported failures are often classified into severityclasses, e.g., as critical or degraded. The critical failures correspond to loss of function(s) and are those of main concern. The rate of critical failures is usually estimated by the number of observed critical failures divided by the exposure time, thus ignoring the observed degraded failures. In the present paper failure data are analyzed, applying an alternative estimate for the critical failure rate, also taking the number of observed degraded failures into account. The model includes two alternative failure mechanisms, one being of the shock type, immediately leading to a critical failure, another resulting in a gradual deterioration, leading to a degraded failure before the critical failure occurs. Failure data on safety valves from the OREDA (Offshore REliability DAta) data base are analyzed using this model. The estimate for the critical failure rate is obtained and compared with the standard estimate

  5. Rotavirus genotype shifts among Swedish children and adults-Application of a real-time PCR genotyping. (United States)

    Andersson, Maria; Lindh, Magnus


    It is well known that human rotavirus group A is the most important cause of severe diarrhoea in infants and young children. Less is known about rotavirus infections in other age groups, and about how rotavirus genotypes change over time in different age groups. Develop a real-time PCR to easily genotype rotavirus strains in order to monitor the pattern of circulating genotypes. In this study, rotavirus strains in clinical samples from children and adults in Western Sweden during 2010-2014 were retrospectively genotyped by using specific amplification of VP 4 and VP 7 genes with a new developed real-rime PCR. A genotype was identified in 97% of 775 rotavirus strains. G1P[8] was the most common genotype representing 34.9%, followed by G2P[4] (28.3%), G9P[8] (11.5%), G3P[8] (8.1%), and G4P[8] (7.9%) The genotype distribution changed over time, from predominance of G1P[8] in 2010-2012 to predominance of G2P[4] in 2013-2014. There were also age-related differences, with G1P[8] being the most common genotype in children under 2 years (47.6%), and G2P[4] the most common in those over 70 years of age (46.1%.). The shift to G2P[4] in 2013-2014 was associated with a change in the age distribution, with a greater number of rotavirus positive cases in elderly than in children. By using a new real-time PCR method for genotyping we found that genotype distribution was age related and changed over time with a decreasing proportion of G1P[8]. Copyright © 2017. Published by Elsevier B.V.

  6. [Definition of acute heart failure]. (United States)

    Metra, Marco; Carbone, Giorgio; Lombardi, Carlo; Borghi, Claudio; Vescovo, Giorgio


    Acute heart failure (AHF) is a potentially life-threatening condition that may arise as a deterioration of a previous heart failure or may be the first presentation of heart failure. Several causes or precipitating factors have been listed, as well as different mechanisms have been described, thus leading to a broad spectrum of clinical presentations. Symptoms and signs of AHF have a strong clinical and prognostic significance and are kept into consideration to guide disease management. In particular, a higher clinical severity or a worse prognosis are associated with lower blood pressure levels, fluid overload, evidence of myocardial ischemia or renal impairment. Putatively, interventions addressed to restore these factors may play a role in the management of AHF.

  7. Learning from Failures in Operations

    DEFF Research Database (Denmark)

    Koch, Christian


    parallelism and fragmentation due to their predominantly quantitative complexity. It is suggested that a number of critical junctions occur in these processes and that obtaining quality and avoiding failures quite often requires a series of competent and situational operation management actions. An empirical...... product. The analysis showed that, among others, design review, project review, commencing and finalizing operations turned out to be critical junctions in the control of failures. Practical implications and improvements are discussed. The focus on critical junctions, points to supply chain management......This paper discusses failures and quality in operations in design and production of buildings. The importance of human action, interpretations and interactions in tackling complexity, fragmentation and disturbances in the building industry is underlined. Building processes encompass requisite...

  8. Development of container failure models

    International Nuclear Information System (INIS)

    Garisto, N.C.


    In order to produce a complete performance assessment for a Canadian waste vault some prediction of container failure times is required. Data are limited; however, the effects of various possible failure scenarios on the rest of the vault model can be tested. For titanium and copper, the two materials considered in the Canadian program, data are available on the frequency of failures due to manufacturing defects; there is also an estimate on the expected size of such defects. It can be shown that the consequences of such small defects in terms of the dose to humans are acceptable. It is not clear, from a modelling point of view, whether titanium or copper are preferable

  9. Genotyping of vacA alleles of Helicobacter pylori strains recovered ...

    African Journals Online (AJOL)

    commonly detected genotypes in the meat-based foods, viz, vegetable sandwich and ready to eat fish, were vacA ... Keywords: Helicobacter pylori, VacA genotypes, Genotyping, Food items ..... Microbiology and Quality Control, Islamic Azad.

  10. Everyday Attention Failures: An Individual Differences Investigation (United States)

    Unsworth, Nash; McMillan, Brittany D.; Brewer, Gene A.; Spillers, Gregory J.


    The present study examined individual differences in everyday attention failures. Undergraduate students completed various cognitive ability measures in the laboratory and recorded everyday attention failures in a diary over the course of a week. The majority of attention failures were failures of distraction or mind wandering in educational…

  11. 4. Nuclear power plant component failures

    International Nuclear Information System (INIS)


    Nuclear power plant component failures are dealt with in relation to reliability in nuclear power engineering. The topics treated include classification of failures, analysis of their causes and impacts, nuclear power plant failure data acquisition and processing, interdependent failures, and human factor reliability in nuclear power engineering. (P.A.). 8 figs., 7 tabs., 23 refs

  12. Dependent failure analysis of NPP data bases

    International Nuclear Information System (INIS)

    Cooper, S.E.; Lofgren, E.V.; Samanta, P.K.; Wong Seemeng


    A technical approach for analyzing plant-specific data bases for vulnerabilities to dependent failures has been developed and applied. Since the focus of this work is to aid in the formulation of defenses to dependent failures, rather than to quantify dependent failure probabilities, the approach of this analysis is critically different. For instance, the determination of component failure dependencies has been based upon identical failure mechanisms related to component piecepart failures, rather than failure modes. Also, component failures involving all types of component function loss (e.g., catastrophic, degraded, incipient) are equally important to the predictive purposes of dependent failure defense development. Consequently, dependent component failures are identified with a different dependent failure definition which uses a component failure mechanism categorization scheme in this study. In this context, clusters of component failures which satisfy the revised dependent failure definition are termed common failure mechanism (CFM) events. Motor-operated valves (MOVs) in two nuclear power plant data bases have been analyzed with this approach. The analysis results include seven different failure mechanism categories; identified potential CFM events; an assessment of the risk-significance of the potential CFM events using existing probabilistic risk assessments (PRAs); and postulated defenses to the identified potential CFM events. (orig.)

  13. A SNP Genotyping Array for Hexaploid Oat

    Directory of Open Access Journals (Sweden)

    Nicholas A. Tinker


    Full Text Available Recognizing a need in cultivated hexaploid oat ( L. for a reliable set of reference single nucleotide polymorphisms (SNPs, we have developed a 6000 (6K BeadChip design containing 257 Infinium I and 5486 Infinium II designs corresponding to 5743 SNPs. Of those, 4975 SNPs yielded successful assays after array manufacturing. These SNPs were discovered based on a variety of bioinformatics pipelines in complementary DNA (cDNA and genomic DNA originating from 20 or more diverse oat cultivars. The array was validated in 1100 samples from six recombinant inbred line (RIL mapping populations and sets of diverse oat cultivars and breeding lines, and provided approximately 3500 discernible Mendelian polymorphisms. Here, we present an annotation of these SNPs, including methods of discovery, gene identification and orthology, population-genetic characteristics, and tentative positions on an oat consensus map. We also evaluate a new cluster-based method of calling SNPs. The SNP design sequences are made publicly available, and the full SNP genotyping platform is available for commercial purchase from an independent third party.

  14. Genotyping of Canine parvovirus in western Mexico. (United States)

    Pedroza-Roldán, César; Páez-Magallan, Varinia; Charles-Niño, Claudia; Elizondo-Quiroga, Darwin; De Cervantes-Mireles, Raúl Leonel; López-Amezcua, Mario Alberto


    Canine parvovirus (CPV) is one of the most common infectious agents related to high morbidity rates in dogs. In addition, the virus is associated with severe gastroenteritis, diarrhea, and vomiting, resulting in high death rates, especially in puppies and nonvaccinated dogs. To date, there are 3 variants of the virus (CPV-2a, CPV-2b, and CPV-2c) circulating worldwide. In Mexico, reports describing the viral variants circulating in dog populations are lacking. In response to this deficiency, a total of 41 fecal samples of suspected dogs were collected from October 2013 through April 2014 in the Veterinary Hospital of the University of Guadalajara in western Mexico. From these, 24 samples resulted positive by polymerase chain reaction, and the viral variant was determined by restriction fragment length polymorphism. Five positive diagnosed samples were selected for partial sequencing of the vp2 gene and codon analysis. The results demonstrated that the current dominant viral variant in Mexico is CPV-2c. The current study describes the genotyping of CPV strains, providing valuable evidence of the dominant frequency of this virus in a dog population from western Mexico. © 2014 The Author(s).

  15. Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a.

    LENUS (Irish Health Repository)

    Moreau, Isabelle


    Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1) examine temporal changes in quasispecies prior to the start of therapy and (2) investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated alpha2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20-30 individual clones in serial serum samples. Genetic parameters, including amino acid Shannon entropy, Hamming distance and genetic distance were calculated for each sample. Treatment outcome was divided into (1) sustained virological responders (SVR) and (2) treatment failure (TF). Our results indicate, (1) quasispecies complexity and diversity are lower in the SVR group, (2) quasispecies vary temporally and (3) genetic heterogeneity at baseline can be use to predict treatment outcome. We discuss the results from the perspective of replicative homeostasis.

  16. Heart failure etiology impacts survival of patients with heart failure

    DEFF Research Database (Denmark)

    Pecini, Redi; Møller, Daniel Vega; Torp-Pedersen, Christian


    BACKGROUND: The impact of heart failure (HF) etiology on prognosis of HF is not well known. METHODS: 3078 patients (median age 75years, 61% male) hospitalized with HF were studied. Patients were classified into six etiology groups: hypertension (HTN, 13.9%), ischemic heart disease (IHD, 42...

  17. Antixenosis of bean genotypes to Chrysodeixis includens (Lepidoptera: Noctuidae

    Directory of Open Access Journals (Sweden)

    Rafaela Morando


    Full Text Available The objective of this work was to evaluate bean genotypes for resistance to soybean looper (Chrysodeixis includens. Initially, free-choice tests were carried out with 59 genotypes, divided into three groups according to leaf color intensity (dark green, light green, and medium green, in order to evaluate oviposition preference. Subsequently, 12 genotypes with high potential for resistance were selected, as well as two susceptible commercial standards. With these genotypes, new tests were performed for oviposition in a greenhouse, besides tests for attractiveness and consumption under laboratory conditions (26±2ºC, 65±10% RH, and 14 h light: 10 h dark photophase. In the no-choice test with adults, in the greenhouse, the 'IAC Jabola', Arcelina 1, 'IAC Boreal', 'Flor de Mayo', and 'IAC Formoso' genotypes were the least oviposited, showing antixenosis-type resistance for oviposition. In the free-choice test with larvae, Arcelina 4, 'BRS Horizonte', 'Pérola', H96A102-1-1-1-52, 'IAC Boreal', 'IAC Harmonia', and 'IAC Formoso' were the less consumed genotypes, which indicates antixenosis to feeding. In the no-choice test, all genotypes (except for 'IAPAR 57' expressed moderate levels of antixenosis to feeding against C. includens larvae.

  18. Porphyromonas gingivalis Fim-A genotype distribution among Colombians (United States)

    Jaramillo, Adriana; Parra, Beatriz; Botero, Javier Enrique; Contreras, Adolfo


    Introduction: Porphyromonas gingivalis is associated with periodontitis and exhibit a wide array of virulence factors, including fimbriae which is encoded by the FimA gene representing six known genotypes. Objetive: To identify FimA genotypes of P. gingivalis in subjects from Cali-Colombia, including the co-infection with Aggregatibacter actinomycetemcomitans, Treponema denticola, and Tannerella forsythia. Methods: Subgingival samples were collected from 151 people exhibiting diverse periodontal condition. The occurrence of P. gingivalis, FimA genotypes and other bacteria was determined by PCR. Results: P. gingivalis was positive in 85 patients. Genotype FimA II was more prevalent without reach significant differences among study groups (54.3%), FimA IV was also prevalent in gingivitis (13.0%). A high correlation (p= 0.000) was found among P. gingivalis, T. denticola, and T. forsythia co-infection. The FimA II genotype correlated with concomitant detection of T. denticola and T. forsythia. Conclusions: Porphyromonas gingivalis was high even in the healthy group at the study population. A trend toward a greater frequency of FimA II genotype in patients with moderate and severe periodontitis was determined. The FimA II genotype was also associated with increased pocket depth, greater loss of attachment level, and patients co-infected with T. denticola and T. forsythia. PMID:26600627

  19. Assessing accuracy of genotype imputation in American Indians.

    Directory of Open Access Journals (Sweden)

    Alka Malhotra

    Full Text Available Genotype imputation is commonly used in genetic association studies to test untyped variants using information on linkage disequilibrium (LD with typed markers. Imputing genotypes requires a suitable reference population in which the LD pattern is known, most often one selected from HapMap. However, some populations, such as American Indians, are not represented in HapMap. In the present study, we assessed accuracy of imputation using HapMap reference populations in a genome-wide association study in Pima Indians.Data from six randomly selected chromosomes were used. Genotypes in the study population were masked (either 1% or 20% of SNPs available for a given chromosome. The masked genotypes were then imputed using the software Markov Chain Haplotyping Algorithm. Using four HapMap reference populations, average genotype error rates ranged from 7.86% for Mexican Americans to 22.30% for Yoruba. In contrast, use of the original Pima Indian data as a reference resulted in an average error rate of 1.73%.Our results suggest that the use of HapMap reference populations results in substantial inaccuracy in the imputation of genotypes in American Indians. A possible solution would be to densely genotype or sequence a reference American Indian population.

  20. Genetic similarity of soybean genotypes revealed by seed protein

    Directory of Open Access Journals (Sweden)

    Nikolić Ana


    Full Text Available More accurate and complete descriptions of genotypes could help determinate future breeding strategies and facilitate introgression of new genotypes in current soybean genetic pool. The objective of this study was to characterize 20 soybean genotypes from the Maize Research Institute "Zemun Polje" collection, which have good agronomic performances, high yield, lodging and drought resistance, and low shuttering by seed proteins as biochemical markers. Seed proteins were isolated and separated by PAA electrophoresis. On the basis of the presence/absence of protein fractions coefficients of similarity were calculated as Dice and Roger and Tanamoto coefficient between pairs of genotypes. The similarity matrix was submitted for hierarchical cluster analysis of un weighted pair group using arithmetic average (UPGMA method and necessary computation were performed using NTSYS-pc program. Protein seed analysis confirmed low level of genetic diversity in soybean. The highest genetic similarity was between genotypes P9272 and Kador. According to obtained results, soybean genotypes were assigned in two larger groups and coefficients of similarity showed similar results. Because of the lack of pedigree data for analyzed genotypes, correspondence with marker data could not be determined. In plant with a narrow genetic base in their gene pool, such as soybean, protein markers may not be sufficient for characterization and study of genetic diversity.

  1. The Danish Heart Failure Registry

    DEFF Research Database (Denmark)

    Schjødt, Inge; Nakano, Anne; Egstrup, Kenneth


    AIM OF DATABASE: The aim of the Danish Heart Failure Registry (DHFR) is to monitor and improve the care of patients with incident heart failure (HF) in Denmark. STUDY POPULATION: The DHFR includes inpatients and outpatients (≥18 years) with incident HF. Reporting to the DHFR is mandatory......: The main variables recorded in the DHFR are related to the indicators for quality of care in patients with incident HF: performance of echocardiography, functional capacity (New York Heart Association functional classification), pharmacological therapy (angiotensin converting enzyme/angiotensin II...

  2. Failures on stainless steel components

    International Nuclear Information System (INIS)

    Haenninen, H.


    Economic losses due to failure mainly by corrosion in process and nuclear industries are considered. In these industries the characteristics of different forms of corrosion and their economic effects are fairly well known and, especially, in nuclear industry the assessment of corrosion related costs has been comprehensive. In both industries the economic losses resulting from environmentally enhanced cracking of stainless steel components and the accompanying failures and outages have been considerable, owing as much to the frequency as the unpredictability of such occurrences. (orig.)

  3. High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuker; Carlton, Victoria E.H.; Karlin-Neumann, George; Sapolsky, Ronald; Zhang, Li; Moorhead, Martin; Wang, Zhigang C.; Richardson, Andrea L.; Warren, Robert; Walther, Axel; Bondy, Melissa; Sahin, Aysegul; Krahe, Ralf; Tuna, Musaffe; Thompson, Patricia A.; Spellman, Paul T.; Gray, Joe W.; Mills, Gordon B.; Faham, Malek


    A major challenge facing DNA copy number (CN) studies of tumors is that most banked samples with extensive clinical follow-up information are Formalin-Fixed Paraffin Embedded (FFPE). DNA from FFPE samples generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking during FFPE fixation and processing. As FFPE protocols may vary widely between labs and samples may be stored for decades at room temperature, an ideal FFPE CN technology should work on diverse sample sets. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from cell line and frozen tumor DNA. Since the MIP probes require only a small ({approx}40 bp) target binding site, we reasoned they may be well suited to assess degraded FFPE DNA. We assessed CN with a MIP panel of 50,000 markers in 93 FFPE tumor samples from 7 diverse collections. For 38 FFPE samples from three collections we were also able to asses CN in matched fresh frozen tumor tissue. Using an input of 37 ng genomic DNA, we generated high quality CN data with MIP technology in 88% of FFPE samples from seven diverse collections. When matched fresh frozen tissue was available, the performance of FFPE DNA was comparable to that of DNA obtained from matched frozen tumor (genotype concordance averaged 99.9%), with only a modest loss in performance in FFPE. MIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples.

  4. MMP-8 genotypes influence the inflammatory response in human endotoxemia. (United States)

    Rella, Judith M; Jilma, Bernd; Fabry, Astrid; Kaynar, A Murat; Mayr, Florian B


    Clinical studies have reported associations between MMP-8 genotypes and clinical outcomes without exploring underlying mechanisms. This study aims to understand the influence of the rs1940475 SNP on downstream chemokine and cytokine response in human endotoxemia. Rs1940475 was genotyped in 44 healthy Caucasian males, who were challenged with an intravenous bolus of 2 ng/kg lipopolysaccharide (LPS). Plasma levels of tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-1α were measured at baseline and 2, 4, 6, and 24 h after LPS infusion with high-sensitivity enzyme immunoassays. Peak TNF levels at 2 h after LPS infusion were significantly higher in subjects with AA genotype compared to subjects with AG or GG genotypes (185 pg/mL [IQR, 154-234] vs. 94 pg/mL [IQR, 65-125] vs. 107 pg/mL [IQR, 80-241], respectively; p = 0.03 between groups). Peak IL-6 levels were trend-wise higher in subjects with AA genotype compared to those with AG or GG genotypes (566 pg/mL [IQR, 294-644] vs. 278 pg/mL [IQR, 184-539] and 329 pg/mL [IQR, 240-492], respectively; p = 0.15 between groups). In contrast, peak MIP-1α at 2 h was highest in GG genotype carriers compared to those with AG or AA genotypes (602 pg/mL [IQR, 449-727] vs. 389 pg/mL [IQR, 375-490] and 510 pg/mL [425-813], respectively; p < 0.03 between groups). AA genotype carriers had highest peak TNF and IL-6 levels after LPS challenge, whereas peak MIP-1α levels were highest in GG carriers. This indicates that the rs1940475 SNP modifies the host response to inflammatory stimuli, which may in part explain previously shown associations with clinical outcomes.

  5. Circulating rotavirus genotypes in the Irish paediatric population prior to the introduction of the vaccination programme. (United States)

    Yandle, Z; Coughlan, S; Drew, R J; O'Flaherty, N; O'Gorman, J; De Gascun, C


    Rotavirus is the leading cause of viral gastroenteritis in children, and it is anticipated that the introduction of the Rotarix™ vaccine (GlaxoSmithKline Biologicals S.A., Rixensart, Belgium) into the Irish immunisation schedule will result in a significant reduction of rotavirus-associated disease. In the pre- and post-vaccination eras, it is important to determine circulating strains of rotavirus to assess vaccine effectiveness, to monitor vaccine failures, and to detect potential emerging strains. This study was a collaboration between the Temple Street Children's University Hospital (TSCUH), Dublin, and the National Virus Reference Laboratory (NVRL), Dublin, to determine the then circulating rotavirus strains in a paediatric hospital. In the 2015/2016 period (July 2015-June 2016) 89 faecal samples from paediatric patients (53 from TSCUH, 36 from other hospitals) were characterised. The results showed G1P[8] to be the predominant genotype (57%), followed by G9P[8] (34%), G4P[8] (6%), G2P[4] (2%), and G12P[8] (1%). This distribution of genotypes is comparable to those found in other European countries prior to vaccination suggesting that the vaccine should be highly efficacious in the Irish population.

  6. Genetic variation of the porcine NR5A1 is associated with meat color. (United States)

    Görres, Andreas; Ponsuksili, Siriluck; Wimmers, Klaus; Muráni, Eduard


    Because of the central role of Steroidogenic factor 1 in the regulation of the development and function of steroidogenic tissues, including the adrenal gland, we chose the encoding gene NR5A1 as a candidate for stress response, meat quality and carcass composition in the domestic pig. To identify polymorphisms of the porcine NR5A1 we comparatively sequenced the coding, untranslated and regulatory regions in four commercial pig lines. Single nucleotide polymorphisms could be found in the 3' UTR and in an intronic enhancer, whereas no polymorphisms were detected in the proximal promoter and coding region. A subset of the detected polymorphisms was genotyped in Piétrain x (German Large White x German Landrace) and German Landrace pigs. For the same animals, carcass composition traits, meat quality characteristics and parameters of adrenal function were recorded. Associations with meat color were found for two of the discovered SNPs in Piétrain x (German Large White x German Landrace) and German Landrace pigs but no connections to parameters of adrenal function could be established. We conclude that NR5A1 variations influence meat color in a hypothalamus-pituitary-adrenal axis independent manner and that further regulatory regions need to be analyzed for genetic variations to understand the discovered effects.

  7. Genotype by sex and genotype by age interactions with sedentary behavior: the Portuguese Healthy Family Study.

    Directory of Open Access Journals (Sweden)

    Daniel M V Santos

    Full Text Available Sedentary behavior (SB expression and its underlying causal factors have been progressively studied, as it is a major determinant of decreased health quality. In the present study we applied Genotype x Age (GxAge and Genotype x Sex (GxSex interaction methods to determine if the phenotypic expression of different SB traits is influenced by an interaction between genetic architecture and both age and sex. A total of 1345 subjects, comprising 249 fathers, 327 mothers, 334 sons and 325 daughters, from 339 families of The Portuguese Healthy Family Study were included in the analysis. SB traits were assessed by means of a 3-d physical activity recall, the Baecke and IPAQ questionnaires. GxAge and GxSex interactions were analyzed using SOLAR 4.0 software. Sedentary behaviour heritability estimates were not always statistically significant (p>0.05 and ranged from 3% to 27%. The GxSex and GxAge interaction models were significantly better than the single polygenic models for TV (min/day, EEsed (kcal/day, personal computer (PC usage and physical activty (PA tertiles. The GxAge model is also significantly better than the polygenic model for Sed (min/day. For EEsed, PA tertiles, PC and Sed, the GxAge interaction was significant because the genetic correlation between SB environments was significantly different from 1. Further, PC and Sed variance heterogeneity among distinct ages were observed. The GxSex interaction was significant for EEsed due to genetic variance heterogeneity between genders and for PC due to a genetic correlation less than 1 across both sexes. Our results suggest that SB expression may be influenced by the interactions between genotype with both sex and age. Further, different sedentary behaviors seem to have distinct genetic architectures and are differentially affected by age and sex.

  8. Evaluation of Soybean and Cowpea Genotypes for Phosphorus Use Efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Kumaga, F. K.; Ofori, K.; Adiku, S. K.; Kugblenu, Y. O.; Asante, W.; Seidu, H. [College of Agriculture and Consumer Sciences, University of Ghana, Legon, Accra (Ghana); Adu-Gyamfi, J. J. [Soil and Water Management and Crop Nutrition Laboratory, International Atomic Energy Agency, Vienna (Austria)


    Initial screening of one hundred and fifty-two (152) and fifty (50) genotypes of soybean and cowpea, respectively, were conducted at the early growth stage to evaluate root traits associated with phosphorus (P) efficiency. Fifty soybean genotypes were subsequently selected and evaluated on a tropical low P soil (Lixisol) for growth and yield under low and adequate P availability. Plants were sampled at twelve and thirty days after sowing and at maturity. Six cowpea genotypes were also selected and evaluated in pots filled with Alfisol under low, moderate and high P availability. Plants were sampled at forty days and assessed for shoot yield and nodulation under low P availability. Using Principal Component Analysis (PCA), Phosphorus Efficiency Index (PEI) was used to determine P efficiency of soybean and cowpea genotypes. A wide variation in root traits for soybean and cowpea at the early growth stage was found, and allometric analysis showed a significant correlation between the root and shoot parameters at this stage. The study provided an opportunity to compare root traits of newly developed cowpea genotypes (early maturing, medium maturing, dual purpose and Striga resistant lines) with older released cultivars. There were significant differences in root length among the groups. In general, dual purpose, Striga resistant and medium/early maturing genotypes showed the longest roots while the older varieties showed the least total root length. Field and pot results also showed differential growth of soybean and cowpea with low P availability. Further, PCA of the results indicated that soybean genotypes could be grouped into three distinct P efficiency categories. Retaining the PC and the relative weight for each genotype in combination with yield potential under high P, four categories of responsiveness to P were obtained. Cowpea genotypes were grouped into three P efficiency categories and two categories of responsiveness to P. The study also found genetic

  9. Failure modes of composite sandwich beams


    Gdoutos E.; Daniel I.M.


    A thorough investigation of failure behavior of composite sandwich beams under three-and four-point bending was undertaken. The beams were made of unidirectional carbon/epoxy facings and a PVC closed-cell foam core. The constituent materials were fully characterized and in the case of the foam core, failure envelopes were developed for general two-dimensional states of stress. Various failure modes including facing wrinkling, indentation failure and core failure were observed and compared wit...

  10. A simple approach to modeling ductile failure.

    Energy Technology Data Exchange (ETDEWEB)

    Wellman, Gerald William


    Sandia National Laboratories has the need to predict the behavior of structures after the occurrence of an initial failure. In some cases determining the extent of failure, beyond initiation, is required, while in a few cases the initial failure is a design feature used to tailor the subsequent load paths. In either case, the ability to numerically simulate the initiation and propagation of failures is a highly desired capability. This document describes one approach to the simulation of failure initiation and propagation.

  11. Leveraging Failure in Design Research (United States)

    Lobato, Joanne; Walters, C. David; Hohensee, Charles; Gruver, John; Diamond, Jaime Marie


    Even in the resource-rich, more ideal conditions of many design-based classroom interventions, unexpected events can lead to disappointing results in student learning. However, if later iterations in a design research study are more successful, the previous failures can provide opportunities for comparisons to reveal subtle differences in…

  12. Failure rate analysis using GLIMMIX

    International Nuclear Information System (INIS)

    Moore, L.M.; Hemphill, G.M.; Martz, H.F.


    This paper illustrates use of a recently developed SAS macro, GLIMMIX, for implementing an analysis suggested by Wolfinger and O'Connell (1993) in modeling failure count data with random as well as fixed factor effects. Interest in this software tool arose from consideration of modernizing the Failure Rate Analysis Code (FRAC), developed at Los Alamos National Laboratory in the early 1980's by Martz, Beckman and McInteer (1982). FRAC is a FORTRAN program developed to analyze Poisson distributed failure count data as a log-linear model, possibly with random as well as fixed effects. These statistical modeling assumptions are a special case of generalized linear mixed models, identified as GLMM in the current statistics literature. In the nearly 15 years since FRAC was developed, there have been considerable advances in computing capability, statistical methodology and available statistical software tools allowing worthwhile consideration of the tasks of modernizing FRAC. In this paper, the approaches to GLMM estimation implemented in GLIMMIX and in FRAC are described and a comparison of results for the two approaches is made with data on catastrophic time-dependent pump failures from a report by Martz and Whiteman (1984). Additionally, statistical and graphical model diagnostics are suggested and illustrated with the GLIMMIX analysis results

  13. Failure to Follow Written Procedures (United States)


    Most tasks in aviation have a mandated written procedure to be followed specifically under the Code of Federal Regulations (CFR) Part 14, Section 43.13(a). However, the incidence of Failure to Follow Procedure (FFP) events continues to be a major iss...

  14. Failure in imperfect anisotropic materials

    DEFF Research Database (Denmark)

    Legarth, Brian Nyvang


    The fundamental cause of crack growth, namely nucleation and growth of voids, is investigated numerically for a two phase imperfect anisotropic material. A unit cell approach is adopted from which the overall stress strain is evaluated. Failure is observed as a sudden stress drop and depending...

  15. Children's Coping with Academic Failure (United States)

    Raftery-Helmer, Jacquelyn N.; Grolnick, Wendy S.


    There is little consensus on how to conceptualize coping after perceived failure and less is known about the contextual resources that may support or undermine the use of specific coping strategies. This study examined parenting in relation to coping using the framework of self-determination theory and examined the motivational processes through…

  16. Exercise Intolerance in Heart Failure

    DEFF Research Database (Denmark)

    Brassard, Patrice; Gustafsson, Finn


    Exercise tolerance is affected in patients with heart failure (HF). Although the inability of the heart to pump blood to the working muscle has been the conventional mechanism proposed to explain the lowered capacity of patients with HF to exercise, evidence suggests that the pathophysiological...

  17. Predicting survival in heart failure

    DEFF Research Database (Denmark)

    Pocock, Stuart J; Ariti, Cono A; McMurray, John J V


    AimsUsing a large international database from multiple cohort studies, the aim is to create a generalizable easily used risk score for mortality in patients with heart failure (HF).Methods and resultsThe MAGGIC meta-analysis includes individual data on 39 372 patients with HF, both reduced...

  18. Rubble Mound Breakwater Failure Modes

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Z., Liu


    The RMBFM-Project (Rubble Mound Breakwater Failure Modes) is sponsored by the Directorate General XII of the Commission of the European Communities under the Contract MAS-CT92- 0042, with the objective of contributing to the development of rational methods for the design of rubble mound breakwate...

  19. [Acute cardiac failure in pheochromocytoma.

    DEFF Research Database (Denmark)

    Jønler, Morten; Munk, Kim


    Pheochromocytoma (P) is an endocrine catecholamine-secreting tumor. Classical symptoms like hypertension, attacks of sweating, palpitations, headache and palor are related to catecholamine discharge. We provide a case of P in a 71 year-old man presenting with acute cardiac failure, severe reduction...

  20. Insulin Signaling and Heart Failure (United States)

    Riehle, Christian; Abel, E. Dale


    Heart failure is associated with generalized insulin resistance. Moreover, insulin resistant states such as type 2 diabetes and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes alters the systemic and neurohumoral milieu leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead (FOXO) transcriptional signaling or glucose transport which may also impair cardiac metabolism, structure and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed. PMID:27034277

  1. Ventilatory disorders in heart failure

    NARCIS (Netherlands)

    Güder, G.


    Introduction: Chronic obstructive pulmonary disease (COPD), heart failure (HF) or both syndromes are the most common reasons for dyspnea in the elderly. Currently there is no standard to diagnose COPD and multiple definitions (fixed ratio [GOLD], lower limit of normal [LLN]) are discussed. Further,

  2. Napoleon’s Strategic Failures (United States)


    of Napoleon‟s strategic naval failures was his obsession with invading Ireland as a way to get at England. There had been numerous occasions where...policies impacting the internal economies of Europe was the significant rise in prices for such items as coffee , saffron, spices and sugar. These

  3. Rilpivirine versus etravirine validity in NNRTI-based treatment failure in Thailand. (United States)

    Teeranaipong, Phairote; Sirivichayakul, Sunee; Mekprasan, Suwanna; Ruxrungtham, Kiat; Putcharoen, Opass


    Etravirine (ETR) and rilpivirine (RPV) are the second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI) for treatment of HIV-1 infection. Etravirine is recommended for patients with virologic failure from first generation NNRTI-based regimen [1]. RPV has profile with similar properties to ETR but this agent is approved for treatment-naïve patients [2]. In Thailand, ETR is approximately 45 times more expensive than RPV. We aimed to study the patterns of genotypic resistance and possibility of using RPV in patients with virologic failure from two common NNRTI-based regimens: efavirenz (EFV)- or nevirapine (NVP)-based regimen. Data of clinical samples with confirmed virologic failure during 2003-2010 were reviewed. We selected the samples from patients who failed EFV- or NVP-based regimen. Resistance-associated mutations (RAMs) were determined by IAS-USA Drug Resistance Mutations. DUET, Monogram scoring system and Stanford Genotypic Resistance Interpretation were applied to determine the susceptibility of ETR and RPV. A total of 2086 samples were analyzed. Samples from 1482 patients with virologic failure from NVP-based regimen treatment failure (NVP group) and 604 patients with virologic failure from EFV-based regimen treatment failure (EFV group) were included. 95% of samples were HIV-1 CRF01_AE subtype. Approximately 80% of samples in each group had one to three NNRTI-RAMs and 20% had four to seven NNRTI-RAMs. 181C mutation was the most common NVP-associated RAM (54.3% vs 14.7%, p<0.01). 103N mutation was the most common EFV-associated RAM (56.5% vs 19.1%, p<0.01). The calculated scores from all three scoring systems were concordant. In NVP group, 165 (11.1%) and 161 (10.9%) patients were susceptible to ETR and RPV, respectively (p=0.81). In EFV group, 195 (32.2%) and 191 (31.6%) patients were susceptible to ETR and RPV, respectively (p=0.81). The proportions of viruses that remained susceptible to ETR and RPV in EFV group were significantly

  4. The pathophysiology of heart failure. (United States)

    Kemp, Clinton D; Conte, John V


    Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Genotyping-by-sequencing data of 272 crested wheatgrass (Agropyron cristatum genotypes

    Directory of Open Access Journals (Sweden)

    Pingchuan Li


    Full Text Available Crested wheatgrass [Agropyron cristatum L. (Gaertn.] is an important cool-season forage grass widely used for early spring grazing. However, the genomic resources for this non-model plant are still lacking. Our goal was to generate the first set of next generation sequencing data using the genotyping-by-sequencing technique. A total of 272 crested wheatgrass plants representing seven breeding lines, five cultivars and five geographically diverse accessions were sequenced with an Illumina MiSeq instrument. These sequence datasets were processed using different bioinformatics tools to generate contigs for diploid and tetraploid plants and SNPs for diploid plants. Together, these genomic resources form a fundamental basis for genomic studies of crested wheatgrass and other wheatgrass species. The raw reads were deposited into Sequence Read Archive (SRA database under NCBI accession SRP115373 ( and the supplementary datasets are accessible in Figshare (10.6084/m9.figshare.5345092. Keywords: Crested wheatgrass, Genotyping-by-sequencing, Diploid, Tetraploid, Raw sequence data

  6. Hepatitis E Virus Genotype 3 in Sewage and Genotype 1 in Acute Hepatitis Cases, Israel (United States)

    Ram, Daniela; Manor, Yossi; Gozlan, Yael; Schwartz, Eli; Ben-Ari, Ziv; Mendelson, Ella; Mor, Orna


    Hepatitis E virus (HEV) is an emerging infectious agent in developed countries. HEV genotypes 1 (G1) and 3 (G3) have been identified in environmental and clinical samples in Europe. In Israel, the overall prevalence of anti-HEV IgG antibodies was found to be 10.6%; however, reports of HEV infection are scarce. In this study, the presence of HEV in Israel was investigated using 169 sewage samples from 32 treatment facilities and 49 samples from acute hepatitis patients, all collected between 2013 and 2015. Fourteen sewage samples, from Haifa (11/18 samples), Tel Aviv (2/29 samples), and Beer Sheva (1/17 samples), regions with good sanitary conditions and middle-high socioeconomic populations, were HEV positive. Among the patient samples, 6.1% (3/49) were HEV positive, all returning travelers from India. Genotype analysis revealed G1 HEV in patients and G3 HEV sequences in sewage. Evidence that HEV could be establishing itself in our region may justify more active surveillance to monitor its spread. PMID:27246446

  7. Connecting functional and statistical definitions of genotype by genotype interactions in coevolutionary studies

    Directory of Open Access Journals (Sweden)

    Katy Denise Heath


    Full Text Available Predicting how species interactions evolve requires that we understand the mechanistic basis of coevolution, and thus the functional genotype-by-genotype interactions (G × G that drive reciprocal natural selection. Theory on host-parasite coevolution provides testable hypotheses for empiricists, but depends upon models of functional G × G that remain loosely tethered to the molecular details of any particular system. In practice, reciprocal cross-infection studies are often used to partition the variation in infection or fitness in a population that is attributable to G × G (statistical G × G. Here we use simulations to demonstrate that within-population statistical G × G likely tells us little about the existence of coevolution, its strength, or the genetic basis of functional G × G. Combined with studies of multiple populations or points in time, mapping and molecular techniques can bridge the gap between natural variation and mechanistic models of coevolution, while model-based statistics can formally confront coevolutionary models with cross-infection data. Together these approaches provide a robust framework for inferring the infection genetics underlying statistical G × G, helping unravel the genetic basis of coevolution.

  8. Association of matrix metalloproteinase-3 -1171(5A>6A polymorphism with cancer risk: a meta-analysis of 41 studies.

    Directory of Open Access Journals (Sweden)

    Xin Yang

    Full Text Available BACKGROUND AND OBJECTIVE: Evidence has shown that matrix metalloproteinases-3 (MMP3 is important for cancer progression. Recent studies about the association between the -1171(5A>6A polymorphism in MMP3 promoter region and cancer risk have yielded conflicting results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 41 studies including 11112 cases and 11091 controls to determine whether the -1171(5A>6A polymorphism of MMP3 was associated with cancer risk. We assessed the strength of association and performed sub-group analyses by cancer types, ethnicity, smoking status, genotyping method, source of controls and sample size. The pooled results revealed that no significant association of the -1171(5A>6A polymorphism with overall cancer risk in any of four models. Further sub-group analysis revealed that individuals with the 6A allele had lower risk of gastrointestinal cancer in two models: heterozygote comparison (6A/5A vs. 5A/5A: OR=0.74, 95%CI: 0.60-0.91; I(2=1.9%, and dominant model (6A/6A+6A/5A vs. 5A/5A: OR=0.77, 95%CI: 0.64-0.94; I(2=29.0%. Additionally, the associations were significant in Asian populations for three models: homozygote comparison (6A/6A vs. 5A/5A, OR=0.68, 95%CI: 0.52-0.90; I(2=26.7%, heterozygote comparison (6A/5A vs. 5A/5A: OR=0.75, 95%CI: 0.58-0.98; I(2=0.0%, and dominant model (6A/6A+6A/5A vs. 5A/5A: OR=0.69, 95%CI: 0.54-0.88; I(2=0.5%. It was noteworthy that we had a contrary finding in non-smokers: the variant 6A/6A homozygote might statistically increase cancer risk compared with 6A/5A+5A/5A genotype (OR=1.92, 95%CI: 1.25-2.96; I(2=72.7%. CONCLUSION: This meta-analysis suggests that the -1171(5A>6A polymorphism in MMP3 promoter region is not associated with overall cancer risk, but it may contribute to decreased cancer risk in Asian population when compared with Caucasian population and significantly reduce the risk of gastrointestinal cancer.

  9. Analysis of the genetic diversity of four rabbit genotypes using ...

    African Journals Online (AJOL)



    May 15, 2013 ... consumption and low cost, it has been widely utilized in genetics analysis in ... isozyme variation among the selected individuals within each rabbit genotype. ... with different embryo survival (Bolet and Theau-Clement, 1994).

  10. Genotype x environment interaction and stability analysis for yield ...

    African Journals Online (AJOL)



    . Combined analysis of variance (ANOVA) for yield and yield components revealed highly significant .... yield stability among varieties, multi-location trials with ... Mean grain yield (kg/ha) of 17 Kabuli-type chickpea genotypes ...

  11. Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections

    DEFF Research Database (Denmark)

    Dalgard, Olav; Weiland, Ola; Noraberg, Geir


    BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting...... in Scandinavia. METHODS: Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography...... was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). CONCLUSION: We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver...

  12. Evaluation of 14 winter bread wheat genotypes in normal irrigation ...

    African Journals Online (AJOL)

    Evaluation of 14 winter bread wheat genotypes in normal irrigation and stress conditions after anthesis stage. ... African Journal of Biotechnology ... Using biplot graphic method, comparison of indices amounts and mean rating of indices for ...

  13. adaptation of introduced mungbean genotypes in uganda abstract

    African Journals Online (AJOL)


    locations in Uganda, to determine the adaptability of introduced mungbean genotypes, and identify ... The six test multi-locations were grouped into two candidate mega-environments for ..... interactions: Challenges and opportunities for.

  14. cyanide cassava genotypes in acid ultisols of south eastern Nigeria

    African Journals Online (AJOL)

    ENGR C.J


    Jan 29, 2014 ... Thirty-eight high and low cyanide cassava genotypes were evaluated for growth and .... sium (K) and sodium (Na) were determined by Flamephoto-metory .... outlined for randomized complete block design (Steel et al., 1997).

  15. Molecular methods for bacterial genotyping and analyzed gene regions

    Directory of Open Access Journals (Sweden)

    İbrahim Halil Yıldırım1, Seval Cing Yıldırım2, Nadir Koçak3


    Full Text Available Bacterial strain typing is an important process for diagnosis, treatment and epidemiological investigations. Current bacterial strain typing methods may be classified into two main categories: phenotyping and genotyping. Phenotypic characters are the reflection of genetic contents. Genotyping, which refers discrimination of bacterial strains based on their genetic content, has recently become widely used for bacterial strain typing. The methods already used in genotypingof bacteria are quite different from each other. In this review we tried to summarize the basic principles of DNA-based methods used in genotyping of bacteria and describe some important DNA regions that are used in genotyping of bacteria. J Microbiol Infect Dis 2011;1(1:42-46.

  16. Effects of nutritional supplementation and genotype on milk ...

    African Journals Online (AJOL)

    Effects of nutritional supplementation and genotype on milk production and fertility of lactating dairy ... Bulletin of Animal Health and Production in Africa ... The objective of this study was to determine effects of nutrition on milk production and ...

  17. Effects of genotype x bradyrhizobium inoculation or x fertilizer n ...

    African Journals Online (AJOL)

    Genotype x inoculation interaction was significant only for protein and oil content in one year. .... main-plot factor. ... components and expected genetic gains invoiving yield srrnin. ... Combined analysis of the cu ltivar experiment was carried.

  18. Characterization of cowpea genotype resistance to Callosobruchus maculatus

    Directory of Open Access Journals (Sweden)

    Maria de Jesus Passos de Castro


    Full Text Available The objective of this work was to characterize the resistance of 50 cowpea (Vigna unguiculata genotypes to Callosobruchus maculatus. A completely randomized design with five replicates per treatment (genotype was used. No-choice tests were performed using the 50 cowpea genotypes to evaluate the preference for oviposition and the development of the weevil. The genotypes IT85 F-2687, MN05-841 B-49, MNC99-508-1, MNC99-510-8, TVu 1593, Canapuzinho-1-2, and Sanzi Sambili show non-preference-type resistance (oviposition and feeding. IT81 D-1045 Ereto and IT81 D-1045 Enramador exhibit antibiosis against C. maculatus and descend from resistant genitors, which grants them potential to be used in future crossings to obtain cowpea varieties with higher levels of resistance.

  19. Multiple centroid method to evaluate the adaptability of alfalfa genotypes

    Directory of Open Access Journals (Sweden)

    Moysés Nascimento


    Full Text Available This study aimed to evaluate the efficiency of multiple centroids to study the adaptability of alfalfa genotypes (Medicago sativa L.. In this method, the genotypes are compared with ideotypes defined by the bissegmented regression model, according to the researcher's interest. Thus, genotype classification is carried out as determined by the objective of the researcher and the proposed recommendation strategy. Despite the great potential of the method, it needs to be evaluated under the biological context (with real data. In this context, we used data on the evaluation of dry matter production of 92 alfalfa cultivars, with 20 cuttings, from an experiment in randomized blocks with two repetitions carried out from November 2004 to June 2006. The multiple centroid method proved efficient for classifying alfalfa genotypes. Moreover, it showed no unambiguous indications and provided that ideotypes were defined according to the researcher's interest, facilitating data interpretation.

  20. A preliminary investigation into genotype x environment interaction ...

    African Journals Online (AJOL)



    Aug 24, 2014 ... Genotype x environment interaction (G x E) in dairy cattle is a contentious ... environments, if it exists, with a negative impact on genetic response ..... interaction for Holstein milk yield in Colombia, Mexico and Puerto Rico.

  1. Giardia and Cryptosporidium species and genotypes in coyotes (Canis latrans). (United States)

    Trout, James M; Santín, Mónica; Fayer, Ronald


    Feces and duodenal scrapings were collected from 22 coyotes (Canis latrans) killed in managed hunts in northeastern Pennsylvania. Polymerase chain reaction (PCR) methods were used to detect Giardia and Cryptosporidium spp. PCR-amplified fragments of Giardia and Cryptosporidium spp. SSU-rRNA genes were subjected to DNA sequence analysis for species/genotype determination. Seven coyotes (32%) were positive for G. duodenalis: three assemblage C, three assemblage D, and one assemblage B. Six coyotes (27%) were positive for Cryptosporidium spp. One isolate shared 99.7% homology with C. muris, whereas five others (23%) shared 100% homology with C. canis, coyote genotype. This is the first report on multiple genotypes of Giardia spp. in coyotes and on the prevalence of Cryptosporidium spp. genotypes in coyotes.

  2. Large SNP arrays for genotyping in crop plants

    Indian Academy of Sciences (India)


    Oct 15, 2012 ... in human has been paralleled by the simultaneous develop- ment of ... In crop plants, the development of large genotyping arrays started much ..... via deep resequencing of reduced representation libraries with the Illumina ...

  3. Efficiency and response of conilon coffee genotypes to nitrogen supply

    African Journals Online (AJOL)



    Aug 31, 2016 ... tolerance to the deficit of these nutrients in the soil. (Colodetti et al., 2014; ... be passive of exploration using genotypes of rapid growth and low nutritional ... amino acids, proteins, nucleotides, hormones and chlorophyll ...

  4. Pollen diversity, viability and floral structure of some Musa genotypes

    African Journals Online (AJOL)

    Prof. Ogunji

    Pollen diversity, viability and floral structure of some Musa genotypes ... at the Faculty of Agriculture & Natural Resources Management farm, Ebonyi State University,. Abakaliki. ..... Roots, tuber, plantains and bananas in human nutrition. Rome,.

  5. High-throughput mouse genotyping using robotics automation. (United States)

    Linask, Kaari L; Lo, Cecilia W


    The use of mouse models is rapidly expanding in biomedical research. This has dictated the need for the rapid genotyping of mutant mouse colonies for more efficient utilization of animal holding space. We have established a high-throughput protocol for mouse genotyping using two robotics workstations: a liquid-handling robot to assemble PCR and a microfluidics electrophoresis robot for PCR product analysis. This dual-robotics setup incurs lower start-up costs than a fully automated system while still minimizing human intervention. Essential to this automation scheme is the construction of a database containing customized scripts for programming the robotics workstations. Using these scripts and the robotics systems, multiple combinations of genotyping reactions can be assembled simultaneously, allowing even complex genotyping data to be generated rapidly with consistency and accuracy. A detailed protocol, database, scripts, and additional background information are available at

  6. Genotype x environment interaction and stability analysis for yield ...

    African Journals Online (AJOL)



    May 6, 2015 ... 4Ethiopian Institute of Agriculture Research, Debre Zeit Agriculture Research Center, Ethiopia. Received .... interaction on seed yield of Kabuli -chickpea genotypes .... becomes important for the chickpea breeders in terms of.

  7. Assessment of genotype x environment interaction on yield and ...

    African Journals Online (AJOL)



    Apr 11, 2011 ... yield and yield components of durum wheat genotypes ... The results of combined analysis of variance showed a strong influence of the ... Stability is defined as the early prediction of environmental im- ... Many resear-.

  8. Genetic diversity of maize genotypes on the basis of morpho ...

    African Journals Online (AJOL)

    Genetic diversity of maize genotypes on the basis of morpho-physiological and simple sequence repeat (SSR) markers. Ashish Kumar, Arunita Rakshit, Naresh K Mangilipelli, Y Varalaxmi, T Vijayalakshmi, Jainender M Vanaja, SK Yadav, B Venkateswarlu, M Maheswari ...

  9. The Comparison of Growth, Slaughter and Carcass Traits of Meat Chicken Genotype Produced by Back-Crossing with A Commercial Broiler Genotype

    Directory of Open Access Journals (Sweden)

    Musa Sarıca


    Full Text Available This study was conducted to determine the growth and some slaughter traits between commercial fast growing chickens and three-way cross M2 genotypes. 260 male female mixed chickens from each genotype was reared 10 replicate per genotype in the same house. Two different slaughtering ages were applied to commercial chickens and slaughtered at 6 and 7 weeks of age for comparing with cross genotypes. F chickens reached to slaughtering age at 42 days, whereas cross groups reached at 49 days. Genotypes consumed same amount of feed until slaughtering ages, but F genotype had better feed conversion ratio. The differences between dressing percentage and carcass parts ratios of genotypes were found significant, and F genotype had higher dressing percentage. Carcass parts of all genotypes were found in acceptable limits.


    Directory of Open Access Journals (Sweden)

    Heni Safitri


    Full Text Available Salinity is one of the most serious problems in rice cultivation. Salinity drastically reduced plant growth and yield, especially at seedling stage. Several rice genotypes have been produced, but their tolerance to salinity has not yet been evaluated. The study aimed to evaluate salinity tolerance of rice genotypes at seedling stage. The glasshouse experiment was conducted at Cimanggu Experimental Station, Bogor, from April to May 2013. Thirteen rice genotypes and two check varieties, namely Pokkali (salt tolerant and IR29 (salt sensitive were tested at seedling stage. The experiment was arranged in a randomized complete block design with three replications and two factors, namely the levels of NaCl (0 and 120 mM and 13 genotypes of rice. Rice seedlings were grown in the nutrient culture (hydroponic supplemented with NaCl at different levels. The growth and salinity injury levels of the genotypes were recorded periodically. The results showed that salinity level of 120 mM NaCl reduced seedling growth of all rice genotypes, but the tolerant ones were survived after 14 days or until the sensitive check variety died. Based on the visual injury symptoms on the leaves, five genotypes, i.e. Dendang, Inpara 5, Inpari 29, IR77674-3B-8-2-2-14-4-AJY2, and IR81493-BBB-6-B- 2-1-2 were tolerant to 120 mM salinity level, while Inpara 4 was comparable to salt sensitive IR29. Hence, Inpara 4 could be used as a salinity sensitive genotype for future research of testing tolerant variety. Further evaluation is needed to confirm their salinity tolerance under field conditions. 

  11. Antioxidant Defense Mechanisms of Salinity Tolerance in Rice Genotypes

    Directory of Open Access Journals (Sweden)

    Mohammad Golam Kibria


    Full Text Available In order to elucidate the role of antioxidant responses in salinity tolerance in rice genotypes under salt stress, experiments were conducted using four rice varieties, including salt-sensitive BRRI dhan 28 and three salt-tolerant varieties BRRI dhan 47, BINA dhan 8 and BINA dhan 10. Thirty-day-old rice seedlings were transplanted into pots. At the active tillering stage (35 d after transplanting, plants were exposed to different salinity levels (0, 20, 40 and 60 mmol/L NaCl. Salt stress caused a significant reduction in growth for all the rice genotypes. Growth reduction was higher in the salt-sensitive genotype than in the salt-tolerant ones, and BINA dhan 10 showed higher salt tolerance in all measured physiological parameters. The reduction in shoot and root biomass was found to be minimal in BINA dhan 10. Chlorophyll content significantly decreased under salt stress except for BINA dhan 10. Proline content significantly increased in salt-tolerant rice genotypes with increased salt concentration, and the highest proline content was obtained from BINA dhan 10 under salt stress. Catalase and ascorbate peroxidase activities significantly decreased in salt-sensitive genotype whereas significantly increased in salt-tolerant ones with increasing salt concentration. However, salt stress significantly decreased guaiacol peroxidase activity in all the rice genotypes irrespective of salt tolerance. K+/Na+ ratio also significantly decreased in shoots and roots of all the rice genotypes. The salt-tolerant genotype BINA dhan 10 maintained higher levels of chlorophyll and proline contents as well as catalase and ascorbate peroxidase activities under salt stress, thus, this might be the underlying mechanism for salt tolerance.

  12. Comparative salinity responses among tomato genotypes and rootstocks

    International Nuclear Information System (INIS)

    Oztekin, G.B.; Tuzel, Y.


    Salinity is a major constraint limiting agricultural crop productivity in the world. However, plant species and cultivars differ greatly in their response to salinity. This study was conducted in a greenhouse to determine the response of 4 commercial tomato rootstocks, 21 cultivars and 8 candidate varieties to salinity stress. Seeds were germinated in peat and when the plants were at the fifth-true leaf stage, salt treatment was initiated except control treatment. NaCl was added to nutrient solution daily with 25 mM concentration and had been reached to 200 mM final concentration. On harvest day, genotypes were classified based on the severity of leaf symptoms caused by NaCl treatment. After symptom scoring, the plants were harvested and leaf number, root length, stem length and diameter per plant were measured. The plants were separated into shoots and roots for dry matter production. Our results showed that, on average, NaCl stress decreased all parameters and the rootstocks gave the highest performance than genotypes. Among all rootstocks, three varieties (2211 and 2275) and ten genotypes (Astona, Astona RN, Caracas, Deniz, Durinta, Export, Gokce, Target, Yeni Talya and 144 HY) were selected as tolerant with slight chlorosis whereas the genotype Malike was selected as sensitive with severe chlorosis. Candidate varieties 2316 and 1482 were the most sensitive ones. Plant growth and dry matter production differed among the tested genotypes. However no correlation was found between plant growth and dry matter production. Rootstock Beaufort gave the highest shoot dry matter although Heman had highest root dry matter. Newton showed more shoot and root dry matter than other genotypes. It is concluded that screening of genotypes based on severity of symptoms at early stage of development and their dry matter production could be used as a tool to indicate genotypic variation to salt stress. (author)

  13. Prevalence of American Foulbrood and Paenibacillus Larvae Genotypes in Bulgaria


    RUSENOVA, Nikolina; PARVANOV, Parvan


    This study aimed to analyse the prevalence of American foulbrood and Paenibacillus larvae genotypes in Bulgaria. For this purpose, data concerning American foulbrood outbreaks were used. Also, available data on the number of destroyed bee families covering a twenty-five-year period (1989 - 2013) was collected from the register of Bulgarian Food Safety Agency. In addition, Paenibacillus larvae genotypes in 15 apiaries were established by rep - PCR with BOXA1R and MBOREP1 primers. Results showe...

  14. Genotype-Specific Measles Transmissibility: A Branching Process Analysis. (United States)

    Ackley, Sarah F; Hacker, Jill K; Enanoria, Wayne T A; Worden, Lee; Blumberg, Seth; Porco, Travis C; Zipprich, Jennifer


    Substantial heterogeneity in measles outbreak sizes may be due to genotype-specific transmissibility. Using a branching process analysis, we characterize differences in measles transmission by estimating the association between genotype and the reproduction number R among postelimination California measles cases during 2000-2015 (400 cases, 165 outbreaks). Assuming a negative binomial secondary case distribution, we fit a branching process model to the distribution of outbreak sizes using maximum likelihood and estimated the reproduction number R for a multigenotype model. Genotype B3 is found to be significantly more transmissible than other genotypes (P = .01) with an R of 0.64 (95% confidence interval [CI], .48-.71), while the R for all other genotypes combined is 0.43 (95% CI, .28-.54). This result is robust to excluding the 2014-2015 outbreak linked to Disneyland theme parks (referred to as "outbreak A" for conciseness and clarity) (P = .04) and modeling genotype as a random effect (P = .004 including outbreak A and P = .02 excluding outbreak A). This result was not accounted for by season of introduction, age of index case, or vaccination of the index case. The R for outbreaks with a school-aged index case is 0.69 (95% CI, .52-.78), while the R for outbreaks with a non-school-aged index case is 0.28 (95% CI, .19-.35), but this cannot account for differences between genotypes. Variability in measles transmissibility may have important implications for measles control; the vaccination threshold required for elimination may not be the same for all genotypes or age groups.

  15. The genetic diversity of hepatitis A genotype I in Bulgaria. (United States)

    Cella, Eleonora; Golkocheva-Markova, Elitsa N; Trandeva-Bankova, Diljana; Gregori, Giulia; Bruni, Roberto; Taffon, Stefania; Equestre, Michele; Costantino, Angela; Spoto, Silvia; Curtis, Melissa; Ciccaglione, Anna Rita; Ciccozzi, Massimo; Angeletti, Silvia


    The purpose of this study was to analyze sequences of hepatitis A virus (HAV) Ia and Ib genotypes from Bulgarian patients to investigate the molecular epidemiology of HAV genotype I during the years 2012 to 2014. Around 105 serum samples were collected by the Department of Virology of the National Center of Infectious and Parasitic Diseases in Bulgaria. The sequenced region encompassed the VP1/2A region of HAV genome. The sequences obtained from the samples were 103. For the phylogenetic analyses, 5 datasets were built to investigate the viral gene in/out flow among distinct HAV subpopulations in different geographic areas and to build a Bayesian dated tree, Bayesian phylogenetic and migration pattern analyses were performed. HAV Ib Bulgarian sequences mostly grouped into a single clade. This indicates that the Bulgarian epidemic is partially compartmentalized. It originated from a limited number of viruses and then spread through fecal-oral local transmission. HAV Ia Bulgarian sequences were intermixed with European sequences, suggesting that an Ia epidemic is not restricted to Bulgaria but can affect other European countries. The time-scaled phylogeny reconstruction showed the root of the tree dating in 2008 for genotype Ib and in 1999 for genotype Ia with a second epidemic entrance in 2003. The Bayesian skyline plot for genotype Ib showed a slow but continuous growth, sustained by fecal-oral route transmission. For genotype Ia, there was an exponential growth followed by a plateau, which suggests better infection control. Bidirectional viral flow for Ib genotype, involving different Bulgarian areas, was observed, whereas a unidirectional flow from Sofia to Ihtiman for genotype Ia was highlighted, suggesting the fecal-oral transmission route for Ia. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  16. Sex and PRNP genotype determination in preimplantation caprine embryos. (United States)

    Guignot, F; Perreau, C; Cavarroc, C; Touzé, J-L; Pougnard, J-L; Dupont, F; Beckers, J-F; Rémy, B; Babilliot, J-M; Bed'Hom, B; Lamorinière, J M; Mermillod, P; Baril, G


    The objective of this study was to test the accuracy of genotype diagnosis after whole amplification of DNA extracted from biopsies obtained by trimming goat embryos and to evaluate the viability of biopsied embryos after vitrification/warming and transfer. Whole genome amplification (WGA) was performed using Multiple Displacement Amplification (MDA). Sex and prion protein (PRNP) genotypes were determined. Sex diagnosis was carried out by PCR amplification of ZFX/ZFY and Y chromosome-specific sequences. Prion protein genotype determination was performed on codons 142, 154, 211, 222 and 240. Embryos were collected at day 7 after oestrus and biopsied either immediately after collection (blastocysts and expanded blastocysts) or after 24 h of in vitro culture (compacted morulae). Biopsied embryos were frozen by vitrification. Vitrified whole embryos were kept as control. DNA of biopsies was extracted and amplified using MDA. Sex diagnosis was efficient for 97.4% of biopsies and PRNP genotyping was determined in 78.7% of biopsies. After embryo transfer, no significant difference was observed in kidding rate between biopsied and vitrified control embryos, whereas embryo survival rate was different between biopsied and whole vitrified embryos (p = 0.032). At birth, 100% of diagnosed sex and 98.2% of predetermined codons were correct. Offspring PRNP profiles were in agreement with parental genotype. Whole genome amplification with MDA kit coupled with sex diagnosis and PRNP genotype predetermination are very accurate techniques to genotype goat embryos before transfer. These novel results allow us to plan selection of scrapie-resistant genotypes and kid sex before transfer of cryopreserved embryo. © 2010 Blackwell Verlag GmbH.

  17. Evaluation of allelopathic potential of safflower genotypes (Carthamus tinctorius L.

    Directory of Open Access Journals (Sweden)

    Motamedi Marzieh


    Full Text Available Forty safflower genotypes were grown under normal irrigation and drought stress. In the first experiment, the allelopathic potential of shoot residues was evaluated using the sandwich method. Each genotype residue (0.4 g was placed in a sterile Petri dish and two layers of agar were poured on that. Radish seeds were placed on agar medium. The radish seeds were cultivated without safflower residues as the controls. The length of the radicle, hypocotyl, and fresh biomass weight and seed germination percentages were measured. A pot experiment was also done on two genotypes with the highest and two with the lowest allelopathic activity selected after screening genotypes in the first experiment. Before entering the reproductive phase, irrigation treatments (normal irrigation and drought stress were applied. Shoots were harvested, dried, milled and mixed with the topsoil of new pots and then radish seeds were sown. The pots with safflower genotypes were used to evaluate the effect of root residue allelopathy. The shoot length, fresh biomass weight, and germination percentage were measured. Different safflower genotypes showed varied allelopathic potential. The results of the first experiment showed that Egypt and Iran-Khorasan genotypes caused maximum inhibitory responses and Australia and Iran-Kerman genotypes resulted in minimum inhibitory responses on radish seedling growth. Fresh biomass weight had the most sensitivity to safflower residues. The results of the pot experiment were consistent with the results of in vitro experiments. Residues produced under drought stress had more inhibitory effects on the measured traits. Safflower root residue may have a higher level of allelochemicals or different allelochemicals than shoot residue.

  18. Analysis of failures in concrete containments

    International Nuclear Information System (INIS)

    Moreno-Gonzalez, A.


    The function of Containment, in an accident event, is to avoid the release of radioactive substances into the surroundings. Containment failure, therefore, is defined as the appearance of leak paths to the external environment. These leak paths may appear either as a result of loss of leaktightness due to degradation of design conditions or structural failure with containment material break. This document is a survey of the state of the art of Containment Failure Analysis. It gives a detailed description of all failure mechanisms, indicating all the possible failure modes and their causes, right from failure resulting from degradation of the materials to structural failure and linear breake failure. Following the description of failure modes, possible failure criteria are identified, with special emphasis on structural failure criteria. These criteria have been obtained not only from existing codes but also from the latest experimental results. A chapter has been dedicated exclusively to failure criteria in conventional structures, for the purpose of evaluating the possibility of application to the case of containment. As the structural behaviour of the containment building is very complex, it is not possible to define failure through a single parameter. It is therefore advisable to define a methodology for containment failure analysis which could be applied to a particular containment. This methodology should include prevailing load and material conditions together with the behaviour of complex conditions such as the liner-anchorage-cracked concrete interaction

  19. Failure analysis and failure prevention in electric power systems

    International Nuclear Information System (INIS)

    Rau, C.A. Jr.; Becker, D.G.; Besuner, P.M.; Cipolla, R.C.; Egan, G.R.; Gupta, P.; Johnson, D.P.; Omry, U.; Tetelman, A.S.; Rettig, T.W.; Peters, D.C.


    New methods have been developed and applied to better quantify and increase the reliability, safety, and availability of electric power plants. Present and potential problem areas have been identified both by development of an improved computerized data base of malfunctions in nuclear power plants and by detailed metallurgical and mechanical failure analyses of selected problems. Significant advances in the accuracy and speed of structural analyses have been made through development and application of the boundary integral equation and influence function methods of stress and fracture mechanics analyses. The currently specified flaw evaluation procedures of the ASME Boiler and Pressure Vessel Code have been computerized. Results obtained from these procedures for evaluation of specific in-service inspection indications have been compared with results obtained utilizing the improved analytical methods. Mathematical methods have also been developed to describe and analyze the statistical variations in materials properties and in component loading, and uncertainties in the flaw size that might be passed by quality assurance systems. These new methods have been combined to develop accurate failure rate predictions based upon probabilistic fracture mechanics. Improved failure prevention strategies have been formulated by combining probabilistic fracture mechanics and cost optimization techniques. The approach has been demonstrated by optimizing the nondestructive inspection level with regard to both reliability and cost. (Auth.)

  20. Genotypic differences in phosphate nutrition of rice (Oryza Sativa L.)

    International Nuclear Information System (INIS)

    Bui Thi Hong Thanh; Zapata, F.; Bowen, G.D.; Kumarasinghe, K.S.


    Phosphate uptake and use by five genotypes of paddy rice were studied at five phosphate levels in pot studies for 49 days. For all five P levels there were marked genotypic differences in shoot growth, plant dry weight, root/shoot ratios, phosphate uptake and translocation, P content of roots and shoots, and phosphorus use efficiency of shoots (PUE, g shoot mg P -1 in shoot). There were significant genotypic differences in root weight (4 P levels) and in uptake/mg root (all P levels). These latter may have resulted from differences in root weight/root length conversion, root hair development or uptake characteristics, factors which were not studied specifically. Differences between genotypes and P levels in the percentage translocation were partly explicable by differences in P uptake/plant (r = 0.72) but especially by differences in root/shoot ratios (r = 0.89). Differences in PUE were largely a factor of P percentage of the tops (r = 0.94) but significant differences between genotypes were shown as a function of % P. Differences in net photosynthesis rates were largely, but not entirely, due to differences in P % of the shoots. Key factors in P uptake and use and genotypic differences are root growth, uptake/mg root, root/shoot ratios and PUE. (author). 9 refs, 2 figs, 3 tabs


    Directory of Open Access Journals (Sweden)

    Glenn eHyman


    Full Text Available Crop improvement efforts have benefited greatly from advances in available data, computing technology and methods for targeting genotypes to environments. These advances support the analysis of genotype by environment interactions to understand how well a genotype adapts to environmental conditions. This paper reviews the use of spatial analysis to support crop improvement research aimed at matching genotypes to their most appropriate environmental niches. Better data sets are now available on soils, weather and climate, elevation, vegetation, crop distribution and local conditions where genotypes are tested in experimental trial sites. The improved data are now combined with spatial analysis methods to compare environmental conditions across sites, create agro-ecological region maps and assess environment change. Climate, elevation and vegetation data sets are now widely available, supporting analyses that were much more difficult even five or ten years ago. While detailed soil data for many parts of the world remains difficult to acquire for crop improvement studies, new advances in digital soil mapping are likely to improve our capacity. Site analysis and matching and regional targeting methods have advanced in parallel to data and technology improvements. All these developments have increased our capacity to link genotype to phenotype and point to a vast potential to improve crop adaptation efforts.

  2. High prevalence of Hepatitis C virus genotype 6 in Vietnam. (United States)

    Pham, Duc Anh; Leuangwutiwong, Pornsawan; Jittmittraphap, Akanitt; Luplertlop, Nattanej; Bach, Hoa Khanh; Akkarathamrongsin, Srunthron; Theamboonlers, Apiradee; Poovorawan, Yong


    This study aimed to update the prevalence of the various Hepatitis C virus genotypes in Vietnamese blood donors. One hundred and three HCV antibody-positive plasma samples were collected from blood donors at the National Institute of Hematology and Blood Transfusion, Hanoi, Vietnam. All specimens were subjected to RT-PCR of the 5' untranslated region (UTR) to confirm the presence of HCV RNA. The core and NS5B regions of thh positive samples were subsequently amplified by RT-PCR followed by direct sequencing and phylogenetic analysis. Seventy out of 103 samples (68.0%) were RNA positive. Core and NS5B were successfully amplified and sequences were obtained for 70 and 65 samples, respectively. Phylogenetic analysis revealed that genotype 6a was the most predominant among Vietnamese blood donors with a prevalence of 37.1% (26/70), followed by genotype 1a at 30.0% (21/70) and genotype 1b at 17.1% (12/70). The prevalence of two other genotype 6 variants, 6e and 61 was 8.6% and 1.4%, respectively. Further analysis of recent studies showed that the geographic distribution of genotype 6 covered mainly southern China and the mainland of Southeast Asia including Vietnam, Laos, Thailand, and Myanmar. The GenBank accession numbers for the sequences reported in this study are FJ768772-FJ768906.

  3. Evaluation of Different Rice Genotypes Tolerance to Saline Irrigation Water

    Directory of Open Access Journals (Sweden)

    S. Jafari Rad


    Full Text Available To study the responses of seven rice genotypes (Khazar, SA13, Deylam, Sange Joe, Sepidrud, 831 and T5 to different levels of irrigation water salinity, and determining grain yield based on tolerance indices, a CRD based factorial pot experiment with five levels of irrigation water salinity (1, 2, 4, 6 and 8 dSm-1 and three replications was carried out at Rice Research Institute of Iran in 2011. Indices such as SSI, TOL, MP, GMP, HM, STI, YI and YSI were calculated and their correlations with grain yield were estimated for both stress and non-stress conditions. Results indicated significant differences among genotypes and the indices within both conditions. Results also showed that STI and MP indices could be considered as the best indices to screen salt tolerant genotypes. Among the genotypes used in the experiment, T5 produced the highest yield in both non-stress (19.71 g/plant and stress (10.69 g/plant conditions, while the lowest yield in normal (11.84 g/plant and stressful (4.29 g/plant conditions was recorded for Deylam and Khazar, respectively. The highest and the lowest percentage of yield reduction were found in Khazar (69.49% and Sange Joe (31.48% in stressful conditions, respectively. Overall, genotypes T5, 831, Sepidrud and Sange Joe can probably be considered as superior high yielding genotypes in both saline and non-saline conditions for further research.

  4. Genotypic differences in phosphate nutrition of rice (Oryza Sativa L.)

    Energy Technology Data Exchange (ETDEWEB)

    Hong Thanh, Bui Thi; Zapata, F [FAO/IAEA Agriculture and Biotechnology Lab., Seibersdorf (Austria). Soils Science Unit; Bowen, G D; Kumarasinghe, K S [Joint FAO/IAEA Div. of Nuclear Techniques in Food and Agriculture, Vienna (Austria). Soil Fertility, Irrigation and Crop Production Section


    Phosphate uptake and use by five genotypes of paddy rice were studied at five phosphate levels in pot studies for 49 days. For all five P levels there were marked genotypic differences in shoot growth, plant dry weight, root/shoot ratios, phosphate uptake and translocation, P content of roots and shoots, and phosphorus use efficiency of shoots (PUE, g shoot mg P{sup -1} in shoot). There were significant genotypic differences in root weight (4 P levels) and in uptake/mg root (all P levels). These latter may have resulted from differences in root weight/root length conversion, root hair development or uptake characteristics, factors which were not studied specifically. Differences between genotypes and P levels in the percentage translocation were partly explicable by differences in P uptake/plant (r = 0.72) but especially by differences in root/shoot ratios (r = 0.89). Differences in PUE were largely a factor of P percentage of the tops (r = 0.94) but significant differences between genotypes were shown as a function of % P. Differences in net photosynthesis rates were largely, but not entirely, due to differences in P % of the shoots. Key factors in P uptake and use and genotypic differences are root growth, uptake/mg root, root/shoot ratios and PUE. (author). 9 refs, 2 figs, 3 tabs.

  5. Distribution of HCV genotypes among different exposure categories in Brazil

    Directory of Open Access Journals (Sweden)

    Oliveira M.L.A.


    Full Text Available Hepatitis C virus (HCV infection is widespread and responsible for more than 60% of chronic hepatitis cases. HCV presents a genetic variability which has led to viral classification into at least 6 genotypes and a series of subtypes. These variants present characteristic geographical distribution, but their association with different responses to treatment with interferon and severity of disease still remains controversial. The aim of this study was to investigate the patterns of distribution of HCV genotypes among different exposure categories in Brazil. Two hundred and fifty anti-HCV positive samples were submitted to HCV-RNA detection by RT-PCR and their genotype was determined by restriction fragment length polymorphism (RFLP analysis. In addition, the genotype/subtype of 60 samples was also determined by a reverse hybridization assay. HCV 1 was the most prevalent (72.0%, followed by type 3 (25.3%, HCV 2 (2.0% and HCV 4 (0.7%. The HCV genotype distribution varied among the different exposure categories, with HCV 1 being more frequent among blood donors, hemophiliacs and hemodialysis patients. A high frequency of HCV 3 was observed in cirrhotic patients, blood donors from the South of Brazil and injecting drug users (IDUs. The general distribution of the HCV genotype in Brazil is similar to that in other regions of the world.

  6. Genetic diversity of some chili (Capsicum annuum L. genotypes

    Directory of Open Access Journals (Sweden)

    M.J. Hasan


    Full Text Available A study on genetic diversity was conducted with 54 Chili (Capsicum annuum L. genotypes through Mohalanobis’s D2 and principal component analysis for twelve quantitative characters viz. plant height, number of secondary branch/plant, canopy breadth , days to first flowering, days to 50% flowering, fruits/plant, 5 fruits weight, fruit length, fruit diameter, seeds/fruit, 1000 seed weight and yield/plant were taken into consideration. Cluster analysis was used for grouping of 54 chili genotypes and the genotypes were fallen into seven clusters. Cluster II had maximum (13 and cluster III had the minimum number (1 of genotypes. The highest inter-cluster distance was observed between cluster I and III and the lowest between cluster II and VII. The characters yield/plant, canopy breadth, secondary branches/plant, plant height and seeds/fruit contributed most for divergence in the studied genotypes. Considering group distance, mean performance and variability the inter genotypic crosses between cluster I and cluster III, cluster III and cluster VI, cluster II and cluster III and cluster III and cluster VII may be suggested to use for future hybridization program.

  7. Performance of Garden Pea Genotypes in Eastern Hills of Nepal

    Directory of Open Access Journals (Sweden)

    Krishna Poudel


    Full Text Available Garden pea (Pisum sativum L is an important winter legume used as fresh vegetables and other drier food products. Despite of its importance as cash crop in many parts of Nepal, much study on various aspects for enhancing production and productivity has yet to be done. Therefore, to evaluate the production performance different genotypes of garden pea in eastern hills agro-ecological conditions present experiments were carried out consecutively for two years (2015 and 2016 at Agricultural Research Station, Pakhribas. The experiment comprised of 11 different genotypes of garden pea including a check variety Arkel. The production performance was evaluated in a completely randomized block design with three replications. The seeds were sown at 50 × 10 cm spacing during first week of October for two years. The result showed that DGP-05 genotype had earliest 104 days after sowing. The DGP-08 genotype showed 13 which were the maximum numbers of pods per plant (13, while DGP-01 showed 8 numbers of seeds as the maximum per pod. The DGP-03 genotype had the longest pod of 9.78 cm among others. The highest fresh pod yield of 18.14 t/ha was achieved from genotype DGP-09 followed by Arkel with (16.32 t/ha.

  8. Characterization of some sunflower genotypes using ISSR markers

    International Nuclear Information System (INIS)

    Mokrani, L.; Nabulsi, I.; MirAli, N.


    Sunflower (Helianthus annuus L.) is grown mostly as a source of vegetable oil of high quality and is especially used in food industry. It is generally produced by multinationals and sold as hybrids. Our research, based on two techniques (ISSR and RAPD), is considered as the first one to be interested in molecular characterization of sunflower genotypes in Syria. We used 25 ISSR primers and 13 RAPD primers to study 29 sunflower genotypes and two reference controls belonging to the same family (Calendula officinalis L. and Targets erecta L.). ISSR results revealed a low polymorphism when compared to other studies. We noticed also 11 genotypes genetically related where percent disagreement values (PDV) didn't exceed 1%, they are 7189 - 7191 - 7184 - 7183 - 443 - 441 - Ghab1 -Ghab2 - Ghab3 - Ghab4 - Ghab5 - Madakh halab - Sarghaya4 -Tarkibi knitra. Sarghaya4 and Tarkibi knitra have indeed the lowest yield and some common morphological characters. At the opposite, the genotype Hysum33 has the highest yield and is genetically distant from the other genotypes. All the genotypes could be used in QTL detection as we didn't notice any similarity between them. (author)

  9. Direct maximum parsimony phylogeny reconstruction from genotype data. (United States)

    Sridhar, Srinath; Lam, Fumei; Blelloch, Guy E; Ravi, R; Schwartz, Russell


    Maximum parsimony phylogenetic tree reconstruction from genetic variation data is a fundamental problem in computational genetics with many practical applications in population genetics, whole genome analysis, and the search for genetic predictors of disease. Efficient methods are available for reconstruction of maximum parsimony trees from haplotype data, but such data are difficult to determine directly for autosomal DNA. Data more commonly is available in the form of genotypes, which consist of conflated combinations of pairs of haplotypes from homologous chromosomes. Currently, there are no general algorithms for the direct reconstruction of maximum parsimony phylogenies from genotype data. Hence phylogenetic applications for autosomal data must therefore rely on other methods for first computationally inferring haplotypes from genotypes. In this work, we develop the first practical method for computing maximum parsimony phylogenies directly from genotype data. We show that the standard practice of first inferring haplotypes from genotypes and then reconstructing a phylogeny on the haplotypes often substantially overestimates phylogeny size. As an immediate application, our method can be used to determine the minimum number of mutations required to explain a given set of observed genotypes. Phylogeny reconstruction directly from unphased data is computationally feasible for moderate-sized problem instances and can lead to substantially more accurate tree size inferences than the standard practice of treating phasing and phylogeny construction as two separate analysis stages. The difference between the approaches is particularly important for downstream applications that require a lower-bound on the number of mutations that the genetic region has undergone.

  10. Association of yield-related traits in founder genotypes and derivatives of common wheat (Triticum aestivum L.

    Directory of Open Access Journals (Sweden)

    Jie Guo


    Full Text Available Abstract Background Yield improvement is an ever-important objective of wheat breeding. Studying and understanding the phenotypes and genotypes of yield-related traits has potential for genetic improvement of crops. Results The genotypes of 215 wheat cultivars including 11 founder parents and 106 derivatives were analyzed by the 9 K wheat SNP iSelect assay. A total of 4138 polymorphic single nucleotide polymorphism (SNP loci were detected on 21 chromosomes, of which 3792 were mapped to single chromosome locations. All genotypes were phenotyped for six yield-related traits including plant height (PH, spike length (SL, spikelet number per spike (SNPS, kernel number per spike (KNPS, kernel weight per spike (KWPS, and thousand kernel weight (TKW in six irrigated environments. Genome-wide association analysis detected 117 significant associations of 76 SNPs on 15 chromosomes with phenotypic explanation rates (R 2 ranging from 2.03 to 12.76%. In comparing allelic variation between founder parents and their derivatives (106 and other cultivars (98 using the 76 associated SNPs, we found that the region 116.0–133.2 cM on chromosome 5A in founder parents and derivatives carried alleles positively influencing kernel weight per spike (KWPS, rarely found in other cultivars. Conclusion The identified favorable alleles could mark important chromosome regions in derivatives that were inherited from founder parents. Our results unravel the genetic of yield in founder genotypes, and provide tools for marker-assisted selection for yield improvement.

  11. Eukaryotic translation initiation factor 5A of wheat: Identification ...

    African Journals Online (AJOL)



    . The available literature indi- cated that the expression of eIF5A was temporal and spatial difference and suppressing eIF5A activation causes pleiotropic effects. Transcript analysis reveals that two tobacco eIF5A genes ...

  12. Understanding of failure and failure of understanding: Aspects of failure in the Old Testament

    Directory of Open Access Journals (Sweden)

    James Alfred Loader


    Full Text Available Taking its cue from Rudolf Bultmann’s famous verdict that the Old Testament is a ‘failure’ (‘Scheitern’, the article reviews three influential negative readings of Israel’s history as told in the Former Prophets. It is then argued that awareness of the theological problem posed by Israel’s history enabled the redactors of both the former and the latter prophetic collections to deal with the element of human failure in a way that facilitated Israel’s retaining of her faith. Next, the sapiential insight in failing human discernment is drawn into the equation. Failure of human action is here interrelated with failure to comprehend God’s order. By virtue of its incorporation into the totality of the Tanak, this insight became a constructive part of Israel’s faith. Therefore the concept of failure comprises more than coming to terms with Israel’s catastrophic history. Since it is encoded in Israel’s Holy Scripture, ‘failure’ is a major concept within the Old Testament internally and is therefore not suitable as a verdict over the Old Testament by an external value judgement. ‘Failure’ thus becomes a key hermeneutical category, not merely so that the Old Testament could become a ‘promise’ for the New Testament to fulfil, but as a manifestation of limits in human religion and thought. Far from undermining self-esteem, constructive use of the concept of her own failure sustained Israel in her catastrophe and should be adopted by Christianity – not least in South Africa, where the biblical message was often misappropriated to bolster apartheid.

  13. Failure modes of composite sandwich beams

    Directory of Open Access Journals (Sweden)

    Gdoutos E.


    Full Text Available A thorough investigation of failure behavior of composite sandwich beams under three-and four-point bending was undertaken. The beams were made of unidirectional carbon/epoxy facings and a PVC closed-cell foam core. The constituent materials were fully characterized and in the case of the foam core, failure envelopes were developed for general two-dimensional states of stress. Various failure modes including facing wrinkling, indentation failure and core failure were observed and compared with analytical predictions. The initiation, propagation and interaction of failure modes depend on the type of loading, constituent material properties and geometrical dimensions.

  14. Cloning of the unculturable parasite Pasteuria ramosa and its Daphnia host reveals extreme genotype-genotype interactions. (United States)

    Luijckx, Pepijn; Ben-Ami, Frida; Mouton, Laurence; Du Pasquier, Louis; Ebert, Dieter


    The degree of specificity in host-parasite interactions has important implications for ecology and evolution. Unfortunately, specificity can be difficult to determine when parasites cannot be cultured. In such cases, studies often use isolates of unknown genetic composition, which may lead to an underestimation of specificity. We obtained the first clones of the unculturable bacterium Pasteuria ramosa, a parasite of Daphnia magna. Clonal genotypes of the parasite exhibited much more specific interactions with host genotypes than previous studies using isolates. Clones of P. ramosa infected fewer D. magna genotypes than isolates and host clones were either fully susceptible or fully resistant to the parasite. Our finding enhances our understanding of the evolution of virulence and coevolutionary dynamics in this system. We recommend caution when using P. ramosa isolates as the presence of multiple genotypes may influence the outcome and interpretation of some experiments. © 2010 Blackwell Publishing Ltd/CNRS.

  15. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance. (United States)

    Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof


    Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1-6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%-0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be

  16. Proinflammatory genotype of interleukin-1 and interleukin-1 receptor antagonist is associated with ESRD in proteinase 3-ANCA vasculitis patients. (United States)

    Borgmann, Stefan; Endisch, Georg; Hacker, Ulrich T; Song, Bong-Seok; Fricke, Harald


    Small-vessel vasculitides are associated with antineutrophil cytoplasmic antibodies (ANCAs). Cytoplasmic ANCAs are targeted mainly against proteinase 3 (PR3), whereas myeloperoxidase (MPO) is the major antigen of perinuclear ANCAs. These relapsing vasculitides show heterogeneous clinical pictures, and disease severity may vary broadly from mild local organ manifestation to acute organ failure (eg, renal failure). We tested whether two cytokine polymorphisms in the interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) genes, known to determine cytokine secretion, are associated with clinical manifestations and outcome of ANCA-associated vasculitides. Polymerase chain reaction and restriction fragment length polymorphism analyses were performed to determine polymorphisms in the IL-1beta and IL-1ra genes in 79 patients with PR3-ANCA, 30 patients with MPO-ANCA vasculitis, and 196 healthy controls. The frequency of the so-called proinflammatory genotype, characterized by high secretion of IL-1beta and low secretion of its antagonist IL-1ra, was increased significantly in patients with PR3-ANCA with end-stage renal disease. Patients with a renal manifestation of PR3-ANCA vasculitis have an increased risk for developing end-stage renal disease when carrying the proinflammatory IL-1beta/IL-1ra genotype. Anti-inflammatory therapy specifically antagonizing the proinflammatory effect of IL-1beta may be a promising treatment for patients with Wegener's granulomatosis with renal manifestations.

  17. Acute renal failure in children

    International Nuclear Information System (INIS)

    Vergesslich, K.A.; Balzar, E.; Weninger, M.; Ponhold, W.; Sommer, G.; Wittich, G.R.; Vienna Univ.


    Acute renal failure (ARF) may be due to obstructive uropathy or renal parenchymal disease. Twenty-five children with acute renal failure secondary to renal parenchymal disease underwent ultrasonographic examination of the kidneys. Changes of renal size and cortical echogenicity were correlated with renal function. All patients presented with bilaterally enlarged kidneys with the exception in renal function resulted in normalization of renal size. With regard to cortical echogenicity two groups were formed. Group A comprised 11 patients whose kidneys had the same echogenicity as the liver, while in group B the kidneys were more echogenic (14 patients). Cortical echogenicity was always increased. Determination of creatinine levels showed a statistically significant difference between group A (3.32 mg% ± 1.40 S.D.) and group B (5.95 mg% ± 1.96 S.D.), p < 0.001. Changes in renal function were paralleled by rapid changes in renal size and cortical echogenicity. (orig.)

  18. Failure modes of laminate structures

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, L.B.; Druce, R.L.; Wilson, M.J.


    Laminate structures composed of alternating thin layers of conductor and dielectric material are commonly used in energy storage and transmission components. The failure of the dielectric layers in regions of high field stress, with applied 60 Hz ac, dc and impulse voltages, was studied. Several geometries were compared, including staggered and flush edges. Electrical trees developed between the laminated dielectric layers. The visual characteristics and growth rates of the electrical trees under ac, dc and impulse stresses were different. Partial discharge detection and analysis was used to measure the inception voltage and discharge activity at the conductor edge voids, to observe tree formation and growth, and to predict impending failure due to dielectric erosion. Electric field distributions were modeled and partial discharge inception levels were estimated from known void geometries. The staggered edge geometry appears to enhance the electric field stress at the recessed electrode.

  19. Shear failure of granular materials (United States)

    Degiuli, Eric; Balmforth, Neil; McElwaine, Jim; Schoof, Christian; Hewitt, Ian


    Connecting the macroscopic behavior of granular materials with the microstructure remains a great challenge. Recent work connects these scales with a discrete calculus [1]. In this work we generalize this formalism from monodisperse packings of disks to 2D assemblies of arbitrarily shaped grains. In particular, we derive Airy's expression for a symmetric, divergence-free stress tensor. Using these tools, we derive, from first-principles and in a mean-field approximation, the entropy of frictional force configurations in the Force Network Ensemble. As a macroscopic consequence of the Coulomb friction condition at contacts, we predict shear failure at a critical shear stress, in accordance with the Mohr-Coulomb failure condition well known in engineering. Results are compared with numerical simulations, and the dependence on the microscopic geometric configuration is discussed. [4pt] [1] E. DeGiuli & J. McElwaine, PRE 2011. doi: 10.1103/PhysRevE.84.041310

  20. Congenital hypopituitarism and renal failure

    Directory of Open Access Journals (Sweden)

    Gaurav Atreja


    Full Text Available Congenital hypopituitarism is potentially fatal in the newborn period but treatable if the diagnosis is made early. We report a neonate who presented with hypothermia and severe hypoglycemia. He also had undescended testis and micropenis. Initial screening revealed panhypopituitarism, which was corrected promptly. He developed renal failure due to initial cardiovascular compromise related to hypotension but recovered quickly with standard management. Magnetic resonance imaging revealed absent stalk of anterior pituitary.